The Pharmacological Management of Oppositional Behaviour, Conduct Problems, and Aggression in Children and Adolescents With Attention-Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, and Conduct Disorder: A Systematic Review and Meta-Analysis. Part 2: Antipsychotics and Traditional Mood Stabilizers

PubMed Central

Pringsheim, Tamara; Hirsch, Lauren; Gardner, David; Gorman, Daniel A

2015-01-01

Objective: Attention-deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) are among the most common psychiatric diagnoses in childhood. Aggression and conduct problems are a major source of disability and a risk factor for poor long-term outcomes. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) of antipsychotics, lithium, and anticonvulsants for aggression and conduct problems in youth with ADHD, ODD, and CD. Each medication was given an overall quality of evidence rating based on the Grading of Recommendations Assessment, Development and Evaluation approach. Results: Eleven RCTs of antipsychotics and 7 RCTs of lithium and anticonvulsants were included. There is moderate-quality evidence that risperidone has a moderate-to-large effect on conduct problems and aggression in youth with subaverage IQ and ODD, CD, or disruptive behaviour disorder not otherwise specified, with and without ADHD, and high-quality evidence that risperidone has a moderate effect on disruptive and aggressive behaviour in youth with average IQ and ODD or CD, with and without ADHD. Evidence supporting the use of haloperidol, thioridazine, quetiapine, and lithium in aggressive youth with CD is of low or very-low quality, and evidence supporting the use of divalproex in aggressive youth with ODD or CD is of low quality. There is very-low-quality evidence that carbamazepine is no different from placebo for the management of aggression in youth with CD. Conclusion: With the exception of risperidone, the evidence to support the use of antipsychotics and mood stabilizers is of low quality. PMID:25886656

Mood dysregulation and stabilization: perspectives from emotional cognitive neuroscience.

PubMed

Yamawaki, Shigeto; Okada, Go; Okamoto, Yasumasa; Liberzon, Israel

2012-06-01

Mood is conceptualized as a long-lasting emotional state, which can have profound implications for mental and physical health. The development of neuroimaging methods has enabled significant advances towards elucidating the mechanisms underlying regulation of mood and emotion; however, our understanding of mood and emotion dysregulation in stress-related psychiatric disorders is still largely lacking. From the cognitive-affective neuroscience perspective, achieving deeper, more mechanistic understanding of mood disorders necessitates detailed understanding of specific components of neural systems involved in mood dysregulation and stabilization. In this review, we provide an overview of neural systems implicated in the development of a long-term negative mood state, as well as those related to emotion and emotion regulation, and discuss their proposed involvement in mood and anxiety disorders.

Changes in mood stabilizer prescription patterns in bipolar disorder.

PubMed

Karanti, Alina; Kardell, Mathias; Lundberg, Ulrika; Landén, Mikael

2016-05-01

Lithium is a first line treatment option in bipolar disorder, but several alternative treatments have been introduced in recent years, such as antiepileptic and atypical antipsychotic drugs. Little is known about how this has changed the prescription patterns. We investigated possible changes in the use of mood stabilizers and antidepressants in Sweden during 2007-2013. Data was collected from Swedish registers: the National Quality Assurance Register for bipolar disorder (BipoläR), the Prescribed Drug Register, and the Patient Register. Logistic regression models with drug use as outcomes were used to adjust for confounding factors such as sex, age, year of registration, and subtypes of bipolar disorder. In both bipolar subtypes, lithium use decreased steadily during the study period, while the use of lamotrigine and quetiapine increased. The use of valproate decreased in bipolar II disorder and the use of olanzapine decreased among women. The use of antidepressant remained principally unchanged but increased somewhat in bipolar I disorder. We only report data from 2007 as the coverage of BipoläR prior to 2007 was too low to allow for reliable analyses. Significant changes in the prescription of drugs in the treatment of bipolar disorder have occurred in recent years in Sweden. Further studies are needed to clarify whether these changes alter the outcome in bipolar disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

Trends in antipsychotic prescriptions for Japanese outpatients during 2006-2012: a descriptive epidemiological study.

PubMed

Kochi, Kenji; Sato, Izumi; Nishiyama, Chika; Tanaka-Mizuno, Sachiko; Doi, Yuko; Arai, Masaru; Fujii, Yosuke; Matsunaga, Toshiyuki; Ogawa, Yusuke; Furukawa, Toshi A; Kawakami, Koji

2017-06-01

This study aimed to assess the trends in antipsychotic prescriptions for outpatients in Japan, where a community-based approach to mental healthcare is emphasized. This descriptive epidemiological study used claims data from 1038 community pharmacies across Japan. Outpatients who were ≥18 years old and receiving their initial antipsychotic prescription during 2006-2012 were evaluated. The annual trends were reported for monotherapies, polypharmacy, antipsychotic doses, and the concurrent prescription of psychotropic medications. The 152 592 outpatients included 101 133 (66%) adults (18-64 years old) and 51 459 (34%) older adults (≥65 years old). Among the adults, second-generation antipsychotic monotherapy prescriptions increased from 49% in 2006 to 71% in 2012, first-generation antipsychotic monotherapy prescriptions decreased from 29 to 14%, and antipsychotic polypharmacy decreased from 23 to 15%, respectively. Among the older adults, second-generation antipsychotic monotherapy prescriptions increased from 64 to 82%, first-generation antipsychotic monotherapy prescriptions decreased from 29 to 12%, and antipsychotic polypharmacy decreased from 7 to 6%, respectively. During the study period, >80% of the adults and >90% of the older adults received antipsychotics at risperidone-equivalent doses of <6 mg/day. Anxiolytics/hypnotics, antidepressants, antiparkinson agents, mood stabilizers, and anti-dementia agents were concurrently prescribed with antipsychotics for 70, 33, 20, 20, and 0.3% of the adults and for 43, 16, 19, 8, and 16% of the older adults, respectively. The present study evaluated large-scale claims-based datasets and found that high-dose prescriptions and antipsychotic polypharmacy among Japanese outpatients were not as prevalent as has been previously thought. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview

PubMed Central

Pompili, Maurizio; Baldessarini, Ross J.; Forte, Alberto; Erbuto, Denise; Serafini, Gianluca; Fiorillo, Andrea; Amore, Mario; Girardi, Paolo

2016-01-01

Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia). We carried out a systematic, computerized search for reports of studies involving antipsychotic drug treatment and suicidal behaviors. A total of 19 reports provide data with preliminary support for potential suicide risk-reducing effects of olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in addition to clozapine, and provide some support for antipsychotic drug treatment in general. These preliminary findings encourage further testing of antipsychotics for effects on suicidal behavior, making use of explicit, pre-planned assessments of suicidal behavior. PMID:27727180

Association of the Centers for Medicare & Medicaid Services' National Partnership to Improve Dementia Care With the Use of Antipsychotics and Other Psychotropics in Long-term Care in the United States From 2009 to 2014.

PubMed

Maust, Donovan T; Kim, H Myra; Chiang, Claire; Kales, Helen C

2018-03-17

The Centers for Medicare & Medicaid Services' National Partnership to Improve Dementia Care in Nursing Homes (hereafter referred to as the partnership) was established to improve the quality of care for patients with dementia, measured by the rate of antipsychotic prescribing. To determine the association of the partnership with trends in prescribing of antipsychotic and other psychotropic medication among older adults in long-term care. This interrupted time-series analysis of a 20% Medicare sample from January 1, 2009, to December 31, 2014, was conducted among 637 426 fee-for-service Medicare beneficiaries in long-term care with Part D coverage. Data analysis was conducted from May 1, 2017, to January 9, 2018. Quarterly prevalence of use of antipsychotic and nonantipsychotic psychotropic medications (antidepressants, mood stabilizers [eg, valproic acid and carbamazepine], benzodiazepines, and other anxiolytics or sedative-hypnotics). Among the 637 426 individuals in the study (446 538 women and 190 888 men; mean [SD] age at entering nursing home, 79.3 [12.1] years), psychotropic use was declining before initiation of the partnership with the exception of mood stabilizers. In the first quarter of 2009, a total of 31 056 of 145 841 patients (21.3%) were prescribed antipsychotics, which declined at a quarterly rate of -0.53% (95% CI, -0.63% to -0.44%; P < .001) until the start of the partnership. At that point, the quarterly rate of decline decreased to -0.29% (95% CI, -0.39% to -0.20%; P < .001), a postpartnership slowing of 0.24% per quarter (95% CI, 0.09%-0.39%; P = .003). The use of mood stabilizers was growing before initiation of the partnership and then accelerated after initiation of the partnership (rate, 0.22%; 95% CI, 0.18%-0.25%; P < .001; rate change, 0.14%; 95% CI, 0.10%-0.18%; P < .001), reaching 71 492 of 355 716 patients (20.1%) by the final quarter of 2014. Antidepressants were the most commonly prescribed

The use of atypical antipsychotics beyond psychoses: efficacy of quetiapine in bipolar disorder.

PubMed

Mundo, Emanuela; Cattaneo, Elisabetta; Zanoni, Silvia; Altamura, A Carlo

2006-06-01

Atypical antpsychotics have been sucessfully used in the treatment of bipolar disorder (BD), either as adjunctive or as monotherapy. Quetiapine is an atypical antipsychotic extensively used in the treatment of psychotic disorders. It has serotonergic and dopaminergic activity and it appears to be selective for the mesolimbic and mesocortical dopamine system. The aim of this paper was to review the recent literature on the use of quetiapine in the treatment of BD. The literature databases currently available online were searched for papers on quetiapine and BD. Papers and reports published between January 1995 and June 2005 were selected and reviewed critically. Augmentative low dose quetiapine was found to be effective in BD partially responsive to conventional mood-stabilizers. Manic and mixed episodes have been the best studied, and quetiapine was found to be effective either as monotherapy or as adjunctive therapy in both randomized clinical trials and open-label studies. Data on the use of quetiapine in bipolar depression showed a significant efficacy and high remission rates. Maintenance data suggested a role of quetiapine as a good alternative to classical mood stabilizers in reducing recurrence rates of BD. A few studies on the efficacy in rapid cycling BD have also been published. Quetiapine is an effective agent for the short- and long-term treatment of BD. The mechanism of action of quetiapine as a mood stabilizer is still unknown. Some preliminary data suggest the involvement of glutamate pathways but further studies are needed to clarify this issue.

Blonanserin-induced Mood Alteration in Schizophrenia and Schizoaffective Disorder: Two Cases.

PubMed

Min, Aran; Kim, Daeho

2013-12-01

We report two outpatients, one with schizophrenia and one with schizoaffective disorder, who developed manic or hypomanic episodes following the initiation of blonanserin during the course of treatment. Blonanserin is a novel antipsychotic that acts as a 5-HT and D2 receptor antagonist. Both patients developed hypomanic episodes within 2 weeks of receiving a small dose (6-8 mg) of blonanserin, and one patient later developed full-blown mania; both episodes ended within 1 month of discontinuing blonanserin. The mood alteration observed in these cases suggests a possible antidepressant effect of blonanserin; thus, clinicians should monitor mood changes when administering this antipsychotic.

FXR1P is a GSK3β substrate regulating mood and emotion processing

PubMed Central

Del’Guidice, Thomas; Latapy, Camille; Rampino, Antonio; Khlghatyan, Jivan; Lemasson, Morgane; Gelao, Barbara; Quarto, Tiziana; Rizzo, Giuseppe; Barbeau, Annie; Lamarre, Claude; Bertolino, Alessandro; Blasi, Giuseppe; Beaulieu, Jean-Martin

2015-01-01

Inhibition of glycogen synthase kinase 3β (GSK3β) is a shared action believed to be involved in the regulation of behavior by psychoactive drugs such as antipsychotics and mood stabilizers. However, little is known about the identity of the substrates through which GSK3β affects behavior. We identified fragile X mental retardation-related protein 1 (FXR1P), a RNA binding protein associated to genetic risk for schizophrenia, as a substrate for GSK3β. Phosphorylation of FXR1P by GSK3β is facilitated by prior phosphorylation by ERK2 and leads to its down-regulation. In contrast, behaviorally effective chronic mood stabilizer treatments in mice inhibit GSK3β and increase FXR1P levels. In line with this, overexpression of FXR1P in the mouse prefrontal cortex also leads to comparable mood-related responses. Furthermore, functional genetic polymorphisms affecting either FXR1P or GSK3β gene expression interact to regulate emotional brain responsiveness and stability in humans. These observations uncovered a GSK3β/FXR1P signaling pathway that contributes to regulating mood and emotion processing. Regulation of FXR1P by GSK3β also provides a mechanistic framework that may explain how inhibition of GSK3β can contribute to the regulation of mood by psychoactive drugs in mental illnesses such as bipolar disorder. Moreover, this pathway could potentially be implicated in other biological functions, such as inflammation and cell proliferation, in which FXR1P and GSK3 are known to play a role. PMID:26240334

Effects of switching to aripiprazole from current atypical antipsychotics on subsyndromal symptoms and tolerability in patients with bipolar disorder.

PubMed

Woo, Young Sup; Bahk, Won-Myong; Park, Young-Min; Chung, Sangkeun; Yoon, Bo-Hyun; Won, Seunghee; Lee, Jeong Goo; Lee, Hwang-Bin; Kim, Won; Jeong, Jong-Hyun; Lee, Kwanghun; Kim, Moon-Doo

2016-09-01

We evaluated the effectiveness of aripiprazole among bipolar patients who had switched to this medication as a result of difficulty maintaining on their prestudy atypical antipsychotics (AAPs) because of subsyndromal mood symptoms or intolerance. This study included 77 bipolar patients who were in syndromal remission with an AAP as monotherapy or with an AAP combined with a mood stabilizer(s) who needed to switch from their present AAP because of subsyndromal symptoms or intolerance. At 24 weeks after switching to aripiprazole, the remission rates on the Montgomery-Åsberg Depression Rating Scale (MADRS) and on both the MADRS and the Young Mania Rating Scale were increased significantly in the full sample and in the inefficacy subgroup. In the inefficacy subgroup, the MADRS score change was significant during the 24 weeks of study. Total cholesterol and prolactin decreased significantly after switching to aripiprazole. The proportion of patients who had abnormal values for central obesity and hypercholesterolemia decreased significantly from baseline to week 24. These findings suggest that a change from the current AAP to aripiprazole was associated with improvement in subsyndromal mood symptoms and several lipid/metabolic or safety profile parameters in patients with bipolar disorder with tolerability concerns or subsyndromal mood symptoms.

Mood stabilizer treatment increases serotonin type 1A receptor binding in bipolar depression

PubMed Central

Nugent, Allison C; Carlson, Paul J; Bain, Earle E; Eckelman, William; Herscovitch, Peter; Manji, Husseini; Zarate, Carlos A; Drevets, Wayne C

2013-01-01

Abnormal serotonin type 1A (5-HT1A) receptor function and binding have been implicated in the pathophysiology of mood disorders. Preclinical studies have consistently shown that stress decreases the gene expression of 5-HT1A receptors in experimental animals, and that the associated increase in hormone secretion plays a crucial role in mediating this effect. Chronic administration of the mood stabilizers lithium and divalproex (valproate semisodium) reduces glucocorticoid signaling and function in the hippocampus. Lithium has further been shown to enhance 5-HT1A receptor function. To assess whether these effects translate to human subject with bipolar disorder (BD), positron emission tomography (PET) and [18F]trans-4-fluoro-N-(2-[4-(2-methoxyphenyl) piperazino]-ethyl)-N-(2-pyridyl) cyclohexanecarboxamide ([18F]FCWAY) were used to acquire PET images of 5-HT1A receptor binding in 10 subjects with BD, before and after treatment with lithium or divalproex. Mean 5-HT1A binding potential (BPP) significantly increased following mood stabilizer treatment, most prominently in the mesiotemporal cortex (hippocampus plus amygdala). When mood state was also controlled for, treatment was associated with increases in BPP in widespread cortical areas. These preliminary findings are consistent with the hypothesis that these mood stabilizers enhance 5-HT1A receptor expression in BD, which may underscore an important component of these agents' mechanism of action. PMID:23926239

Blonanserin-induced Mood Alteration in Schizophrenia and Schizoaffective Disorder: Two Cases

PubMed Central

Min, Aran

2013-01-01

We report two outpatients, one with schizophrenia and one with schizoaffective disorder, who developed manic or hypomanic episodes following the initiation of blonanserin during the course of treatment. Blonanserin is a novel antipsychotic that acts as a 5-HT and D2 receptor antagonist. Both patients developed hypomanic episodes within 2 weeks of receiving a small dose (6-8 mg) of blonanserin, and one patient later developed full-blown mania; both episodes ended within 1 month of discontinuing blonanserin. The mood alteration observed in these cases suggests a possible antidepressant effect of blonanserin; thus, clinicians should monitor mood changes when administering this antipsychotic. PMID:24465254

Negative moods and the motivated remembering of past selves: the role of implicit theories of personal stability.

PubMed

McFarland, Cathy; Buehler, Roger

2012-02-01

This research program explored how the positivity of people's memories of their past personal attributes is influenced by their desire to cope with negative mood states. The studies tested the hypothesis that beliefs and motives regarding the stability of personality will determine whether people idealize or derogate their earlier attributes in an attempt to repair distressing feelings. When knowledge structures or motives implying personal change are activated, people should derogate their past selves in response to negative moods; in contrast, when these factors imply personal stability, people should idealize their past selves in response to negative moods. Studies 1-3, which assessed the impact of mood negativity (neutral vs. negative) and theories (or motives) regarding personal change (change vs. stability) on the positivity of people's memories of their past attributes, supported this reasoning. Study 4 extended these findings by examining how an underlying mediating variable--mood-repair motivation--guides the effect of negative moods on recall of past selves. Implications of the results for research on temporal comparison, mood-congruent recall, and posttraumatic growth are discussed.

The use of atypical antipsychotics beyond psychoses: efficacy of quetiapine in bipolar disorder

PubMed Central

Mundo, Emanuela; Cattaneo, Elisabetta; Zanoni, Silvia; Altamura, A Carlo

2006-01-01

Background and rationale Atypical antpsychotics have been sucessfully used in the treatment of bipolar disorder (BD), either as adjunctive or as monotherapy. Quetiapine is an atypical antipsychotic extensively used in the treatment of psychotic disorders. It has serotonergic and dopaminergic activity and it appears to be selective for the mesolimbic and mesocortical dopamine system. The aim of this paper was to review the recent literature on the use of quetiapine in the treatment of BD. Methods The literature databases currently available online were searched for papers on quetiapine and BD. Papers and reports published between January 1995 and June 2005 were selected and reviewed critically. Results Augmentative low dose quetiapine was found to be effective in BD partially responsive to conventional mood-stabilizers. Manic and mixed episodes have been the best studied, and quetiapine was found to be effective either as monotherapy or as adjunctive therapy in both randomized clinical trials and open-label studies. Data on the use of quetiapine in bipolar depression showed a significant efficacy and high remission rates. Maintenance data suggested a role of quetiapine as a good alternative to classical mood stabilizers in reducing recurrence rates of BD. A few studies on the efficacy in rapid cycling BD have also been published. Conclusions Quetiapine is an effective agent for the short- and long-term treatment of BD. The mechanism of action of quetiapine as a mood stabilizer is still unknown. Some preliminary data suggest the involvement of glutamate pathways but further studies are needed to clarify this issue. PMID:19412458

Extrapyramidal side effects of antipsychotic treatment: scope of problem and impact on outcome.

PubMed

Tandon, Rajiv; Jibson, Michael D

2002-06-01

Previously, clinicians worked with antipsychotic drugs (conventional or typical) that almost invariably caused extrapyramidal symptoms (EPS) at clinically effective doses. This led to the false impression that all antipsychotics were the same, and that EPS were an unavoidable consequence of effective antipsychotic therapy. EPS adversely impact several aspects of antipsychotic efficacy and tolerability, thereby worsening outcome of afflicted individuals. EPS reduce beneficial effects of antipsychotic treatment on the negative, cognitive, and mood symptom domains, while increasing the risk of tardive dyskinesia and reducing compliance. By definition, the newer generation of "atypical" antipsychotic agents are significantly better than conventional agents with regard to EPS (i.e., they are clinically effective at doses at which they do not cause EPS). Pharmacologically, this difference is expressed in the greater degree of separation between respective dose response curves for antipsychotic and EPS effects observed for "atypical" in contrast to conventional agents. Clinically, this EPS advantage of atypical antipsychotics translates into several important benefits, including better negative symptom efficacy, less dysphoria, less impaired cognition, a lower risk of TD, and better overall outcome.

Neuroprotective effect of atypical antipsychotics in cognitive and non-cognitive behavioral impairment in animal models

PubMed Central

He, Jue; Kong, Jiming

2009-01-01

Antipsychotic drugs are divided into two groups: typical and atypical. Recent clinical studies show atypical antipsychotics have advantages over typical antipsychotics in a wide variety of neuropsychiatric conditions, in terms of greater efficacy for positive and negative symptoms, beneficial effects on cognitive functioning, and fewer extra pyramidal side effects in treating schizophrenia. As such, atypical antipsychotics may be effective in the treatment of depressive symptoms associated with psychotic and mood disorders, posttraumatic stress disorder and psychosis in Alzheimer disease. In this paper, we describe the effects and potential neurochemical mechanisms of action of atypical antipsychotics in several animal models showing memory impairments and/or non-cognitive behavioral changes. The data provide new insights into the mechanisms of action of atypical antipsychotics that may broaden their clinical applications. PMID:19372744

Mood instability is a common feature of mental health disorders and is associated with poor clinical outcomes

PubMed Central

Lloyd, Theodore; Jackson, Richard; Ball, Michael; Shetty, Hitesh; Broadbent, Matthew; Geddes, John R; Stewart, Robert; McGuire, Philip; Taylor, Matthew

2015-01-01

Objectives Mood instability is a clinically important phenomenon but has received relatively little research attention. The objective of this study was to assess the impact of mood instability on clinical outcomes in a large sample of people receiving secondary mental healthcare. Design Observational study using an anonymised electronic health record case register. Setting South London and Maudsley NHS Trust (SLaM), a large provider of inpatient and community mental healthcare in the UK. Participants 27 704 adults presenting to SLaM between April 2006 and March 2013 with a psychotic, affective or personality disorder. Exposure The presence of mood instability within 1 month of presentation, identified using natural language processing (NLP). Main outcome measures The number of days spent in hospital, frequency of hospital admission, compulsory hospital admission and prescription of antipsychotics or non-antipsychotic mood stabilisers over a 5-year follow-up period. Results Mood instability was documented in 12.1% of people presenting to mental healthcare services. It was most frequently documented in people with bipolar disorder (22.6%), but was common in people with personality disorder (17.8%) and schizophrenia (15.5%). It was associated with a greater number of days spent in hospital (β coefficient 18.5, 95% CI 12.1 to 24.8), greater frequency of hospitalisation (incidence rate ratio 1.95, 1.75 to 2.17), greater likelihood of compulsory admission (OR 2.73, 2.34 to 3.19) and an increased likelihood of prescription of antipsychotics (2.03, 1.75 to 2.35) or non-antipsychotic mood stabilisers (2.07, 1.77 to 2.41). Conclusions Mood instability occurs in a wide range of mental disorders and is not limited to affective disorders. It is generally associated with relatively poor clinical outcomes. These findings suggest that clinicians should screen for mood instability across all common mental health disorders. The data also suggest that targeted interventions for

Evidence for use of mood stabilizers and anticonvulsants in the treatment of nonaffective disorders in children and adolescents.

PubMed

Amaladoss, Alfred; Roberts, Nasreen; Amaladoss, Franklin

2010-01-01

Mood stabilizers and anticonvulsants have been frequently used to control behaviors in children and adolescent with nonaffective disorders. The purpose of this study was to review the literature to evaluate the evidence of these agents as treatment options in this subset of patients. We reviewed all the literature between 1949 and 2009 on the use of anticonvulsants and mood stabilizers in controlling severe behavior dysregulation and aggression in child and adolescent who do not meet the criteria for any mood disorder. The review revealed a total of 19 studies. Of the different mood stabilizers/anticonvulsants, both lithium and divalproex showed some promise in treating children and adolescents with nonmood disorders. Larger studies are nevertheless needed to support the ongoing use of these current anticonvulsants and mood stabilizers in children and adolescents with nonmood disorders. Also, further investigation to the potential use in the long term would need to be established, bearing in mind the balance of side effects and treatment benefit.

Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial.

PubMed

Yatham, L N; Beaulieu, S; Schaffer, A; Kauer-Sant'Anna, M; Kapczinski, F; Lafer, B; Sharma, V; Parikh, S V; Daigneault, A; Qian, H; Bond, D J; Silverstone, P H; Walji, N; Milev, R; Baruch, P; da Cunha, A; Quevedo, J; Dias, R; Kunz, M; Young, L T; Lam, R W; Wong, H

2016-08-01

Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania. Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes, the optimal duration is unknown. As many atypical antipsychotics cause weight gain and metabolic syndrome, they should not be continued unless the benefits outweigh the risks. This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder (n=159) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate. Patients were randomized to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at (i) entry ('0-weeks' group) or (ii) at 24 weeks after entry ('24-weeks' group) or (iii) continuation of risperidone or olanzapine for the full duration of the study ('52-weeks' group). The primary outcome measure was time to relapse of any mood episode. Compared with the 0-weeks group, the time to any mood episode was significantly longer in the 24-weeks group (hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.33, 0.86) and nearly so in the 52-weeks group (HR: 0.63; 95% CI: 0.39, 1.02). The relapse rate was similar in the 52-weeks group compared with the 24-weeks group (HR: 1.18; 95% CI: 0.71, 1.99); however, sub-group analysis showed discordant results between the two antipsychotics (HR: 0.48, 95% CI: 0.17; 1.32 olanzapine patients; HR: 1.85, 95% CI: 1.00, 3.41 risperidone patients). Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups. These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse. Whether continuation of olanzapine beyond this period reduces relapse risk remains unclear

Use of atypical antipsychotics in the elderly: a clinical review

PubMed Central

Gareri, Pietro; Segura-García, Cristina; Manfredi, Valeria Graziella Laura; Bruni, Antonella; Ciambrone, Paola; Cerminara, Gregorio; De Sarro, Giovambattista; De Fazio, Pasquale

2014-01-01

The use of atypical antipsychotic drugs in the elderly has become wider and wider in recent years; in fact, these agents have novel receptor binding profiles, good efficacy with regard to negative symptoms, and reduced extrapyramidal symptoms. However, in recent years, the use of both conventional and atypical antipsychotics has been widely debated for concerns about their safety in elderly patients affected with dementia and the possible risks for stroke and sudden death. A MEDLINE search was made using the words elderly, atypical antipsychotics, use, schizophrenia, psychosis, mood disorders, dementia, behavioral disorders, and adverse events. Some personal studies were also considered. This paper reports the receptor binding profiles and the main mechanism of action of these drugs, together with their main use in psychiatry and the possible adverse events in elderly people. PMID:25170260

Self-harm, Unintentional Injury, and Suicide in Bipolar Disorder During Maintenance Mood Stabilizer Treatment: A UK Population-Based Electronic Health Records Study.

PubMed

Hayes, Joseph F; Pitman, Alexandra; Marston, Louise; Walters, Kate; Geddes, John R; King, Michael; Osborn, David P J

2016-06-01

Self-harm is a prominent cause of morbidity in patients with bipolar disorder and is strongly associated with suicide. There is evolving evidence that lithium use may reduce suicidal behavior, in addition to concerns that the use of anticonvulsants may increase self-harm. Information is limited about the effects of antipsychotics when used as mood stabilizer treatment. Rates of unintentional injury are poorly defined in bipolar disorder, and understanding drug associations with this outcome may shed light on mechanisms for lithium's potential antisuicidal properties through reduction in impulsive aggression. To compare rates of self-harm, unintentional injury, and suicide in patients with bipolar disorder who were prescribed lithium, valproate sodium, olanzapine, or quetiapine fumarate. This investigation was a propensity score (PS)-adjusted and PS-matched longitudinal cohort study in a nationally representative UK sample using electronic health records data collected between January 1, 1995, and December 31, 2013. Participants included all patients diagnosed as having bipolar disorder who were prescribed lithium, valproate, olanzapine, or quetiapine as maintenance mood stabilizer treatment. The primary outcome was any form of self-harm. Secondary outcomes were unintentional injury and suicide. Of the 14 396 individuals with a diagnosis of BPD, 6671 were included in the cohort, with 2148 prescribed lithium, 1670 prescribed valproate, 1477 prescribed olanzapine, and 1376 prescribed quetiapine as maintenance mood stabilizer treatment. Self-harm rates were lower in patients prescribed lithium (205; 95% CI, 175-241 per 10 000 person-years at risk [PYAR]) compared with those prescribed valproate (392; 95% CI, 334-460 per 10 000 PYAR), olanzapine (409; 95% CI, 345-483 per 10 000 PYAR), or quetiapine (582; 95% CI, 489-692 per 10 000 PYAR). This association was maintained after PS adjustment (hazard ratio [HR], 1.40; 95% CI, 1.12-1.74 for valproate, olanzapine

Further Characterization of the Predictive Validity of the Brattleboro Rat Model for Antipsychotic Efficacy

PubMed Central

Feifel, D.; Shilling, P. D.; Melendez, G.

2014-01-01

Our laboratory and others have reported that Brattleboro (BRAT) rats, a Long Evans (LE) strain with a single gene mutation, have inherent deficits in prepulse inhibition (PPI) homologous to those observed in schizophrenia patients and that these deficits are reversed by antipsychotic drugs (APDs). To further evaluate the potential predictive validity of BRAT rat PPI for APDs, we compared the effects of acute subcutaneous administration of the typical APD chlorpromazine to that of three psychotropic drugs without antipsychotic efficacy, the antidepressant imipramine, the anxiolytic diazepam and the anticonvulsant mood stabilizer valproic acid on male and female BRAT rat PPI. Male and female BRAT rats exhibited baseline (saline treatment) PPI that was not different from each other (21.1 % and 21.3 %, respectively) and low compared to those historically exhibited by LE rats (approximately 59 %). Chlorpromazine facilitated PPI in male and female BRAT rats, whereas imipramine, diazepam, and valproic acid had no significant effect on PPI. These results suggest that PPI in the BRAT rat responds specifically to drugs with APD efficacy but not psychotropic drugs of different therapeutic families. PMID:21106605

[French Society for Biological Psychiatry and Neuropsychopharmacology task force: Formal Consensus for the prescription of depot antipsychotics].

PubMed

Samalin, L; Abbar, M; Courtet, P; Guillaume, S; Lancrenon, S; Llorca, P-M

2013-12-01

Compliance is often partial with oral antipsychotics and underestimated for patients with serious mental illness. Despite their demonstrated advantages in terms of relapse prevention, depot formulations are still poorly used in routine. As part of a process to improve the quality of care, French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) Task Force elaborated a Formal Consensus for the prescription of depot antipsychotics in clinical practice. The Task Force recommends as first-line choice, the use of long-acting injectable (LAI) second-generation antipsychotics in patients with schizophrenia, schizoaffective disorder and delusional disorder. They can be considered as a second-line option as a monotherapy to prevent manic recurrence or in combination with mood stabilizer to prevent depressive recurrence in the maintenance treatment of bipolar disorder. LAI second-generation antipsychotics can also be used after a first episode of schizophrenia. Depot neuroleptics are not recommended during the early course of schizophrenia and are not appropriate in bipolar disorder. They are considered as a second-line option for maintenance treatment in schizophrenia. LAI formulations should be systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. LAI antipsychotics can be used preferentially for non-compliant patients with frequent relapses or aggressive behaviors. A specific information concerning the advantages and inconveniences of the LAI formulations, in the framework of shared-decision making must be delivered to each patient. Recommendations for switching from one oral/LAI form to another LAI and for using LAI antipsychotics in specific populations (pregnant women, elderly patients, subjects in a precarious situation, and subjects having to be treated in a prison establishment) are also proposed. Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

Healthcare costs associated with treatment of bipolar disorder using a mood stabilizer plus adjunctive aripiprazole, quetiapine, risperidone, olanzapine or ziprasidone.

PubMed

Jing, Yonghua; Kim, Edward; You, Min; Pikalov, Andrei; Tran, Quynh-Van

2009-06-01

Bipolar disorder has an associated economic burden due to its treatment, including medication and hospitalization costs as well as costs associated with treatment of comorbid conditions. This study compared healthcare costs in patients treated with a mood stabilizer and adjunctive aripiprazole versus adjunctive olanzapine, quetiapine, risperidone or ziprasidone. A retrospective propensity score-matched cohort study was conducted in the LabRx integrated claims database from January 2003 to December 2006. Patients (18-65 years) with bipolar disorder and 180 days of pre-index enrolment without atypical treatment and 90 days post-index enrolment were eligible. Mood stabilizer therapy was initiated prior to index atypical prescription. Generalized gamma regressions were used to compare the total healthcare costs of adjunctive aripiprazole treatment and treatment with adjunctive olanzapine, quetiapine, risperidone or ziprasidone. After controlling for differences in baseline characteristics and pre-index cost, psychiatric costs and subtotal psychiatric and general medical costs were higher for all adjunctive atypicals than adjunctive aripiprazole (p<0.001). Based on gamma regressions cost ratios, there was no significant difference in general medical costs between aripiprazole and ziprasidone, olanzapine, or quetiapine; risperidone general medical costs were 18% higher versus aripiprazole (p=0.041). Aripiprazole pharmacy costs were higher than quetiapine and risperidone (p<0.001) but not olanzapine or ziprasidone. Total healthcare costs were higher for ziprasidone, olanzapine, or risperidone (p<0.001) but not quetiapine. Methodological restriction of patients to those newly initiated on an atypical antipsychotic and incomplete medication history limit the generalizability of the findings. Adjunctive aripiprazole may have economic benefits over other atypicals in terms of lower psychiatric treatment costs than adjunctive olanzapine, quetiapine, risperidone or ziprasidone

Effect of mood stabilizing agents on agonist-induced calcium mobilization in human platelets.

PubMed Central

Kusumi, I; Koyama, T; Yamashita, I

1994-01-01

The effect of mood stabilizing agents such as lithium, carbamazepine, valproic acid and clonazepam on serotonin(5-HT)- or thrombin-induced intracellular calcium (Ca) mobilization was studied in the platelets of healthy subjects using the fluorescent Ca indicator fura-2. After incubating platelet-rich plasma with these drugs for one or four hours, there was no significant difference in either basal Ca2+ concentration or 5-HT-stimulated Ca response between each agent treatment and control. 5-HT- or thrombin-induced Ca mobilization was not altered by four weeks of lithium carbonate administration in healthy volunteers. These results indicate that these mood stabilizers fail to affect the agonist-stimulated intracellular Ca mobilizing pathway either in vitro or ex vivo in the platelets of healthy subjects. Images Fig. 1 PMID:8031747

Clinical characteristics and long-term response to mood stabilizers in patients with bipolar disorder and different age at onset

PubMed Central

Dell’Osso, Bernardo; Buoli, Massimiliano; Riundi, Riccardo; D’Urso, Nazario; Pozzoli, Sara; Bassetti, Roberta; Mundo, Emanuela; Altamura, A Carlo

2009-01-01

Introduction Bipolar disorder (BD) is a prevalent, comorbid, and impairing condition. Potential predictors of response to pharmacological treatment are object of continuous investigation in patients with BD. The present naturalistic study was aimed to assess clinical features and long-term response to mood stabilizers in a sample of bipolar subjects with different ages at onset. Methods The study sample included 108 euthymic patients, diagnosed as affected by BD, either type I or II, according to the DSM-IV-TR, who were started on mood stabilizer treatment. Patients were followed-up for 24 months and the occurrence of any mood episode collected. At the end of the follow-up, patients were divided in 3 subgroups according to the age at onset (early-onset ≤30 years, middle-onset >30–≤45 years, and late-onset >45 years, respectively) and the long-term response to mood stabilizers was compared between them along with other clinical features. Results The three subgroups showed significant differences in terms of clinical and demographic features and, with respect to long-term response to mood stabilizers, the early-onset subgroup showed a better outcome in terms of reduction of major depressive episodes during the 24-month follow-up compared to the other subgroups (one way ANOVA, F = 3.57, p = 0.032). Conclusions Even though further controlled studies are needed to clarify the relationship between age at onset and outcome in BD, the present follow-up study suggests clinical peculiarities and different patterns of response to mood stabilizers across distinct subgroups of patients with BD and different ages at onset. PMID:19649214

A 20-Year multi-followup longitudinal study assessing whether antipsychotic medications contribute to work functioning in schizophrenia.

PubMed

Harrow, Martin; Jobe, Thomas H; Faull, Robert N; Yang, Jie

2017-10-01

To assess the long-term effectiveness of antipsychotic medications in facilitating work functioning in patients with schizophrenia we conducted longitudinal multifollowup research on 139 initially psychotic patients. The 70 patients with schizophrenia and 69 initially psychotic mood disordered control patients were followed up 6 times over 20 years. We compared the influence on work functioning of patients with schizophrenia continuously prescribed antipsychotics with patients with schizophrenia not prescribed antipsychotics, using statistical controls for inter-subject differences. While antipsychotics reduce or eliminate flagrant psychosis for most patients with schizophrenia at acute hospitalizations, four years later and continually until the 20 year followups, patients with schizophrenia not prescribed antipsychotics had significantly better work functioning. The work performance of the patients who were continuously prescribed antipsychotics was at a low rate and did not improve over time. Multiple other factors also interfere with work functioning. The data suggest that some patients with schizophrenia not prescribed antipsychotics for prolonged periods can function relatively well. Multiple other factors are associated with poor post-hospital work performance. The longitudinal data raise questions about prolonged treatment of schizophrenia with antipsychotic medications. Copyright © 2017 Elsevier B.V. All rights reserved.

Correlates of attitudes towards mood stabilizers in individuals with bipolar disorder.

PubMed

Chang, Ching-Wen; Sajatovic, Martha; Tatsuoka, Curtis

2015-02-01

Attitudes towards medication are believed to be important for medication adherence and social factors are believed to have effects on attitudes. Only a limited literature has focused on how attitudes to medication may correlate with social factors relevant to medication adherence among individuals with bipolar disorder (BPD). This secondary analysis of baseline data from a longitudinal study examined the relationships between attitudes towards mood stabilizers and psychosocial variables. Community mental health clinic patients (n = 122) were assessed on the outcome variable of medication attitudes as measured by the Attitudes towards Mood Stabilizers Questionnaire (AMSQ). Independent variables included education as well as standardized measures of psychiatric symptom severity, alcohol and drug problem severity, health locus of control (the belief that one's health is self-determined versus determined by factors outside of one's own control), and psychosocial support. A hierarchical multiple regression model evaluated the relationship between AMSQ and these variables. More positive medication attitudes were seen in individuals with higher levels of social support and in those who held a stronger belief that their health outcomes are determined by others, such as family or clinicians. Education, symptom severity, alcohol problem severity and drug problem severity were not significant attitudinal correlates. Attitudes towards mood stabilizers are correlated with both the support a person receives from others in their social network and how much a person believes others can influence his or her health. Clinicians need to be aware of the importance of the social environment as it relates to medication attitudes and more research is needed on how treatment attitudes may actually translate into medication adherence behavior. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Use of antipsychotic medication and suicidality--the Northern Finland Birth Cohort 1966.

PubMed

Rissanen, Ina; Jääskeläinen, Erika; Isohanni, Matti; Koponen, Hannu; Joukamaa, Matti; Alaräisänen, Antti; Miettunen, Jouko

2012-09-01

In addition to psychoses, antipsychotic drugs are nowadays also prescribed for other psychiatric disturbances, such as mood disorders. We wanted to find out whether there is any association between the use of antipsychotic drugs and suicidality in cases of psychotic and non-psychotic disorders. Our sample was the population-based Northern Finland 1966 Birth Cohort. Information on the use of prescribed drugs was collected in 1997 from the nationwide medication register and with a postal questionnaire (N = 8218). The presence of suicidal ideation was assessed cross-sectionally using the Symptom Check List-25 questionnaire. We studied associations between suicidal ideation, adjusted for symptoms of depression and anxiety, and antipsychotic medication in different diagnostic groups (schizophrenia, other psychosis and no psychosis). Individuals receiving antipsychotic medication (n = 70, 0.9%) had in general more suicidal ideation regardless of diagnostic group, although the associations diminished when taking other symptoms into account. There were no statistically significant differences between those taking typical and atypical antipsychotics. In the non-psychotic group, higher antipsychotic doses were associated with more suicidal ideation even when adjusted for symptoms of depression and anxiety (p < 0.05). In the cases of schizophrenia or other forms of psychosis, no such associations were observed. Our results suggest that one should take suicidal ideation into account when prescribing antipsychotic medication, especially for off-label use. Copyright © 2012 John Wiley & Sons, Ltd.

Mood-stabilizing effects of rapamycin and its analog temsirolimus: relevance to autophagy.

PubMed

Kara, Nirit Z; Flaisher-Grinberg, Shlomit; Anderson, Grant W; Agam, Galila; Einat, Haim

2018-06-01

Accumulated data support a relationship between mood disorders and cellular plasticity and resilience, some suggesting relevance to autophagy. Our previous data show that pharmacological enhancement of autophagy results in antidepressant-like effects in mice. The current study was designed to further examine the effects of autophagy enhancement on mood by testing the effects of subchronic treatment with the mammalian target of rapamycin (mTOR) inhibitors and autophagy enhancers rapamycin and temsirolimus in a model for mania and in a model for antidepressant action, respectively. The results show that rapamycin reduced mania-like aggression and reward-seeking behaviors, with no effects on locomotion. Temsirolimus reduced depression-related immobility in the forced-swim test without effects on locomotion in the open field or on anxiety-related measures in the elevated plus maze. Taken together with our previous findings, these data support the notion that enhancing autophagy may have mood-stabilizing effects.

The rapid suicide protection of mood stabilizers on patients with bipolar disorder: A nationwide observational cohort study in Taiwan.

PubMed

Tsai, Chia-Jui; Cheng, Chin; Chou, Po-Han; Lin, Ching-Heng; McInnis, Melvin G; Chang, Chia-Li; Lan, Tsuo-Hung

2016-05-15

The suicide rate is high among bipolar disorder (BD) patients. Previous studies have focused on the anti-suicidal effect of long-term treatment with mood stabilizers but less on the immediate preventive effects of interventions. The aim of the study was to evaluate the short-term and immediate anti-suicidal effects of mood stabilizers on recent-onset BD patients. The National Health Insurance Database (NHID) of Taiwan was used to perform a nationwide cohort observation study of suicide behaviors in bipolar disorder. All the recent-onset BD patients (ICD-9-CM code 296 except 296.2 and 296.3) diagnosed between 2000-2005 were collected (n=5091) and followed through 2009. The primary endpoint was the presence of a suicide code or the end of observation; exposure to mood stabilizers in the final month of observation was the independent variable. The hazard ratios (HRs) of suicide-related events, completed suicide, and all-cause mortality were significantly lower for those treated with lithium, divalproex, or carbamazepine compared with no use in the last month (HRs of suicide-related events were 0.10, 0.14 and 0.10, respectively, and all-cause mortality HRs were 0.03; P<0.0001); there was no significant difference in HR between the mood stabilizers. The NIHD does not provide information on the severity, mood status, or treatment adherence of BD patients. Neither substance-related disorder nor personality disorder were included in the analysis. We focused on the effect of the final prescription time period, not the long-term protective effect. The immediate recent use of any mood stabilizer significantly lowers the rate of death, suicide, or suicidal behavior in BD. Copyright © 2016 Elsevier B.V. All rights reserved.

Antipsychotic Management of Schizoaffective Disorder: A Review.

PubMed

Lindenmayer, Jean-Pierre; Kaur, Amandeep

2016-04-01

Schizoaffective disorder (SAD) is an incapacitating illness that presents clinicians with challenges in terms of both its diagnosis and its psychopharmacological management. Most studies conducted on the psychopharmacological treatment of SAD also include patients with schizophrenia or other psychotic illnesses, thereby providing an unspecific view to the clinician as to the best way of treating patients with SAD. The objective of this article is to review studies on evidence-based treatment of patients with SAD. We conducted a systematic literature search in MEDLINE/PubMed for full-text studies in the English language using the terms 'Schizoaffective and treatment' or 'antipsychotic schizoaffective'. Our review found relatively few studies with either an active comparator or placebo that examined the efficacy of antipsychotics for patients with SAD without an admixture of patients with schizophrenia. Only oral paliperidone extended release (ER), paliperidone long-acting injection (LAI), and risperidone have been shown to be effective and safe in reducing psychotic as well as affective components in acutely ill SAD patients in controlled studies. Paliperidone ER and LAI have also been shown to be efficacious in the maintenance treatment phase of SAD patients. While no supportive data exist, it is possible that other atypical antipsychotics may have similar efficacy to the two mentioned above. We conclude with a number of research recommendations for the study of treatment options for patients with SAD. First, there is a need for studies with patients specifically diagnosed with SAD for both the acute and the maintenance phase. The sample size needs to be adequate to allow a primary analysis of efficacy and to allow for analysis of the SAD subtypes: depressed and bipolar. Another recommendation is the need for studies of patients with SAD stratified into patients with and without mood stabilizers or antidepressants to allow the examination of the adjunctive role of

Predicting Pharmacokinetic Stability by Multiple Oral Administration of Atypical Antipsychotics

PubMed Central

Aoki, Kazuo; Sakiyama, Yojiro; Ohnishi, Takashi; Sugita, Makoto

2013-01-01

Lower fluctuation, i.e., lower peak-to-trough plasma-concentration variation at steady-state pharmacokinetics, has several advantages for the treatment of schizophrenia with antipsychotics. The reduction of peak concentration can decrease the risk of dose-dependent side effects, such as extrapyramidal symptom and somnolence, and by contrast the increase in trough concentration can decrease the incidence of lack of efficacy due to subtherapeutic drug concentration. Using a one-compartment simulation technique with pharmacokinetic parameters of each atypical antipsychotic collected from package inserts, the fluctuation index was calculated. Among the antipsychotics, the indices varied from 0.018 to 1.9, depending on dosing regimens, formulations and several pharmacokinetic properties. The order of simulated fluctuation index is active-moiety aripiprazole (b.i.d.)

Treatment-resistant Schizophrenia: Evidence-based Strategies

PubMed Central

Englisch, Susanne; Zink, Mathias

2012-01-01

Treatment-resistant symptoms complicate the clinical course of schizophrenia, and a large proportion of patients do not reach functional recovery. In consequence, polypharmacy is frequently used in treatment-refractory cases, addressing psychotic positive, negative and cognitive symptoms, treatment-emergent side effects caused by antipsychotics and comorbid depressive or obsessive-compulsive symptoms. To a large extent, such strategies are not covered by pharmacological guidelines which strongly suggest antipsychotic monotherapy. Add-on strategies comprise combinations of several antipsychotic agents and augmentations with mood stabilizers; moreover, antidepressants and experimental substances are applied. Based on the accumulated evidence of clinical trials and meta-analyses, combinations of clozapine with certain second-generation antipsychotic agents and the augmentation of antipsychotics with antidepressants seem recommendable, while the augmentation with mood stabilizers cannot be considered superior to placebo. Forthcoming investigations will have to focus on innovative pharmacological agents, the clinical spectrum of cognitive deficits and the implementation of cognitive behavioral therapy. PMID:22654380

Intraoperative floppy-iris syndrome associated with use of antipsychotic drugs.

PubMed

Matsuo, Masato; Sano, Ichiya; Ikeda, Yoshifumi; Fujihara, Etsuko; Tanito, Masaki

2016-08-01

We report 3 cases of intraoperative floppy-iris syndrome (IFIS) during cataract surgery in patients without a history of selective α1-blocker use but with a long-term history of antipsychotic drug use. We reviewed previously reported cases of antipsychotic drug-associated IFIS cases. Observational case series. In case 1, bilateral IFIS developed in a 39-year-old man with chronic angle-closure glaucoma. He had used several classes of antipsychotic drugs to treat schizophrenia, including the first-generation antipsychotic drugs haloperidol and chlorpromazine, the dopamine system stabilizer aripiprazole, the dopamine serotonin antagonists olanzapine and quetiapine, and the serotonin dopamine antagonists risperidone and blonanserin for 7 years. In case 2, a 63-year-old woman with schizophrenia had used aripiprazole, quetiapine, and risperidone for more than 10 years. In case 3, a 65-year-old woman with an organic mental disorder had used haloperidol for more than 10 years. At least 5 cases of antipsychotic drug-induced IFIS have been reported in the literature. Any class of antipsychotic drugs can cause IFIS. Although antipsychotic drug-induced IFIS can be mild, surgeons should be alert to the possibility of IFIS when they treat patients with current and past use of antipsychotic drugs. Copyright © 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Is there an association between suicide attempt and delay of initiation of mood stabilizers in bipolar I disorder?

PubMed

Nery-Fernandes, Fabiana; Quarantini, Lucas C; Guimarães, José L; de Oliveira, Irismar R; Koenen, Karestan C; Kapczinski, Flavio; Miranda-Scippa, Ângela

2012-02-01

Little is known about the extent to which delay of initiation of mood-stabilizing treatment may influence outcomes in bipolar patients (BP). In this study, our aim was to investigate the association between delay of mood stabilizer treatment in bipolar patients and lifetime history of suicide attempts. A consecutive sample of 268 bipolar I outpatients from two teaching hospitals in Brazil was recruited. The assessment included a socio-demographic history form, a clinical interview regarding clinical variables and the Structured Clinical Interview for DSM-IV. Participants were divided into three groups: BP that initiated the first mood stabilizer in the same year of the first episode of the disease (FMS≤1), between 1 and 5 years after the first episode of the disease (15). The mean time from the first episode until the first mood stabilizer medication was 8.6 years (SD 9.8 years). The FMS>5 group, showed a higher lifetime prevalence of suicide attempts than the other two groups (PR=1.75, 95% CI: 1.24-2.47), p=0.001. These results remained significant after adjusting for potential confounders, (PR=1.82, 95% CI: 1.29-2.60), p=0.001. This study evaluated patients retrospectively and does not permit a cause-effect relationship. The present study supports the importance of early diagnosis and early intervention for BP in order to limit the potentially lethal impact of the disease. Copyright © 2011 Elsevier B.V. All rights reserved.

Switching antipsychotic medications.

PubMed

Weiden, P J; Aquila, R; Dalheim, L; Standard, J M

1997-01-01

Compared with conventional antipsychotics, the so-called "atypical" antipsychotics promise improved side effect profiles and better control of the symptoms of schizophrenia. Therefore, most patients currently taking conventional antipsychotics could potentially benefit from a switch to an atypical antipsychotic. Often, the key issue in deciding whether to switch is the presence of countervailing factors that mitigate against the change. This paper discusses the indications and contraindications for switching antipsychotics, plus issues that require consideration before a switch is made. Also, the advantages and disadvantages of various switching techniques are discussed, with a particular focus on the newer antipsychotic olanzapine.

Use of atypical antipsychotics for treatment-resistant major depressive disorder.

PubMed

Papakostas, George I; Shelton, Richard C

2008-12-01

Despite the progressive increase in the number of pharmacologic agents with potential antidepressant activity, many patients suffering from major depressive disorder (MDD) continue to be symptomatic. Clearly, an urgent need exists to develop safer, better tolerated, and more effective treatments for MDD. Use of atypical antipsychotic agents as adjunctive treatment for treatment-resistant MDD (TRD) represents one such effort toward novel pharmacotherapy development. Atypical antipsychotic agents have been hypothesized to be beneficial in treating mood disorders, including TRD, as a result of their complex mechanisms of action. After an initial series of positive case reports, series, and small clinical trials, subsequent larger-scale projects have yielded conflicting results. However, more recently, larger-scale clinical trials have supported the effectiveness of at least some of these medications. This review summarizes the existing data regarding the effectiveness of these medications in treating TRD, including biochemical rationale and clinical data.

Antipsychotics and Amotivation

PubMed Central

Fervaha, Gagan; Takeuchi, Hiroyoshi; Lee, Jimmy; Foussias, George; Fletcher, Paul J; Agid, Ofer; Remington, Gary

2015-01-01

Antipsychotic drugs are thought to produce secondary negative symptoms, which can also exacerbate primary negative symptoms. In the present study, we examined whether motivational deficits in particular were related to antipsychotic treatment in patients with schizophrenia in a dose-dependent manner. Five hundred and twenty individuals with schizophrenia who were receiving antipsychotic monotherapy for at least 6 months and followed prospectively were included in the present study. Participants were receiving one of five antipsychotic medications (olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone), and analyses were conducted for patients receiving each drug separately. Analysis of covariance models were constructed to examine the effect of antipsychotic dose on level of motivational impairment, controlling for selected demographic and clinical variables (eg, positive symptoms). Level of motivation, or deficits therein, were evaluated using a derived measure from the Quality of Life Scale, and in addition with scores derived from the Positive and Negative Syndrome Scale. Antipsychotic dose was not related to the level of amotivation for any of the medications examined. Moreover, severity of sedation was not significantly related to the degree of amotivation. One hundred and twenty-one individuals were identified as antipsychotic-free at baseline, and after 6 months of antipsychotic treatment, no change in motivation was found. Chronic treatment with antipsychotics does not necessarily impede or enhance goal-directed motivation in patients with schizophrenia. It is possible that the negative impact of antipsychotics in this regard is overstated; conversely, the present results also indicate that we must look beyond antipsychotics in our efforts to improve motivation. PMID:25567425

Antipsychotics and amotivation.

PubMed

Fervaha, Gagan; Takeuchi, Hiroyoshi; Lee, Jimmy; Foussias, George; Fletcher, Paul J; Agid, Ofer; Remington, Gary

2015-05-01

Antipsychotic drugs are thought to produce secondary negative symptoms, which can also exacerbate primary negative symptoms. In the present study, we examined whether motivational deficits in particular were related to antipsychotic treatment in patients with schizophrenia in a dose-dependent manner. Five hundred and twenty individuals with schizophrenia who were receiving antipsychotic monotherapy for at least 6 months and followed prospectively were included in the present study. Participants were receiving one of five antipsychotic medications (olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone), and analyses were conducted for patients receiving each drug separately. Analysis of covariance models were constructed to examine the effect of antipsychotic dose on level of motivational impairment, controlling for selected demographic and clinical variables (eg, positive symptoms). Level of motivation, or deficits therein, were evaluated using a derived measure from the Quality of Life Scale, and in addition with scores derived from the Positive and Negative Syndrome Scale. Antipsychotic dose was not related to the level of amotivation for any of the medications examined. Moreover, severity of sedation was not significantly related to the degree of amotivation. One hundred and twenty-one individuals were identified as antipsychotic-free at baseline, and after 6 months of antipsychotic treatment, no change in motivation was found. Chronic treatment with antipsychotics does not necessarily impede or enhance goal-directed motivation in patients with schizophrenia. It is possible that the negative impact of antipsychotics in this regard is overstated; conversely, the present results also indicate that we must look beyond antipsychotics in our efforts to improve motivation.

Behavioral Weight Loss Treatment in Antipsychotic Treated Youth.

PubMed

Nicol, Ginger E; Kolko, Rachel P; Mills, Monica; Gunnarsdottir, Thrudur; Yingling, Michael D; Schweiger, Julia A; Lenze, Eric J; Newcomer, John W; Wilfley, Denise

2016-05-01

Antipsychotic-treated youth have increased risk for the development of obesity and type 2 diabetes. Behavioral weight loss treatments show promise in reducing obesity and diabetes risk in antipsychotic treated adults, but have received no study in antipsychotic treated youth. We describe a rationale for behavioral weight loss interventions in high-weight antipsychotic treated youth, and report behavioral, anthropomorphic, and metabolic findings from a case series of obese antipsychotic-treated adolescents participating in a short-term, family-based behavioral weight loss intervention. We adapted the Traffic Light Plan, a 16-week family-based weight loss intervention that promotes healthy energy balance using the colors of the traffic light to categorize the nutritional value of foods and intensity of physical activity, adapting a social ecological framework to address health behavior change in multiple social contexts. The intervention was administered to three obese adolescents with long-term antipsychotic medication exposure. Efficacy of the intervention was evaluated with a battery of anthropomorphic and metabolic assessments including weight, body mass index percentile, whole body adiposity, liver fat content, and fasting plasma glucose and lipids. Participants and their parents also filled out a treatment satisfaction questionnaire upon study completion. Two males and 1 female (all aged 14 years) participated. All 3 participants attended all 16 sessions, and experienced beneficial changes in adiposity, fasting lipids and liver fat content associated with weight stabilization or weight loss. Adolescents and their parents all reported a high level of satisfaction with the treatment. Family-based behavioral weight loss treatment can be feasibly delivered and is acceptable to antipsychotic-treated youth and their families. Randomized controlled trials are needed to fully evaluate the effectiveness and acceptability of behavioral weight loss interventions in

Regulation of cellular plasticity and resilience by mood stabilizers: the role of AMPA receptor trafficking

PubMed Central

Du, Jing; Quiroz, Jorge A.; Gray, Neil A.; Szabo, Steve T.; Zarate Jr, Carlos A.; Manji, Husseini K.

2004-01-01

There is increasing evidence from a variety of sources that severe mood disorders are associated with regional reductions in brain volume, as well as reductions in the number, size, and density of glia and neurons in discrete brain areas. Although the precise pathophysiology underlying these morphometric changes remains to be fully elucidated, the data suggest that severe mood disorders are associated with impairments of structural plasticity and cellular resilience. In this context, it is noteworthy that a growing body of data suggests that the glutamaiergic system (which is known to play a major role in neuronal plasticity and cellular resilience) may be involved in the pathophysiology and treatment of mood disorders. Glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) GluR1 receptor trafficking plays a critical role in regulating various forms of neural plasticity. It is thus noteworthy that recent studies have shown that structurally dissimilar mood stabilizers lithium and valproate regulate GluR1 receptor subunit trafficking and localization at synapses. These studies suggest that regulation of glutamatergically mediated synaptic plasticity may play a role in the treatment of mood disorders, and raises the possibility that agents more directly affecting synaptic GluR1 represent novel therapies for these devastating illnesses. PMID:22034247

Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods

PubMed Central

2013-01-01

Background Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) study, a federally funded, randomized trial comparing two pharmacologic strategies against a control condition to manage SGA-related weight gain. Methods The design and methodology considerations of the IMPACT trial are described and embedded in a description of health risks associated with antipsychotic-related weight gain and the limitations of currently available research. Results The IMPACT study is a 4-site, six month, randomized, open-label, clinical trial of overweight/obese youth ages 8–19 years with pediatric schizophrenia-spectrum and bipolar-spectrum disorders, psychotic or non-psychotic major depressive disorder, or irritability associated with autistic disorder. Youth who have experienced clinically significant weight gain during antipsychotic treatment in the past 3 years are randomized to either (1) switch antipsychotic plus healthy lifestyle education (HLE); (2) add metformin plus HLE; or (3) HLE with no medication change. The primary aim is to compare weight change (body mass index z-scores) for each pharmacologic intervention with the control condition. Key secondary assessments include percentage body fat, insulin resistance, lipid profile, psychiatric symptom stability (monitored independently by the pharmacotherapist and a blinded evaluator), and all-cause and specific cause discontinuation. This study is ongoing, and the targeted sample size is 132 youth. Conclusion Antipsychotic-related weight gain is an important public health issue for youth requiring

Sleep Disturbances in Mood Disorders.

PubMed

Rumble, Meredith E; White, Kaitlin Hanley; Benca, Ruth M

2015-12-01

The article provides an overview of common and differentiating self-reported and objective sleep disturbances seen in mood-disordered populations. The importance of considering sleep disturbances in the context of mood disorders is emphasized, because a large body of evidence supports the notion that sleep disturbances are a risk factor for onset, exacerbation, and relapse of mood disorders. In addition, potential mechanisms for sleep disturbance in depression, other primary sleep disorders that often occur with mood disorders, effects of antidepressant and mood-stabilizing drugs on sleep, and the adjunctive effect of treating sleep in patients with mood disorders are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Protocol for a Systematic Review and Meta-Analysis of Lithium, Anticonvulsive or atypical antipsychotic Drugs for Treatment of Refractory Obsessive-Compulsive Disorder.

PubMed

Soleimani, R; Jalali, M M; Keshtkar, A; Jalali, S M

2017-01-01

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that causes significant distress to the afflicted individual. About half of OCD patients treated with an adequate trial of serotonin reuptake inhibitors fail to fully respond to treatment and continue to exhibit significant symptoms. Therefore, there is a need for other agents to alleviate the symptoms of these disorders. In spite of considerable research including numerous randomized controlled trials and systematic reviews, there exists uncertainty regarding what treatments are effective. In this systematic review, we evaluated the efficacy of mood stabilizers in treatment-refractory OCD. We conducted a meta-analysis of all randomized clinical trials evaluating lithium, anticonvulsive agents or atypical antipsychotic drugs for OCD to determine which therapies show more effective than a placebo, in reducing obsessive-compulsive symptoms. We acquired eligible studies through a systematic search of Cochrane Central Registry of Controlled Trials, MEDLINE, EMBASE, PsycINFO, Scopus, ProQuest and Google scholar. We conducted meta-analyses to establish the effect of lithium, anticonvulsive agents, or atypical antipsychotic drugs on patient-important outcomes when possible. To assess relative effects of treatments, we constructed a random effect model. Our review was the first to evaluate all treatments for OCD, to provide the relative effectiveness of lithium, anticonvulsive agents, or atypical antipsychotic drugs, and prioritize patient-important outcomes with a focus on functional gains. Our review facilitated the evidence-based management of patients with resistant OCD, and identified the key areas for future research.

Epigenetic Mechanisms in Mood Disorders: Targeting Neuroplasticity

PubMed Central

Fass, Daniel M.; Schroeder, Frederick A.; Perlis, Roy H.; Haggarty, Stephen J.

2013-01-01

Developing novel therapeutics and diagnostic tools based upon an understanding of neuroplasticity is critical in order to improve the treatment and ultimately the prevention of a broad range of nervous system disorders. In the case of mood disorders, such as major depressive disorder and bipolar disorder, where diagnoses are based solely on nosology rather than pathophysiology, there exists a clear unmet medical need to advance our understanding of the underlying molecular mechanisms and to develop fundamentally new mechanism experimental medicines with improved efficacy. In this context, recent preclinical molecular, cellular, and behavioral findings have begun to reveal the importance of epigenetic mechanisms that alter chromatin structure and dynamically regulate patterns of gene expression that may play a critical role in the pathophysiology of mood disorders. Here, we will review recent advances involving the use of animal models in combination with genetic and pharmacological probes to dissect the underlying molecular mechanisms and neurobiological consequence of targeting this chromatin-mediated neuroplasticity. We discuss evidence for the direct and indirect effects of mood stabilizers, antidepressants, and antipsychotics, among their many other effects, on chromatin-modifying enzmyes and on the epigenetic state of defined genomic loci, in defined cell types and in specific regions of the brain. These data, as well as findings from patient-derived tissue, have also begun to reveal alterations of epigenetic mechanisms in the pathophysiology and treatment of mood disorders. We summarize growing evidence supporting the notion that selectively targeting chromatin-modifying complexes, including those containing histone deacetylases (HDACs), provides a means to reversibly alter the acetylation state of neuronal chromatin and benefically impact neuronal activity-regulated gene transcription and mood-related behaviors. Looking beyond current knowledge, we discuss

Endocannabinoid system dysfunction in mood and related disorders.

PubMed

Ashton, C H; Moore, P B

2011-10-01

The endocannabinoid (EC) system is widely distributed throughout the brain and modulates many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids. This article examines the therapeutic potential of cannabinoids in psychiatric disorders. An overview is presented of the literature focussed on the functions of the EC system, its dysfunction in mood disorders and the therapeutic potential of exogenous cannabinoids. We propose (hypothesize) that the EC system, which is homoeostatic in cortical excitation and inhibition, is dysfunctional in mood and related disorders. Anandamide, tetrahydrocannabinol (THC) and cannabidiol (CBD) variously combine antidepressant, antipsychotic, anxiolytic, analgesic, anticonvulsant actions, suggesting a therapeutic potential in mood and related disorders. Currently, cannabinoids find a role in pain control. Post mortem and other studies report EC system abnormalities in depression, schizophrenia and suicide. Abnormalities in the cannabinoid-1 receptor (CNR1) gene that codes for cannabinoid-1 (CB1) receptors are reported in psychiatric disorders. However, efficacy trials of cannabinoids in psychiatric disorders are limited but offer some encouragement. Research is needed to elucidate the role of the EC system in psychiatric disorders and for clinical trials with THC, CBD and synthetic cannabinoids to assess their therapeutic potential. © 2011 John Wiley & Sons A/S.

Treatment Options for the Cardinal Symptoms of Disruptive Mood Dysregulation Disorder

PubMed Central

Tourian, Leon; LeBoeuf, Amélie; Breton, Jean-Jacques; Cohen, David; Gignac, Martin; Labelle, Réal; Guile, Jean-Marc; Renaud, Johanne

2015-01-01

Objective: DSM-5 has added a new developmentally appropriate child and adolescent mood disorder subtype called disruptive mood dysregulation disorder (DMDD). The core features of DMDD are temper outbursts (manifested by either verbal rages and/or physical aggression) and unrelenting irritability or anger. Currently, the literature is lacking a thorough review of the possible treatment options for the cardinal symptoms constituting DMDD. The objective of this article is to provide a thorough review of peer-reviewed studies on the subject of pharmacological treatment options for children and adolescents with the cardinal symptoms of DMDD. Methods: Relevant articles for this study were obtained through Pubmed, Medline, PsychINFO and PsychINDEXplus using the key words: “adolescents,” “children,” “paediatric,” “youth,” “irritability,” “temper outbursts,” “aggression,” “rage,” “disruptive behaviour,” “treatment,” “dysphoria,” “autism,” “mental retardation/intellectual disability,” “impulsivity,” “ADHD,” “oppositional defiant disorder,” and “conduct disorder.” A total of 823 studies were generated; only English studies focusing on pharmacological treatment were retained. Results: Currently there are no established guidelines or thorough reviews summarizing the treatment of DMDD. Pharmacotherapeutic treatment options of both aggression and chronic irritability include: antidepressants/selective norepinephrine reuptake inhibitors, mood stabilizers, psychostimulants, antipsychotics, and alpha-2 agonists. Conclusion: Treatment options of severe, persistent irritability in youth are numerous, and a consensual treatment algorithm has not yet emerged from the literature. Further studies and clinical trials are warranted to determine efficacious and safe treatment modalities. PMID:26336379

The Effects of Antipsychotic Quality Reporting on Antipsychotic and Psychoactive Medication Use.

PubMed

Bowblis, John R; Lucas, Judith A; Brunt, Christopher S

2015-08-01

The objective of this study is to examine how nursing homes changed their use of antipsychotic and other psychoactive medications in response to Nursing Home Compare's initiation of publicly reporting antipsychotic use in July 2012. The study includes all state recertification surveys (n = 40,415) for facilities six quarters prior and post the initiation of public reporting. Using a difference-in-difference framework, the change in use of antipsychotics and other psychoactive medications is compared for facilities subject to public reporting and facilities not subject to reporting. The percentage of residents using antipsychotics, hypnotics, or any psychoactive medication is found to decline after public reporting. Facilities subject to reporting experienced an additional decline in antipsychotic use (-1.94 vs. -1.40 percentage points) but did not decline as much for hypnotics (-0.60 vs. -1.21 percentage points). Any psychoactive use did not vary with reporting status, and the use of antidepressants and anxiolytics did not change. Public reporting of an antipsychotic quality measure can be an effective policy tool for reducing the use of antipsychotic medications--though the effect many only exist in the short run. © Health Research and Educational Trust.

"I love you forever (more or less)" - stability and change in adolescents' romantic love status and associations with mood states.

PubMed

Bajoghli, Hafez; Farnia, Vahid; Joshaghani, Narges; Haghighi, Mohammad; Jahangard, Leila; Ahmadpanah, Mohammad; Sadeghi Bahmani, Dena; Holsboer-Trachsler, Edith; Brand, Serge

2017-01-01

Experiencing romantic love is an important part of individual development. Here, we investigated stability and change in romantic love and psychological correlates, including mood states, anxiety, and sleep, among Iranian adolescents over a period of 8 months. Two hundred and one adolescents who had taken part in a previous study were contacted; 157 responded. Participants completed a questionnaire covering sociodemographic data, current state of love, and mood, including symptoms of depression, anxiety (state and trait), and hypomania. They also completed a sleep and activity log. Of 64 participants formerly in love, 45 were still in love; of 86 participants not in love at baseline, 69 were still not in love (overall stability, 76%); 17 had fallen in love recently while 19 were no longer in love. Significant and important changes in mood and anxiety were observed in that experiencing romantic love was associated with higher anxiety scores. Hypomania scores increased in those newly in love, and decreased in those in a longer-lasting romantic relationship. Sleep and sleep-related variables were not associated with romantic love status. These findings suggest that, among Iranian adolescents, the state of love is fairly stable, and that love status seems to be associated with specific states of mood and anxiety.

The Effects of Antipsychotic Quality Reporting on Antipsychotic and Psychoactive Medication Use

PubMed Central

Bowblis, John R; Lucas, Judith A; Brunt, Christopher S

2015-01-01

Objective The objective of this study is to examine how nursing homes changed their use of antipsychotic and other psychoactive medications in response to Nursing Home Compare’s initiation of publicly reporting antipsychotic use in July 2012. Research Design and Subjects The study includes all state recertification surveys (n = 40,415) for facilities six quarters prior and post the initiation of public reporting. Using a difference-in-difference framework, the change in use of antipsychotics and other psychoactive medications is compared for facilities subject to public reporting and facilities not subject to reporting. Principal Findings The percentage of residents using antipsychotics, hypnotics, or any psychoactive medication is found to decline after public reporting. Facilities subject to reporting experienced an additional decline in antipsychotic use (−1.94 vs. −1.40 percentage points) but did not decline as much for hypnotics (−0.60 vs. −1.21 percentage points). Any psychoactive use did not vary with reporting status, and the use of antidepressants and anxiolytics did not change. Conclusion Public reporting of an antipsychotic quality measure can be an effective policy tool for reducing the use of antipsychotic medications—though the effect many only exist in the short run. PMID:25600861

Neurobehavioral impact of menopause on mood.

PubMed

Alexander, Jeanne Leventhal; Dennerstein, Lorraine; Woods, Nancy Fugate; Kotz, Krista; Halbreich, Uriel; Burt, Vivien; Richardson, Gregg

2007-11-01

The menopausal transition is a time of risk for mood change ranging from distress to minor depression to major depressive disorder in a vulnerable subpopulation of women in the menopausal transition. Somatic symptoms have been implicated as a risk factor for mood problems, although these mood problems have also been shown to occur independently of somatic symptoms. Mood problems have been found to increase in those with a history of mood continuum disorders, but can also occur de novo as a consequence of the transition. Stress has been implicated in the etiology and the exacerbation of these mood problems. Estrogen and add-back testosterone have both been shown to positively affect mood and well-being. In most cases, the period of vulnerability to mood problems subsides when the woman's hormonal levels stabilize and she enters full menopause.

Novel antipsychotics: issues and controversies. Typicality of atypical antipsychotics.

PubMed Central

Stip, E

2000-01-01

The typicality of atypical antipsychotic drugs remains debatable. Preclinical studies and findings from randomized, controlled and open trials of clozapine, olanzapine, risperidone, quetiapine, sertindole, ziprasidone and a substituted benzamide were examined. A MEDLINE search was conducted using key words, including "extrapyramidal side effects," "cognition," "schizophrenia" and the generic drug names. Over 140 articles from peer-reviewed journals were reviewed, some of which were based on a meta-analysis. New-generation neuroleptic agents were found to have greater efficacy on the negative symptoms of schizophrenia and to cause fewer unwanted extrapyramidal side effects (EPS) than the traditional antipsychotic drugs. On one hand, atypical neuroleptic agents could be strictly defined as any neuroleptic agent with antipsychotic effects at a dosage that does not cause extrapyramidal side effects. Thus, clozapine is regarded as the "standard" atypical antipsychotic drug. On the other hand, typicality is about dimension rather than category, and we suggest the use of the term "spectrum of atypicality." For example, an emphasis is placed on quetiapine to illustrate where a new compound fits in this spectrum. Although dose-related, atypicality may be more a question of prescription attitude than of a specific characteristic of a compound. The degree to which a new compound is clinically superior to another atypical antipsychotic drug, in terms of improving positive, negative or affective symptoms, cognitive function and long-term outcome, will require further a priori hypotheses based on conceptual frameworks that are clinically meaningful. In addition, the results from industry-sponsored trials should be more comparable to those obtained from investigator-leading trials. Finally, the patient characteristics that define a patient's response to a specific antipsychotic drug are unknown. PMID:10740987

Impact of present and past antipsychotic side effects on attitude toward typical antipsychotic treatment and adherence.

PubMed

Lambert, M; Conus, P; Eide, P; Mass, R; Karow, A; Moritz, S; Golks, D; Naber, D

2004-11-01

(1) determine which antipsychotic side effects (SE) schizophrenic patients consider the most distressing during treatment with typical antipsychotics, (2) measure the impact of actual and past SE on patients' attitude toward antipsychotics and (3) assess the influence of both on adherence. The 213 schizophrenics, treated with conventional antipsychotics, were recruited in two psychiatric hospitals in Hamburg. Subjects were assessed about type and severity of present and past side effects and their attitude and adherence to antipsychotic treatment. The 82 (39%) patients presented present SE while 131 (61%) did not. Sexual dysfunctions (P < 0.001), extrapyramidal (P < 0.05) and psychic side effects (P < 0.05) were rated as significantly subjectively more distressing than sedation or vegetative side effects. Patients presenting with present SE compared with patients without present SE had a significantly more negative general attitude toward antipsychotics (P < 0.05), were more doubtful about their efficacy (P < 0.01) and were less likely to encourage a relative to take such a medication in case of need (P < 0.001). A regression analysis indicated that nonadherence was mainly influenced by negative general and efficacy attitudes toward antipsychotics and the experience of past or present antipsychotic side effects. All antipsychotic side effects, present or past, can have a durable negative impact on patient's attitude toward antipsychotic treatment and adherence. Non-adherence is mainly determined, among other factors, by these negative attitudes, which are partly influenced by the experience of past or present antipsychotic-induced side effects.

Forecasting Medicaid Expenditures for Antipsychotic Medications.

PubMed

Slade, Eric P; Simoni-Wastila, Linda

2015-07-01

The ongoing transition from use of mostly branded to mostly generic second-generation antipsychotic medications could bring about a substantial reduction in Medicaid expenditures for antipsychotic medications, a change with critical implications for formulary restrictions on second-generation antipsychotics in Medicaid. This study provided a forecast of the impact of generics on Medicaid expenditures for antipsychotic medications. Quarterly (N=816) state-level aggregate data on outpatient antipsychotic prescriptions in Medicaid between 2008 and 2011 were drawn from the Medicaid state drug utilization database. Annual numbers of prescriptions, expenditures, and cost per prescription were constructed for each antipsychotic medication. Forecasts of antipsychotic expenditures in calendar years 2016 and 2019 were developed on the basis of the estimated percentage reduction in Medicaid expenditures for risperidone, the only second-generation antipsychotic available generically throughout the study period. Two models of savings from generic risperidone use were estimated, one based on constant risperidone prices and the other based on variable risperidone prices. The sensitivity of the expenditure forecast to expected changes in Medicaid enrollment was also examined. In the main model, annual Medicaid expenditures for antipsychotics were forecasted to decrease by $1,794 million (48.8%) by 2016 and by $2,814 million (76.5%) by 2019. Adjustment for variable prices of branded medications and changes in Medicaid enrollment only moderately affected the magnitude of these reductions. Within five years, antipsychotic expenditures in Medicaid may decline to less than half their current levels. Such a spending reduction warrants a reassessment of the continued necessity of formulary restrictions for second-generation antipsychotics in Medicaid.

Incidence and risk factors of suicide reattempts within 1 year after psychiatric hospital discharge in mood disorder patients.

PubMed

Ruengorn, Chidchanok; Sanichwankul, Kittipong; Niwatananun, Wirat; Mahatnirunkul, Suwat; Pumpaisalchai, Wanida; Patumanond, Jayanton

2011-01-01

The incidence and risk factors of suicide reattempts within 1 year after psychiatric hospital discharge in mood disorder patients remain uninvestigated in Thailand. To determine incidence and risk factors of suicide reattempts within 1 year after psychiatric hospital discharge in mood disorder patients. A retrospective cohort study was conducted by reviewing medical charts at Suanprung Psychiatric Hospital, Chiang Mai, Thailand. Mood disorder patients, diagnosed with the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes F31.x, F32.x, and F33.x, who were admitted owing to suicide attempts between October 2006 and May 2009 were eligible. The influence of sociodemographic and clinical risk factors on suicide reattempts was investigated using Cox's proportional-hazards regression analysis. Of 235 eligible mood disorder patients, 36 (15.3%) reattempted suicide (median 109.5 days, range 1-322), seven (3.0%) completed suicide (median 90 days, range 5-185), and 192 (84.2%) neither reattempted nor completed suicide during follow-up. Of all nonfatal suicide reattempts, 14 patients (38.9%) did so within 90 days. Among suicide completers, one (14.3%) did so 5 days after discharge, and four (57.1%) did so within 90 days. The following three risk factors explained 73.3% of the probability of suicide reattempts: over two previous suicide attempts before the index admission (adjusted hazard ratio [HR] 2.48; 95% confidence interval [CI] 1.07-5.76), being concomitantly prescribed typical and atypical antipsychotics (adjusted HR 4.79; 95% CI 1.39-16.52) and antidepressants, and taking a selective serotonin reuptake inhibitor alone (adjusted HR 5.08; 95% CI 1.14-22.75) or concomitantly with norepinephrine and/or serotonin reuptake inhibitors (adjusted HR 6.18; 95% CI 1.13-33.65). Approximately 40% of suicide reattempts in mood disorder patients occurred within 90 days after psychiatric hospital discharge. For mood disorders and when

Mood disorders: neurocognitive models.

PubMed

Malhi, Gin S; Byrow, Yulisha; Fritz, Kristina; Das, Pritha; Baune, Bernhard T; Porter, Richard J; Outhred, Tim

2015-12-01

In recent years, a number of neurocognitive models stemming from psychiatry and psychology schools of thought have conceptualized the pathophysiology of mood disorders in terms of dysfunctional neural mechanisms that underpin and drive neurocognitive processes. Though these models have been useful for advancing our theoretical understanding and facilitating important lines of research, translation of these models and their application within the clinical arena have been limited-partly because of lack of integration and synthesis. Cognitive neuroscience provides a novel perspective for understanding and modeling mood disorders. This selective review of influential neurocognitive models develops an integrative approach that can serve as a template for future research and the development of a clinically meaningful framework for investigating, diagnosing, and treating mood disorders. A selective literature search was conducted using PubMed and PsychINFO to identify prominent neurobiological and neurocognitive models of mood disorders. Most models identify similar neural networks and brain regions and neuropsychological processes in the neurocognition of mood, however, they differ in terms of specific functions attached to neural processes and how these interact. Furthermore, cognitive biases, reward processing and motivation, rumination, and mood stability, which play significant roles in the manner in which attention, appraisal, and response processes are deployed in mood disorders, are not sufficiently integrated. The inclusion of interactions between these additional components enhances our understanding of the etiology and pathophysiology of mood disorders. Through integration of key cognitive functions and understanding of how these interface with neural functioning within neurocognitive models of mood disorders, a framework for research can be created for translation to diagnosis and treatment of mood disorders. © 2015 John Wiley & Sons A/S. Published by John

Antipsychotic Therapy-Induced New Onset Diabetic Ketoacidosis.

PubMed

Agrawal, Yashwant; Lingala, Kiran; Tokala, Hemasri; Kalavakunta, Jagadeesh K

Atypical antipsychotics are very widely used for various psychiatric ailments because of their less extrapyramidal side effects. Various reports of disturbances in glucose metabolism in the form of new onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, diabetic ketoacidosis, hyperosmolar nonketotic coma, acute pancreatitis, and increased adiposity have been reported. We present a case of new onset diabetic ketoacidosis in a patient without a history of glucose intolerance who was being treated with olanzapine for bipolar disorder. He presented in hyperglycemic, hyperosmolar, hyperketotic state with hyperkalemia, and peaked T waves on electrocardiogram. He was treated with vigorous intravenous hydration, insulin, and kaexylate which stabilized his metabolic profile. He was discontinued off of his olanzapine and started on resperidol for his bipolar disorder. Over the course of 6 months, the patient was discontinued off of his insulin and has been doing well on his follow-up appointments. This case highlights the necessity of close blood glucose monitoring of patient on atypical antipsychotic medications irrespective of their diabetic status.

[Prescribed drug use for bipolar disorder type I and II in clinical practice].

PubMed

Persson, Charlotte; Kardell, Mathias; Karanti, Alina; Isgren, Anniella; Annerbrink, Kristina; Landen, Mikael

2017-01-10

Prescribed drug use for bipolar disorder type I and II in clinical practice Practice guidelines based on available evidence and clinical consensus are available for the treatment of bipolar disorder. We surveyed to which extent those guidelines are implemented in clinical practice in Sweden. We analysed pharmacological treatment in patients with bipolar disorder in 2015 using the national quality register for bipolar disorder (BipoläR). We compared bipolar disorder type I (BDI) with type bipolar disorder type II (BDII). The vast majority of patients were prescribed a mood stabilizer either as monotherapy or as a part of combination therapy (BDI 87%, BDII 83%, p<0.001). Whereas lithium was the most common mood stabilizer in type I (BDI 65%, BDII 40%, p<0.001), lamotrigine was the most common mood stabilizer in type II (BDI 18%, BDII 42%, p<0.001). Antidepressants were less common in BDI than BDII (35% vs. 53%, p<0.001). Antipsychotic drugs (first or second generation) were more frequently used in BDI than BDII (49% vs 35%, p<0.001). Central stimulants were rarely used (BDI 3.1%, BDII 6.6%, p<0.001). Combining a mood stabilizer with an antipsychotic drug was more common in BDI than BDII (27% vs. 12%, p<0.001), whereas combining a mood stabilizer with an antidepressant was less common in BDI than BDII (16% vs 28%, p<0.001). We conclude that most patients are prescribed mood stabilizers and that the differences between BDI and BDII are rational given the differences in clinical manifestations. The use of antidepressants is surprisingly high given the long-standing debate about the risk and effectiveness of this class in bipolar disorder.

Novel Antipsychotics in the Treatment of Behavioral Disturbances and Psychoses Associated With Neurodegenerative Disorders

PubMed Central

Masand, Prakash S.

2000-01-01

Behavioral disturbances and psychosis are common features of neurodegenerative disorders and may be drug induced, intrinsic to the underlying pathology, or both. These disturbances, including psychotic and mood symptoms, apathy, aggression and other behavioral symptoms, and superimposed delirium, cause a great amount of disability to the patient and stress on the caregiver. Conventional neuroleptics have been shown to be effective in the treatment of these symptoms, but unacceptable side effects may occur. However, the novel antipsychotics, with their lower risk of inducing extrapyramidal symptoms, have shown promise in the treatment of behavioral disturbances and psychosis associated with neurodegenerative disorders. PMID:15014653

Matching the bipolar patient and the mood stabilizer.

PubMed

Gelenberg, Alan J; Pies, Ronald

2003-01-01

Bipolar disorder poses many treatment challenges, including "matching" a particular patient with the optimal treatment regimen. Although there are a number of extant guidelines to assist the clinician in selecting treatment, these recommendations are largely based on general variables and fail to take into account the subtleties and complications that confront a clinician in practice. An analysis of predictors of medication response in bipolar disorder provides a basis for matching patients with optimal medication regimens. Response to treatment may depend on the polarity of an episode or on clinical features such as mixed or psychotic symptomatology and rate of cycling. Comorbid psychiatric disorders such as substance abuse, anxiety disorders, or attention-deficit/hyperactivity disorder should also be considered in designing a treatment regimen. Similarly, medical conditions, especially metabolic abnormalities or kidney insufficiency, must be taken into account. Selection of medication may also involve an analysis of demographic factors, including family and personal history of response to a particular agent. When selecting the most appropriate mood stabilizer for a patient--particularly when polypharmacy is required--the clinician should keep potential side effects and drug interactions in mind. Randomized, controlled studies in bipolar populations are needed to further characterize optimal matching of patient and medication.

Chronobiology and mood disorders

PubMed Central

Wirz-Justice, Anna

2003-01-01

The clinical observations of diurnal variation of mood and early morning awakening in depression have been incorporated into established diagnostic systems, as has the seasonal modifier defining winter depression (seasonal affective disorder, SAD). Many circadian rhythms measured in depressive patients are abnormal: earlier in timing, diminished in amplitude, or of greater variability. Whether these disturbances are of etiological significance for the role of circadian rhythms in mood disorders, or a consequence of altered behavior can only be dissected out with stringent protocols (eg, constant routine or forced desynchrony). These protocols quantify contributions of the circadian pacemaker and a homeostatic sleep process impacting on mood, energy, appetite, and sleep. Future studies will elucidate any allelic mutations in “circadian clock” –related or “sleep”-related genes in depression. With respect to treatment, antidepressants and mood stabilizers have no consistent effect on circadian rhythmicity. The most rapid antidepressant modality known so far is nonpharmacological: total or partial sleep deprivation in the second half of the night. The disadvantage of sleep deprivation, that most patients relapse after recovery sleep, can be prevented by coadministration of lithium, pindolol, serotonin (5-HT) reuptake inhibitors, bright light, or a subsequent phase-advance procedure. Phase advance of the sleep-wake cycle alone also has rapid effects on depressed mood, which lasts longer than sleep deprivation. Light is the treatment of choice for SAD and may prove to be useful for nonseasonal depression, alone or as an adjunct to medication. Chronobiological concepts emphasize the important role of zeitgebers to stabilize phase, light being the most important, but dark (and rest) periods, regularity of social schedules and meal times, and use of melatonin or its analogues should also be considered. Advances in chronobiology continue to contribute novel

Antiepileptic Drugs with Mood Stabilizing Properties and Their Relation with Psychotropic Drug Use in Institutionalized Epilepsy Patients with Intellectual Disability

ERIC Educational Resources Information Center

Leunissen, C. L. F.; de la Parra, N. M.; Tan, I. Y.; Rentmeester, Th. W.; Vader, C. I.; Veendrick-Meekes, M. J. B. M.; Aldenkamp, A. P.

2011-01-01

A large number of patients with epilepsy and intellectual disability take medication, amongst which antiepileptic and psychotropic drugs, often simultaneously. Certain antiepileptic drugs have mood-stabilizing properties, e.g. carbamazepine, valproic acid and lamotrigine. The aim of this study was to investigate whether the use of these…

Psychotic and Bipolar Disorders: Antipsychotic Drugs.

PubMed

Holder, Sarah D; Edmunds, Alaina L; Morgan, Sherri

2017-04-01

Antipsychotic drugs block dopamine receptors and are used to manage psychosis as well as other mental illnesses that may or may not have psychotic features, such as bipolar disorders and major depressive disorder. First-generation antipsychotic drugs are more likely to cause adverse effects such as extrapyramidal symptoms and tardive dyskinesia. Adverse effects of second-generation antipsychotic drugs typically are related to metabolic abnormalities such as weight gain, abnormal blood glucose levels, and elevated lipid levels. Neuroleptic malignant syndrome is a rare but serious adverse effect of antipsychotic drugs that causes mental status changes, hyperthermia, and generalized rigidity. Timely diagnosis is essential due to a high risk of related morbidities if the syndrome remains untreated. Some adverse effects of antipsychotics can be identified and managed so that patients can continue beneficial therapy while minimizing the physiologic consequences. Patients taking antipsychotic drugs should be monitored regularly for adverse effects. Antipsychotics are also associated with potential drug interactions, the most lethal being prolongation of the QT interval, which can lead to fatal arrhythmias. Antipsychotic drugs can be used in special populations, such as pregnant women, children, and elderly patients, per recommendation from a mental health subspecialist. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Personality disorders: review and clinical application in daily practice.

PubMed

Angstman, Kurt B; Rasmussen, Norman H

2011-12-01

Personality disorders have been documented in approximately 9 percent of the general U.S. population. Psychotherapy, pharmacotherapy, and brief interventions designed for use by family physicians can improve the health of patients with these disorders. Personality disorders are classified into clusters A, B, and C. Cluster A includes schizoid, schizotypal, and paranoid personality disorders. Cluster B includes borderline, histrionic, antisocial, and narcissistic personality disorders. Cluster C disorders are more prevalent and include avoidant, dependent, and obsessive-compulsive personality disorders. Many patients with personality disorders can be treated by family physicians. Patients with borderline personality disorder may benefit from the use of omega-3 fatty acids, second-generation antipsychotics, and mood stabilizers. Patients with antisocial personality disorder may benefit from the use of mood stabilizers, antipsychotics, and antidepressants. Other therapeutic interventions include motivational interviewing and solution-based problem solving.

[Creativity and antipsychotic drugs].

PubMed

Murry, P; Torrecuadrada, J L

1997-09-01

For the authors, the creative abilities of a schizophrenic patient are indicators of the therapeutic efficacy of an antipsychotic treatment and the incidence of adverse effects. The new antipsychotic drugs available, unlike conventional neuroleptics, show enhanced efficacy and do not exacerbate the negative symptoms. They may even alleviate them. With regard to clozapine, the authors illustrate the foregoing by two examples of a favorable course in two patients. Clozapine induced an indisputable clinical improvement and hence the opportunity for undeniable artistic activity. Lastly, the new antipsychotics contribute to changing the image that we have of schizophrenic patients.

"Extended" antipsychotic dosing in the maintenance treatment of schizophrenia: a double-blind, placebo-controlled trial.

PubMed

Remington, Gary; Seeman, Philip; Feingold, Alan; Mann, Steve; Shammi, Chekkera; Kapur, Shitij

2011-08-01

In the treatment of schizophrenia, all currently available oral antipsychotics are administered at least once daily, with strict adherence strongly encouraged to minimize risk of relapse. Based on a better understanding of the brain kinetics of antipsychotics, we have proposed a variation of this approach, "extended" dosing, which allows for intermittent but regular dosing. We carried out a randomized, double-blind, placebo-controlled trial evaluating 35 individuals with DSM-IV-defined schizophrenia who had been stabilized on antipsychotic therapy. Over a 6-month interval, 18 subjects received their medication as usual (daily), while 17 received their antipsychotic therapy every second day (extended). Outcome measures included clinical scales to assess symptoms (Brief Psychiatric Rating Scale [the primary outcome measure], Calgary Depression Scale), illness severity (Clinical Global Impressions-Severity of Illness scale), and relapse (ie, rehospitalization) rates. Side effects were also assessed, including movement disorders (Barnes Akathisia Scale, Simpson-Angus Scale, Abnormal Involuntary Movement Scale) and weight. The study was conducted from February 2003 to July 2007. Individuals in the extended dosing group were not at greater risk of symptom exacerbation, relapse, or rehospitalization; indeed, more rehospitalizations occurred in those receiving regular dosing. At the same time, though, there was no indication that side effects were significantly reduced in the extended dosing group. These results challenge the long-standing dogma that oral antipsychotics must be administered daily in stabilized patients with schizophrenia. Further studies with larger samples are needed to replicate these findings, as well as to elucidate whether postulated clinical advantages can be established and determined to outweigh potential risks. clinicaltrials.gov Identifier: NCT00431574. © Copyright 2011 Physicians Postgraduate Press, Inc.

Antipsychotics activate the TGFβ pathway effector SMAD3

PubMed Central

Cohen, T.; Sundaresh, S.; Levine, F.

2014-01-01

Although effective in treating an array of neurological disorders, antipsychotics are associated with deleterious metabolic side effects. Through high-throughput screening, we previously identified phenothiazine antipsychotics as modulators of the human insulin promoter. Here, we extended our initial finding to structurally diverse typical and atypical antipsychotics. We then identified the TGFβ pathway as being involved in the effect of antipsychotics on the insulin promoter, finding that antipsychotics activated SMAD3, a downstream effector of the TGFβ pathway, through a receptor distinct from the TGFβ receptor family and known neurotransmitter receptor targets of antipsychotics. Of note, antipsychotics that do not cause metabolic side effects did not activate SMAD3. In vivo relevance was demonstrated by reanalysis of gene expression data from human brains treated with antipsychotics, which showed altered expression of SMAD3 responsive genes. This work raises the possibility that antipsychotics could be designed that retain beneficial CNS activity while lacking deleterious metabolic side effects. PMID:22290122

Mood-Stabilizing Anticonvulsants, Spina Bifida, and Folate Supplementation: Commentary.

PubMed

Patel, Neil; Viguera, Adele C; Baldessarini, Ross J

2018-02-01

High risks of neural tube defects and other teratogenic effects are associated with exposure in early pregnancy to some anticonvulsants, including in women with bipolar disorder. Based on a semistructured review of recent literature, we summarized findings pertaining to this topic. Valproate and carbamazepine are commonly used empirically (off-label) for putative long-term mood-stabilizing effects. Both anticonvulsants have high risks of teratogenic effects during pregnancy. Risks of neural tube defects (especially spina bifida) and other major malformations are especially great with valproate and can arise even before pregnancy is diagnosed. Standard supplementation of folic acid during pregnancy can reduce risk of spontaneous spina bifida, but not that associated with valproate or carbamazepine. In contrast, lamotrigine has regulatory approval for long-term use in bipolar disorder and appears not to have teratogenic effects in humans. Lack of protective effects against anticonvulsant-associated neural tube defects by folic acid supplements in anticipation of and during pregnancy is not widely recognized. This limitation and high risks of neural tube and other major teratogenic effects, especially of valproate, indicate the need for great caution in the use of valproate and carbamazepine to treat bipolar disorder in women of child-bearing age.

Associations between mood instability and emotional processing in a large cohort of bipolar patients.

PubMed

Bilderbeck, A C; Reed, Z E; McMahon, H C; Atkinson, L Z; Price, J; Geddes, J R; Goodwin, G M; Harmer, C J

2016-11-01

Aberrant emotional biases have been reported in bipolar disorder (BD), but results are inconsistent. Despite the clinical relevance of chronic mood variability in BD, there is no previous research investigating how the extent of symptom fluctuations in bipolar disorder might relate to emotional biases. This exploratory study investigated, in a large cohort of bipolar patients, whether instability in weekly mood episode symptoms and other clinical and demographic factors were related to emotional bias as measured in a simple laboratory task. Participants (N = 271, BDI = 206, BDII = 121) completed an 'emotional categorization and memory' task. Weekly self-reported symptoms of depression and mania were collected prospectively. In linear regression analyses, associations between cognitive bias and mood variability were explored together with the influence of demographic and clinical factors, including current medication. Greater accuracy in the classification of negative words relative to positive words was associated with greater instability in depressive symptoms. Furthermore, greater negative bias in free recall was associated with higher instability in manic symptoms. Participants diagnosed with BDII, compared with BDI, showed overall better word recognition and recall. Current antipsychotic use was associated with reduced instability in manic symptoms but this did not impact on emotional processing performance. Emotional processing biases in bipolar disorder are related to instability in mood. These findings prompt further investigation into the underpinnings as well as clinical significance of mood instability.

Second generation antipsychotics for schizophrenia.

PubMed

Feltus, M S; Gardner, D M

1999-01-01

To provide a narrative review based on clinically relevant evidence specific to the issues surrounding the use of the second generation antipsychotics in schizophrenia. MEDLINE and Cochrane Library searches were performed to identify literature pertinent to the available and anticipated novel antipsychotics in North America. Articles that were selected included clinical trials, clinical practice guidelines, reviews and pharmacoeconomic analyses researching the efficacy and safety of the second generation antipsychotics including comparative studies among these agents. Related editorials, letters and newsletter commentaries were reviewed from a variety of sources to provide enhanced depth. Following the advent of clozapine in the 1980s, three other second generation antipsychotics (risperidone, olanzapine and quetiapine) have become available, with others (eg, ziprasidone) expected in the near future. The single major advance with these agents is their reduced propensity for extrapyramidal side effects and tardive dyskinesia. However, clinicians should be aware of the differential risk for these side effects. The purported advantage for negative symptoms compared with conventional agents has been inconsistent and may not be clinically important. The availability of a wide selection of antipsychotics has heralded the possibility of more effective management of the complex symptoms of schizophrenia. However, this has also made the choice of optimal treatment difficult. It is essential that practitioners understand how these agents compare with each other and with conventional antipsychotics.

Abnormal brain activation during emotion processing of euthymic bipolar patients taking different mood stabilizers.

PubMed

Li, Linling; Ji, Erni; Tang, Fei; Qiu, Yunhai; Han, Xue; Zhang, Shengli; Zhang, Zhiguo; Yang, Haichen

2018-06-16

Numerous functional magnetic resonance imaging studies have been conducted to elucidate emotion processing of patients with bipolar disorder (BD), but due to different inclusion criteria used, especially for the history of medication use, the results for euthymic BD patients are inconsistent. For this reason, brain functional effects of psychopharmacological treatments on BD patients have been investigated by numerous fMRI studies, but there is no existing report for brain functional effects of different mood stabilizers. In this study, we compared the emotion processing in BD patients treated by two popularly used mood stabilizer, lithium (N = 13; 30 ± 9 years) and valproate (N = 16; 33 ± 8 years), as well as healthy controls (HC; N = 16; 29 ± 7 years). Two emotional tasks were applied in this study: one used emotional pictures of everyday objects and scenes, and another used emotional facial expression pictures. The main findings were that BD on lithium showed increased fMRI activation in the right dorsal anterior cingulate cortex and bilateral lingual gyrus in response to the positive pictures relative to neutral pictures compared with BD on valproate and HC. Besides, no abnormal activation was observed in the amygdala. Limitations of this study comprise the small sample size and the cross-sectional design. Therefore, the results were suggestive of a different effect of lithium and valproate on brain activities during emotion processing but no causal role can be proposed. The enduring impairments in euthymic state could provide clues to the brain regions involved in the primary pathology of BD.

Antipsychotics and physical attractiveness.

PubMed

Seeman, Mary V

2011-10-01

Antipsychotics are effective in treating the symptoms of schizophrenia, but they may induce adverse effects, some of which-those that impact negatively on physical appearance-have not been sufficiently discussed in the psychiatric literature. Through a narrative review, to catalog antipsychotic side effects that interfere with physical attractiveness and to suggest ways of addressing them. PubMed databases were searched for information on the association between "antipsychotic side effects" and "attractiveness" using those two search phrases plus the following terms: "weight," "teeth," "skin," "hair," "eyes," "gait," "voice," "odor." Data from relevant qualitative and quantitative articles were considered, contextualized, and summarized. Antipsychotics, as a group, increase weight and may lead to dry mouth and bad breath, cataracts, hirsutism, acne, and voice changes; they may disturb symmetry of gait and heighten the risk for tics and spasms and incontinence, potentially undermining a person's attractiveness. Clinicians need to be aware of the impact of therapeutic drugs on appearance and how important this issue is to patients. Early in treatment, they need to plan preventive and therapeutic strategies.

Atypical antipsychotics and glucose homeostasis.

PubMed

Bergman, Richard N; Ader, Marilyn

2005-04-01

Persistent reports have linked atypical antipsychotics with diabetes, yet causative mechanisms responsible for this linkage are unclear. Goals of this review are to outline the pathogenesis of nonimmune diabetes and to survey the available literature related to why antipsychotics may lead to this disease. We accessed the literature regarding atypical antipsychotics and glucose homeostasis using PubMed. The search included English-language publications from 1990 through October 2004. Keywords used included atypical antipsychotics plus one of the following: glucose, insulin, glucose tolerance, obesity, or diabetes. In addition, we culled information from published abstracts from several national and international scientific meetings for the years 2001 through 2004, including the American Diabetes Association, the International Congress on Schizophrenia Research, and the American College of Neuropsychopharmacology. The latter search was necessary because of the paucity of well-controlled prospective studies. We examined publications with significant new data or publications that contributed to the overall comprehension of the impact of atypical antipsychotics on glucose metabolism. We favored original peer-reviewed articles and were less likely to cite single case studies and/or anecdotal information. Approximately 75% of the fewer than 150 identified articles were examined and included in this review. Validity of data was evaluated using the existence of peer-review status as well as our own experience with methodology described in the specific articles. The metabolic profile caused by atypical antipsychotic treatment resembles type 2 diabetes. These agents cause weight gain in treated subjects and may induce obesity in both visceral and subcutaneous depots, as occurs in diabetes. Insulin resistance, usually associated with obesity, occurs to varying degrees with different antipsychotics, although more comparative studies with direct assessment of resistance are

Novel antipsychotics and severe hyperlipidemia.

PubMed

Meyer, J M

2001-08-01

Newer atypical antipsychotics demonstrate superior effectiveness, with a diminished incidence of extrapyramidal side effects compared with older typical antipsychotics, but they have been associated with the development of obesity and new-onset diabetes. A small number of reports documenting modest hypertriglyceridemia related to newer antipsychotics have implicated fluperlapine, clozapine, and, most recently, olanzapine. This study summarizes the results of 14 cases of severe hypertriglyceridemia (>600 mg/dL) associated with olanzapine and quetiapine therapy occurring among inpatients at Oregon State Hospital, including 7 patients whose serum triglyceride levels exceeded 1,000 mg/ dL. Four of these patients also developed new-onset diabetes. Nine cases occurred during the first 8 months of treatment, with three cases identified within 3 months of commencing olanzapine or quetiapine therapy. Weight gain in olanzapine and quetiapine groups was modest (12.3 lb and 8.5 lb, respectively) and did not correlate with the severity of hypertriglyceridemia. Biochemical causes for severe hypertriglyceridemia associated with novel antipsychotics are unclear, but clinical monitoring of serum lipids must be added to the concerns about the metabolic consequences of therapy with certain newer antipsychotic agents.

Mood stability in Parkinson disease following deep brain stimulation: a 6-month prospective follow-up study.

PubMed

Chopra, Amit; Abulseoud, Osama A; Sampson, Shirlene; Lee, Kendall H; Klassen, Bryan T; Fields, Julie A; Matsumoto, Joseph Y; Adams, Andrea C; Stoppel, Cynthia J; Geske, Jennifer R; Frye, Mark A

2014-01-01

Deep brain stimulation for Parkinson disease has been associated with psychiatric adverse effects including anxiety, depression, mania, psychosis, and suicide. The purpose of this study was to evaluate the safety of deep brain stimulation in a large Parkinson disease clinical practice. Patients approved for surgery by the Mayo Clinic deep brain stimulation clinical committee participated in a 6-month prospective naturalistic follow-up study. In addition to the Unified Parkinson's Disease Rating Scale, stability and psychiatric safety were measured using the Beck Depression Inventory, Hamilton Depression Rating Scale, and Young Mania Rating scale. Outcomes were compared in patients with Parkinson disease who had a psychiatric history to those with no co-morbid psychiatric history. The study was completed by 49 of 54 patients. Statistically significant 6-month baseline to end-point improvement was found in motor and mood scales. No significant differences were found in psychiatric outcomes based on the presence or absence of psychiatric comorbidity. Our study suggests that patients with Parkinson disease who have a history of psychiatric co-morbidity can safely respond to deep brain stimulation with no greater risk of psychiatric adverse effect occurrence. A multidisciplinary team approach, including careful psychiatric screening ensuring mood stabilization and psychiatric follow-up, should be viewed as standard of care to optimize the psychiatric outcome in the course of deep brain stimulation treatment. © 2013 Published by The Academy of Psychosomatic Medicine on behalf of The Academy of Psychosomatic Medicine.

Atypical antipsychotics for psychosis in adolescents.

PubMed

Kumar, Ajit; Datta, Soumitra S; Wright, Stephen D; Furtado, Vivek A; Russell, Paul S

2013-10-15

Schizophrenia often presents in adolescence, but current treatment guidelines are based largely on studies of adults with psychosis. Over the past decade, the number of studies on treatment of adolescent-onset psychosis has increased. The current systematic review collates and critiques evidence obtained on the use of various atypical antipsychotic medications for adolescents with psychosis. To investigate the effects of atypical antipsychotic medications in adolescents with psychosis. We reviewed in separate analyses various comparisons of atypical antipsychotic medications with placebo or a typical antipsychotic medication or another atypical antipsychotic medication or the same atypical antipsychotic medication but at a lower dose. We searched the Cochrane Schizophrenia Group Register (October 2011), which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies and contacted study authors and relevant pharmaceutical companies to ask for more information. We included all relevant randomised controlled trials (RCTs) that compared atypical antipsychotic medication with placebo or another pharmacological intervention or with psychosocial interventions, standard psychiatric treatment or no intervention in children and young people aged 13 to 18 years with a diagnosis of schizophrenia, schizoaffective disorder, acute and transient psychoses or unspecified psychosis. We included studies published in English and in other languages that were available in standardised databases. Review authors AK and SSD selected the studies, rated the quality of the studies and performed data extraction. For dichotomous data, we estimated risk ratios (RRs) with 95% confidence intervals (CIs) using a fixed-effect model. When possible, for binary data presented in the 'Summary of findings' table, we calculated illustrative comparative risks. We summated continuous data using the mean difference (MD). Risk of

Psychopharmacology and Aggression: II. A Meta-Analysis of Nonstimulant Medication Effects on Overt Aggression-Related Behaviors in Youth with SED.

ERIC Educational Resources Information Center

Connor, Daniel R.; Boone, R. Thomas; Steingard, Ronald J.; Lopez, Ivan D.; Melloni, Richard H., Jr.

2003-01-01

Meta-analysis of 33 studies examined effect size for nonstimulant medications on symptoms of overt aggression-related behaviors in children and adolescents with serious emotional and behavioral disturbances. Thirty-seven independent effects were found for neuroleptic, atypical antipsychotic, mood stabilizer, antidepressant, and adrenergic agents…

Atypical and Typical Antipsychotics in the Schools

ERIC Educational Resources Information Center

Noggle, Chad A.; Dean, Raymond S.

2009-01-01

The use of antipsychotic medications within the school-age population is rapidly increasing. Although typical antipsychotics may be used in rare cases, this influx is largely secondary to the availability of the atypical antipsychotics. Reduction of possible adverse effects and increased efficacy represent the primary basis for the atypical…

The Effectiveness of Mood Stabilizers and Antiepileptic Medication for the Management of Behaviour Problems in Adults with Intellectual Disability: A Systematic Review

ERIC Educational Resources Information Center

Deb, S.; Chaplin, R.; Sohanpal, S.; Unwin, G.; Soni, R.; Lenotre, L.

2008-01-01

Background: Psychotropic medications are used to manage behaviour problems in adults with intellectual disability (ID). One group of psychotropic medication are mood stabilizers such as lithium and some antiepileptic drugs. Method: A comprehensive systematic review was performed to determine the evidence base for the effectiveness of mood…

Relationship Between Temperament and Character Traits, Mood, and Medications in Bipolar I Disorder.

PubMed

Chavez, Sergio B; Alvarado, Luis A; Gonzalez, Robert

2016-01-01

Bipolar I disorder is an illness causing mood shifts that can result in personality and character trait alterations. The relationship between mood and personality and character traits in bipolar I disorder is unclear at this time. We conducted a study from February 2009 to March 2010 that included 42 subjects with bipolar I disorder, which was confirmed using the Structured Clinical Interview for DSM-IV Axis I Disorders. Mood was assessed via the Young Mania Rating Scale (YMRS) and the 30-item Clinician-rated Inventory of Depressive Symptomatology (IDS-C). Temperament and character traits were assessed via the Temperament and Character Inventory (TCI). Multivariate analysis was used to test relationships between mood and temperament and character traits with the effects of possible cofactors taken into account (eg, age, gender, medications). We noted a positive correlation between YMRS scores and persistence ( P = .046) and a trend toward positive correlation with novelty seeking ( P = .054). There was a positive correlation between higher IDS-C scores and harm avoidance ( P < .001) and a negative correlation with self-directedness scores ( P < .001). Antipsychotic use was positively correlated with the character trait self-directedness ( P = .008), with a trend toward a positive correlation with reward dependence ( P = .056). Lithium was negatively correlated with reward dependence ( P = .047) and self-transcendence ( P = .028), with a trend toward a negative correlation with novelty seeking ( P = .053). The findings of our study suggest that some personality and character traits may vary according to mood state and medications in patients with bipolar I disorder. Prospective and longitudinal studies are required to fully characterize the relationships between personality and character traits and mood state in bipolar I disorder.

Add-on clinical effects of selective antagonist of 5HT6 receptors AVN-211 (CD-008-0173) in patients with schizophrenia stabilized on antipsychotic treatment: pilot study.

PubMed

Morozova, Margarita A; Lepilkina, Taisiya A; Rupchev, Georgy E; Beniashvily, Allan G; Burminskiy, Denis S; Potanin, Sergey S; Bondarenko, Evgeny V; Kazey, Vasily I; Lavrovsky, Yan; Ivachtchenko, Alexandre V

2014-08-01

The serotoninergic system as a target for add-on treatment seems to be a promising approach in patients with schizophrenia. To clarify if selective 5HT-6 antagonist AVN-211 (CD-008-0173) adds clinical and cognitive effects to stable antipsychotic treatment. A randomized, double-blind, placebo-controlled, add-on, 4r-week trial in 47 schizophrenia patients (21 patients receiving study drug and 26 receiving placebo) who were stabilized on antipsychotic medication was performed. Seventeen patients from the study drug group and 25 patients from the placebo group completed the trial. Treatment effects were measured using clinical rating scales and attention tests. With no differences at baseline, there was a significant difference between the groups in Positive and Negative Syndrome Scale (PANSS) positive subscale score (p = 0.058) in favor of patients in the treatment group at the endpoint. The PANSS positive subscore (p = 0.0068) and Clinical Global Impression-Severity (CGI-S) (p = 0.048) score significantly changed only in the treatment group. Only in the placebo group were significant changes in Calgary Depression Rating Scale (CDRS) total score registered. The indices of attention tests at endpoint did not show differences between the groups, with the exception of the scope of change in the results of the subtest VIII of the Wechsler Adult Intelligence Scale (WAIS), which showed difference between the groups (p = 0.02) and was significantly larger in the treatment group. Only inside the study drug group, significant changes in selectivity and continuous attention were observed regarding total correct responses (p = 0.0038) and reaction time (p = 0.058) in the Continuous Attention Task (CAT) test. Selective 5HT6 antagonist AVN-211 (CD-008-0173) added antipsychotic and some procognitive (attention) effects to antipsychotic medication.

Challenges and Promises of Pediatric Psychopharmacology.

PubMed

Giles, Lisa L; Martini, D Richard

2016-08-01

Most prescriptions for psychotropic medications are written by primary care physicians, yet pediatricians, many of whom are teaching residents and medical students about pediatric psychopharmacology, often feel inadequately trained to treat mental health concerns. Over the past several decades, the number, size, and quality of psychopharmacologic studies in youth has greatly increased. Here we review the current evidence for efficacy and safety of each of the major pharmacologic drug classes in youth (psychostimulants, antidepressants, mood stabilizers, and antipsychotics). Psychostimulants have a robust body of literature supporting their evidence as first-line treatment for attention-deficit/hyperactivity disorder. Selective serotonin reuptake inhibitors (SSRIs) have documented efficacy for pediatric depression and multiple different anxiety disorders with childhood onset. Combining cognitive-behavioral therapy with SSRI treatment enhances treatment benefit and minimizes adverse events of medication. Mood stabilizers, including lithium and anticonvulsant medications, have a less robust strength of evidence and come with more problematic side effects. However, they are increasingly prescribed to youth, often to treat irritability, mood lability, and aggression, along with treatment of bipolar disorder. Antipsychotics have long been a mainstay of treatment for childhood-onset schizophrenia, and in recent years, the evidence base for providing antipsychotics to youth with bipolar mania and autistic disorder has grown. Most concerning with antipsychotics are the metabolic side effects, which appear even more problematic in youth than adults. By better understanding the evidence-based psychopharmacologic interventions, academic pediatricians will be able to treat patients and prepare future pediatrician to address the growing mental health care needs of youth. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Methodological approaches and magnitude of the clinical unmet need associated with amotivation in mood disorders.

PubMed

Calabrese, Joseph R; Fava, Maurizio; Garibaldi, George; Grunze, Heinz; Krystal, Andrew D; Laughren, Thomas; Macfadden, Wayne; Marin, Robert; Nierenberg, Andrew A; Tohen, Mauricio

2014-10-01

There is growing research interest in studying motivational deficits in different neuropsychiatric disorders because these symptoms appear to be more common than originally reported and negatively impact long-term functional outcomes. However, there is considerable ambiguity in the terminology used to describe motivational deficits in the scientific literature. For the purposes of this manuscript, the term "amotivation" will be utilised in the context of mood disorders, since this is considered a more inclusive/appropriate term for this patient population. Other challenges impacting the study of amotivation in mood disorders, include: appropriate patient population selection; managing or controlling for potential confounding factors; the lack of gold-standard diagnostic criteria and assessment scales; and determination of the most appropriate study duration. This paper summarises the search for a consensus by a group of experts in the optimal approach to studying amotivation in mood disorders. The consensus of this group is that amotivation in mood disorders is a legitimate therapeutic target, given the magnitude of the associated unmet needs, and that proof-of-concept studies should be conducted in order to facilitate subsequent larger investigations. The focus of this manuscript is to consider the study of amotivation, as a residual symptom of major depressive disorder (MDD) or bipolar depression (BD), following adequate treatment with a typical antidepressant or mood stabiliser/antipsychotic, respectively. There is a paucity of data studying amotivation in mood disorders. This manuscript provides general guidance on the most appropriate study design(s) and methodology to assess potential therapeutic options for the management of residual amotivation in mood disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Antipsychotic interventions in prodromal psychosis: safety issues.

PubMed

Liu, Chen-Chung; Demjaha, Arsime

2013-03-01

In recent years, psychopharmacological intervention in prodromal psychosis, also known as the ultra-high risk (UHR) mental state for psychosis, has attracted much attention. Whilst it has been shown that antipsychotic use in UHR individuals may be effective in potentially delaying or even averting progression to frank psychosis, their use in subjects that do not necessarily convert to psychosis has raised considerable ethical concerns because of their adverse effects. Recent treatment guidelines for patients at UHR for psychosis recommend the use of antipsychotics only in exceptional conditions and with great precautions. To date only a few studies have investigated the use of antipsychotic medications in UHR patients and the potential benefits and risks related to their use in prodromal psychosis remain unclear. We review here all published studies that included UHR patients treated with antipsychotics, regardless of study design. These studies were all of second-generation antipsychotics, given that first-generation antipsychotics cannot be recommended because of their adverse drug reactions. We specifically examine the available descriptions of adverse reactions of the individual antipsychotic medication in each study and discuss the potential effects of various demographic and clinical factors that may impact on safety issues of pharmacological interventions in UHR patients. Clinical trials to date investigating potential benefits of antipsychotic treatments in preventing transition to psychosis were of relatively short duration and have involved a small number of patients. Whilst it appears that pharmacological intervention at this stage may be effective in both reducing the psychopathology and decreasing transition rates, and is potentially safe, in the absence of sufficient evidence-based knowledge to guide treatment, definitive clinical recommendations and guidelines cannot be derived. Certain adverse events take time to develop, such as metabolic syndrome

History and therapeutic rationale of long acting antipsychotics.

PubMed

De Risio, Alessandro; Lang, Antonella P

2014-02-01

Despite their widespread use, long acting antipsychotics, are often regarded with prejudice, due to fears of punishment, control and insufficient evolution towards psychosocial development of psychotic patients raised by their improper utilization. Another major shortcoming of long-acting antipsychotics is the impossibility of altering their dosage if side-effects appear. However, long-acting antipsychotics proved effective in schizophrenia and other severe psychotic disorders as a consequence of stable dose administration, leading to reduction of relapses and increased treatment adherence. Therapeutic opportunities have also risen after introduction of newer long acting second generation antipsychotics in recent years. Newer long-acting antipsychotics were developed to tackle the need for pharmacotherapy enhancing adherence in integrated rehabilitation programmes. This review is an outline of the development and introduction of older and newer long-acting antipsychotics in the treatment of schizophrenia and other psychoses, with considerations on past and present pharmacological and therapeutic issues.

Assessing Side Effects of Pharmacotherapy Treatment of Bipolar Disorder: A 20-Year Review of the Literature

ERIC Educational Resources Information Center

Matson, Johnny L.; Gonzalez, Melissa L.; Smith, Kimberly R.; Terlonge, Cindy; Thorson, Ryan T.; Dixon, Dennis R.

2006-01-01

A substantial literature on the effective treatment of bipolar disorder has begun to appear, particularly in the last 20 years.The majority of treatments studied have employed medications, particularly mood stabilizers, a typical antipsychotics and antidepressants. Most treatments produce side effects and medications are no exception. A review of…

The prefrontal cortex: a target for antipsychotic drugs.

PubMed

Artigas, F

2010-01-01

At therapeutic doses, classical antipsychotic drugs occupy a large proportion of subcortical dopamine D2 receptors, whereas atypical antipsychotics preferentially occupy cortical 5-HT(2) receptors. However, the exact cellular and network basis of their therapeutic action is not fully understood. To review the mechanism of action of antipsychotic drugs with a particular emphasis on their action in the prefrontal cortex (PFC). The PFC controls a large number of higher brain functions altered in schizophrenia. Histological studies indicate the presence of a large proportion of PFC neurons expressing monoaminergic receptors sensitive to the action of atypical- and to a lesser extentclassical antipsychotic drugs. Functional studies also indicate that both drug families act at PFC level. Atypical antipsychotic drugs likely exert their therapeutic activity by a preferential action on PFC neurons, thus modulating the PFC output to basal ganglia circuits. Classical antipsychotics also interact with these PFC targets in addition to blocking massively striatal D2 receptors.

Newer antipsychotics and upcoming molecules for schizophrenia.

PubMed

George, Melvin; Amrutheshwar, Radhika; Rajkumar, Ravi Philip; Kattimani, Shivanand; Dkhar, Steven Aibor

2013-08-01

The management of schizophrenia has seen significant strides over the last few decades, due to the increasing availability of a number of antipsychotics. Yet, the diminished efficacy in relation to the negative and cognitive symptoms of schizophrenia, and the disturbing adverse reactions associated with the current antipsychotics, reflect the need for better molecules targeting unexplored pathways. To review the salient features of the recently approved antipsychotics; namely, iloperidone, asenapine, lurasidone and blonanserin. We discuss the advantages, limitations and place in modern pharmacotherapy of each of these drugs. In addition, we briefly highlight the new targets that are being explored. Promising strategies include modulation of the glutamatergic and GABAergic pathways, as well as cholinergic systems. Although regulatory bodies have approved only a handful of antipsychotics in recent years, the wide spectrum of targets that are being explored could eventually bring out antipsychotics with improved efficacy and acceptability, as well as the potential to revolutionize psychiatric practice.

Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder

PubMed Central

Josiassen, Richard C.; Kane, John M.; Liang, Grace S.; Burke, Joshua; O’Brien, Christopher F.

2017-01-01

Background The short-term safety profile of once-daily valbenazine (NBI-98854) has been evaluated in several double-blind, placebo-controlled (DBPC) trials in adults with tardive dyskinesia (TD) who had a diagnosis of schizophrenia/schizoaffective (SCHZ) disorder or mood disorder. Studies with longer treatment duration (up to 48 weeks) were conducted to evaluate the long-term safety of this novel drug in subjects with TD. Methods The pooled long-term exposure (LTE) population included valbenazine-treated subjects from 3 studies: KINECT (NCT01688037: 6-week DBPC, 6-week open-label); KINECT 3 (NCT02274558: 6-week DBPC, 42-week blinded extension, 4-week drug-free follow-up); KINECT 4 (NCT02405091: 48-week open-label, 4-week drug-free follow-up). Safety assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms (ECGs), and extrapyramidal symptom (EPS) scales. Psychiatric stability was monitored using the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) (SCHZ subgroup), as well as the Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) (mood subgroup). All data were analyzed descriptively. Results The LTE population included 430 subjects (KINECT, n = 46; KINECT 3, n = 220; KINECT 4, n = 164), 71.7% with SCHZ and 28.3% with a mood disorder; 85.5% were taking an antipsychotic (atypical only, 69.8%; typical only or typical + atypical, 15.7%). In the LTE population, treatment-emergent AEs (TEAEs) and discontinuations due to AEs were reported in 66.5% and 14.7% of subjects, respectively. The TEAE incidence was lower in the SCHZ subgroup (64.4%) than in the mood subgroup (71.9%). The 3 most common TEAEs in the SCHZ subgroup were urinary tract infection (UTI, 6.1%), headache (5.8%), and somnolence (5.2%). The 3 most common TEAEs in the mood subgroup were headache (12.4%), UTI (10.7%), and somnolence (9.1%). Mean score changes from baseline to end of treatment

Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder.

PubMed

Josiassen, Richard C; Kane, John M; Liang, Grace S; Burke, Joshua; O'Brien, Christopher F

2017-08-01

The short-term safety profile of once-daily valbenazine (NBI-98854) has been evaluated in several double-blind, placebo-controlled (DBPC) trials in adults with tardive dyskinesia (TD) who had a diagnosis of schizophrenia/schizoaffective (SCHZ) disorder or mood disorder. Studies with longer treatment duration (up to 48 weeks) were conducted to evaluate the long-term safety of this novel drug in subjects with TD. The pooled long-term exposure (LTE) population included valbenazine-treated subjects from 3 studies: KINECT (NCT01688037: 6-week DBPC, 6-week open-label); KINECT 3 (NCT02274558: 6-week DBPC, 42-week blinded extension, 4-week drug-free follow-up); KINECT 4 (NCT02405091: 48-week open-label, 4-week drug-free follow-up). Safety assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms (ECGs), and extrapyramidal symptom (EPS) scales. Psychiatric stability was monitored using the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) (SCHZ subgroup), as well as the Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) (mood subgroup). All data were analyzed descriptively. The LTE population included 430 subjects (KINECT, n = 46; KINECT 3, n = 220; KINECT 4, n = 164), 71.7% with SCHZ and 28.3% with a mood disorder; 85.5% were taking an antipsychotic (atypical only, 69.8%; typical only or typical + atypical, 15.7%). In the LTE population, treatment-emergent AEs (TEAEs) and discontinuations due to AEs were reported in 66.5% and 14.7% of subjects, respectively. The TEAE incidence was lower in the SCHZ subgroup (64.4%) than in the mood subgroup (71.9%). The 3 most common TEAEs in the SCHZ subgroup were urinary tract infection (UTI, 6.1%), headache (5.8%), and somnolence (5.2%). The 3 most common TEAEs in the mood subgroup were headache (12.4%), UTI (10.7%), and somnolence (9.1%). Mean score changes from baseline to end of treatment (Week 48) indicated that

Antipsychotics and associated risk of out-of-hospital cardiac arrest.

PubMed

Weeke, P; Jensen, A; Folke, F; Gislason, G H; Olesen, J B; Fosbøl, E L; Wissenberg, M; Lippert, F K; Christensen, E F; Nielsen, S L; Holm, E; Kanters, J K; Poulsen, H E; Køber, L; Torp-Pedersen, C

2014-10-01

Antipsychotic drugs have been associated with sudden cardiac death, but differences in the risk of out-of-hospital cardiac arrest (OHCA) associated with different antipsychotic drug classes are not clear. We identified all OHCAs in Denmark (2001-2010). The risk of OHCA associated with antipsychotic drug use was evaluated by conditional logistic regression analysis in case-time-control models. In total, 2,205 (7.6%) of 28,947 OHCA patients received treatment with an antipsychotic drug at the time of the event. Overall, treatment with any antipsychotic drug was associated with OHCA (odds ratio (OR) = 1.53, 95% confidence interval (CI): 1.23-1.89), as was use with typical antipsychotics (OR = 1.66, CI: 1.27-2.17). By contrast, overall, atypical antipsychotic drug use was not (OR = 1.29, CI: 0.90-1.85). Two individual typical antipsychotic drugs, haloperidol (OR = 2.43, CI: 1.20-4.93) and levomepromazine (OR = 2.05, CI: 1.18-3.56), were associated with OHCA, as was one atypical antipsychotic drug, quetiapine (OR = 3.64, CI: 1.59-8.30).

Hormone-Related Migraine Headaches and Mood Disorders: Treatment with Estrogen Stabilization.

PubMed

Warnock, Julia K; Cohen, Lawrence J; Blumenthal, Harvey; Hammond, Jordan E

2017-01-01

Because estrogens and the trigeminal system are inherently linked, prescribers who are treating a woman with a hormonally related mood disorder and migraine headaches should consider hormonal options to optimize the patient's treatment. This article discusses the interrelationships of estrogen, serotonin, and the trigeminal system as they relate to menstrual migraine occurrence and hormone-related mood symptoms. In addition, clinical examples are provided to facilitate the prescribers treating women during reproductive transitions in which declining estrogens are related to their suffering. © 2016 Pharmacotherapy Publications, Inc.

Antipsychotic Treatment and Tobacco Craving in People With Schizophrenia.

PubMed

Wehring, Heidi J; Heishman, Stephen J; McMahon, Robert P; Liu, Fang; Feldman, Stephanie; Raley, Heather; Weiner, Elaine; Kelly, Deanna L

2017-01-01

Nicotine dependence is high in schizophrenia, and craving is known to impact relapse during quit attempts. We compared tobacco craving in smokers with schizophrenia treated with different antipsychotics. Mean craving scores were lowest in participants receiving first-generation antipsychotics, although these differences were not statistically significant. Craving with clozapine was not lower than with other antipsychotics. Further research is needed to determine whether differences in craving exist between antipsychotic classes.

Antipsychotic prescribing in older people.

PubMed

Neil, Wendy; Curran, Stephen; Wattis, John

2003-09-01

Antipsychotic medications have made a significant contribution to the care of the mentally ill people over the past 50 years, with good evidence that both typical and atypical agents are effective in the treatment of schizophrenia and related conditions. In addition they are widely used to good effect in other disorders including psychotic depression, dementia and delirium. Both typical and atypical agents may cause severe side-effects and, in the elderly in particular, there is an increased propensity for drug interactions. If used with care, antipsychotics are usually well tolerated, especially the atypical drugs. Although antipsychotics are effective at reducing psychotic symptoms their limitations should be recognised. They do not 'cure' the underlying illness, and the management of psychotic and behavioural symptoms must take into consideration treatment of physical illness as well as psychosocial interventions. In addition, the antipsychotic effect may take one to two weeks to be evident so doses should not be increased too rapidly. Often small doses are effective in the elderly if they are given sufficient time to work. As our understanding of the mechanisms of psychosis improves it is hoped that new drugs will be developed with novel mechanisms of action with improved efficacy and reduced side-effects. There are several drugs in development, some sharing similarities to currently available agents whilst others have novel mechanisms of actions involving glutamate and nicotinic receptors. Pharmacogenetics is also likely to be increasingly important over the next few years. As the genetic basis of many psychiatric disorders becomes more clearly established it is likely that drugs specifically designed for particular sub-groups of receptors will be developed. Finally, although the pharmacological treatment of psychotic disorders in younger people has been given considerable attention, there is a paucity of good quality research on antipsychotic drug use in

Impact of Atypical Antipsychotic Therapy on Leptin, Ghrelin, and Adiponectin

PubMed Central

Jin, Hua; Meyer, Jonathan M.; Mudaliar, Sunder; Jeste, Dilip V.

2009-01-01

Background Many adverse effects of atypical antipsychotic treatment are associated with antagonism of monoamine receptors; however, data indicate that important metabolic effects, such as hypertriglyceridemia and impairment in glucose/insulin homeostasis, may not be related to these mechanisms, leading investigators to explore alternative hypotheses. Promising candidates include a possible impact of antipsychotics on peptide hormonal regulators of metabolic control such as leptin, ghrelin, and adiponectin. The purpose of this review is to summarize recent data on changes in these hormones during atypical antipsychotic treatment. Methods A Medline search was performed for papers published from January 1999 to January 2007 using key words antipsychotic, atypical antipsychotic, and individual atypical antipsychotic drug names cross-referenced with leptin, ghrelin, and adiponectin. Results The bulk of the published work focused on changes in body weight and serum leptin, with far less data on ghrelin, and adiponectin, and non-weight metabolic changes. Leptin changes were directly related to a medication’s weight gain liability, with no added antipsychotic effects on leptin signaling. Conflicting results emerged for the other markers, but all three long-term studies on ghrelin showed increased levels in patients on atypical antipsychotics with weight gain liabilities. Conclusions Leptin increases during antipsychotic treatment are a result of weight gain rather than a direct impact of atypical antipsychotics on leptin physiology. Preliminary long-term data show increased ghrelin levels, but this finding must be replicated. The association with antipsychotic effects on glucose and lipid metabolism and these hormones remains virtually unstudied. Future research should indicate whether ghrelin and other peptide hormones may be useful predictors of weight gain or metabolic changes in patients on antipsychotics. PMID:18206351

Antipsychotic-induced akathisia in delirium: A systematic review

PubMed Central

FORCEN, FERNANDO ESPI; MATSOUKAS, KONSTANTINA; ALICI, YESNE

2017-01-01

Objective Akathisia is a neuropsychiatric syndrome characterized by subjective and objective restlessness. It is a common side effect in patients taking antipsychotics and other psychotropics. Patients with delirium are frequently treated with antipsychotic medications that are well known to induce akathisia as a side effect. However, the prevalence, phenomenology, and management of akathisia in patients with delirium remain largely unknown. The purpose of this review was to examine the medical literature in order to establish the current state of knowledge regarding the prevalence of antipsychotic-induced akathisia in patients with delirium. Method A systematic review of the literature was conducted using the EMBASE, MEDLINE, PsycINFO, and CINAHL databases. Some 10 studies addressing the incidence of akathisia in patients taking antipsychotic medication for delirium were identified and included in our review. Results The included studies reported a variable prevalence of antipsychotic-induced akathisia. A higher prevalence was found in patients taking haloperidol. Among atypical antipsychotics, paliperidone and ziprasidone were associated with a higher risk of akathisia. The risk for akathisia appeared to be a dose-related phenomenon. Significance of results Studies using specific scales for evaluation of akathisia in delirium are lacking. Some populations, such as patients with cancer or terminally ill patients in palliative care settings taking antipsychotics for the treatment of delirium, could be at higher risk for development of akathisia as a side effect. PMID:26087817

Applications of time-series analysis to mood fluctuations in bipolar disorder to promote treatment innovation: a case series.

PubMed

Holmes, E A; Bonsall, M B; Hales, S A; Mitchell, H; Renner, F; Blackwell, S E; Watson, P; Goodwin, G M; Di Simplicio, M

2016-01-26

Treatment innovation for bipolar disorder has been hampered by a lack of techniques to capture a hallmark symptom: ongoing mood instability. Mood swings persist during remission from acute mood episodes and impair daily functioning. The last significant treatment advance remains Lithium (in the 1970s), which aids only the minority of patients. There is no accepted way to establish proof of concept for a new mood-stabilizing treatment. We suggest that combining insights from mood measurement with applied mathematics may provide a step change: repeated daily mood measurement (depression) over a short time frame (1 month) can create individual bipolar mood instability profiles. A time-series approach allows comparison of mood instability pre- and post-treatment. We test a new imagery-focused cognitive therapy treatment approach (MAPP; Mood Action Psychology Programme) targeting a driver of mood instability, and apply these measurement methods in a non-concurrent multiple baseline design case series of 14 patients with bipolar disorder. Weekly mood monitoring and treatment target data improved for the whole sample combined. Time-series analyses of daily mood data, sampled remotely (mobile phone/Internet) for 28 days pre- and post-treatment, demonstrated improvements in individuals' mood stability for 11 of 14 patients. Thus the findings offer preliminary support for a new imagery-focused treatment approach. They also indicate a step in treatment innovation without the requirement for trials in illness episodes or relapse prevention. Importantly, daily measurement offers a description of mood instability at the individual patient level in a clinically meaningful time frame. This costly, chronic and disabling mental illness demands innovation in both treatment approaches (whether pharmacological or psychological) and measurement tool: this work indicates that daily measurements can be used to detect improvement in individual mood stability for treatment innovation (MAPP).

Applications of time-series analysis to mood fluctuations in bipolar disorder to promote treatment innovation: a case series

PubMed Central

Holmes, E A; Bonsall, M B; Hales, S A; Mitchell, H; Renner, F; Blackwell, S E; Watson, P; Goodwin, G M; Di Simplicio, M

2016-01-01

Treatment innovation for bipolar disorder has been hampered by a lack of techniques to capture a hallmark symptom: ongoing mood instability. Mood swings persist during remission from acute mood episodes and impair daily functioning. The last significant treatment advance remains Lithium (in the 1970s), which aids only the minority of patients. There is no accepted way to establish proof of concept for a new mood-stabilizing treatment. We suggest that combining insights from mood measurement with applied mathematics may provide a step change: repeated daily mood measurement (depression) over a short time frame (1 month) can create individual bipolar mood instability profiles. A time-series approach allows comparison of mood instability pre- and post-treatment. We test a new imagery-focused cognitive therapy treatment approach (MAPP; Mood Action Psychology Programme) targeting a driver of mood instability, and apply these measurement methods in a non-concurrent multiple baseline design case series of 14 patients with bipolar disorder. Weekly mood monitoring and treatment target data improved for the whole sample combined. Time-series analyses of daily mood data, sampled remotely (mobile phone/Internet) for 28 days pre- and post-treatment, demonstrated improvements in individuals' mood stability for 11 of 14 patients. Thus the findings offer preliminary support for a new imagery-focused treatment approach. They also indicate a step in treatment innovation without the requirement for trials in illness episodes or relapse prevention. Importantly, daily measurement offers a description of mood instability at the individual patient level in a clinically meaningful time frame. This costly, chronic and disabling mental illness demands innovation in both treatment approaches (whether pharmacological or psychological) and measurement tool: this work indicates that daily measurements can be used to detect improvement in individual mood stability for treatment innovation (MAPP

Paliperidone for the treatment of schizoaffective disorder.

PubMed

Alphs, Larry; Fu, Dong-Jing; Turkoz, Ibrahim

2016-01-01

Schizoaffective disorder (SCA) is a complex mental illness characterized by psychosis and affective symptoms. Treatment usually involves concomitant therapy with antipsychotics, mood stabilizers, and/or antidepressants. Effective treatment must address acute symptoms, maintain long-term stability, promote recovery, and improve patient functioning. Data from 3 pivotal studies evaluating the acute and maintenance treatment of SCA with paliperidone are reviewed. Two formulations of paliperidone have been studied for these indications: an extended-release oral formulation (NCT00397033, NCT00412373) and long-acting injectable once-monthly paliperidone palmitate (NCT01193153). The reported effects of these formulations on psychotic, depressive, and manic symptoms are discussed. Both formulations were found to be safe and effective for the acute and maintenance treatment of SCA. Of critical importance for this treatment population is that rapid improvement was seen in all major symptoms of SCA, including psychosis, depression, and mania. Mediation analyses suggest that the known antipsychotic effects of paliperidone occur independently of its antidepressant effects. Both formulations of the drug are effective when used as monotherapy or adjunctively with antidepressants or mood stabilizers. Beyond symptom control, both formulations improved patient functioning and increased patient satisfaction.

Multiple Antipsychotic Medication Use in Autism Spectrum Disorder.

PubMed

Wink, Logan K; Pedapati, Ernest V; Horn, Paul S; McDougle, Christopher J; Erickson, Craig A

2017-02-01

The purpose of this study was to explore the use of multiple antipsychotic medications in patients with autism spectrum disorder (ASD) by reviewing the longitudinal medication management of 1100 patients consecutively treated for behavioral symptoms associated with ASD at a tertiary care specialty clinic. We identified all patients with ASD treated with daily doses of two or more antipsychotics for at least two visits at our clinic. For each patient meeting inclusion criteria, diagnostic and demographic data were collected. To evaluate clinical need and effectiveness of antipsychotic medications in this sample, we reviewed symptoms targeted with each antipsychotic medication and concomitant medications prescribed. Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scale ratings had been completed at the time of each visit, and the duration of treatment with antipsychotic medications was determined. To evaluate the safety and tolerability of antipsychotic medication use in ASD, we reviewed reported adverse effects and calculated body mass index (BMI) change with treatment. Seventy patients met the inclusion criteria (6.4% of our sample). The majority of patients were moderately to severely ill Caucasian males, as determined by baseline mean CGI-S of 4.7 (SD = 0.8), and were diagnosed with autistic disorder and comorbid intellectual disability. The mean age was 15.1 years (SD = 10.9), the primary targeted symptoms were agitation/irritability, physical aggression, and self-injury. The majority of patients remained on two or more antipsychotics for >1 year. In this population, patients demonstrated greater symptomatic improvement and generally tolerated treatment without significant adverse effects. The use of two or more antipsychotic medications may be increasingly common in patients with ASD. This retrospective study demonstrates that this treatment approach may be of some clinical benefit, and is generally well

The Potential Risks of Commonly Prescribed Antipsychotics

PubMed Central

Aneja, Alka; Rahman, Atiq; Megna, James; Freemont, Wanda; Shiplo, Mohammed; Nihilani, Nikil; Lee, Kathy

2005-01-01

Chlorpromazine, haloperidol, fluphenazine, clozapine, risperidone, quetiapine, olanzapine, ziprasidone, and aripiprazole are antipsychotics commonly used in psychiatric medicine. Approximately one third of pregnant women with psychotic symptoms use antipsychotics at least once. This review will discuss the effects of antipsychotic use during pregnancy and lactation on the fetus and infant. Although adequate and well-controlled studies have not been done in any one of these antipsychotic drugs, animal studies have revealed evidence of teratogenic or embryo/fetotoxic effects in all of them. Toxicities include skeletal malformations, central nervous system (CNS) defects, cleft palate, cardiac abnormalities, decreased fetal growth, and fetal death. For example, in pregnant women, congenital malformations and perinatal death have been reported with chlorpromazine use. Both chlorpromazine and fluphenazine in monotherapy have been shown to cause extrapyramidal symptoms and respiratory distress in infants born to mothers treated with these medications. Haloperidol use during pregnancy has been linked to severe limb reduction defects. Effects of antipsychotic use in lactating mothers are mostly unknown. However, the use of chlorpromazine has been reported to result in drowsiness and lethargy in breastfed infants. Additionally, clozapine has been reported to cause sedation, decreased suckling, restlessness, irritability, seizures, and cardiovascular instability of infants were also reported with clozapine use in lactating mother. Use of antipsychotic drugs by pregnant and lactating mother may only be justified if the potential benefit outweighs the potential risk to the fetus. PMID:21152171

Switching stable patients with schizophrenia from their oral antipsychotics to aripiprazole lauroxil: a post hoc safety analysis of the initial 12-week crossover period.

PubMed

Weiden, Peter J; Du, Yangchun; Liu, Chih-Chin; Stanford, Arielle D

2018-06-26

Switching antipsychotic medications is common in patients with schizophrenia who are experiencing persistent symptoms or tolerability issues associated with their current drug regimen. This analysis assessed the safety of switching from an oral antipsychotic to the long-acting injectable antipsychotic aripiprazole lauroxil (AL). This was a post hoc analysis of outpatients with schizophrenia who were prescribed an oral antipsychotic and who enrolled in an international, open-label, long-term (52-week) safety study of AL. The analysis focused on the first 3 injections of AL 882 mg over 12 weeks, divided into the immediate 4-week crossover period between the first and second AL injections (initiation phase) and the subsequent 8 weeks (stabilization phase). Patients were grouped by preswitch oral antipsychotic medication, and safety and clinical symptoms were assessed. In total, 190 patients had switched from one of the following oral antipsychotic medications: aripiprazole, conventional antipsychotics, risperidone/paliperidone, olanzapine, or quetiapine. The 12-week completion rate was high (92.1%) and similar across the different preswitch oral antipsychotic groups. Overall, adverse event (AE) rates experienced over 12 weeks were modest; no AEs were considered serious. The most common AEs in the initiation phase were injection site pain (5.8%), insomnia (5.8%), and akathisia (3.2%). No apparent relationship was observed between preswitch medication and early-onset AEs. Mean Positive and Negative Syndrome Scale total scores remained stable during this period across preswitch antipsychotic groups. Switching from an oral antipsychotic to AL was feasible in an outpatient setting for patients with schizophrenia, and the 12-week retention rate was favorable.

Atypical antipsychotic usage among Asian Americans and Pacific Islanders.

PubMed

Takeshita, Junji; Goebert, Deborah; Else, Iwalani; Carlton, Barry; Matsu, Courtenay; Guerrero, Anthony

2014-09-01

Previous studies have shown significant ethnic differences in prescribing patterns of two or more antipsychotics. This study examined changes in atypical and typical antipsychotic prescriptions among Asian Americans and Pacific Islanders. Five hundred consecutive charts were reviewed for antipsychotics at the time of admission and discharge from each of two inpatient psychiatric facilities in Hawai'i. Multiple antipsychotic prescription rates were 9% at intake and 6% at discharge. For the ethnic groups studied, there were no statistically significant differences by patient ethnicity regarding antipsychotics at intake (χ(2) = 29.2, df = 21, P = .110) or discharge (χ(2) = 20.5, df = 24, P = .667). There were no significant differences in prescription and polypharmacy patterns among Asian Americans and Pacific Islanders ethnic groups in this study.

[Antipsychotic prescription assessment in general practice: metabolic effects].

PubMed

Gignoux-Froment, F; de Montleau, F; Saravane, D; Verret, C

2012-12-01

Second-generation antipsychotics have improved living conditions of patients affected by severe mental illness. Some of them can induce weight gain with metabolic complications. Furthermore, they are prescribed to vulnerable patients, with comorbidity and high cardiovascular mortality rate. Prevention of a metabolic syndrome by simple measures improves patient's physical health. General practitioners are privileged partners for psychiatrists. This study was conducted to assess the prevention and management of a metabolic syndrome in patients treated with antipsychotics in general practice. With this in mind, at first we needed to explore how general practitioners prescribe antipsychotics. To assess the general practice, we interviewed 204 general practitioners in the Hauts-de-Seine. Our database was the yellow pages of this area (September 2007). We then conducted a random draw using random digits. We called 507 general practitioners, 410 of whom were sent a questionnaire. We received the return of 204 questionnaires. Each questionnaire consisted of four parts: the general practitioner's profile, psychiatry in his/her practice, the prescription of antipsychotics and the management of metabolic syndromes in patients treated with antipsychotics. The general practitioner's response rate was 49.7%. The results show that although they prescribe antipsychotics, general practitioners need more information on these molecules and on their side effects. Indeed 57% of them feel they are not given enough information on antipsychotics, but 69% have already initiated antipsychotic treatment and 17% do so regularly. Furthermore, a metabolic syndrome is insufficiently detected by general practitioners, although they know of its prevalence after the introduction of antipsychotic treatment. Thus, 81% reported having been confronted with this problem, but only 54% of them calculated the body mass index of patients taking antipsychotics, and 26% measured waist circumference. These

Atypical Antipsychotic Drugs and the Risk of Sudden Cardiac Death

PubMed Central

Ray, Wayne A.; Chung, Cecilia P.; Murray, Katherine T.; Hall, Kathi; Stein, C. Michael

2009-01-01

Background Users of typical antipsychotics have increased risk of serious ventricular arrhythmias and sudden cardiac death. However, less is known regarding the cardiac safety of the atypical antipsychotic drugs, which have largely replaced the older agents in clinical practice. Methods We calculated the adjusted incidence of sudden cardiac death among current users of antipsychotics in a retrospective cohort of Tennessee Medicaid enrollees. The primary analysis included 44,218 and 46,089 baseline users of single typical and atypical drugs, respectively, and 186,600 matched nonuser controls. To assess residual confounding related to antipsychotic indication, we performed a secondary analysis of antipsychotic users with no baseline diagnosis of schizophrenia or related psychoses, propensity-score matched with nonusers. Results Current users of both typical and atypical antipsychotics had greater rates of sudden cardiac death than did nonusers of any antipsychotic, with adjusted incidence-rate ratios (IRRs) of 2.00 (95% CI, 1.69–2.35) and 2.27 (1.89–2.73), respectively. Former antipsychotic users had no significantly increased risk (IRR = 1.13 [0.98–1.30]). For both classes of drugs, the risk for current users increased significantly with dose. For typical antipsychotics the IRRs increased from 1.31 (0.97–1.77) for low doses to 2.42 (1.91–3.06) for high doses (p<.001). For atypical agents the IRRs increased from 1.59 (1.03–2.46) for low doses to 2.86 (2.25–3.65) for high doses (p=.015). The IRR for atypical vs typical antipsychotics was 1.14 (.93–1.39). Similar findings were present in the propensity-score matched cohort. Conclusion Current users of both typical and atypical antipsychotics had a similar, dose-related increased risk of sudden cardiac death. PMID:19144938

Antipsychotic metabolic effects: weight gain, diabetes mellitus, and lipid abnormalities.

PubMed

McIntyre, R S; McCann, S M; Kennedy, S H

2001-04-01

To review published and nonpublished literature describing changes in weight, glucose homeostasis, and lipid milieu with antipsychotics. A Medline search was completed using the words weight gain, diabetes mellitus, cholesterol, triglycerides, risperidone, clozapine, olanzapine, quetiapine, ziprasidone, predictors, prolactin, obesity, and conventional antipsychotics. Publications, including original articles, review articles, letters to the editor, abstracts or posters presented at professional meetings in the last 4 years, and references from published articles, were collected. Manufacturers, including Eli Lilly Canada Inc, JanssenOrtho Inc, Pfizer Canada Inc, AstraZeneca Inc, and Novartis Pharmaceuticals, were contacted to retrieve additional medical information. The topic of antipsychotic-induced weight gain is understudied, and there are relatively few well-controlled studies. Weight gain as a side effect has been described with both conventional and atypical antipsychotics. Moreover, some atypical antipsychotics are associated with de novo diabetes mellitus and increased serum triglyceride levels. Predictors of weight gain may be age, baseline body mass index, appetite stimulation, previous antipsychotic exposure, and antipsychotic treatment duration. Significant weight gain is reported with the existing atypical antipsychotics. The weight gain described is highly distressing to patients, may reduce treatment adherence, and may increase the relative risk for diabetes mellitus and hypertriglyceridemia. Physicians employing these agents should routinely monitor weight, fasting blood glucose, and lipid profiles.

Antipsychotic-Induced Dopamine Supersensitivity Psychosis: Pharmacology, Criteria, and Therapy.

PubMed

Chouinard, Guy; Samaha, Anne-Noël; Chouinard, Virginie-Anne; Peretti, Charles-Siegfried; Kanahara, Nobuhisa; Takase, Masayuki; Iyo, Masaomi

2017-01-01

The first-line treatment for psychotic disorders remains antipsychotic drugs with receptor antagonist properties at D2-like dopamine receptors. However, long-term administration of antipsychotics can upregulate D2 receptors and produce receptor supersensitivity manifested by behavioral supersensitivity to dopamine stimulation in animals, and movement disorders and supersensitivity psychosis (SP) in patients. Antipsychotic-induced SP was first described as the emergence of psychotic symptoms with tardive dyskinesia (TD) and a fall in prolactin levels following drug discontinuation. In the era of first-generation antipsychotics, 4 clinical features characterized drug-induced SP: rapid relapse after drug discontinuation/dose reduction/switch of antipsychotics, tolerance to previously observed therapeutic effects, co-occurring TD, and psychotic exacerbation by life stressors. We review 3 recent studies on the prevalence rates of SP, and the link to treatment resistance and psychotic relapse in the era of second-generation antipsychotics (risperidone, paliperidone, perospirone, and long-acting injectable risperidone, olanzapine, quetiapine, and aripiprazole). These studies show that the prevalence rates of SP remain high in schizophrenia (30%) and higher (70%) in treatment-resistant schizophrenia. We then present neurobehavioral findings on antipsychotic-induced supersensitivity to dopamine from animal studies. Next, we propose criteria for SP, which describe psychotic symptoms and co-occurring movement disorders more precisely. Detection of mild/borderline drug-induced movement disorders permits early recognition of overblockade of D2 receptors, responsible for SP and TD. Finally, we describe 3 antipsychotic withdrawal syndromes, similar to those seen with other CNS drugs, and we propose approaches to treat, potentially prevent, or temporarily manage SP. © 2017 S. Karger AG, Basel.

Role of paliperidone extended-release in treatment of schizoaffective disorder

PubMed Central

Canuso, Carla M; Turkoz, Ibrahim; Fu, Dong Jing; Bossie, Cynthia A

2010-01-01

Schizoaffective disorder is characterized by the presence of symptoms of both schizophrenia and a major mood disorder. The coexistence of these symptoms can be difficult to manage, and these patients are generally treated with antipsychotics as well as mood stabilizers and/or antidepressants. Additionally, no established treatment guidelines exist for this disorder. This review describes the combined results of two international, double-blind, placebo-controlled clinical studies of paliperidone extended-release (ER), an atypical antipsychotic recently approved in the US for the treatment of schizoaffective disorder. Subjects in these six-week trials were aged 18–65 years, had a diagnosis of schizoaffective disorder based on the Structural Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) Disorders, and were experiencing an acute exacerbation. The subjects from these studies had significant symptomatology as evidenced by a mean (standard deviation) baseline Positive and Negative Syndrome Scale total score of 92.8 (13.0). Based on Young Mania Rating Scale and/or a 21-item Hamilton Rating Scale for Depression score of ≥16 at baseline, 79.5% and 66.9% of subjects presented with prominent manic and depressive symptoms, respectively, and 46.4% presented with mixed symptoms. Approximately half (45%) of subjects were taking adjunctive mood stabilizers and/or antidepressants. Paliperidone ER was found to be effective in improving psychotic and mood symptoms in these subjects. Paliperidone ER was also effective as monotherapy or adjunctive to mood stabilizers and/or antidepressants for subjects with prominent manic, depressive, or mixed symptoms at baseline. No new tolerability signals were observed in this population. To the best of our awareness, these pooled data provide the largest data set of patients with schizoaffective disorder, and extend our knowledge of disease characteristics and treatment response. PMID

Role of paliperidone extended-release in treatment of schizoaffective disorder.

PubMed

Canuso, Carla M; Turkoz, Ibrahim; Fu, Dong Jing; Bossie, Cynthia A

2010-10-05

Schizoaffective disorder is characterized by the presence of symptoms of both schizophrenia and a major mood disorder. The coexistence of these symptoms can be difficult to manage, and these patients are generally treated with antipsychotics as well as mood stabilizers and/or antidepressants. Additionally, no established treatment guidelines exist for this disorder. This review describes the combined results of two international, double-blind, placebo-controlled clinical studies of paliperidone extended-release (ER), an atypical antipsychotic recently approved in the US for the treatment of schizoaffective disorder. Subjects in these six-week trials were aged 18-65 years, had a diagnosis of schizoaffective disorder based on the Structural Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) Disorders, and were experiencing an acute exacerbation. The subjects from these studies had significant symptomatology as evidenced by a mean (standard deviation) baseline Positive and Negative Syndrome Scale total score of 92.8 (13.0). Based on Young Mania Rating Scale and/or a 21-item Hamilton Rating Scale for Depression score of ≥16 at baseline, 79.5% and 66.9% of subjects presented with prominent manic and depressive symptoms, respectively, and 46.4% presented with mixed symptoms. Approximately half (45%) of subjects were taking adjunctive mood stabilizers and/or antidepressants. Paliperidone ER was found to be effective in improving psychotic and mood symptoms in these subjects. Paliperidone ER was also effective as monotherapy or adjunctive to mood stabilizers and/or antidepressants for subjects with prominent manic, depressive, or mixed symptoms at baseline. No new tolerability signals were observed in this population. To the best of our awareness, these pooled data provide the largest data set of patients with schizoaffective disorder, and extend our knowledge of disease characteristics and treatment response.

Raloxifene Plus Antipsychotics Versus Placebo Plus Antipsychotics in Severely Ill Decompensated Postmenopausal Women With Schizophrenia or Schizoaffective Disorder: A Randomized Controlled Trial.

PubMed

Weiser, Mark; Levi, Linda; Burshtein, Shimon; Hagin, Michal; Matei, Valentin P; Podea, Delia; Micluția, Ioana; Tiugan, Alexandru; Păcală, Bogdan; Grecu, Iosif Gabos; Noy, Adam; Zamora, Daisy; Davis, John M

2017-07-01

Several single-center studies have found raloxifene, an estrogen agonist, to be effective in ameliorating symptoms of schizophrenia in stable patients as augmentation of antipsychotics. This multicenter study assessed whether raloxifene plus antipsychotic treatment, in comparison to placebo plus antipsychotics, improves symptoms or cognition in severely ill decompensated schizophrenia patients. In this 16-week, double-blind, randomized, placebo-controlled study, 200 severely ill, decompensated postmenopausal women who met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder were recruited from January 2011 to December 2012 and were randomized to receive either raloxifene 120 mg/d plus antipsychotics or placebo plus antipsychotics. The primary outcome measure was Positive and Negative Syndrome Scale (PANSS) total score at the end of the trial. The placebo plus antipsychotics group experienced statistically significant improvement in PANSS total score (P < .001) compared to the raloxifene plus antipsychotics group, using mixed models for repeated measures, with results favoring placebo by 4.5 points (95% CI, 2.3-6.7). These results were clearly outside the 95% confidence interval. This negative effect was more pronounced in patients who had more frequent relapses and in those with baseline PANSS scores of 100 or higher. There were no differences between groups in Clinical Global Impression Scale-Severity scores or Composite Brief Assessment of Cognition in Schizophrenia scores at 16 weeks (P > .3). Baseline follicle-stimulating hormone and estradiol levels did not alter the drug-placebo differences. Individuals in the active treatment arm showed worse outcome than those in the placebo arm, most likely as a result of chance variation, but the results unequivocally show no benefit of antipsychotics plus raloxifene versus antipsychotics plus placebo in this large randomized, double-blind, placebo-controlled trial in postmenopausal women. These data do not

[Antipsychotic-drug-induced hyperprolactinemia: physiopathology, clinical features and guidance].

PubMed

Besnard, I; Auclair, V; Callery, G; Gabriel-Bordenave, C; Roberge, C

2014-02-01

Hyperprolactinemia is a frequent but neglected adverse effect observed in patients treated with antipsychotic-drugs. In this review, we summarize its physiopathogenetic mechanism, its clinical manifestations in men and women, and the way to manage it. Prolactin is a hormone secreted by lactotroph cells in the anterior pituitary. Its synthesis and release are under the control of peptides, steroids and neurotransmitters. The main inhibitory regulation is made by dopamine, which binds dopamine receptors D2 on the membrane of lactotroph cells. Antipsychotic-drugs block these receptors and thus remove the inhibitory effect of dopamine on prolactin secretion. All antipsychotic-drugs block D2 receptors and all can induce hyperprolactinemia. Nonetheless, it seems that the faster the antipsychotic-drug dissociates from D2 receptors, the lesser the increase of prolactin in the plasma. Another way to explain hyperprolactinemia is the ability of antipsychotic-drugs to cross the blood-brain barrier. The role of their metabolites should also be considered. For these reasons, one can distinguish prolactin-raising (conventional neuroleptics, amisulpride, risperidone) and prolactin-sparing (clozapine, aripiprazole, olanzapine) antipsychotics. An English study showed that 18% of men and 47% of women treated with antipsychotics for severe mental illness had a prolactin level above the normal range. Hyperprolactinemia is in fact more frequent in women than in men. Sometimes it is asymptomatic, but the higher the prolactin level is, the more patients have clinical manifestations. Some symptoms are due to the hypogonadism caused by prolactin, which disturbs hypothalamic-pituitary axis function, and others are due to direct effects on target tissues. Consequently, patients can suffer from sexual dysfunction, infertility, amenorrhea, gynecomastia or galactorrhoea. Data suggest that these symptoms are common, but patients don't mention them spontaneously and clinicians underestimate their

Antipsychotic Response Worsens With Postmenopausal Duration in Women With Schizophrenia.

PubMed

González-Rodríguez, Alexandre; Catalán, Rosa; Penadés, Rafael; Ruiz Cortés, Victoria; Torra, Mercè; Seeman, Mary V; Bernardo, Miquel

2016-12-01

The loss of estrogens in the menopause may lead to increased vulnerability for psychotic relapse, poor clinical outcome, and a need for increased antipsychotic dose. However, confounders such as cumulative estrogen exposure and time since menopause have been inadequately studied. Our aim was to investigate potential variables capable of influencing antipsychotic response in a sample of postmenopausal women with schizophrenia. Sixty-four postmenopausal schizophrenic women were followed in a 12-week prospective treatment-by-clinical requirement study. Duration of reproductive years was considered an indirect measure of lifetime cumulative estrogens exposure. Psychopathological assessment included the following: Positive and Negative Syndrome Scale, Personal and Social Performance, and Clinical Global Impression-Schizophrenia Scale. Response was defined as a reduction of 30% or more of Positive and Negative Syndrome Scale total scores. Antipsychotic adherence was assessed by plasma level monitoring at 4 weeks. Regression analyses were performed to investigate the association between potential confounding factors and antipsychotic response. Forty-two participants (66%) were found to be antipsychotic responders. Time since menopause was significantly and negatively associated with overall antipsychotic response, explaining almost 42% of the variance of the model used. Smoking and cumulative estrogen exposures were associated with improvement in negative symptoms. Smoking and time since menopause were associated with improvement in excitement symptoms, and smoking was positively associated with improvement in depressive and cognitive symptoms. Time since menopause was significantly negatively associated with antipsychotic response in postmenopausal schizophrenic women, suggesting a decline in antipsychotic response after menopause. The neurobiological basis for antipsychotic response may include a role for estrogen and nicotine receptors.

Concurrent Oral Antipsychotic Drug Use Among Schizophrenia Patients Initiated on Long-Acting Injectable Antipsychotics Post-Hospital Discharge.

PubMed

Doshi, Jalpa A; Pettit, Amy R; Stoddard, Jeffrey J; Zummo, Jacqueline; Marcus, Steven C

2015-08-01

Pharmacological treatment is central to effective management of schizophrenia. Prescribing clinicians have an increasing array of options from which to choose, and oral antipsychotic polypharmacy is common in routine clinical practice. Practice guidelines recommend long-acting injectable (LAI) formulations, typically viewed as monotherapeutic alternatives, for patients with established nonadherence. Yet there are limited data on the prevalence and nature of concurrent oral antipsychotic prescriptions in patients receiving LAIs. Our observational, claims-based study examined the frequency and duration of concurrent oral prescriptions in 340 Medicaid patients receiving LAI therapy. Specifically, we examined patients with a recent history of nonadherence and hospitalization for schizophrenia and included both first-generation antipsychotic depot medications (fluphenazine decanoate, haloperidol decanoate) and more recently available second-generation injectables (LAI risperidone, paliperidone palmitate). Of all patients initiated on LAIs, 75.9% had a concurrent oral antipsychotic prescription in the 6 months post-hospital discharge. Patients receiving concurrent prescriptions were frequently prescribed an oral formulation of their LAI agent, but many first-generation LAI users received a concurrent second-generation oral medication. The lowest rate of concurrent prescribing (58.8%) was found with paliperidone palmitate, whereas the highest rate was with LAI risperidone (88.9%). Overlap in oral and LAI prescriptions typically occurred for a substantial period of time (ie, >30 days) and for a notable percentage of the days covered by LAIs (often 50% or more). Our findings highlight the need to further examine such prescribing patterns, to probe the reasons for them, and to clarify the optimal roles of different antipsychotic treatments in clinical practice.

Patterns of Antipsychotic Prescribing by Physicians to Young Children.

PubMed

Huskamp, Haiden A; Horvitz-Lennon, Marcela; Berndt, Ernst R; Normand, Sharon-Lise T; Donohue, Julie M

2016-12-01

Antipsychotic use among young children has grown rapidly despite a lack of approval by the U.S. Food and Drug Administration (FDA) for broad use in this age group. Characteristics of physicians who prescribed antipsychotics to young children were identified, and prescribing patterns involving young children and adults were compared. Physician-level prescribing data from IMS Health's Xponent database were linked with American Medical Association Masterfile data and analyzed. The sample included all U.S. psychiatrists and a random sample of 5% of family medicine physicians who wrote at least ten antipsychotic prescriptions per year from 2008 to 2011 (N=31,713). Logistic and hierarchical binomial regression models were estimated to examine physician prescribing for children ages zero to nine, and the types and numbers of ingredients used for children versus adults ages 20 to 64 were compared. Among antipsychotic prescribers, 42.2% had written at least one antipsychotic prescription for young children. Such prescribing was more likely among physicians age ≤39 versus ≥60 (odds ratio [OR]=1.70) and physicians in rural versus nonrural areas (OR=1.11) and was less likely among males (OR=.93) and graduates of a top-25 versus a lower-ranked U.S. medical school (OR=.87). Among physicians who prescribed antipsychotics to young children and adults, 75.0% of prescriptions for children and 35.7% of those for adults were for drugs with an FDA-approved indication for that age. Fewer antipsychotic agents were prescribed for young children (median=2) versus adults (median=7). Prescribing antipsychotics for young children was relatively common, but prescribing patterns differed between young children and adults.

[Lithium and anticonvulsants in the treatment of mania and in the prophylaxis of recurrences].

PubMed

Salvi, Virginio; Cat Berro, Alberto; Bechon, Elisa; Bogetto, Filippo; Maina, Giuseppe

2011-01-01

A mood stabilizer is an agent effective in treating both poles of the illness and at the same time being able to prevent both manic and depressive episodes in bipolar disorder. According to a broader definition, a mood stabilizer should be effective in decreasing the frequency or severity of any type of episode in bipolar disorder, without worsening the frequency or severity of episodes of opposite polarity. According to this, anticonvulsants and atypical antipsychotics can be considered as mood stabilizers. In this paper we review the use of lithium and other anticonvulsants that have proved effective in randomized controlled trials of the treatment of manic episodes and prevention of recurrences of bipolar disorder. Lithium and valproate are considered as first-line treatment options for acute mania while evidence regarding carbamazepine is insufficient to consider it as a first-line agent. Patients who fail to respond to first-line treatments may benefit from the adjunct of an atypical antipsychotic such as olanzapine, quetiapine, risperidone or aripiprazole. Lithium retains the strongest evidence of efficacy in the prophylaxis of manic episodes, lamotrigine in the prevention of depressive episodes. Valproate and carbamazepine have no indication for long-term treatment of bipolar disorder. Lithium can still be considered a gold standard in the treatment of manic episodes as well as in the prophylaxis of recurrences. Other anticonvulsants should be employed in particular situations, such as valproic acid in the treatment of mania and lamotrigine in the prevention of depressive recurrences.

Characteristics and the trajectory of psychotropic medication use in general and antipsychotics in particular among adults with an intellectual disability who exhibit aggressive behaviour.

PubMed

Deb, S; Unwin, G; Deb, T

2015-01-01

A high proportion of adults with an intellectual disability (ID) are known to receive psychotropic medications for the management of aggressive behaviour in the absence of any psychiatric diagnosis. Despite this widespread use of psychotropic medication in general and antipsychotic medication in particular, no study has reported the trajectory of psychotropic medication use using a prospective design. We have prospectively studied a community, clinic-based sample of 100 adults with ID and aggressive behaviour over a 6-month period for use of psychotropic medication in general and antipsychotics in particular, and compared them with demographic, psychiatric and behavioural variables. Psychotropic medications were used for 89% of patients at baseline (T1) and 90% at 6 months' (T2) follow-up. Risperidone was the most commonly used antipsychotic medication followed by chlorpromazine, haloperidol, olanzapine, zuclopenthixol and quetiapine. Other commonly used medications were SSRI antidepressants such as citalopram, paroxetine and fluoxetine followed by mood stabilisers such as carbamazepine and sodium valproate. Although in a high proportion of cases carbamazepine and sodium valproate were used to treat epilepsy per se. A high proportion (45%) received more than one (polypharmacy) psychotropic medication at T1; however, this proportion decreased slightly to 41% at T2. As for antipsychotic prescribing specifically, a similar proportion received them at T1 (75%) and T2 (73%), with polypharmacy of antipsychotics remaining similar at T1 (10%) and at T2 (9%). Twenty-three per cent and 20% of patients received over 300 mg/day of chlorpromazine equivalent dose of antipsychotics at T1 and T2 respectively. However, there was an overall significant reduction in the severity of aggressive behaviour between T1 and T2. Higher doses of antipsychotic prescribing were positively correlated with more severe aggressive behaviour, physical aggression towards objects, self

Antipsychotic induced weight gain in schizophrenia:mechanisms and management.

PubMed

Rege, Sanil

2008-05-01

The aim of the present paper was to describe the mechanisms and management of antipsychotic-induced weight gain in schizophrenia patients. A comprehensive literature review of all available articles on the mechanisms and management of antipsychotic-induced weight gain was done by searching databases PsychINFO and PubMed. A summary of the available guidelines for monitoring of antipsychotic-induced weight gain and metabolic syndrome is also provided. There has been a substantial increase in the number of studies investigating the mechanisms and management of antipsychotic-induced weight gain after 2002. These include advances in the understanding of pharmacogenomics of weight gain and several randomized controlled trials (RCTs) evaluating pharmacological and psychological treatments to promote weight loss. The most effective strategy for prevention of weight gain is the choice of antipsychotic medication with low weight gain potential. In individuals with established weight gain and metabolic issues, switching to an antipsychotic agent with lower weight gain potential and/or lifestyle modifications with physical activity are most effective in promoting weight loss. Pharmacological agents such as orlistat and sibutramine are effective in general obesity but have not been sufficiently evaluated in antipsychotic-induced weight gain. The case to prescribe routine pharmacological treatment to promote weight loss is weak. Long-term, pragmatic studies are required to inform clinical practice. Weight gain in schizophrenia is associated with significant physical and psychological morbidity. Achieving an optimal trade-off between effectiveness and side-effects of antipsychotic agents, although difficult, is achievable. This should be based on three main principles: (i) a shared decision-making model between the patient, clinician and carer(s) when choosing an antipsychotic; (ii) a commitment to baseline and follow-up monitoring with explicit identification of the responsible

A pragmatic approach to the diagnosis and treatment of mixed features in adults with mood disorders.

PubMed

McIntyre, Roger S; Lee, Yena; Mansur, Rodrigo B

2016-12-01

Mixed features specifier (MFS) is a new nosological entity defined and operationalized in the Diagnostic and Statistical Manual of Mental Disorders (DSM), 5th Edition. The impetus to introduce the MFS and supplant mixed states was protean, including the lack of ecological validity, high rates of misdiagnosis, and guideline discordant treatment for mixed states. Mixed features specifier identifies a phenotype in psychiatry with greater illness burden, as evidenced by earlier age at onset, higher episode frequency and chronicity, psychiatric and medical comorbidity, suicidality, and suboptimal response to conventional antidepressants. Mixed features in psychiatry have historical, conceptual, and nosological relevance; MFS according to DSM-5, is inherently neo-Kraepelinian insofar as individuals with either Major Depressive Disorder (MDD) or Bipolar Disorder (BD) may be affected by MFS. Clinicians are encouraged to screen all patients presenting with a major depressive episode (or hypomanic episode) for MFS. Although "overlapping symptoms" were excluded from the diagnostic criteria (eg, agitation, anxiety, irritability, insomnia), clinicians are encouraged to probe for these nonspecific symptoms as a possible proxy of co-existing MFS. In addition to conventional antidepressants, second generation antipsychotics and/or conventional mood stabilizers (eg, lithium) may be considered as first-line therapies for individuals with a depressive episode as part of MDD or BD with mixed features.

Antipsychotic doses among community-dwelling persons with Alzheimer disease in Finland.

PubMed

Taipale, Heidi; Koponen, Marjaana; Tanskanen, Antti; Tolppanen, Anna-Maija; Tiihonen, Jari; Hartikainen, Sirpa

2014-08-01

Use of antipsychotics for treatment of behavioral and psychological symptoms of dementia is frequent among persons with Alzheimer disease (AD). Doses used in long-term therapy have not been previously reported. We describe antipsychotic doses used among community-dwelling persons with AD and investigate factors associated with high-dose use. The MEDALZ-2005 (Medication use and Alzheimer disease) cohort is a nationwide sample including all persons with clinically diagnosed AD at the end of year 2005 in Finland (n = 28,093). Data including prescriptions, comorbidities, and hospital discharge diagnoses were collected from nationwide registers. Antipsychotic doses in monotherapy were investigated during 2006 to 2009. Among 8920 antipsychotic users, 4% (n = 336) used antipsychotics with high dose. Typical antipsychotics were more often used with high dose than atypical antipsychotics. High-dose use was associated with younger age (<80 years) (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.36-2.15]), male sex (OR, 1.52; CI, 1.21-1.91), history of psychiatric disorder (OR, 3.25; CI, 2.54-4.15), and inversely associated with Charlson Comorbidity Index score (score 1: OR, 0.74; CI, 0.57-0.97; score ≥2: OR, 0.68; CI, 0.47-0.97). In conclusion, the majority of persons with AD used antipsychotics with low or medium dose. Typical antipsychotics were more often used with high dose than atypical antipsychotics, which indicates a need for precise dosing instructions in the treatment of behavioral and psychological symptoms of dementia. Clinicians should regularly assess dosing levels especially among men and those with history of psychiatric disorder.

Mental health nurses' views about antipsychotic medication side effects.

PubMed

Stomski, N J; Morrison, P; Meehan, T

2016-08-01

WHAT IS KNOWN ON THE SUBJECT?: The only previous quantitative study that examined nurses' use of assessment tools to identify antipsychotic medication side effects found that about 25% of mental health nurses were using assessment tools. No previous studies have examined factors that influence the manner in which mental health nurses assess antipsychotic medication side effects. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: One-third of the respondents were not aware of any antipsychotic medication side-effect assessment tool, and only one-quarter were currently using an assessment tool. 'Service responsibility' was significantly associated with ongoing use of antipsychotic medication assessment tools, indicating that respondents with more positive attitudes to their service were more likely to continue using antipsychotic medication assessment tools. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The low level of awareness and use of antipsychotic medication side-effect assessment tools indicates that nursing educational institutions should incorporate more detail about these tools in course content, and emphasize in particular the benefits that result from the use of these tools in clinical practice. Service processes contributed significantly to the use of antipsychotic medication assessment tools, which indicates that managers need to foster workplace cultures that promote routine use of these tools. Introduction Limited evidence suggests that only a minority of mental health nurses regularly use standardized assessment tools to assess antipsychotic medication side effects, but the factors that contribute to the non-routine use of these tools remain unknown. Aim To examine Australian mental health nurses' awareness of, and attitudes towards, side-effect assessment tools, and also identify factors the influence the use of these tools. Methods A cross-sectional survey was undertaken through distributing an online questionnaire via email to members of the Australian

Sudden cardiac death secondary to antidepressant and antipsychotic drugs

PubMed Central

Sicouri, Serge; Antzelevitch, Charles

2008-01-01

A number of antipsychotic and antidepressant drugs are known to increase the risk of ventricular arrhythmias and sudden cardiac death. Based largely on a concern over QT prolongation and the development of life-threatening arrhythmias, a number of antipsychotic drugs have been temporarily or permanently withdrawn from the market or their use restricted. Some antidepressants and antipsychotics have been linked to QT prolongation and the development of Torsade de pointes arrhythmias, whereas others have been associated with a Brugada syndrome phenotype and the development of polymorphic ventricular arrhythmias. This review examines the mechanisms and predisposing factors underlying the development of cardiac arrhythmias, and sudden cardiac death, associated with antidepressant and antipsychotic drugs in clinical use. PMID:18324881

Moods as spotlights: the influence of mood on accessibility effects.

PubMed

Avramova, Yana R; Stapel, Diederik A

2008-09-01

Three studies explore the manner in which one's mood may affect the use and impact of accessible information on judgments. Specifically, the authors demonstrated that positive and negative moods differentially influence the direction of accessibility effects (assimilation, contrast) by determining whether abstract traits or concrete actor-trait links are primed. Study 1 investigated the impact of positive versus negative mood on the judgmental impact of trait-implying behaviors and found that positive moods lead to assimilation and negative moods to contrast. In Study 2, this effect was replicated in a subliminal priming paradigm. In Study 3, it was demonstrated that the type of information activated by trait-implying behaviors is indeed mood dependent, such that abstract trait information is activated in a positive mood, whereas specific actor-trait links are activated in a negative mood.

Intramuscular preparations of antipsychotics: uses and relevance in clinical practice.

PubMed

Altamura, A Cario; Sassella, Francesca; Santini, Annalisa; Montresor, Clauno; Fumagalli, Sara; Mundo, Emanuela

2003-01-01

Intramuscular formulations of antipsychotics can be sub-divided into two groups on the basis of their pharmacokinetic features: short-acting preparations and long-acting or depot preparations. Short-acting intramuscular formulations are used to manage acute psychotic episodes. On the other hand, long-acting compounds, also called "depot", are administered as antipsychotic maintenance treatment to ensure compliance and to eliminate bioavailability problems related to absorption and first pass metabolism. Adverse effects of antipsychotics have been studied with particular respect to oral versus short- and long-acting intramuscular formulations of the different compounds. For short-term intramuscular preparations the main risk with classical compounds are hypotension and extrapyramidal side effects (EPS). Data on the incidence of EPS with depot formulations are controversial: some studies point out that the incidence of EPS is significantly higher in patients receiving depot preparations, whereas others show no difference between oral and depot antipsychotics. Studies on the strategies for switching patients from oral to depot treatment suggest that this procedure is reasonably well tolerated, so that in clinical practice depot antipsychotic therapy is usually begun while the oral treatment is still being administered, with gradual tapering of the oral dose. Efficacy, pharmacodynamics and clinical pharmacokinetics of haloperidol decanoate, fluphenazine enanthate and decanoate, clopenthixol decanoate, zuclopenthixol decanoate and acutard, flupenthixol decanoate, perphenazine enanthate, pipothiazine palmitate and undecylenate, and fluspirilene are reviewed. In addition, the intramuscular preparations of atypical antipsychotics and clinical uses are reviewed. Olanzapine and ziprasidone are available only as short-acting preparations, while risperidone is to date the only novel antipsychotic available as depot formulation. To date, acutely ill, agitated psychotic patients

Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug.

PubMed

Zuardi, A W; Crippa, J A S; Hallak, J E C; Moreira, F A; Guimarães, F S

2006-04-01

A high dose of delta9-tetrahydrocannabinol, the main Cannabis sativa (cannabis) component, induces anxiety and psychotic-like symptoms in healthy volunteers. These effects of delta9-tetrahydrocannabinol are significantly reduced by cannabidiol (CBD), a cannabis constituent which is devoid of the typical effects of the plant. This observation led us to suspect that CBD could have anxiolytic and/or antipsychotic actions. Studies in animal models and in healthy volunteers clearly suggest an anxiolytic-like effect of CBD. The antipsychotic-like properties of CBD have been investigated in animal models using behavioral and neurochemical techniques which suggested that CBD has a pharmacological profile similar to that of atypical antipsychotic drugs. The results of two studies on healthy volunteers using perception of binocular depth inversion and ketamine-induced psychotic symptoms supported the proposal of the antipsychotic-like properties of CBD. In addition, open case reports of schizophrenic patients treated with CBD and a preliminary report of a controlled clinical trial comparing CBD with an atypical antipsychotic drug have confirmed that this cannabinoid can be a safe and well-tolerated alternative treatment for schizophrenia. Future studies of CBD in other psychotic conditions such as bipolar disorder and comparative studies of its antipsychotic effects with those produced by clozapine in schizophrenic patients are clearly indicated.

The evolution of antipsychotic switch and polypharmacy in natural practice--a longitudinal perspective.

PubMed

Tsutsumi, Chisa; Uchida, Hiroyuki; Suzuki, Takefumi; Watanabe, Koichiro; Takeuchi, Hiroyoshi; Nakajima, Shinichiro; Kimura, Yoshie; Tsutsumi, Yuichiro; Ishii, Koichi; Imasaka, Yasushi; Kapur, Shitij

2011-08-01

Most patients with schizophrenia first start with a single antipsychotic, and yet most finally end up 'switching' or using 'polypharmacy'. The objective of this study was to examine the evolution of antipsychotic switch and polypharmacy in the real-world from a longitudinal perspective. A systematic review of longitudinal antipsychotic prescriptions in 300 patients with schizophrenia (ICD-10) for up to 2 years after their first visit to one of the 4 participating psychiatric clinics in Tokyo, Japan between January, 2007 and June, 2008, was conducted. Reasons for prescription change were also examined. The evolution of switching and polypharmacy was studied, and prescribed doses were compared to suggested dose ranges by the Texas Medication Algorithm Project (TMAP). 208 patients started their antipsychotic treatment with monotherapy. 34.1% of the patients gave up monotherapy with an initial antipsychotic to move to antipsychotic switch (27.4%) and/or polypharmacy (17.8%) within 2 years. The main reason for antipsychotic switch was 'ineffectiveness'; interestingly, this happened despite the fact that the monotherapy dose was below the recommended range in 47.4% of the antipsychotic switch. In a subgroup of 100 patients who started as antipsychotic-free, 2-year prevalence rates of switching and antipsychotic polypharmacy were 27.0% and 18.0%, respectively, and polypharmacy was resorted to after a median of 1 antipsychotic had been tried for 84 days (median). These findings raise a concern that physicians may perform an antipsychotic switch without exploring the entire dose range and resort to antipsychotic polypharmacy without trying an adequate number of antipsychotics. Copyright © 2011 Elsevier B.V. All rights reserved.

International trends in antipsychotic use: A study in 16 countries, 2005-2014.

PubMed

Hálfdánarson, Óskar; Zoëga, Helga; Aagaard, Lise; Bernardo, Miquel; Brandt, Lena; Fusté, Anna Coma; Furu, Kari; Garuoliené, Kristina; Hoffmann, Falk; Huybrechts, Krista F; Kalverdijk, Luuk J; Kawakami, Koji; Kieler, Helle; Kinoshita, Takuya; Litchfield, Melisa; López, Soffy C; Machado-Alba, Jorge E; Machado-Duque, Manuel E; Mahesri, Mufaddal; Nishtala, Prasad S; Pearson, Sallie-Anne; Reutfors, Johan; Saastamoinen, Leena K; Sato, Izumi; Schuiling-Veninga, Catharina C M; Shyu, Yu-Chiau; Skurtveit, Svetlana; Verdoux, Hélène; Wang, Liang-Jen; Yahni, Corinne Zara; Bachmann, Christian J

2017-10-01

The objective of this study was to assess international trends in antipsychotic use, using a standardised methodology. A repeated cross-sectional design was applied to data extracts from the years 2005 to 2014 from 16 countries worldwide. During the study period, the overall prevalence of antipsychotic use increased in 10 of the 16 studied countries. In 2014, the overall prevalence of antipsychotic use was highest in Taiwan (78.2/1000 persons), and lowest in Colombia (3.2/1000). In children and adolescents (0-19 years), antipsychotic use ranged from 0.5/1000 (Lithuania) to 30.8/1000 (Taiwan). In adults (20-64 years), the range was 2.8/1000 (Colombia) to 78.9/1000 (publicly insured US population), and in older adults (65+ years), antipsychotic use ranged from 19.0/1000 (Colombia) to 149.0/1000 (Taiwan). Atypical antipsychotic use increased in all populations (range of atypical/typical ratio: 0.7 (Taiwan) to 6.1 (New Zealand, Australia)). Quetiapine, risperidone, and olanzapine were most frequently prescribed. Prevalence and patterns of antipsychotic use varied markedly between countries. In the majority of populations, antipsychotic utilisation and especially the use of atypical antipsychotics increased over time. The high rates of antipsychotic prescriptions in older adults and in youths in some countries merit further investigation and systematic pharmacoepidemiologic monitoring. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Clinical practice variations in prescribing antipsychotics for patients with schizophrenia.

PubMed

Owen, Richard R; Fischer, Ellen P; Kirchner, JoAnn E; Thrush, Carol R; Williams, D Keith; Cuffel, Brian J; Elliott, Carl E; Booth, Brenda M

2003-01-01

Few studies have examined the variations among individual physicians in prescribing antipsychotics for schizophrenia. This study examined clinical practice variations in the route and dosage of antipsychotic medication prescribed for inpatients with schizophrenia by 11 different psychiatrists. The sample consisted of 130 patients with a DSM-III-R diagnosis of schizophrenia who had received inpatient care at a state hospital or Veterans Affairs medical center in the southeastern United States in 1992-1993. Mixed-effects regression models were developed to explore the influence of individual physicians and hospitals on route of antipsychotic administration (oral or depot) and daily antipsychotic dose, controlling for patient case-mix variables (age, race, sex, duration of illness, symptom severity, and substance-abuse diagnosis). The average daily antipsychotic dose was 1092 +/- 892 chlorpromazine mg equivalents. Almost half of the patients (48%) were prescribed doses above or below the range recommended by current practice guidelines. The proportion of patients prescribed depot antipsychotics was significantly different at the 2 hospitals, as was the antipsychotic dose prescribed at discharge. Individual physicians and patient characteristics were not significantly associated with prescribing practices. These data, which were obtained before clinical practice guidelines were widely disseminated, provide a benchmark against which to examine more current practice variations in antipsychotic prescribing. The results raise several questions about deviations from practice guidelines in the pharmacological treatment of schizophrenia. To adequately assess quality and inform and possibly further develop clinical practice guideline recommendations for schizophrenia, well-designed research studies conducted in routine clinical settings are needed.

Mood-Congruent Memory and Natural Mood: New Evidence.

ERIC Educational Resources Information Center

Mayer, John D.; And Others

1995-01-01

Presents new evidence that everyday mood does bring about a hypothesized effect on memory, termed mood-congruent memory (MCM). Results of three studies provided evidence for MCM among normal individuals (n=614). Findings support prior studies and bolster notions that mood and memory constantly covary in everyday experience. (RJM)

Can metabolic side effects of antipsychotics be reversed by lifestyle changes?

PubMed

Bolger, Alistair; Verdolini, Norma; Agius, Mark

2014-11-01

Antipsychotics, particularly atypical antipsychotics, are known to have metabolic side effects such as; weight gain, hyperlipidaemia and insulin resistance. This is problematic as metabolic syndrome can be a precursor to many diseases, including type II diabetes and coronary heart disease. In an attempt to overcome these side-effects, lifestyle changes have been recommended in tandem with commencement of atypical antipsychotics, but is this effective at halting metabolic syndrome? There is some evidence suggesting that lifestyle changes can reduce weight gain caused by atypical antipsychotics. However, there seems to be a paucity of evidence about whether this correlates with correction of metabolic dysregulation. Moreover, there is a lack of research into the precise mechanism of metabolic syndrome as caused by atypical antipsychotics,as well as a lack of evidence into how exercise remedies this. Furthermore, there is research to suggest that the pathophysiology of psychosis may lead to metabolic dysregulation independently of treatment. Lifestyle changes should still be part of a treatment as they seem to partially reverse metabolic changes seen with atypical antipsychotics. However, more research is needed to identify weight independent mechanisms for metabolic dysregulation seen in those taking atypical antipsychotics in order to solve this pressing issue.

Lipid profile in antipsychotic drug users: A comparative study

PubMed Central

Roohafza, Hamidreza; Khani, Azam; Afshar, Hamid; Garakyaraghi, Mohammad; Amirpour, Afshin; Ghodsi, Basir

2013-01-01

BACKGROUND Schizophrenic patients who receive antipsychotic drugs may be highly prone to metabolic disorders such as weight gain, dyslipidemia, and insulin resistance. The objective of the present study was to compare the effect of atypical and conventional antipsychotics on lipid profile. METHODS 128 schizophrenic patients were enrolled into the study. Patients were divided into two groups. One group had received one type of atypical antipsychotic drug, and, the other, one type of conventional antipsychotic drug. They were considered as atypical and conventional groups. Moreover, both groups had not used any other antipsychotic drugs during the past year. Demographic data and food frequency questionnaire were completed by the participants. Serum triglyceride, total cholesterol (TC), high-density lipoprotein and low-density lipoprotein (LDL) cholesterols, and apolipoprotein A and B (Apo B) were tested by blood sample drawing after 12 hours of fasting through the antecubital vein. Student’s t-test was used to compare atypical and conventional groups. RESULTS There was no significant difference in age, gender, duration of illness, period of drug consumption, and age at onset of illness in the two groups. Patients in the atypical group used clozapine and risperidone (46.9%) more than olanzapine. In the conventional group 81.3% of patients used phenothiazines. Comparison between lipid profile in the conventional and atypical groups showed a significantly higher mean in TC (P = 0.01), LDL (P = 0.03), and Apo B (P = 0.01) in conventional group than the atypical group. CONCLUSION In schizophrenic patients, the level of lipid profile had been increased in both atypical and conventional antipsychotic users, especially conventional users, so the effect of antipsychotic drugs should be investigated periodically. PMID:23766777

Subjective experience and mental side-effects of antipsychotic treatment.

PubMed

Gerlach, J; Larsen, E B

1999-01-01

Many schizophrenic patients have a negative attitude towards antipsychotic drugs. This attitude is not only due to lack of insight into the disease, lack of recognition of the beneficial effects of the drugs, and to objective side-effects. The negative attitude is to a high degree due to mental side-effects and a sceptical opinion about antipsychotic medication in general. In a study of 53 chronic schizophrenic out-patients receiving maintenance depot antipsychotic treatment, we found that 60% were positive about the treatment, 32% were ambivalent and 8% had a negative attitude. Only 60% complained of side-effects, even though 94% had objective side-effects. Mental side-effects such as subjective akathisia, dysphoria and emotional indifference were most often observed by the patients, while hypokinesia and hyperkinesia were least noticed by them, but most often observed by the physician. No correlation was found between the patients' subjective assessment of their quality of life and the degree of psychosis and side-effects. With the new atypical antipsychotics this situation seems to be changing. These new drugs are primarily characterized by a lower level of motor extrapyramidal side-effects (EPS), and with fewer motor EPS, fewer mental EPS can be expected. In recent studies comparing the new antipsychotics with haloperidol, better effects have been observed with regard to negative symptoms and depression, and this may at least in part be a reflection of a lower level of mental side-effects of the atypical antipsychotics. This improved clinical profile of new antipsychotics is extremely valuable in the context of an integrated treatment in schizophrenia, consisting of early intervention, psychosocial rehabilitation and family/patient psycho-education.

Plasma BDNFs level initially and post treatment in acute mania: comparison between ECT and atypical antipsychotic treatment and healthy controls.

PubMed

Karamustafalioglu, Nesrin; Genc, Abdullah; Kalelioglu, Tevfik; Tasdemir, Akif; Umut, Gokhan; Incir, Said; Akkuş, Mustafa; Emul, Murat

2015-08-01

Inconsistent findings concerning brain-derived neurotrophic factor (BDNF) levels across different episodes in bipolar disorder have been reported, which is also in line with the treatment effects on BDNF levels in acute mania. We aimed to compare plasma BDNF level alterations after pure antipsychotic drug or ECT plus antipsychotic drug treatment in acute mania. Sixty-eight patients with mania were divided into two treatment arms: the antipsychotic treatment arm (AP) and electroconvulsive therapy (ECT)+AP arm. In addition, 30 healthy controls were included in the study. There was no significant statistical difference according to mean age, education level, marital and working status between patients and healthy controls. The initial serum BDNF level in patients with acute mania was significantly lower than healthy controls. The initial BDNF level between the ECT arm and AP arm was not significant. The BDNF level decreased significantly after reaching remission in patients with acute mania. The change in BDNF level in the AP arm was not significant while in the ECT arm it was significant after treatment. In this study, for the first time we revealed a significant decrease in BDNF levels after ECT sessions in acute manic patients. Besides clinical remission after treatment in acute mania, the decrement in BDNF levels does not seem to be related to clinical response. Thus cumulative effects of mood episodes for the ongoing decrease in BDNF levels might be borne in mind despite the achievement of remission and/or more time being required for an increase in BDNF levels after treatment. © The Author(s) 2015.

Antidepressants and mood stabilizers effects on histone deacetylase expression in C57BL/6 mice: Brain region specific changes.

PubMed

Ookubo, Masanori; Kanai, Hirohiko; Aoki, Harusuke; Yamada, Naoto

2013-09-01

To determine whether treatment with various antidepressants or mood stabilizers leads to region-specific changes, we investigated the effects of their subchronic (14 days of intraperitoneal injection) administration on the tissue concentration of monoamines, dopamine, serotonin, and norepinephrine, and the protein expression of acetylated histone H3 (AcH3) and histone deacetylases (HDACs) in the mouse striatum (ST), nucleus accumbens (Acb), hippocampus (Hip), cingulate cortex (Cg), and amygdala (Amy). Subchronic administration with the antidepressants (S)-citalopram oxalate (ECM), duloxetine hydrochloride (DLX), and mirtazapine (MIR) commonly induced significant increases in dopamine and serotonin levels in the ST and Cg. By contrast, no common profiles for dopamine, serotonin, or norepinephrine were identified in the Acb, Hip, or Amy. Treatment with sodium valproate (VPA), lithium chloride (Li), lamotrigine (LTG), levetiracetam (LTM), olanzapine (OLZ), clozapine (CLZ), clomipramine (CLM), ECM, and DLX induced significant increases in AcH3 expression in the Acb, while treatment with CLM, ECM, DLX, MIR, carbamazepine (CBZ), LTG, LTM, OLZ, or CLZ induced significant increases in HDAC2 and HDAC3 in the ST. CLM, MIR, VPA, CBZ, LTG, LTM, OLZ, or CLZ induced significant increases in HDAC3 in the Cg, and ECM, DLX, MIR, VPA, CBZ, LTG, LTM, or OLZ resulted in significant increases in HDAC5 in the Amy. Collectively, the changes of monoamine content were restricted for mood stabilizer effects, but increased expression of HDAC2, HDAC3, or HDAC5 in the ST, Cg, or Amy was often found, supporting the possibility that antidepressant-like effects involve epigenetic modifications associated with changes in HDAC expression. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ironic processes in the mental control of mood and mood-related thought.

PubMed

Wegner, D M; Erber, R; Zanakos, S

1993-12-01

The mental control of mood and mood-related thought was investigated. In Experiment 1, Ss reminiscing about a happy or sad event were asked to make their mood positive, were given no instructions, or were asked to make their mood negative. Ss attempting mood control without an imposed cognitive load were successful, whereas those who attempted control while rehearsing a 9-digit number not only failed to control their moods but also showed self-reported mood change opposite the mood they intended to create. In Experiment 2, Ss attempting to control mood-related thoughts under cognitive load showed increased accessibility of those thoughts contrary to the direction of intended control in a Stroop-type color-naming task.

Heterogeneity of response to antipsychotics from multiple disorders in the schizophrenia spectrum.

PubMed

Garver, D L; Holcomb, J A; Christensen, J D

2000-12-01

Antipsychotic response after the initiation of neuroleptic treatment shows wide variation in schizophrenic patient populations. In this overview, the authors suggest that the variance in antipsychotic drug response within schizophrenia can be reduced by resolving the schizophrenias into several discrete "endophenotypes," each with different etiologic underpinnings. Studies relating differences in the relative speed or completeness of antipsychotic response to differences in distribution of 2 biological markers with possible etiologic significance are reviewed. Such studies had assessed recently hospitalized, neuroleptic-free patients undergoing exacerbation of nonaffective psychotic disorders. Prior to initiation of neuroleptic, the cohort of patients had been assessed for the quantity of the dopamine metabolite homovanillic acid in plasma (pHVA) and had undergone the first of 2 magnetic resonance imaging (MRI) studies for analyses of ventricle volumes. A second MRI was subsequently performed during a period of (partial) remission to determine within-patient stability of ventricular volumes. These selected studies assessed the distribution of pHVA and distribution of rates of ventricular change, with non-normal distributions resolved by K-means clustering. The speed and completeness of neuroleptic-induced antipsychotic response were related to 3 clusters of patients delineated by modal distributions of pHVA and of apparent rates of ventricular change. At least 3 unique "endophenotypes" of the "group of the schizophrenias" can be defined with respect to speed and completeness of antipsychotic response. Each endophenotype appears to show at least one unique biological feature that differentiates it from a normal comparison group. A rapidly responsive psychosis was associated with excessive production of dopamine, as identifiable by elevation of pHVA and a "good-prognosis" course. A delayed-response psychosis had low-to-normal pHVA, clinically demonstrated persistent

Detecting and Managing Adverse Effects of Antipsychotic Medications: Current State of Play.

PubMed

Ames, Donna; Carr-Lopez, Sian M; Gutierrez, Mary A; Pierre, Joseph M; Rosen, Jennifer A; Shakib, Susan; Yudofsky, Lynn M

2016-06-01

Antipsychotics are some of the most frequently prescribed medications not only for psychotic disorders and symptoms but also for a wide range of on-label and off-label indications. Because second-generation antipsychotics have largely replaced first-generation antipsychotics as first-line options due to their substantially decreased risk of extrapyramidal side effects, attention has shifted to other clinically concerning adverse events associated with antipsychotic therapy. The focus of this article is to update the nonextrapyramidal side effects associated with second-generation antipsychotics. Issues surrounding diagnosis and monitoring as well as clinical management are addressed. Published by Elsevier Inc.

Regional variation in physician adoption of antipsychotics: Impact on US Medicare expenditures

PubMed Central

Donohue, Julie M.; Normand, Sharon-Lise T.; Horvitz-Lennon, Marcela; Men, Aiju; Berndt, Ernst R.; Huskamp, Haiden A.

2016-01-01

Background Regional variation in US Medicare prescription drug spending is driven by higher prescribing of costly brand-name drugs in some regions. This variation likely arises from differences in the speed of diffusion of newly-approved medications. Second-generation antipsychotics were widely adopted for treatment of severe mental illness and for several off-label uses. Rapid diffusion of new psychiatric drugs likely increases drug spending but its relationship to non-drug spending is unclear. The impact of antipsychotic diffusion on drug and medical spending is of great interest to public payers like Medicare, which finance a majority of mental health spending in the U.S. Aims We examine the association between physician adoption of new antipsychotics and antipsychotic spending and non-drug medical spending among disabled and elderly Medicare enrollees. Methods We linked physician-level data on antipsychotic prescribing from an all-payer dataset (IMS Health's Xponent™) to patient-level data from Medicare. Our physician sample included 16,932 U.S. psychiatrists and primary care providers with ≥10 antipsychotic prescriptions per year from 1997-2011. We constructed a measure of physician adoption of 3 antipsychotics introduced during this period (quetiapine, ziprasidone and aripiprazole) by estimating a shared frailty model of the time to first prescription for each drug. We then assigned physicians to one of 306 U.S. hospital referral regions (HRRs) and measured the average propensity to adopt per region. Using 2010 data for a random sample of 1.6 million Medicare beneficiaries, we identified 138,680 antipsychotic users. A generalized linear model with gamma distribution and log link was used to estimate the effect of region-level adoption propensity on beneficiary-level antipsychotic spending and non-drug medical spending adjusting for patient demographic and socioeconomic characteristics, health status, eligibility category, and whether the antipsychotic was

Controversies about a common etiology for eating and mood disorders

PubMed Central

Rossetti, Clara; Halfon, Olivier; Boutrel, Benjamin

2014-01-01

Obesity and depression represent a growing health concern worldwide. For many years, basic science and medicine have considered obesity as a metabolic illness, while depression was classified a psychiatric disorder. Despite accumulating evidence suggesting that obesity and depression may share commonalities, the causal link between eating and mood disorders remains to be fully understood. This etiology is highly complex, consisting of multiple environmental and genetic risk factors that interact with each other. In this review, we sought to summarize the preclinical and clinical evidence supporting a common etiology for eating and mood disorders, with a particular emphasis on signaling pathways involved in the maintenance of energy balance and mood stability, among which orexigenic and anorexigenic neuropeptides, metabolic factors, stress responsive hormones, cytokines, and neurotrophic factors. PMID:25386150

Conventional versus novel antipsychotics: changing concepts and clinical implications.

PubMed Central

Remington, G; Chong, S A

1999-01-01

Novel antipsychotics represent a significant advance in the treatment of schizophrenia after many years of few developments. The conventional antipsychotics are potent D2 antagonists, but fail to achieve a response in about 30% of cases. They are also associated with a high rate of extrapyramidal side effects. The greater and broader spectrum of efficacy combined with the reduced short- and long-term side effects of the new drugs such as quetiapine, risperidone, olanzapine and ziprasidone, contribute to a fresh optimism for the pharmacotherapy of schizophrenia. These novel agents are now driving further advances in schizophrenia research through a growing understanding of their pharmacological and clinical profiles. Clozapine, the first novel antipsychotic, has relatively low activity at D2 receptors, a high affinity for D4 receptors and a greater 5-HT2 (serotonin) than D2 antagonism. Hence, clozapine and other novel antipsychotics can be classified as such by this latter characteristic. However, some of these drugs have D2 occupancy greater than 60% (the clinical response threshold), while others have a lower D2 occupancy. The novel antipsychotics according have also been classified according to their activity on different neurotransmitter systems. While more effective, novel antipsychotics are not a panacea; they have limitations and side effects. In clinical practice, the American Psychiatric Association recommends either a conventional or novel antipsychotic for initial treatment of schizophrenia, whereas Canadian guidelines recommend novel agents. These agents should also be considered for treatment of refractory schizophrenia. Patients whose schizophrenia does not respond to one of these agents may respond to another. Future research should involve longer clinical trials, given the long periods needed to establish efficacy, and should address many remaining questions about the novel agents. PMID:10586534

Sexual side effects associated with conventional and atypical antipsychotics.

PubMed

Compton, M T; Miller, A H

2001-01-01

The sexual side effects of psychotropic medications are becoming increasingly recognized in clinical psychiatry. The magnitude of the problem of sexual side effects associated with antipsychotic medications has yet to be fully elucidated, but a multitude of references in the literature demonstrate the importance of these side effects in both men and women. All currently used antipsychotic medications are associated with sexual side effects of various types. Although each antipsychotic medication may have a specific side effect profile determined by its various receptor affinities and by the degree to which it elevates serum prolactin, there is currently no evidence that specific side effects can be predicted. Sexual side effects can be categorized according to the phase of the sexual response cycle with which they interfere. Suggestions for clinical evaluation and treatment options are provided, including risk factor modification, dose reduction, switching agents, and addition of other agents. Sexual side effects associated with conventional and atypical antipsychotic medications represent an underestimated and understudied set of side effects that may diminish a patient's quality of life and lead to treatment noncompliance. Clinicians prescribing antipsychotic medications should be familiar with the classification, evaluation, and treatment of these side effects.

Utilization and costs of antipsychotic agents: a Canadian population-based study, 1996-2006.

PubMed

Alessi-Severini, Silvia; Biscontri, Robert G; Collins, David M; Kozyrskyj, Anita; Sareen, Jitender; Enns, Murray W

2008-05-01

This study evaluated the prescribing patterns and costs for antipsychotic agents in the population of the Canadian province of Manitoba over the past decade. A population-based study of antipsychotic utilization and costs was conducted on data collected from the administrative databases of the Manitoba Population Health Data Repository and the Statistics Canada census between index years 1996 and 2006 (April 1, 1995, through March 31, 2006). The total annual number of antipsychotic prescriptions dispensed in Manitoba increased by 227% between 1996 and 2006, and the prevalence of antipsychotic users increased by 62% over the same time interval. The fastest-growing segment of antipsychotic users in Manitoba appears to be young males, who increased from .16% in 1996 to .88% in 2006. The highest numbers of prescriptions were reported for schizophrenia, dementia, and conduct disorder. Annual expenditures for antipsychotics increased from $1.7 million in 1996 to $22.0 million in 2006 (expenditures are in Canadian dollars). The cost of second-generation agents reached 80% of total antipsychotic expenditures in 2006; risperidone was the most prescribed agent in all age groups of patients. The per-patient annual cost of antipsychotic pharmacotherapy increased by approximately 680% between 1996 and 2006 in Manitoba. The number of antipsychotic prescriptions and the prevalence of users of antipsychotic medications increased significantly in Manitoba over the study period, despite a steady-state population of approximately 1.2 million. Incremental costs relative to the use of antipsychotic medications can be explained by the market penetration of the second-generation agents and their expanded use in the treatment of various diagnoses.

Randomized Trial of the Effect of Four Second-Generation Antipsychotics and One First-Generation Antipsychotic on Cigarette Smoking, Alcohol, and Drug Use in Chronic Schizophrenia.

PubMed

Mohamed, Somaia; Rosenheck, Robert A; Lin, Haiqun; Swartz, Marvin; McEvoy, Joseph; Stroup, Scott

2015-07-01

No large-scale randomized trial has compared the effect of different second-generation antipsychotic drugs and any first-generation drug on alcohol, drug and nicotine use in patients with schizophrenia. The Clinical Antipsychotic Trial of Intervention Effectiveness study randomly assigned 1432 patients formally diagnosed with schizophrenia to four second-generation antipsychotic drugs (olanzapine, risperidone quetiapine, and ziprasidone) and one first-generation antipsychotic (perphenazine) and followed them for up to 18 months. Secondary outcome data documented cigarettes smoked in the past week and alcohol and drug use severity ratings. At baseline, 61% of patients smoked, 35% used alcohol, and 23% used illicit drugs. Although there were significant effects of time showing reduction in substance use over the 18 months (all p < 0.0001), this study found no evidence that any antipsychotic was robustly superior to any other in a secondary analysis of data on substance use outcomes from a large 18-month randomized schizophrenia trial.

Comparison of Unlicensed and Off-Label Use of Antipsychotics Prescribed to Child and Adolescent Psychiatric Outpatients for Treatment of Mental and Behavioral Disorders with Different Guidelines: The China Food and Drug Administration Versus the FDA.

PubMed

Zhu, Xiuqing; Hu, Jinqing; Sun, Bin; Deng, Shuhua; Wen, Yuguan; Chen, Weijia; Qiu, Chang; Shang, Dewei; Zhang, Ming

2018-04-01

This study aims to compare the prevalence of unlicensed and off-label use of antipsychotics among child and adolescent psychiatric outpatients with guidelines proposed by the China Food and Drug Administration (CFDA) and the U.S. Food and Drug Administration (FDA), and to identify factors associated with inconsistencies between the two regulations. A retrospective analysis of 29,326 drug prescriptions for child and adolescent outpatients from the Affiliated Brain Hospital of Guangzhou Medical University was conducted. Antipsychotics were classified as "unlicensed" or "off-label use" according to the latest pediatric license information registered by the CFDA and the FDA or the package inserts of antipsychotics authorized by the CFDA or the FDA for the treatment of pediatric mental and behavioral disorders, respectively. Binary logistic regression analysis was performed to assess factors associated with inconsistencies between the two regulations. The total unlicensed use, according to the CFDA analysis, was higher than that found in the FDA analysis (74.14% vs. 22.04%, p < 0.001). However, the total off-label use, according to the FDA analysis, was higher than that found in the CFDA analysis (46.53% vs. 15.77%, p < 0.001). Antipsychotic drug classes, age group, number of diagnoses, and diagnosis of schizophrenia and schizotypal and delusional disorders were associated with inconsistent unlicensed use. Antipsychotic drug classes, age group, number of prescribed psychotropic drugs, gender, diagnosis of schizophrenia and schizotypal and delusional disorders, diagnosis of mood [affective] disorders, diagnosis of mental retardation, and diagnosis of psychological development disorders were associated with inconsistent off-label use. The difference in prevalence of total unlicensed and off-label use of antipsychotics between the two regulations was statistically significant. This inconsistency could be partly attributed to differences in pediatric license

Use of Antipsychotics Pre- and Post-Dissemination of CATIE Data

PubMed Central

Kalali, Amir H.; Lieberman, Jeffrey; Hsiao, John; Keefe, Richard; Stroup, Scott

2007-01-01

We investigated the share of branded and generic antipsychotics before and after the publication of the CATIE results in September, 2005. According to our data, the publication of the CATIE results has had very little impact on new patient starts. To determine the impact of CATIE on use of olanzapine (Zyprexa®) subsequent to first line therapy, we also examined product share for switch/add patients. We found that since the publication of the CATIE results, the use of olanzapine has stabilized, following a decline subsequent to first line therapy, and may potentially be growing very slowly. An expert commentary is provided on the data. PMID:20806026

Prophylactic use of olanzapine and quetiapine from pregnancy to the postpartum period in women with bipolar disorder: a case series.

PubMed

Uguz, Faruk

2017-11-01

The management of bipolar disorder in pregnant and postpartum women is one of the most difficult issues in clinical practice. Data on the efficacy of mood stabilizers, except lithium and antipsychotics, in the maintenance treatment of bipolar disorders during pregnancy and postpartum period are very limited. This report presents results of prophylaxis with olanzapine and quetiapine with regard to affective episodes in pregnancy to the postpartum period.

Antipsychotic medication for early episode schizophrenia

PubMed Central

Bola, John; Kao, Dennis; Soydan, Haluk; Adams, Clive E

2014-01-01

Background Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are unclear. There have been numerous suggestions that people with early episodes of schizophrenia appear to respond differently than those with multiple prior episodes. The number of episodes may moderate response to drug treatment. Objectives To assess the effects of antipsychotic medication treatment on people with early episode schizophrenia spectrum disorders. Search methods We searched the Cochrane Schizophrenia Group register (July 2007) as well as references of included studies. We contacted authors of studies for further data. Selection criteria Studies with a majority of first and second episode schizophrenia spectrum disorders comparing initial antipsychotic medication treatment with placebo, milieu, or psychosocial treatment. Data collection and analysis Working independently, we critically appraised records from 681 studies, of which five studies met inclusion criteria. We calculated risk ratios (RR) and their 95% confidence intervals (CI) where possible. For continuous data, we calculated mean difference (MD). We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results Five studies (combined total n=998) met inclusion criteria. Four studies (n=724) provided leaving the study early data and results suggested that individuals treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (Chlorpromazine: 3 RCTs n=353, RR 0.4 CI 0.3 to 0.5, NNT 3.2, Fluphenaxine: 1 RCT n=240, RR 0.5 CI 0.3 to 0.8, NNT 5; Thioridazine: 1 RCT n=236, RR 0.44 CI 0.3 to 0.7, NNT 4.3, Trifulperazine: 1 RCT n=94, RR 0.96 CI 0.3 to 3.6). Two studies contributed data to assessment of adverse effects and present a general pattern of more frequent side effects among individuals treated with typical antipsychotic medications

[Cost-effectiveness of Antipsychotics in the Maintenance Treatment of Schizophrenia in Colombia].

PubMed

Quitian Reyes, Hoover; Arciniegas Barrera, Jair Alberto; Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos

2016-01-01

Assess the cost-effectiveness of the antipsychotics for treatment of schizophrenia. A five-year Markov model was built form patients with schizophrenia on the stage of maintenance. Costs were taken from the perspective of the Colombian health care system (Sistema General de Seguridad Social en Salud). The effectiveness was measured in years of life under the same maintenance plan. The Markov model indicated clozapine as the as the most cost-effective alternative between the first line antipsychotics and haloperidol is it when comparing other antipsychotics. Clozapine it's the cost-effectiveness strategy among the first line of antipsychotics and haloperidol is it among the other antipsychotics. Strategies prioritizing the use of cost-effective antipsychotics could improve the resources allocation in the Colombian health care system. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Atypical antipsychotic medications to control symptoms of delirium in children and adolescents.

PubMed

Turkel, Susan Beckwitt; Jacobson, Julienne; Munzig, Elizabeth; Tavaré, C Jane

2012-04-01

Atypical antipsychotics have been documented to be effective in the management of delirium in adults, but despite considerable need, their use has been less studied in pediatric patients. A retrospective chart review was done to describe the use of atypical antipsychotics in controlling symptoms of delirium in children and adolescents. Pharmacy records at Children's Hospital Los Angeles were reviewed to identify patients to whom antipsychotic agents were dispensed over a 24-month period. Psychiatric inpatient consultations during the same 24-month period were reviewed. Patients 1-18 years old diagnosed with delirium given antipsychotics constituted the study population. Delirium Rating Scale-Revised-98 (DRS-R98) scores were retrospectively calculated, when possible, at time antipsychotic was started to confirm the initial diagnosis of delirium and evaluate symptom severity, and again when antipsychotic was stopped, to assess symptom response. Olanzapine (n=78), risperidone (n=13), and quetiapine (n=19) were used during the 2 years of the study. Mean patient age, length of treatment, and response were comparable for the three medications. For patients with two DRS-R98 scores available (n=75/110), mean DRS-R98 scores decreased significantly (p<0.001) with antipsychotic without significant adverse side effects. Although randomized placebo-controlled studies are needed, atypical antipsychotic medications appeared to be effective and safe for managing delirium symptoms in pediatric patients while underlying etiology was addressed.

Food and mood.

PubMed

Ottley, C

A number of specific nutrients and other active substances in foods are thought to have a direct impact on mood. Carol Ottley explores the evidence linking food with aspects of mood and behaviour. Areas covered include premenstrual syndrome, chocolate craving, mood swings, and how we eat in relation to specific mood states such as fear, happiness and anxiety.

Increasing use of atypical antipsychotics and anticonvulsants during pregnancy

PubMed Central

Epstein, Richard A.; Bobo, William V.; Shelton, Richard C.; Arbogast, Patrick G.; Morrow, James A.; Wang, Wei; Chandrasekhar, Rameela; Cooper, William O.

2013-01-01

Purpose To quantify maternal use of atypical antipsychotics, typical antipsychotics, anticonvulsants and lithium during pregnancy. Methods Tennessee birth and death records were linked to Tennessee Medicaid data to conduct a retrospective cohort study of 296,817 women enrolled in Tennessee Medicaid throughout pregnancy who had a live birth or fetal death from 1985 to 2005. Results During the study time period, the adjusted rate of use of any study medication during pregnancy increased from nearly 14 to 31 per 1,000 pregnancies (β = 0.08, 95% CI = 0.07, 0.09). Significant increases were reported in use of anticonvulsants alone among mothers with pain and other psychiatric disorders, atypical antipsychotics alone among mothers with bipolar disorders, schizophrenia, unipolar depressive disorders, and other psychiatric disorders, and more than one studied medication for mothers with epilepsy, pain disorders, bipolar disorders, unipolar depressive disorders, and other psychiatric disorders. Significant decreases were reported in use of lithium alone and typical antipsychotics alone for all clinically meaningful diagnosis groups. Conclusions There was a substantial increase in use of atypical antipsychotics alone, anticonvulsants alone, and medications from multiple studied categories among Tennessee Medicaid-insured pregnant women during the study period. Further examination of the maternal and fetal consequences of exposure to these medications during pregnancy is warranted. PMID:23124892

Influences of Mood Variability, Negative Moods, and Depression on Adolescent Cigarette Smoking

PubMed Central

Weinstein, Sally M.; Mermelstein, Robin J.

2013-01-01

Understanding the emotional risk factors for cigarette smoking in adolescence can greatly inform prevention efforts. The current study examined prospective relationships between three affective dimensions – negative mood variability, overall negative mood, and depression, affect-related smoking motives, and future smoking patterns among adolescents. The current study expands on prior research by using real-time methods to assess mood and by focusing on a key developmental transition in smoking behavior: the progression from experimentation or low level, infrequent use to higher use. Ninth and 10th grade students (N = 461; 55% girls) provided data on cigarette use at a baseline and follow-up 15-month wave, and also provided ecological momentary assessments of negative moods via palmtop computers for one week at each wave. Negative mood was examined via the means of negative mood reports at each wave, and mood variability was examined via the intraindividual standard deviations of negative mood reports at each wave. Depressive symptoms and smoking motives were also assessed. Findings supported a complex self-medication model of smoking escalation in adolescence whereby mood-smoking relationships differed by affect dimension and gender. For girls, greater negative mood variability at baseline significantly predicted rapid escalation in smoking over time, whereas depressive symptoms and overall negative mood were unrelated to girls’ smoking patterns. In contrast, overall negative mood significantly predicted boys’ smoking escalation among those with affect-related motives for smoking. Results thus suggest that inconsistent mood-smoking relations in past work may be driven by the complex interrelationships among affect vulnerabilities, gender, and smoking patterns. PMID:23438244

Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings.

PubMed

Navari, S; Dazzan, P

2009-11-01

The potential effects of antipsychotic drugs on brain structure represent a key factor in understanding neuroanatomical changes in psychosis. This review addresses two issues: (1) do antipsychotic medications induce changes in total or regional human brain volumes and (2) do such effects depend on antipsychotic type? A systematic review of studies reporting structural brain magnetic resonance imaging (MRI) measures: (1) directly in association with antipsychotic use; and (2) in patients receiving lifetime treatment with antipsychotics in comparison with drug-naive patients or healthy controls. We searched Medline and EMBASE databases using the medical subject heading terms: 'antipsychotics' AND 'brain' AND (MRI NOT functional). The search included studies published up to 31 January 2007. Wherever possible, we reported the effect size of the difference observed. Thirty-three studies met our inclusion criteria. The results suggest that antipsychotics act regionally rather than globally on the brain. These volumetric changes are of a greater magnitude in association with typical than with atypical antipsychotic use. Indeed, there is evidence of a specific effect of antipsychotic type on the basal ganglia, with typicals specifically increasing the volume of these structures. Differential effects of antipsychotic type may also be present on the thalamus and the cortex, but data on these and other brain areas are more equivocal. Antipsychotic treatment potentially contributes to the brain structural changes observed in psychosis. Future research should take into account these potential effects, and use adequate sample sizes, to allow improved interpretation of neuroimaging findings in these disorders.

The antipsychotic landscape: dopamine and beyond.

PubMed

Morrison, Paul D; Murray, Robin M

2018-04-01

Until recently, the actions of antipsychotic and pro-psychotic drugs have largely been evaluated in the framework of neuronal doctrine - namely, that neurons communicate by releasing transmitters, and that psychiatric disorders are caused by neurotransmitter imbalances. Moreover, the majority of studies have focused on single transmitter systems - neglecting the fact that in the nervous system, different transmitter systems work in concert and impact on not only their immediate receptors but also downstream pathways that shape structural plasticity. In this review, we discuss the history of understanding the antipsychotic and pro-psychotic actions of drugs, recent developments and future perspectives.

Quality use of antipsychotic medicines inresidential aged care facilities in New Zealand.

PubMed

Ndukwe, Henry C; Nishtala, Prasad S; Wang, Ting; Tordoff, June M

2016-12-01

INTRODUCTION Antipsychotic medicines are used regularly or when required in residential aged care facilities to treat symptoms of dementia, but have been associated with several adverse effects. AIM The aim of this study was to examine 'quality use' of antipsychotic medicines in residential aged care facilities in New Zealand, by surveying nurse managers. METHODS A cross-sectional survey was mailed to 318 nurse managers working in a nationally representative sample of aged care facilities. A purpose-developed, pre-tested, 22-item structured questionnaire was used to explore practice related to the quality use of antipsychotic medicines. RESULTS Overall, 31.4% of nurse managers responded to the survey. They mostly (88%) had ≥ 1 year's relevant work experience and 83% of facilities provided care for those within the range of 21 to 100 residents. Respondents reported that staff education on dementia management occurred early in employment. Two-thirds of participants reported non-pharmacological interventions were commonly used for managing challenging behaviours, while less than half (45%) cited administering antipsychotic medicine. Respondents reported 'managing behavioural symptoms' (81%) as one of the main indications for antipsychotic use. Frequently identified adverse effects of antipsychotic medicines were drowsiness or sedation (64%) and falls (61%). Over 90% reported general practitioners reviewed antipsychotic use with respect to residents' target behaviour 3-monthly, and two-thirds used an assessment tool to appraise residents' behaviour. DISCUSSION Staff education on dementia management soon after employment and resident 3-monthly antipsychotic medicine reviews were positive findings. However, a wider use of behavioural assessment tools might improve the care of residents with dementia and the quality use of antipsychotic medicines.

Atypical antipsychotic use and outcomes in an urban maternal mental health service.

PubMed

Hatters Friedman, Susan; Moller-Olsen, Charmian; Prakash, Chandni; North, Abigail

2016-08-01

Objective Despite many women suffering from psychosis in their childbearing years, limited data exist about the use of atypical antipsychotic agents in pregnancy. Atypical antipsychotic agents are often used to treat bipolar disorder, instead of lithium or valproate because of the known teratogenicity of those agents. As well, atypical antipsychotics are often prescribed in anxiety disorders and depression. This study sought to describe pregnancy outcomes for women prescribed atypical antipsychotics during pregnancy. Methods This retrospective review included all cases treated by Auckland Maternal Mental Health services in which atypical antipsychotic agents were utilized during pregnancy over three years. Results Over the three years, 45 pregnant women were prescribed atypical antipsychotic agents, most commonly quetiapine or olanzapine. Two-fifths (40%) were diagnosed with bipolar disorder and almost one-third (31%) with a psychotic disorder. Two-thirds (64%) were prescribed multiple psychotropic medications during their pregnancy. Instrumental delivery rates were elevated at 38%. A minority (13%) of the women developed gestational diabetes mellitus. Although 7% of infants were born premature, all were born after 35 weeks. Two major malformations were noted, similar to baseline community rates. Conclusions This naturalistic study adds to the limited literature about treatment with atypical antipsychotic agents in pregnancy, though not adequately powered to detect small differences in malformations or obstetrical outcomes. It also highlights the myriad of indications for which pregnant women are prescribed atypical antipsychotics, and the multiple other risk factors seen in this population.

Cost-effectiveness of antipsychotics for outpatients with chronic schizophrenia.

PubMed

Obradovic, M; Mrhar, A; Kos, M

2007-12-01

The aim of the present analysis was to evaluate the cost-effectiveness of alternative treatments for outpatients with chronic schizophrenia from the healthcare payer's perspective. Decision analysis was used to evaluate the cost-effectiveness of the following antipsychotic drugs: amisulpride, aripiprazole, haloperidol (oral formulation), haloperidol (depot formulation), olanzapine, quetiapine, risperidone (oral formulation), risperidone (depot formulation) and ziprazidone. Clinical and economic outcomes were modelled over 1-year time horizon. Effectiveness was measured as a percentage of patients in remission. Clinical parameters used in the model included compliance rates, rehospitalisation rates for compliant and non-compliant patients, duration and frequency of hospitalisation, and adverse event rates. One-way sensitivity analysis was performed to test the robustness of the model. The most effective treatment was treatment with olanzapine where 64.1% of patients remained in remission. The least effective treatment was treatment with quetiapine where 32.7% of patients remained in remission. Overall costs ranged from 3,726.78 Euro for haloperidol to 8,157.03 Euro for risperidone in depot formulation. Inpatient costs represented the major part of costs for most of antipsychotic drugs. Typical antipsychotic drugs had substantially smaller outpatient costs (6.5%) compared with atypical antipsychotics (37.9%). In the base case scenario the non-dominated treatment strategies were haloperidol, haloperidol decanoate and olanzapine. Additionally, risperidone can also be considered to be part of the efficient frontier based on the sensitivity analysis results. Among second-generation antipsychotics, which have a better safety profile than first-generation antipsychotics, olanzapine and risperidone showed to be the most cost-effective treatment strategies for outpatient treatment of chronic schizophrenia.

[Treatment of Adult Schizophrenic Patients With Depot Antipsychotics].

PubMed

Jaramillo González, Luis Eduardo; Gómez Restrepo, Carlos; García Valencia, Jenny; de la Hoz Bradford, Ana María; Ávila-Guerra, Mauricio; Bohórquez Peñaranda, Adriana

2014-01-01

To determine the indications of long-acting antipsychotic injection and what its effectiveness and safety in adult patients with schizophrenia during the treatment maintenance phase. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. The literature review shows that the evidence has moderate to low quality. 8 articles were used. The risk of relapse was lower with depot risperidone and paliperidone palmitate when compared with placebo. For the risk of hospitalizations comparing depot antipsychotics (APD) versus oral AP, the result is inconclusive. Globally the second-generation APD had a lower risk of discontinuation when compared with placebo. The second generation AP had higher risk of extrapyramidal syndromes than placebo, as in the use of antiparkinsonian. The comparison of second-generation AP injections versus placebo showed an increased risk of early weight gain. The use of depot antipsychotics in the maintenance phase of adult patients diagnosed with schizophrenia is recommended if there is no adherence to oral antipsychotics as the patient's preference. It is not recommended depot antipsychotics in the acute phase of schizophrenia in adults. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Incidence of Tardive Dyskinesia with Atypical and Conventional Antipsychotic Medications: Prospective Cohort Study

PubMed Central

Woods, Scott W.; Morgenstern, Hal; Saksa, John R.; Walsh, Barbara C.; Sullivan, Michelle C.; Money, Roy; Hawkins, Keith A.; Gueorguieva, Ralitza V.; Glazer, William M.

2011-01-01

Objective Most previous studies of the incidence of tardive dyskinesia with atypical compared to conventional antipsychotics have not had tardive dyskinesia as their primary focus. The current study aimed to compare the incidence of tardive dyskinesia with atypical vs. conventional antipsychotics using methods similar to those from a previous prospective cohort study at our site in the 1980s. Method 352 initially tardive dyskinesia-free psychiatric outpatients were examined for a new diagnosis of tardive dyskinesia every 6 months for up to 4 years at a community mental health center. At baseline, subjects were receiving conventional antipsychotics only (23%), atypicals only (64%), or both (14%). Only 26 subjects had never received conventional antipsychotics. Results Compared with subjects treated with conventional antipsychotics alone since the previous visit, the adjusted tardive dyskinesia incidence rate-ratio for subjects treated with atypical antipsychotics alone was 0.68 (95% confidence interval 0.29 to 1.64). The incidence and prevalence of tardive dyskinesia was similar to previous findings at this site in the 1980s. Conclusion The incidence of tardive dyskinesia with recent exposure to atypical antipsychotics alone was more similar to that for conventional antipsychotics than in most previous studies. Despite high penetration of atypical antipsychotics into clinical practice, the incidence and prevalence of tardive dyskinesia appeared relatively unchanged since the 1980s. Clinicians should continue to monitor for tardive dyskinesia, and researchers should continue to pursue efforts to treat or prevent it. PMID:20156410

Use of second-generation antipsychotic agents for sleep and sedation: a provider survey.

PubMed

Hermes, Eric D A; Sernyak, Michael; Rosenheck, Robert

2013-04-01

Anecdotal evidence suggests that second-generation antipsychotic agents are increasingly used to treat sleep problems. This study sought to quantify the proportion of new prescriptions for second-generation antipsychotic agents started for sleep/sedation and the correlates of such use. A cross-sectional survey of provider decision making at the time second-generation antipsychotic agents were prescribed, documenting the reasons for the medication, patient demographics, psychiatric and medical diagnoses, patient health characteristics, and provider background. A single Veterans Affairs Medical Center over a 20-month period. Prescribers of second-generation antipsychotic agents. N/A. Seven hundred seven (32.2%) of 2,613 surveys indicated sleep/sedation was at least one reason for using a second-generation anti-psychotic agent, whereas for 266 (12.1%) it was the only reason. Quetiapine was most frequently prescribed overall as well as for sleep/sedation (47.0% and 73.6% respectively). Second-generation antipsychotic agent use for sleep/sedation was unrelated to sociodemographic characteristics, least likely in patients with schizophrenia or bipolar disorder, and most likely as a newly started second-generation antipsychotic agent. Sleep/sedation is a common reason given for new prescriptions of second-generation antipsychotic agents. Quetiapine is most frequently used for this purpose. A greater understanding of why providers use second-generation antipsychotic agents rather than safer and less costly alternatives for sleep problems may advance the development of interventions to reduce adverse effects.

Contextual and behavioral control of antipsychotic sensitization induced by haloperidol and olanzapine.

PubMed

Zhang, Chen; Li, Ming

2012-02-01

Repeated administration of haloperidol (HAL) and olanzapine (OLZ) causes a progressively enhanced disruption of the conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined the extent to which antipsychotic-induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or the PCP (3.2 mg/kg, subcutaneously) hyperlocomotion model under HAL or OLZ for 5 consecutive days. Then they were switched to the other model and tested for the expression of sensitization. Finally, all rats were switched back to the original model and retested for the expression of sensitization. Repeated HAL or OLZ treatment progressively disrupted avoidance responding and decreased PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a different model, rats previously treated with HAL or OLZ did not show a stronger inhibition of CAR-induced or PCP-induced hyperlocomotion than those treated with these drugs for the first time; however, they did show such an effect when tested in the original model in which they received repeated antipsychotic treatment. These findings suggest that the expression of antipsychotic sensitization is strongly influenced by the testing environment and/or selected behavioral response under certain experimental conditions. Distinct contextual cues and behavioral responses may develop an association with unconditional drug effects through a Pavlovian conditioning process. They may also serve as occasion setters to modulate the expression of sensitized responses. As antipsychotic sensitization mimics the clinical

Contextual and behavioral control of antipsychotic sensitization induced by haloperidol and olanzapine

PubMed Central

Zhang, Chen; Li, Ming

2011-01-01

Repeated administration of haloperidol and olanzapine causes a progressively enhanced disruption of conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined to the extent to which antipsychotic-induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or PCP (3.2 mg/kg, sc) hyperlocomotion model under haloperidol or olanzapine for five consecutive days. Then they were switched to the other model and tested for the expression of sensitization. Finally, all rats were switched back to the original model and retested for the expression of sensitization. Repeated haloperidol or olanzapine treatment progressively disrupted avoidance responding and decreased PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a different model, rats previously treated with haloperidol or olanzapine did not show a stronger inhibition of CAR or PCP-induced hyperlocomotion than those treated with these drugs for the first time; however, they did show such an effect when tested in the original model in which they received repeated antipsychotic treatment. These findings suggest that the expression of antipsychotic sensitization is strongly influenced by the testing environment and/or selected behavioral response under certain experimental conditions. Distinct contextual cues and behavioral responses may enter an association with unconditional drug effects via a Pavlovian conditioning process. They may also serve as occasion-setters to modulate the expression of sensitized responses. Because antipsychotic sensitization mimics

Effects of aripiprazole once-monthly on symptoms of schizophrenia in patients switched from oral antipsychotics.

PubMed

Peters-Strickland, Timothy; Zhao, Cathy; Perry, Pamela P; Eramo, Anna; Salzman, Phyllis M; McQuade, Robert D; Johnson, Brian R; Sanchez, Raymond

2016-12-01

To assess the effects of aripiprazole once-monthly 400 mg (AOM 400) on clinical symptoms and global improvement in schizophrenia after switching from an oral antipsychotic. In a multicenter, open-label, mirror-image, naturalistic study in patients with schizophrenia (>1 year, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision [DSM-IV-TR] criteria), changes in efficacy measures were assessed during prospective treatment (6 months) with AOM 400 after switching from standard-of-care oral antipsychotics. During prospective treatment, patients were cross-titrated to oral aripiprazole monotherapy (1-4) weeks followed by open-label AOM 400 (24 weeks). Mean change from baseline of the open-label AOM 400 phase in Positive and Negative Syndrome Scale (PANSS) scores (total, positive and negative subscales) and Clinical Global Impression-Severity (CGI-S) scores; mean CGI-Improvement (CGI-I) score; and proportion of responders (≥30% decrease from baseline in PANSS total score or CGI-I score of 1 [very much improved] or 2 [much improved]) were assessed. PANSS and CGI-S scores improved from baseline (P<0.0001) and CGI-I demonstrated improvement at all time points. By the end of the study, 49.0% of patients were PANSS or CGI-I responders. In a community setting, patients with schizophrenia who were stabilized at baseline and switched to AOM 400 from oral antipsychotics showed clear improvements in clinical symptoms.

Increasing use of atypical antipsychotics and anticonvulsants during pregnancy.

PubMed

Epstein, Richard A; Bobo, William V; Shelton, Richard C; Arbogast, Patrick G; Morrow, James A; Wang, Wei; Chandrasekhar, Rameela; Cooper, William O

2013-07-01

To quantify maternal use of atypical antipsychotics, typical antipsychotics, anticonvulsants, and lithium during pregnancy. Tennessee birth and death records were linked to Tennessee Medicaid data to conduct a retrospective cohort study of 296,817 women enrolled in Tennessee Medicaid throughout pregnancy who had a live birth or fetal death from 1985 to 2005. During the study time period, the adjusted rate of use of any study medication during pregnancy increased from nearly 14 to 31 per 1000 pregnancies (β = 0.08, 95% CI = 0.07, 0.09). Significant increases were reported in use of anticonvulsants alone among mothers with pain and other psychiatric disorders, atypical antipsychotics alone among mothers with bipolar disorders, schizophrenia, unipolar depressive disorders, and other psychiatric disorders, and more than one studied medication for mothers with epilepsy, pain disorders, bipolar disorders, unipolar depressive disorders, and other psychiatric disorders. Significant decreases were reported in use of lithium alone and typical antipsychotics alone for all clinically meaningful diagnosis groups. There was a substantial increase in use of atypical antipsychotics alone, anticonvulsants alone, and medications from multiple studied categories among Tennessee Medicaid-insured pregnant women during the study period. Further examination of the maternal and fetal consequences of exposure to these medications during pregnancy is warranted. Copyright © 2012 John Wiley & Sons, Ltd.

Use of Academic Detailing With Audit and Feedback to Improve Antipsychotic Pharmacotherapy.

PubMed

Brunette, Mary F; Cotes, Robert O; de Nesnera, Alexander; McHugo, Gregory; Dzebisashvili, Nino; Xie, Haiyi; Bartels, Stephen J

2018-06-08

Second-generation antipsychotics vary in their propensity to cause serious cardiometabolic side effects. In addition, use of two or more antipsychotics (polypharmacy) may lead to additive side effects and has not been shown to be consistently more effective than monotherapy. This study examined the use of academic detailing with audit and feedback to improve antipsychotic prescribing practices, including antipsychotic polypharmacy and utilization of medication with high or low risk of cardiometabolic side effects ("high risk" or "low risk," respectively). Four intervention sessions were provided over two years to psychiatric care providers at community mental health centers. Segmented regression within the general estimating equation model framework used Medicaid pharmacy claims to examine prescribing patterns before and after the intervention among all beneficiaries (67,721 person-months) over a five-year period. After the intervention, 10.9% of beneficiaries with antipsychotic claims were on polypharmacy, compared with 13.1% before the invention. Use of high-risk and low-risk antipsychotics did not change. The final adjusted polypharmacy model showed that antipsychotic polypharmacy decreased among young adults and adults ages 40 or older compared with beneficiaries ages 30-39 (β=-.02, p=.04, and β=-.02, p=.007, respectively). The raw proportion of beneficiaries on high- and low-risk agents did not change, although final adjusted models demonstrated changes in use of high- and low-risk agents by diagnosis and risk group. Polypharmacy decreased among young and older adults after academic detailing with audit and feedback. Although further research is needed, this low-intensity intervention may help mental health systems reduce antipsychotic polypharmacy.

Generic penetration in the retail atypical antipsychotic market.

PubMed

Lenderts, Susan; Kalali, Amir H; Buckley, Peter

2010-03-01

In this article, we explore the penetration of generic atypical antipsychotics in the United States market before and after the availability of generic risperidone in July 2008. Analysis suggests that, overall, generic penetration into the atypical antipsychotic market has grown from approximately three percent in January 2008 to more than 25 percent in December 2009. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.

Generic Penetration in the Retail Atypical Antipsychotic Market

PubMed Central

Kalali, Amir H; Buckley, Peter

2010-01-01

In this article, we explore the penetration of generic atypical antipsychotics in the United States market before and after the availability of generic risperidone in July 2008. Analysis suggests that, overall, generic penetration into the atypical antipsychotic market has grown from approximately three percent in January 2008 to more than 25 percent in December 2009. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty. PMID:20436769

The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2003 update.

PubMed

Miller, Alexander L; Hall, Catherine S; Buchanan, Robert W; Buckley, Peter F; Chiles, John A; Conley, Robert R; Crismon, M Lynn; Ereshefsky, Larry; Essock, Susan M; Finnerty, Molly; Marder, Stephen R; Miller, Del D; McEvoy, Joseph P; Rush, A John; Saeed, Sy A; Schooler, Nina R; Shon, Steven P; Stroup, Scott; Tarin-Godoy, Bernardo

2004-04-01

The Texas Medication Algorithm Project (TMAP) has been a public-academic collaboration in which guidelines for medication treatment of schizophrenia, bipolar disorder, and major depressive disorder were used in selected public outpatient clinics in Texas. Subsequently, these algorithms were implemented throughout Texas and are being used in other states. Guidelines require updating when significant new evidence emerges; the antipsychotic algorithm for schizophrenia was last updated in 1999. This article reports the recommendations developed in 2002 and 2003 by a group of experts, clinicians, and administrators. A conference in January 2002 began the update process. Before the conference, experts in the pharmacologic treatment of schizophrenia, clinicians, and administrators reviewed literature topics and prepared presentations. Topics included ziprasidone's inclusion in the algorithm, the number of antipsychotics tried before clozapine, and the role of first generation antipsychotics. Data were rated according to Agency for Healthcare Research and Quality criteria. After discussing the presentations, conference attendees arrived at consensus recommendations. Consideration of aripiprazole's inclusion was subsequently handled by electronic communications. The antipsychotic algorithm for schizophrenia was updated to include ziprasidone and aripiprazole among the first-line agents. Relative to the prior algorithm, the number of stages before clozapine was reduced. First generation antipsychotics were included but not as first-line choices. For patients refusing or not responding to clozapine and clozapine augmentation, preference was given to trying monotherapy with another antipsychotic before resorting to antipsychotic combinations. Consensus on algorithm revisions was achieved, but only further well-controlled research will answer many key questions about sequence and type of medication treatments of schizophrenia.

Brain norepinephrine system as a target for antidepressant and mood stabilizing medications.

PubMed

Dremencov, Eliyahu; el Mansari, Mostafa; Blier, Pierre

2009-11-01

There are numerous lines of evidence pointing to norepinephrine being of crucial importance in pathophysiology of anxiety and mood disorders. First, norepinephrine projections innervate the limbic system, suggesting the involvement of norepinephrine in the regulation of emotions and cognition. Second, norepinephrine closely interacts with serotonin and dopamine systems, which also play very important roles in the regulation of mood. Third, it has been shown that various agents which increase norepinephrine availability, such as norepinephrine reuptake inhibitors, are also effective antidepressant drugs. And fourth, the depletion of norepinephrine causes a resurgence of depressive symptoms after successful treatment with antidepressant drugs. These observations suggest that the intensification of norepinephrine transmission can be beneficial in the treatment of affective disorders. However, various psychotropic medications have indirect effect on norepinephrine transmission. This review examines the effects of psychiatric medications on the norepinephrine system and proposes how they might be used to improve treatment outcome.

An explorative study of school performance and antipsychotic medication.

PubMed

van der Schans, J; Vardar, S; Çiçek, R; Bos, H J; Hoekstra, P J; de Vries, T W; Hak, E

2016-09-21

Antipsychotic therapy can reduce severe symptoms of psychiatric disorders, however, data on school performance among children on such treatment are lacking. The objective was to explore school performance among children using antipsychotic drugs at the end of primary education. A cross-sectional study was conducted using the University Groningen pharmacy database linked to academic achievement scores at the end of primary school (Dutch Cito-test) obtained from Statistics Netherlands. Mean Cito-test scores and standard deviations were obtained for children on antipsychotic therapy and reference children, and statistically compared using analyses of covariance. In addition, differences in subgroups as boys versus girls, ethnicity, household income, and late starters (start date within 12 months of the Cito-test) versus early starters (start date > 12 months before the Cito-test) were tested. In all, data from 7994 children could be linked to Cito-test scores. At the time of the Cito-test, 45 (0.6 %) were on treatment with antipsychotics. Children using antipsychotics scored on average 3.6 points lower than the reference peer group (534.5 ± 9.5). Scores were different across gender and levels of household income (p < 0.05). Scores of early starters were significantly higher than starters within 12 months (533.7 ± 1.7 vs. 524.1 ± 2.6). This first exploration showed that children on antipsychotic treatment have lower school performance compared to the reference peer group at the end of primary school. This was most noticeable for girls, but early starters were less affected than later starters. Due to the observational cross-sectional nature of this study, no causality can be inferred, but the results indicate that school performance should be closely monitored and causes of underperformance despite treatment warrants more research.

Lean Methodology Reduces Inappropriate Use of Antipsychotics for Agitation at a Psychiatric Hospital.

PubMed

Goga, Joshana K; Depaolo, Antonio; Khushalani, Sunil; Walters, J Ken; Roca, Robert; Zisselman, Marc; Borleis, Christopher

2017-01-01

To Evaluate the Effects of Applying Lean Methodology-Improving Quality Increasing Efficiency by Eliminating Waste and Reducing Costs-An Approach To Decrease the Prescribing Frequency of Antipsychotics for The Indication of Agitation. Historically Controlled Study. Bheppard Pratt Health System is the Largest Private Provider of Psychiatric Care in Maryland With a Total Bed Capacity of 300. There Were 4 337 Patient Days From November 1 2012 to October 31 2013 on the Dementia Unit. All Patients Admitted on the Dementia Unit Were 65 Years of Age and Older with a Primary Diagnosis of Dementia. our Multidisciplinary Team Used Lean Methodology to Identify the Root Causes and Interventions Necessary to Reduce Inappropriate Antipsychotic Use. The Primary Outcome Was Rate of Inappropriately Indicating Agitation as the Rationale When Prescribing Antipsychotic Medications. There Was a 90% (P < 0.001) Reduction in Rate Of Antipsychotic Prescribing with an Indication of Agitation. The Lean Methodology Interventions Led To A 90% (P < 0.001) Reduction in the Rate of Antipsychotic Prescribing with an Indication of Agitation and a 10% Rate Reduction in Overall Antipsychotic Prescribing. Key Words: Agitation Alzheimer's Antipsychotics Behavioral and Psychological Symptoms of Dementia Centers For Medicare & Medicaid Services Dementia Root-cause Analysis. BPSD = Behavioral and Psychological Symptoms of Dementia CATIE-AD = Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease EMR = Electronic Medical Records GAO = Government Accountability Office GNCIS = Geriatric Neuropsychiatric Clinical Indicator Scale.

[Treatment practices in the management of patients with bipolar disorder in France. The TEMPPO study].

PubMed

Nuss, P; de Carvalho, W; Blin, P; Arnaud, R; Filipovics, A; Loze, J-Y; Dillenschneider, A

2012-02-01

TEMPPO is an observational, cross-sectional and multicentre study, initiated in the French metropolitan territory in 2009. Set up from a random sample of 135 psychiatrists, it has observed the procedures for therapeutic management of a population (n=619) of their outpatients (respectively 197 and 422 in public and private practice) with bipolar disorder type I or II disorders (DSM-IV). The patients who were followed were mostly very sick. Every patient received a pharmacological treatment. The prescription included at least one mood stabilizer or an antipsychotic (71 % atypical) in 78 % and 56 % of cases respectively. Treatment regimen changes were frequent (61 % of patients had at least one change in treatment during the last 12 months). A single molecule by therapeutic class was generally prescribed. The presence of an antipsychotic in combination therapy was often associated with the severity or difficulty of care of the patient (mixed states, severity of the global functioning impairment, manic states, high number of hospitalizations and history of suicide attempt). The combination of two antipsychotics is found only in the difficult situations of manic states. Patients with severe depressive phase are those who benefit from the combination mood stabilizer+antipsychotic+antidepressant (16 % of the sample). In this study, the prescription of antidepressants significantly differs from recommendations for good prescribing practices. Indeed antidepressants were commonly prescribed in mixed-phase (63 %), particularly as a monotherapy in 5 % of cases. It was also found in patients in euthymic phase (48 %), manic phase (12 %) and hypomanic phase (29 %). The prescription of atypical antipsychotics (monotherapy or combination) is now fully established in the management of all phases of the disease. The importance of non-pharmacological treatment is acknowledged by psychiatrists and proposed whether a psychotherapeutic support, information about the disease and

Effects of antipsychotic drugs on cardiovascular variability in participants with bipolar disorder

PubMed Central

Linder, Jonathan R.; Sodhi, Simrit K.; Haynes, William G.; Fiedorowicz, Jess G.

2014-01-01

Objective The risk for cardiovascular diseases is elevated in persons with bipolar disorder. However, it remains unknown how much of this excess risk is secondary to pharmacologic treatment. We tested the hypothesis that current and cumulative antipsychotic drug exposure is associated with increased cardiovascular risk as indicated by lower heart rate variability (HRV) and increased blood pressure variability (BPV). Methods 55 individuals with bipolar disorder (33±7 years; 67% female) underwent non-invasive electrocardiogram assessment of time- and frequency-domain HRV, as well as BPV analysis. Medication histories were obtained through systematic review of pharmacy records for the past five years. Results Current antipsychotic exposure was associated with lower SDNN. Second generation antipsychotics were associated with lower SDNN and RMSSD. There was no significant relationship between five-year antipsychotic exposure and HRV in subjects with bipolar disorder. Exploratory analysis revealed a possible link between SSRI exposure and increased low frequency spectral HRV. Conclusions Current antipsychotic use (particularly second generation antipsychotics with high affinities for the D2S receptor) is associated with reduced autonomic-mediated variability of heart rate. The absence of an association with cumulative exposure suggests that the effects are acute in onset, and may therefore relate more to altered autonomic function than structural cardiovascular abnormalities. Future studies should prospectively examine effects of these antipsychotics on autonomic function. PMID:24590543

Expected incidence of tardive dyskinesia associated with atypical antipsychotics.

PubMed

Glazer, W M

2000-01-01

Given the problematic nature of tardive dyskinesia in persons taking conventional antipsychotics, evaluation of newer atypical antipsychotic agents should include a systematic assessment of tardive dyskinesia liability. Results of a prospective double-blind, randomized study of schizophrenic patients who participated in 3 preclinical olanzapine studies and were treated with 5 to 20 mg/day of olanzapine (N = 1192) or haloperidol (N = 522) recently indicated a significantly lower risk of development of tardive dyskinesia with olanzapine treatment than haloperidol treatment. This article discusses the known effects of atypical antipsychotic medications on tardive dyskinesia movements (both withdrawal and persistent) and the incidence rate of tardive dyskinesia among schizophrenic patients undergoing long-term treatment with olanzapine or haloperidol.

Antipsychotic-induced weight gain: a comprehensive research synthesis.

PubMed

Allison, D B; Mentore, J L; Heo, M; Chandler, L P; Cappelleri, J C; Infante, M C; Weiden, P J

1999-11-01

The purpose of this study was to estimate and compare the effects of antipsychotics-both the newer ones and the conventional ones-on body weight. A comprehensive literature search identified 81 English- and non-English-language articles that included data on weight change in antipsychotic-treated patients. For each agent, a meta-analysis and random effects metaregression estimated the weight change after 10 weeks of treatment at a standard dose. A comprehensive narrative review was also conducted on all articles that did not yield quantitative information but did yield important qualitative information. Placebo was associated with a mean weight reduction of 0.74 kg. Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine. Among newer antipsychotic agents, mean increases were as follows: clozapine, 4.45 kg; olanzapine, 4.15 kg; sertindole, 2.92 kg; risperidone, 2.10 kg; and ziprasidone, 0.04 kg. Insufficient data were available to evaluate quetiapine at 10 weeks. Both conventional and newer antipsychotics are associated with weight gain. Among the newer agents, clozapine appears to have the greatest potential to induce weight gain, and ziprasidone the least. The differences among newer agents may affect compliance with medication and health risk.

Decrease in Statewide Antipsychotic Prescribing after Implementation of Child and Adolescent Psychiatry Consultation Services.

PubMed

Barclay, Rebecca P; Penfold, Robert B; Sullivan, Donna; Boydston, Lauren; Wignall, Julia; Hilt, Robert J

2017-04-01

To learn if a quality of care Medicaid child psychiatric consultation service implemented in three different steps was linked to changes in statewide child antipsychotic utilization. Washington State child psychiatry consultation program primary data and Medicaid pharmacy division antipsychotic utilization secondary data from July 1, 2006, through December 31, 2013. Observational study in which consult program data were analyzed with a time series analysis of statewide antipsychotic utilization. All consultation program database information involving antipsychotics was compared to Medicaid pharmacy division database information involving antipsychotic utilization. Washington State's total child Medicaid antipsychotic utilization fell from 0.51 to 0.25 percent. The monthly prevalence of use fell by a mean of 0.022 per thousand per month following the initiation of elective consults (p = .004), by 0.065 following the initiation of age/dose triggered mandatory reviews (p < .001), then by another 0.022 following the initiation of two or more concurrent antipsychotic mandatory reviews (p = .001). High-dose antipsychotic use fell by 57.8 percent in children 6- to 12-year old and fell by 52.1 percent in teens. Statewide antipsychotic prescribing for Medicaid clients fell significantly at different rates following each implementation step of a multilevel consultation and best-practice education service. © Health Research and Educational Trust.

[Paroxysmal perceptual alteration in comparison with hallucination--a review of its clinical reports and discussion of its pathophysiological mechanism in the present day, when second generation antipsychotics are widely used].

PubMed

Watanabe, Ken

2009-01-01

The syndrome of paroxysmal perceptual alteration (PPA) was first described by Yamaguchi in 1985. Since then, many PPA cases have been reported, and its pathophysiological mechanism has been proposed: a suppressed (blocked) mesolimbic and mesocortical dopaminergic system and sequential compensatory increase of noradrenergic neuronal activity are crucial for the occurrence of PPA. PPA is characterized by hypersensitivity of perception, psychedelic experience (brightening of colors, sharpening of contrast, visual distortion, etc.), and somatic schema disorder (one feels that one is floating, one's extremities are being pulled and elongated, etc.). PPA in chronic schizophrenic patients occurs abruptly like an attack mainly in the evening, often precipitated by fatigue. During the attack, patients also suffer from mood and thought alteration (anxiety, agitation, depressive mood, and inability to distract their thoughts from one thing), but they are aware that symptoms of PPA are not real and apprehensive about them. The attack ceases gradually and spontaneously while the patient rests or sleeps. These clinical features are clearly different from those of schizophrenic hallucinations. It is believed that PPA is closely related to neuroleptic treatment by conventional antipsychotics. I reported the prevalence of PPA as 4.0% in 1991 when high potential D2 blocking agents were prevailing. The occurrence of PPA has been significantly reduced to the present, when second generation (atypical) antipsychotics are prevailing. However, in my inquiry in 2004, the prevalence of PPA was 3.6% in cases treated with risperidone (RIS), while the rates were 0 in cases treated with olanzapine (OLZ), quetiapine (QTP), and perospirone (PRS). Several cases of PPA have been reported in patients who were treated with OLZ and PRS. Until now, no cases of PPA have been reported who were treated with QTP and aripiprazole (APZ). The prevalence of PPA among cases treated with these second generation

Antipsychotic Use Among Nursing Home Residents Admitted with Hip Fracture

PubMed Central

Jung, Hye–Young; Meucci, Marissa; Unruh, Mark Aaron; Mor, Vincent; Dosa, David

2012-01-01

Background/Objectives Widespread use of antipsychotic medications among skilled nursing home (NH) residents for off-label indications has become a concern of clinicians and policy makers. The objective of this study was to evaluate the association between receiving antipsychotics and the outcomes of a cohort of NH patients with and without presumed delirium after hip fracture. Design Population based cohort study. Setting 11,119 nursing homes nationwide, from 01 January 2000 to 31 December 2007. Participants First-time NH admits with hip fracture (N=77,759). Measurements The Nursing Home Confusion Assessment Method was utilized to identify residents with no delirium, subsyndromal delirium, and full delirium. Propensity score reweighting was used with analyses stratified by delirium level. Results Among patients with no delirium symptoms, about 5 percent (n = 3,250) received antipsychotic drugs. These individuals were less likely to be discharged home (OR 0.68; P < 0.001), had a higher likelihood of death prior to nursing home discharge (OR 1.28; P = 0.03), stayed in nursing homes longer (β 2.83; P = 0.05), and had less functional improvement at discharge (β -0.47; P = 0.03). Receipt of antipsychotics among participants with mild delirium was associated with a lower likelihood of discharge home (OR 0.74; P = 0.03). Conclusion Among NH residents with hip fracture and no delirium symptoms, use of antipsychotics was associated with worse outcomes, with the exception of rehospitalization. No clear benefits were associated with antipsychotic use for those with presumed delirium. PMID:23252409

Combined Treatment with the Mood Stabilizers Lithium and Valproate Produces Multiple Beneficial Effects in Transgenic Mouse Models of Huntington's Disease

PubMed Central

Chiu, Chi-Tso; Liu, Guangping; Leeds, Peter; Chuang, De-Maw

2011-01-01

Emerging evidence suggests that the mood stabilizers lithium and valproate (VPA) have broad neuroprotective and neurotrophic properties, and that these occur via inhibition of glycogen synthase kinase 3 (GSK-3) and histone deacetylases (HDACs), respectively. Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by impaired movement, cognitive and psychiatric disturbances, and premature death. We treated N171-82Q and YAC128 mice, two mouse models of HD varying in genetic backgrounds and pathological progressions, with a diet containing therapeutic doses of lithium, VPA, or both. Untreated, these transgenic mice displayed a decrease in levels of GSK-3β serine 9 phosphorylation and histone H3 acetylation in the striatum and cerebral cortex around the onset of behavioral deficits, indicating a hyperactivity of GSK-3β and HDACs. Using multiple well-validated behavioral tests, we found that co-treatment with lithium and VPA more effectively alleviated spontaneous locomotor deficits and depressive-like behaviors in both models of HD mice. Furthermore, compared with monotherapy with either drug alone, co-treatment more successfully improved motor skill learning and coordination in N171-82Q mice, and suppressed anxiety-like behaviors in YAC128 mice. This combined treatment consistently inhibited GSK-3β and HDACs, and caused a sustained elevation in striatal as well as cortical brain-derived neurotrophic factor and heat shock protein 70. Importantly, co-treatment markedly prolonged median survival of N171-82Q mice from 31.6 to 41.6 weeks. Given that there is presently no proven treatment for HD, our results suggest that combined treatment with lithium and VPA, two mood stabilizers with a long history of safe use in humans, may have important therapeutic potential for HD patients. PMID:21796107

Foster care, externalizing disorders, and antipsychotic use among Medicaid-enrolled youths.

PubMed

Vanderwerker, Lauren; Akincigil, Ayse; Olfson, Mark; Gerhard, Tobias; Neese-Todd, Sheree; Crystal, Stephen

2014-10-01

The authors investigated the extent to which clinical diagnoses of externalizing disorders explain higher rates of antipsychotic use by foster care youths. Medicaid claims data from 44 states for 2009 for youths in foster care (N=301,894) and those not in foster care (N=5,092,574) were analyzed, excluding those with schizophrenia, bipolar disorder, autism, and major depressive disorder. Logistic regressions assessed the relationship between foster care, externalizing disorders, and antipsychotic use. Foster care youths had higher rates of externalizing disorders than the comparison group (attention-deficit hyperactivity disorder, 17.3% versus 6.5%; disruptive behavior disorder, 7.2% versus 2.5%; conduct disorder, 2.3% versus .5%) and greater antipsychotic use (7.4% versus 1.4%). Foster care remained a significant predictor of antipsychotic use after control for demographic and diagnostic covariates, including externalizing disorders (adjusted odds ratio=2.59, 95% confidence interval=2.54-2.63). High rates of externalizing disorder diagnoses only partially explained elevated levels of antipsychotic use in this vulnerable population.

Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: nuances and pragmatics of the association.

PubMed

Sarkar, Siddharth; Gupta, Nitin

2017-08-01

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal adverse event associated with the use of antipsychotics. Although atypical antipsychotics were initially considered to carry no risk of NMS, reports have accumulated over time implicating them in NMS causation. Almost all atypical antipsychotics have been reported to be associated with NMS. The clinical profile of NMS caused by certain atypical antipsychotics such as clozapine has been reported to be considerably different from the NMS produced by typical antipsychotics, with diaphoresis encountered more commonly, and rigidity and tremor encountered less frequently. This article briefly discusses the evidence relating to the occurrence, presentation and management of NMS induced by atypical antipsychotics.

Seeking Insights About Cycling Mood Disorders via Anonymized Search Logs

PubMed Central

White, Ryen W; Horvitz, Eric

2014-01-01

Background Mood disorders affect a significant portion of the general population. Cycling mood disorders are characterized by intermittent episodes (or events) of the disease. Objective Using anonymized Web search logs, we identify a population of people with significant interest in mood stabilizing drugs (MSD) and seek evidence of mood swings in this population. Methods We extracted queries to the Microsoft Bing search engine made by 20,046 Web searchers over six months, separately explored searcher demographics using data from a large external panel of users, and sought supporting information from people with mood disorders via a survey. We analyzed changes in information needs over time relative to searches on MSD. Results Queries for MSD focused on side effects and their relation to the disease. We found evidence of significant changes in search behavior and interests coinciding with days that MSD queries are made. These include large increases (>100%) in the access of nutrition information, commercial information, and adult materials. A survey of patients diagnosed with mood disorders provided evidence that repeated queries on MSD may come with exacerbations of mood disorder. A classifier predicting the occurrence of such queries one day before they are observed obtains strong performance (AUC=0.78). Conclusions Observed patterns in search behavior align with known behaviors and those highlighted by survey respondents. These observations suggest that searchers showing intensive interest in MSD may be patients who have been prescribed these drugs. Given behavioral dynamics, we surmise that the days on which MSD queries are made may coincide with commencement of mania or depression. Although we do not have data on mood changes and whether users have been diagnosed with bipolar illness, we see evidence of cycling in people who show interest in MSD and further show that we can predict impending shifts in behavior and interest. PMID:24568936

Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics.

PubMed

Selle, V; Schalkwijk, S; Vázquez, G H; Baldessarini, R J

2014-03-01

Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants, second-generation antipsychotics, or lithium for acute major depressive episodes in patients diagnosed with type I or II bipolar disorder and applied random-effects meta-analysis to evaluate their efficacy, comparing outcomes based on standardized mean drug-placebo differences (SMD) in improvement, relative response rates (RR), and number-needed-to-treat (NNT). We identified 24 trials of 10 treatments (lasting 7.5 weeks, with ≥ 50 collaborating sites/trial) that met eligibility criteria: lamotrigine (5 trials), quetiapine (5), valproate (4), 2 each for aripiprazole, olanzapine, ziprasidone, and 1 each for carbamazepine, lithium, lurasidone, and olanzapine-fluoxetine. Overall, pooled drug-over-placebo responder-rate superiority (RR) was moderate (29% [CI: 19-40%]), and NNT was 8.2 (CI: 6.4-11). By SMD, apparent efficacy ranked: olanzapine + fluoxetine ≥ valproate > quetiapine > lurasidone > olanzapine, aripiprazole, and carbamazepine; ziprasidone was ineffective, and lithium remains inadequately studied. Notably, drugs were superior to placebo in only 11/24 trials (5/5 with quetiapine, 2/4 with valproate), and only lamotrigine, quetiapine and valproate had > 2 trials. Treatment-associated mania-like reactions were uncommon (drugs: 3.7%; placebo: 4.7%). Controlled trials of non-antidepressant treatments for bipolar depression remain scarce, but findings with olanzapine-fluoxetine, lurasidone, quetiapine, and perhaps carbamazepine and valproate were encouraging; lithium requires adequate testing. © Georg Thieme Verlag KG Stuttgart · New York.

Oculomotor and Neuropsychological Effects of Antipsychotic Treatment for Schizophrenia

PubMed Central

Hill, S. Kristian; Reilly, James L.; Harris, Margret S. H.; Khine, Tin; Sweeney, John A.

2008-01-01

Cognitive enhancement has become an important target for drug therapies in schizophrenia. Treatment development in this area requires assessment approaches that are sensitive to procognitive effects of antipsychotic and adjunctive treatments. Ideally, new treatments will have translational characteristics for parallel human and animal research. Previous studies of antipsychotic effects on cognition have relied primarily on paper-and-pencil neuropsychological testing. No study has directly compared neurophysiological biomarkers and neuropsychological testing as strategies for assessing cognitive effects of antipsychotic treatment early in the course of schizophrenia. Antipsychotic-naive patients with schizophrenia were tested before treatment with risperidone and again 6 weeks later. Matched healthy participants were tested over a similar time period. Test-retest reliability, effect sizes of within-subject change, and multivariate/univariate analysis of variance were used to compare 3 neurophysiological tests (visually guided saccade, memory-guided saccade, and antisaccade) with neuropsychological tests covering 4 cognitive domains (executive function, attention, memory, and manual motor function). While both measurement approaches showed robust neurocognitive impairments in patients prior to risperidone treatment, oculomotor biomarkers were more sensitive to treatment-related effects on neurocognitive function than traditional neuropsychological measures. Further, unlike the pattern of modest generalized cognitive improvement suggested by neuropsychological measures, the oculomotor findings revealed a mixed pattern of beneficial and adverse treatment-related effects. These findings warrant further investigation regarding the utility of neurophysiological biomarkers for assessing cognitive outcomes of antipsychotic treatment in clinical trials and in early-phase drug development. PMID:17932088

Gaze-fixation to happy faces predicts mood repair after a negative mood induction.

PubMed

Sanchez, Alvaro; Vazquez, Carmelo; Gomez, Diego; Joormann, Jutta

2014-02-01

The present study tested the interplay between mood and attentional deployment by examining attention to positive (i.e., happy faces) and negative (i.e., angry and sad faces) stimuli in response to experimental inductions of sad and happy mood. Participants underwent a negative, neutral, or positive mood induction procedure (MIP) which was followed by an assessment of their attentional deployment to emotional faces using eye-tracking technology. Faces were selected from the Karolinska Directed Emotional Faces (KDEF) database (Lundqvist, Flykt, & Öhman, 1998). In the positive MIP condition, analyses revealed a mood-congruent relation between positive mood and greater attentional deployment to happy faces. In the negative MIP condition, however, analyses revealed a mood-incongruent relation between increased negative mood and greater attentional deployment to happy faces. Furthermore, attentional deployment to happy faces after the negative MIP predicted participants' mood recovery at the end of the experimental session. These results suggest that attentional processing of positive information may play a role in mood repair, which may have important clinical implications. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Thiol Disulfide Homeostasis in Schizophrenic Patients Using Atypical Antipsychotic Drugs

PubMed Central

Ersan, Etem Erdal; Aydin, Hüseyin; Erdoğan, Serpil; Erşan, Serpil; Alişik, Murat; Bakir, Sevtap; Erel, Özcan; Koç, Derya

2018-01-01

Objective Schizophrenia is a severe, debilitating mental disorder characterized by behavioral abnormalities. Although several studies have investigated the role of oxidative stress and the effects of antipsychotic drugs on oxidative markers in schizophrenia, adequate information is not available on these issues. The aim of this study is to determine the changes in oxidative status and thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs. Methods Thirteen schizophrenic patients using atypical antipsychotic drugs and 30 healthy controls were included this study. The concentrations of total oxidant status (TOS), total antioxidant status (TAS), native thiol, total thiol, and disulfide levels were determined in the study population. Results The TAS (p=0.001), total thiol, and native thiol levels (p<0.001) were higher in the patients compared to the controls, whereas the TOS and disulfide levels were lower in the patients than in the controls (p<0.001). Conclusion These results may suggest that atypical antipsychotic drugs have a useful therapeutic effect by reducing oxidative stress via the inhibition of the formation of disulfide bonds. The study population number was one of the limitations of this study. Therefore, further studies are needed to establish the association between thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs. PMID:29397665

Chocolate: food for moods.

PubMed

Wong, S Y; Lua, P L

2011-08-01

Chocolate is a popular food and its consumption has long been associated with enjoyment and pleasure. The effect of chocolate on mood too has long been recognised. Chocolate is thought to have interactions with neurotransmitters which contribute to mood modulation and appetite regulation. However, the evidence in chocolate and mood studies remains highly controversial. As more is known about the influence of chocolate on mood, the reasons for these effects appear increasingly complex and inter-related. We reviewed chocolate's properties and the principal hypotheses addressing its mood altering propensities. The relationship between chocolate and mood are highly complex, combining psychopharmacological components, nutritional and sensory characteristics of the food. Individual and situational differences on chocolate consumption may also exert influence on mood and the mixed results in previous research indicate that the direction of the association remains unclear. The association between chocolate consumption and emotions warrants further multi-prong investigations to substantiate chocolate's mood alterating propensity.

Does mental health staffing level affect antipsychotic prescribing? Analysis of Italian national statistics.

PubMed

Starace, Fabrizio; Mungai, Francesco; Barbui, Corrado

2018-01-01

In mental healthcare, one area of major concern identified by health information systems is variability in antipsychotic prescribing. While most studies have investigated patient- and prescriber-related factors as possible reasons for such variability, no studies have investigated facility-level characteristics. The present study ascertained whether staffing level is associated with antipsychotic prescribing in community mental healthcare. A cross-sectional analysis of data extracted from the Italian national mental health information system was carried out. For each Italian region, it collects data on the availability and use of mental health facilities. The rate of individuals exposed to antipsychotic drugs was tested for evidence of association with the rate of mental health staff availability by means of univariate and multivariate analyses. In Italy there were on average nearly 60 mental health professionals per 100,000 inhabitants, with wide regional variations (range 21 to 100). The average rate of individuals prescribed antipsychotic drugs was 2.33%, with wide regional variations (1.04% to 4.01%). Univariate analysis showed that the rate of individuals prescribed antipsychotic drugs was inversely associated with the rate of mental health professionals available in Italian regions (Kendall's tau -0.438, p = 0.006), with lower rates of antipsychotic prescriptions in regions with higher rates of mental health professionals. After adjustment for possible confounders, the total availability of mental health professionals was still inversely associated with the rate of individuals exposed to antipsychotic drugs. The evidence that staffing level was inversely associated with antipsychotic prescribing indicates that any actions aimed at decreasing variability in antipsychotic prescribing need to take into account aspects related to the organization of the mental health system.

Summary of the comparative effectiveness review on off-label use of atypical antipsychotics.

PubMed

Maher, Alicia R; Theodore, George

2012-06-01

Conventional and atypical antipsychotic medications are approved by the FDA for treatment of schizophrenia and bipolar disorder. Over many decades, the widespread use of conventional antipsychotics produced various side effects requiring additional medications, such as the atypical antipsychotics. Beginning in 2006, 9 atypical antipsychotic drugs have been approved by the FDA for indications that were previously off-label uses: aripiprazole (as augmentation for major depressive disorder [MDD] and for autism spectrum disorders), asenapine, clozapine, iloperidone, olanzapine (in combination with fluoxetine for MDD and bipolar depression), paliperidone, quetiapine (quetiapine and quetiapine XR [extended release] as monotherapy in bipolar depression and quetiapine XR as augmentation for MDD), risperidone (for autism spectrum disorders), and ziprasidone. In 2006, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review on the comparative effectiveness of off-label uses of atypical antipsychotics. Since that time, numerous studies have been published evaluating these therapies in various new off-label uses; new or increased adverse effects have been observed with off-label uses; new atypical antipsychotics have been approved; and previously off-label uses have been approved for some atypical antipsychotics. Hence, AHRQ published an updated review in September 2011 that summarized the benefits and harms of atypical antipsychotics in the treatment of attention-deficit hyperactivity disorder/attention deficit disorder (ADHD), anxiety, behavioral disturbances of dementia and severe geriatric agitation, depression, eating disorders, insomnia, obsessive-compulsive disorder (OCD), personality disorder, post-traumatic stress disorder (PTSD), substance use and dependence disorders, and Tourette's syndrome. The new report also investigated topics for which data in the previous report were found to be insufficient to make conclusions, including

Patient, Physician and Organizational Influences on Variation in Antipsychotic Prescribing Behavior.

PubMed

Tang, Yan; Chang, Chung-Chou H; Lave, Judith R; Gellad, Walid F; Huskamp, Haiden A; Donohue, Julie M

2016-03-01

Physicians face the choice of multiple ingredients when prescribing drugs in many therapeutic categories. For conditions with considerable patient heterogeneity in treatment response, customizing treatment to individual patient needs and preferences may improve outcomes. To assess variation in the diversity of antipsychotic prescribing for mental health conditions, a necessary although not sufficient condition for personalizing treatment. To identify patient caseload, physician, and organizational factors associated with the diversity of antipsychotic prescribing. Using 2011 data from Pennsylvania's Medicaid program, IMS Health's HCOSTM database, and the AMA Masterfile, we identified 764 psychiatrists who prescribed antipsychotics to 10 patients. We constructed three physician-level measures of diversity/concentration of antipsychotic prescribing: number of ingredients prescribed, share of prescriptions for most preferred ingredient, and Herfindahl-Hirschman index (HHI). We used multiple membership linear mixed models to examine patient caseload, physician, and healthcare organizational predictors of physician concentration of antipsychotic prescribing. There was substantial variability in antipsychotic prescribing concentration among psychiatrists, with number of ingredients ranging from 2-17, share for most preferred ingredient from 16%-85%, and HHI from 1,088-7,270. On average, psychiatrist prescribing behavior was relatively diversified; however, 11% of psychiatrists wrote an average of 55% of their prescriptions for their most preferred ingredient. Female prescribers and those with smaller shares of disabled or serious mental illness patients had more concentrated prescribing behavior on average. Antipsychotic prescribing by individual psychiatrists in a large state Medicaid program varied substantially across psychiatrists. Our findings illustrate the importance of understanding physicians' prescribing behavior and indicate that even among specialties

Survey on schizophrenia treatment in Mexico: perception and antipsychotic prescription patterns

PubMed Central

Apiquian, Rogelio; Fresán, Ana; de la Fuente-Sandoval, Camilo; Ulloa, Rosa-Elena; Nicolini, Humberto

2004-01-01

Background Since the introduction of antipsychotics, especially the so called atypicals, the treatment of schizophrenia has shown important improvements. At the present time, it is preferred to label clozapine and other antipsychotics sharing similar profiles as second-generation antipsychotics (SGAs). These medications have been proposed by some experts as a first line treatment for schizophrenia. It is critical to have reliable data about antipsychotic prescription in Mexico and to create management guidelines based on expert meetings and not only on studies carried out by the pharmaceutical industry. Only this approach will help to make the right decisions for the treatment of schizophrenia. Methods A translated version of Rabinowitz's survey was used to evaluate antipsychotic prescription preferences and patterns in Mexican psychiatrists. The survey questionnaire was sent by mail to 200 psychiatrists from public institutions and private practice in Mexico City and Guadalajara, Mexico. Results Recommendations for antipsychotics daily doses at different stages of the treatment of schizophrenia varied widely. Haloperidol was considered as the first choice for the treatment of positive symptoms. On the contrary, risperidone was the first option for negative symptoms. For a patient with a high susceptibility for developing extrapyramidal symptoms (EPS), risperidone was the first choice. It was also considered that SGAs had advantages over typical antipsychotics in the management of negative symptoms, cognitive impairment and fewer EPS. Besides, there was a clear tendency for prescribing typical antipsychotics at higher doses than recommended and inadequate doses for the atypical ones. Conclusions Some of the obstacles for the prescription of SGAs include their high cost, deficient knowledge about their indications and dosage, the perception of their being less efficient for the treatment of positive symptoms and the resistance of some Mexican physicians to change

Mixed states in bipolar disorder - changes in DSM-5 and current treatment recommendations.

PubMed

Betzler, Felix; Stöver, Laura Apollonia; Sterzer, Philipp; Köhler, Stephan

2017-11-01

Mixed states in affective disorders represent a particular challenge in clinical routine, characterized by a complicated course of treatment and a worse treatment response. Clinical features of mixed states and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria are presented and critical discussed. We then performed a systematic review using the terms 'bipolar', 'mixed' and 'randomized' to evaluate current treatment options. For pharmacological treatment of mixed states in total, there is still insufficient data from RCTs. However, there is some evidence for efficacy in mixed states from RCTs for atypical antipsychotics, especially olanzapine, aripiprazole and asenapine as well as mood stabilizers as valproate and carbamazepine. Mixed states are of a high clinical relevance and the DSM-5 criteria substantially reduced the diagnostic threshold. Besides advantages of a better characterization of patients with former DSM-IV-defined mixed episodes, disadvantages arise for example differential diagnoses with a substantial overlap in symptoms such as borderline personality disorders. Atypical antipsychotics, valproate and carbamazepine demonstrated efficacy in a limited sample of RCTs. The number of RCTs in the treatment of mixed states is highly limited. Furthermore, nearly all studies were funded by pharmaceutical companies which may lead to an underestimation of classical mood stabilizers such as lithium.

[Ingesta de hidratos de carbono y ácidos grasos de la dieta en sujetos con esquizofrenia y trastorno bipolar, y su asociación con parámetros antropométricos].

PubMed

Santillana T, Natalia; Cavieres F, Álvaro; Vega S, Claudia

2016-09-01

People with psychiatric disorders have higher rates of obesity, diabetes mellitus and dyslipidemia. These comorbidities are associated with the underlying psychopathology and drug therapy. To determine the quality and quantity of carbohydrates and fatty acids in the diet and their association with anthropometric parameters in subjects with schizophrenia and bipolar disorders. We studied 30 patients with schizophrenia and bipolar disorders in treatment with atypical antipsychotics or mood stabilizers. Three 24-hour recall dietary surveys were carried out. Glycemic index, intake of carbohydrates and fatty acids (g/day) were calculated, and the ratio of saturated, monounsaturated and polyunsaturated fatty acids was determined. Body mass index, waist circumference (WC) and body fat percentage were evaluated. The average intakes of carbohydrates and fatty acids were 295 ± 111 and 73 ± 38 g/day respectively. The mean glycemic index was 59% ± 5.4, while the ratio of saturated, monounsaturated and polyunsaturated fatty acids was 2: 1.4: 0.6. No association between dietary and anthropometric variables was found. Patients using second-generation antipsychotics had a significantly higher waist circumference than those using mood stabilizing drugs. We found no association between the amount and quality of carbohydrate or fatty acid dietary intake and anthropometric parameters.

Energy under-reporting in adults with mood disorders: prevalence and associated factors.

PubMed

Davison, Karen M

2013-09-01

Little is known about relationships of energy under-reporting in mental health populations. Using data from a sample of individuals with mood disorders (n = 97), demographic, food intake and body-related, psychological, lifestyle, and condition-specific factors were examined in relationship to energy under-reporting. More than two-thirds (70%) were considered under-reporters based on Goldberg's classifications. Differences were found between energy under-reporters and accurate reporters for diet quality, sex, body mass index (BMI), weight change after taking psychiatric medications, and for those taking mood stabilizers (all p's < 0.05). Regression analyses indicated there was lower prevalence of under-reporting as diet quality improved, if individuals experienced weight change after taking psychiatric medication, or were females (p < 0.05). The prevalence of under-reporting was more than 1.3 times in those taking mood stabilizers versus those not taking this psychiatric medication [Prevalence ratio (PR) = 1.30, 95% CI 1.01-1.66, p < 0.05]. Further research of under-reporting in mental health populations will enable targeted approaches to improve accuracy of diet reporting and inferences made about nutrition and mental health.

Behavior Disorders in Persons with Mental Retardation Receiving Antipsychotic Medication.

ERIC Educational Resources Information Center

Ono, Yoshiro

1998-01-01

The behavior disorders of 54 Japanese individuals with mental retardation receiving antipsychotic medication were compared to 52 subjects receiving anticonvulsants and 202 subjects without medication. Results found the problem behaviors of subjects receiving antipsychotic drugs were more severe and severity of disability was associated with higher…

The impact of antipsychotic polytherapy costs in the public health care in Sao Paulo, Brazil.

PubMed

Razzouk, Denise; Kayo, Monica; Sousa, Aglaé; Gregorio, Guilherme; Cogo-Moreira, Hugo; Cardoso, Andrea Alves; Mari, Jair de Jesus

2015-01-01

Guidelines for the treatment of psychoses recommend antipsychotic monotherapy. However, the rate of antipsychotic polytherapy has increased over the last decade, reaching up to 60% in some settings. Studies evaluating the costs and impact of antipsychotic polytherapy in the health system are scarce. To estimate the costs of antipsychotic polytherapy and its impact on public health costs in a sample of subjects with psychotic disorders living in residential facilities in the city of Sao Paulo, Brazil. A cross-sectional study that used a bottom-up approach for collecting costs data in a public health provider's perspective. Subjects with psychosis living in 20 fully-staffed residential facilities in the city of Sao Paulo were assessed for clinical and psychosocial profile, severity of symptoms, quality of life, use of health services and pharmacological treatment. The impact of polytherapy on total direct costs was evaluated. 147 subjects were included, 134 used antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There were no significant differences in clinical and psychosocial characteristics between polytherapy and monotherapy groups. Four variables explained 30% of direct costs: the number of antipsychotics, location of the residential facility, time living in the facility and use of olanzapine. The costs of antipsychotics corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health services use when excluding accommodation costs. Olanzapine costs corresponded to 51% of all psychotropic costs. Antipsychotic polytherapy is a huge economic burden to public health service, despite the lack of evidence supporting this practice. Great variations on antipsychotic costs explicit the need of establishing protocols for rational antipsychotic prescriptions and consequently optimising resource allocation. Cost-effectiveness studies are necessary to estimate the best value for money among antipsychotics, especially in low and middle

The Impact of Antipsychotic Polytherapy Costs in the Public Health Care in Sao Paulo, Brazil

PubMed Central

Razzouk, Denise; Kayo, Monica; Sousa, Aglaé; Gregorio, Guilherme; Cogo-Moreira, Hugo; Cardoso, Andrea Alves; Mari, Jair de Jesus

2015-01-01

Introduction Guidelines for the treatment of psychoses recommend antipsychotic monotherapy. However, the rate of antipsychotic polytherapy has increased over the last decade, reaching up to 60% in some settings. Studies evaluating the costs and impact of antipsychotic polytherapy in the health system are scarce. Objective To estimate the costs of antipsychotic polytherapy and its impact on public health costs in a sample of subjects with psychotic disorders living in residential facilities in the city of Sao Paulo, Brazil. Method A cross-sectional study that used a bottom-up approach for collecting costs data in a public health provider´s perspective. Subjects with psychosis living in 20 fully-staffed residential facilities in the city of Sao Paulo were assessed for clinical and psychosocial profile, severity of symptoms, quality of life, use of health services and pharmacological treatment. The impact of polytherapy on total direct costs was evaluated. Results 147 subjects were included, 134 used antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There were no significant differences in clinical and psychosocial characteristics between polytherapy and monotherapy groups. Four variables explained 30% of direct costs: the number of antipsychotics, location of the residential facility, time living in the facility and use of olanzapine. The costs of antipsychotics corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health services use when excluding accommodation costs. Olanzapine costs corresponded to 51% of all psychotropic costs. Conclusion Antipsychotic polytherapy is a huge economic burden to public health service, despite the lack of evidence supporting this practice. Great variations on antipsychotic costs explicit the need of establishing protocols for rational antipsychotic prescriptions and consequently optimising resource allocation. Cost-effectiveness studies are necessary to estimate the best value for money

Side effect burden of antipsychotic drugs in real life - Impact of gender and polypharmacy.

PubMed

Iversen, Trude Seselie Jahr; Steen, Nils Eiel; Dieset, Ingrid; Hope, Sigrun; Mørch, Ragni; Gardsjord, Erlend Strand; Jørgensen, Kjetil Nordbø; Melle, Ingrid; Andreassen, Ole A; Molden, Espen; Jönsson, Erik G

2018-03-02

Antipsychotic-associated side effects are well known and represent a significant treatment challenge. Still, few large studies have investigated the overall side effect burden of antipsychotics in real-life settings. To describe the occurrence of side effects and perceived burden of antipsychotics in a large naturalistic sample, taking polypharmacy and patient characteristics into account. Patients (n=1087) with psychotic disorders were assessed for side effects using the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale in addition to assessment of clinical and pharmacological data. Statistical analyses were performed controlling for possible confounding factors. Use of antipsychotics showed significant associations to neurologic and sexual symptoms, sedation and weight gain, and >75% of antipsychotics-users reported side effects. More side effects were observed in patients using several antipsychotics (p=0.002), with increasing total dose (p=0.021) and with antipsychotics in combinations with other psychotropic drugs. Patients and investigators evaluated the side effect burden differently, particularly related to severity, gender and antipsychotics dose. Twice as many females described side effect burden as severe (p=0.004). Patients with psychotic disorders have a high occurrence of symptoms associated with use of antipsychotics, and polypharmacy and female gender are seemingly risk factors for reporting a severe side effect burden. Due to the cross-sectional design evaluation of causality is tentative, and these findings should be further investigated in prospective studies. Copyright © 2017 Elsevier Inc. All rights reserved.

A Pilot Study Investigating TNF-α as a Potential Intervening Variable of Atypical Antipsychotic Associated Metabolic Syndrome in Bipolar Disorder

PubMed Central

Prossin, A. R.; Zalcman, S. S.; Evans, S. J.; McInnis, M. G.; Ellingrod, V. L.

2013-01-01

Background Strong associations exist between tumor necrosis factor-α (TNF-α) and metabolic syndrome (MetS). While TNF-α is associated with Bipolar depression, its role in atypical antipsychotic (AAP) associated MetS in Bipolar Disorder (BD) is unclear. Here we investigate the potential intervening role TNF-α in the indirect relationship between AAP treatment and MetS in BD. Materials and Methods Using a cross-sectional design, 99 euthymic BD volunteers were stratified by presence/absence of MetS (NCEP-ATP-III). Serum TNF-α concentration, determined via chemiluminescent immunometric assays, was compared between groups (i.e. MetS or no MetS). We investigated the intervening effect of TNF-α on the relation between AAP treatment and MetS in BD using regression techniques. Results Treatment with antipsychotics believed associated with a higher risk for MetS (i.e. AAPs; olanzapine, quetiapine, risperidone, paliperidone, clozapine), was found to be associated with significantly greater TNF-α (F1,88=11.2, p=0.001, mean difference of 1.7 +/− 0.51) and a higher likelihood of MetS (F1,88=4.5, p=0.036) than in those not receiving treatment with an AAP. Additionally, TNF-α was greater (trending towards significance; T52=2.0, p=0.05) in BD volunteers with MetS and was found to have a statistically significant effect on the indirect relationship between AAP treatment and elevated waist circumference in these BD volunteers. Discussion These results identify TNF-α as a potential intervening variable of AAP associated MetS in BD, not previously identified in this population. Future prospective studies could assess the predictive potential of TNF-α in determining risk of AAP associated MetS in BD. Given previous evidence relating TNF-α and mood state in BD, this study increases the importance in understanding the role of TNF-α in “mind-body” interactions and renews discussions of the utility of research into the clinical efficacy of TNF-α antagonist treatment in

Antipsychotic Treatment Reduces Indices of Oxidative Stress in First-Episode Psychosis Patients

PubMed Central

Haring, Liina; Vasar, Eero; Vasar, Veiko; Zilmer, Mihkel

2016-01-01

38 first-episode psychosis (FEP) patients and 37 control subjects were recruited for the study of indices of oxidative stress (OxS). The main purpose of the study was to compare the OxS statuses (serum total antioxidant capacity (TAC), total level of peroxides (TPX), oxidative stress index (OSI), and ratio oxidized methionine (Met-SO) to methionine (Met)) between antipsychotic-naïve FEP patients and individuals without a history of psychiatric disorders. Subsequently, the impact of 7-month antipsychotic treatment was evaluated on the OxS status in FEP patients. An attempt was made to assess links between OxS signature and inflammation markers. The oxidative stress indices remained generally unchanged in antipsychotic-naïve FEP patients compared to control subjects. Despite that, there was a significant correlation between the levels of TPX and EGF (endothelial growth factor) in FEP patients. This correlation disappeared after antipsychotic treatment of FEP patients. Moreover, antipsychotic treatment was associated with a significant reduction in OxS indices, including TPX, OSI, and ratio between Met-SO and Met. By contrast, in chronic SCZ patients we established a significant high-grade OxS. In conclusion, the markers of total antioxidative capacity, lipid peroxidation, and protein oxidation revealed no high-grade OxS in FEP patients. Nevertheless, antipsychotic treatment induced a considerable anti-inflammatory effect. OxS levels were also significantly decreased if compared in FEP patients before and after antipsychotic treatment. PMID:27528889

Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: nuances and pragmatics of the association

PubMed Central

Sarkar, Siddharth; Gupta, Nitin

2017-01-01

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal adverse event associated with the use of antipsychotics. Although atypical antipsychotics were initially considered to carry no risk of NMS, reports have accumulated over time implicating them in NMS causation. Almost all atypical antipsychotics have been reported to be associated with NMS. The clinical profile of NMS caused by certain atypical antipsychotics such as clozapine has been reported to be considerably different from the NMS produced by typical antipsychotics, with diaphoresis encountered more commonly, and rigidity and tremor encountered less frequently. This article briefly discusses the evidence relating to the occurrence, presentation and management of NMS induced by atypical antipsychotics. PMID:28811916

Mood effects on attitude judgments: independent effects of mood before and after message elaboration.

PubMed

Bless, H; Mackie, D M; Schwarz, N

1992-10-01

This study investigated the independent effects of induced mood on the encoding of persuasive messages and on the assessment of attitude judgments. In Experiment 1, positive or negative mood was induced either before the encoding of a counterattitudinal message or before the assessment of attitude judgments. When mood was induced before message presentation, Ss in a bad mood were more persuaded by strong than by weak arguments, whereas Ss in a good mood were equally persuaded by strong and by weak arguments. When Ss encoded the message in a neutral mood, however, the advantage of strong over weak arguments was more pronounced when Ss were in a good rather than in a bad mood at the time of attitude assessment. In Experiment 2, Ss exposed to a counterattitudinal message composed of either strong or weak arguments formed either a global evaluation or a detailed representation of the message. Positive, negative, or neutral mood was then induced. Ss in a good mood were most likely and Ss in a negative mood least likely to base their reported attitudes on global evaluations.

Neuromotor Adverse Effects in 342 Youth During 12 Weeks of Naturalistic Treatment With 5 Second-Generation Antipsychotics.

PubMed

Carbon, Maren; Kapoor, Sandeep; Sheridan, Eva; Al-Jadiri, Aseel; Azzo, Sally; Sarkaria, Tania; Kane, John M; Saito, Ema; Correll, Christoph U

2015-09-01

Second-generation antipsychotic (SGA) effects in youth were monitored to quantify extrapyramidal side effects (EPS) and to identify risk profiles for treatment-emergent EPS. Data were analyzed for the nonrandomized, prospective Second-generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) inception cohort study. EPS were assessed at baseline and 4, 8, and 12 weeks after naturalistic SGA initiation for schizophrenia, mood, disruptive behavior, and autism spectrum disorders using the Simpson-Angus Scale (SAS), Barnes Akathisia Scale, Abnormal Involuntary Movement Scale (AIMS), and Treatment Emergent Side Effect Scale. Drug-induced parkinsonism was defined by incident mean SAS score >0.33, anticholinergic initiation, or increasing total SAS score ≥2 in patients with baseline EPS. In 342 youth aged 13.6 ± 3.5 years (male = 58.2%, antipsychotic-naive = 65.8%), 15.2% developed drug-induced parkinsonism. Raw SGA-grouped drug-induced parkinsonism rates were as follows: quetiapine = 1.5%, olanzapine = 13.8%, risperidone = 16.1%, ziprasidone = 20.0%, and aripiprazole = 27.3%. SGA type, dose, higher age, and lower baseline functioning were jointly associated with drug-induced parkinsonism (R(2) = 0.18; p < .0001). Controlling for these factors, drug-induced parkinsonism rates were significantly lower only for quetiapine and olanzapine. Subjectively reported EPS (5%), EPS-related treatment discontinuation (3.3%), and anticholinergic initiation (3%) were infrequent. Anticholinergic initiation was most frequent with risperidone (10.2%; p = .0004). Treatment-emergent dyskinesia ranged from 4.5% (aripiprazole) to 15.5% (olanzapine). SGA type, younger age, white race/ethnicity, and baseline AIMS were jointly associated with treatment-emergent dyskinesia (R(2) = 0.31; p < .0001). Controlling for these factors, treatment-emergent dyskinesia rates differed among SGA subgroups, with higher rates with olanzapine and ziprasidone. At baseline

Doubtful association of antipsychotic polypharmacy and high dosage with cognition in chronic schizophrenia.

PubMed

Kontis, Dimitrios; Theochari, Eirini; Kleisas, Spyridon; Kalogerakou, Stamatina; Andreopoulou, Angeliki; Psaras, Rafael; Makris, Yannis; Karouzos, Charalambos; Tsaltas, Eleftheria

2010-10-01

Despite consistent recommendations for antipsychotic monotherapy, antipsychotic polypharmacy (the use of two or more antipsychotic agents) and the administration of excessive doses (higher than 1000 mgr/day of chloropromazine equivalents) is a common practice in schizophrenia. The therapeutic and adverse effects of this practice are poorly studied, in particular with regards to the cognitive symptoms of the disease. In this cross-sectional study we investigated the cognitive effects of antipsychotic polypharmacy and excessive doses in 53 patients with chronic schizophrenia using non-verbal cognitive tasks involving speed of movement, memory and executive functions. No significant difference in performance scores was found between the groups under polypharmacy and monotherapy, or the groups receiving either excessive or normal doses of antipsychotics. Since these groups did not also differ in demographic, clinical, other pharmacologic parameters, in the relative anticholinergic potency of antipsychotics, or in intelligence scores, we raise doubts about the association of polypharmacy and excessive doses with non-verbal cognitive performance in chronic schizophrenia. Copyright © 2010 Elsevier Inc. All rights reserved.

Metabolic effects of antipsychotics in prepubertal children: a retrospective chart review.

PubMed

Ebert, Tanya; Midbari, Yael; Shmilovitz, Ronen; Kosov, Ira; Kotler, Moshe; Weizman, Abraham; Ram, Anca

2014-05-01

Antipsychotics, especially atypical ones, are in common use in children and adolescents with psychotic or affective spectrum disorders, as well as in various other psychopathologies. The adverse effects of atypical antipsychotics in children and adolescents are similar to those seen in adults, and include weight gain, elevated blood glucose levels, and hyperlipidemia. In this retrospective chart review, we compared these adverse events in children who were treated with typical, atypical, or no antipsychotic treatment. The medical charts of 72 children, 65 boys and 7 girls, were reviewed. All children were 6-13 years old (mean age 9.5±1.7 years). In total, 48 children received antipsychotic treatment, and 24 children were in the control group. Data were extracted from the medical charts, including weight, height, body mass index (BMI), blood pressure, aspartate transaminase (AST), alanine transaminase (ALT), triglycerides, total cholesterol, and glucose blood levels. We examined the values in the beginning of the antipsychotic treatment and at release from the hospital in the study group, and at admission and in the end of the drug-free period or at release from the hospital (a duration of at least 4 weeks) in the control group. The average weight gain was 3.9±3.8 kg in the atypical antipsychotic treatment (AAT) group, 1.1±4.4 kg in the typical antipsychotic treatment (TAT) group, and 0.23±2.9 kg in the control group. The average increase in BMI was 15.1±22.0 percentiles in the AAT group, 6.4±14.2 percentiles in the TAT group, and 1.6±12.5 percentiles in the control group. No statistically significant difference was found in the increase in height percentile. There were no significant differences in the rates of elevated values of serum triglycerides, cholesterol, AST, ALT, or fasting blood glucose. We found a significant increase in both absolute weight gain and BMI percentile following atypical antipsychotic treatment. In contrast, typical

Dopamine and incentive learning: a framework for considering antipsychotic medication effects.

PubMed

Beninger, Richard J

2006-12-01

Hyperfunction of brain dopamine (DA) systems is associated with psychosis in schizophrenia and the medications used to treat schizophrenia are DA receptor blockers. DA also plays a critical role in incentive learning produced by rewarding stimuli. Using DA as the link, these results suggest that psychosis in schizophrenia can be understood from the point of view of excessive incentive learning. Incentive learning is mediated through the non-declarative memory system and may rely on the striatum or medial prefrontal cortex depending on the task. Typical and atypical antipsychotics differentially affect expression of the immediate early gene c-fos, producing greater activity in the striatum and medial prefrontal cortex, respectively. This led to the hypothesis that performance of schizophrenic patients on tasks that depend on the striatum or medial prefrontal cortex will be differentially affected by their antipsychotic medication. Results from a number of published papers supported this dissociation. Furthermore, the effects of two atypical drugs, clozapine and olanzapine, on c-fos expression were different from another atypical, risperidone that resembles the typical antipsychotics. Similarly, in tests of incentive learning, risperidone acted like the typical antipsychotics. Thus, typical and atypical antipsychotic drugs differed in the types of cognitive performance they affected and, furthermore, members of the atypical class differed in their effects on cognition. It remains the task of researchers and clinicians to sort out the symptoms associated with the endogenous illness from possible iatrogenic symptoms resulting from the antipsychotic medications used to treat schizophrenia.

Usefulness of atypical antipsychotics and choline esterase inhibitors in delirium: a review.

PubMed

Grover, S; Mattoo, S K; Gupta, N

2011-03-01

Delirium is characterized by disturbances of consciousness, attention, cognition, perception, emotions, sleep, and psychomotor activity. Management of delirium involves ensuring safety, improving functioning, identifying and treating the illness underlying the delirium, and use of antipsychotics or benzodiazepines to control behavioural symptoms and prevent mortality. Haloperidol continues to be the most commonly used antipsychotic in delirium. However, in recent times data have emerged which suggest that atypical antipsychotics may be as efficacious as haloperidol in the treatment of delirium. This review intends to review the data with respect to usefulness of atypical antipsychotics in the treatment of delirium. Besides atypical antipsychotics, data with respect to another group of medications - cholinesterase inhibitors are also reviewed. Electronic and manual searches were conducted to identify all the relevant studies and case reports/case series. Evidence suggests that risperidone, olanzapine and quetiapine are as efficacious as haloperidol in the treatment of delirium but have lesser side effects. Data for other atypical antipsychotics are scarce. The data on cholinesterase inhibitors for treatment and prevention of delirium are beginning to accumulate, but do not seem to be convincing. Our review suggests that risperidone, olanzapine and quetiapine are good alternatives to haloperidol in the treatment of delirium. © Georg Thieme Verlag KG Stuttgart · New York.

Incidence of tardive dyskinesia with atypical versus conventional antipsychotic medications: a prospective cohort study.

PubMed

Woods, Scott W; Morgenstern, Hal; Saksa, John R; Walsh, Barbara C; Sullivan, Michelle C; Money, Roy; Hawkins, Keith A; Gueorguieva, Ralitza V; Glazer, William M

2010-04-01

Most previous studies of the incidence of tardive dyskinesia with atypical antipsychotics compared with conventional antipsychotics have not had tardive dyskinesia as their primary focus. The current study aimed to compare the incidence of tardive dyskinesia with atypical vs conventional antipsychotics using methods similar to those from a previous prospective cohort study at our site in the 1980s. Three hundred fifty-two initially tardive dyskinesia-free psychiatric outpatients (diagnosed at baseline using the Structured Clinical Interview for DSM-IV) were examined for a new diagnosis of tardive dyskinesia (using the Abnormal Involuntary Movement Scale and Glazer-Morgenstern criteria) every 6 months for up to 4 years at a community mental health center. At baseline, subjects were receiving conventional antipsychotics only (23%), atypicals only (64%), or both (14%). Only 26 subjects had never received conventional antipsychotics. Baseline evaluations were conducted from November 2000 through May 2003. Follow-ups were conducted through February 2005. Compared with subjects treated with conventional antipsychotics alone since the previous visit, the adjusted tardive dyskinesia incidence rate-ratio for subjects treated with atypical antipsychotics alone was 0.68 (95% CI, 0.29-1.64). The incidence and prevalence of tardive dyskinesia was similar to previous findings at this site in the 1980s. The incidence of tardive dyskinesia with recent exposure to atypical antipsychotics alone was more similar to that for conventional antipsychotics than in most previous studies. Despite high penetration of atypical antipsychotics into clinical practice, the incidence and prevalence of tardive dyskinesia appeared relatively unchanged since the 1980s. Clinicians should continue to monitor for tardive dyskinesia, and researchers should continue to pursue efforts to treat or prevent it. Copyright 2010 Physicians Postgraduate Press, Inc.

Prophylactic antipsychotic use for postoperative delirium: a systematic review and meta-analysis.

PubMed

Hirota, Tomoya; Kishi, Taro

2013-12-01

Although antipsychotics have been used empirically to prevent the development of postoperative delirium, there has been no confirming evidence to support their use. Thus, we conducted a systematic review and a meta-analysis to elucidate their efficacy and tolerability in surgical patients. MEDLINE, EMBASE, the Cochrane Library databases, CINAHL, and PsycINFO were searched up to February 2013 without language restrictions, using the following keywords: (antipsychotics OR [nonproprietary name of each antipsychotic medication, separated by OR]) AND delirium AND (randomized OR random OR randomly). Randomized controlled trials comparing prophylactic use of antipsychotics with placebo in surgical patients were included. Two authors extracted and scrutinized the data. The risk ratio (RR), 95% confidence interval (CI), number needed to treat (NNT), and standardized mean difference were used. Six studies (3 haloperidol, 1 olanzapine, and 2 risperidone) including 1,689 surgical patients were identified. The results showed significant efficacy in reducing the occurrence of delirium (RR = 0.50, 95% CI = 0.34 to 0.73, P = .0003; NNT = 7, P = .001, 6 studies). Sensitivity analysis showed that second-generation antipsychotics were superior to placebo (RR = 0.36, P < .00001; NNT = 4, P < .00001), whereas haloperidol failed to show superiority to placebo. There were no statistically significant differences between groups in severity of delirium, discontinuation rate, or rates of several adverse events. Our results suggest that second-generation antipsychotics are more beneficial than placebo for preventing the incidence of delirium. Among patients who do develop delirium, the severity of delirium is not reduced in those who received prophylactic antipsychotics. © Copyright 2013 Physicians Postgraduate Press, Inc.

Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers

PubMed Central

Pappas, Andrea L.; Bey, Alexandra L.; Wang, Xiaoming; Rossi, Mark; Kim, Yong Ho; Yan, Haidun; Porkka, Fiona; Duffney, Lara J.; Phillips, Samantha M.; Cao, Xinyu; Ding, Jin-dong; Rodriguiz, Ramona M.; Yin, Henry H.; Wetsel, William C.

2017-01-01

Genetic defects in the synaptic scaffolding protein gene, SHANK2, are linked to a variety of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, intellectual disability, and bipolar disorder, but the molecular mechanisms underlying the pleotropic effects of SHANK2 mutations are poorly understood. We generated and characterized a line of Shank2 mutant mice by deleting exon 24 (Δe24). Shank2Δe24–/– mice engage in significantly increased locomotor activity, display abnormal reward-seeking behavior, are anhedonic, have perturbations in circadian rhythms, and show deficits in social and cognitive behaviors. While these phenotypes recapitulate the pleotropic behaviors associated with human SHANK2-related disorders, major behavioral features in these mice are reminiscent of bipolar disorder. For instance, their hyperactivity was augmented with amphetamine but was normalized with the mood stabilizers lithium and valproate. Shank2 deficiency limited to the forebrain recapitulated the bipolar mania phenotype. The composition and functions of NMDA and AMPA receptors were altered at Shank2-deficient synapses, hinting toward the mechanism underlying these behavioral abnormalities. Human genetic findings support construct validity, and the behavioral features in Shank2 Δe24 mice support face and predictive validities of this model for bipolar mania. Further genetic studies to understand the contribution of SHANK2 deficiencies in bipolar disorder are warranted. PMID:29046483

Metabolic Signature of Antipsychotics Used in the Treatment of Autism

DTIC Science & Technology

2015-10-01

4. TITLE AND SUBTITLE Metabolic Signature of Antipsychotics used in the Treatment of Autism Metabolic Signature of Antipsychotics used in the...treatment of autism 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0611 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Nira Ben-Jonathan 5d. PROJECT NUMBER

Staff Knowledge of the Side Effects of Anti-Psychotic Medication

ERIC Educational Resources Information Center

Fretwell, Christine; Felce, David

2007-01-01

Background: Anti-psychotic medications are widely prescribed to people with intellectual disabilities and have a range of negative side effects. The aim was to identify the level of knowledge of anti-psychotic medications and their side effects among key carers or home managers of adults with intellectual disabilities living in residential group…

Targeting Glutamatergic Signaling for the Development of Novel Therapeutics for Mood Disorders

PubMed Central

Machado-Vieira, R.; Salvadore, G.; Ibrahim, L.; DiazGranados, N.; Zarate, C.A.

2009-01-01

There have been no recent advances in drug development for mood disorders in terms of identifying drug targets that are mechanistically distinct from existing ones. As a result, existing antidepressants are based on decades-old notions of which targets are relevant to the mechanisms of antidepressant action. Low rates of remission, a delay of onset of therapeutic effects, continual residual depressive symptoms, relapses, and poor quality of life are unfortunately common in patients with mood disorders. Offering alternative options is requisite in order to reduce the individual and societal burden of these diseases. The glutamatergic system is a promising area of research in mood disorders, and likely to offer new possibilities in therapeutics. There is increasing evidence that mood disorders are associated with impairments in neuroplasticity and cellular resilience, and alterations of the glutamatergic system are known to play a major role in cellular plasticity and resilience. Existing antidepressants and mood stabilizers have prominent effects on the glutamate system, and modulating glutamatergic ionotropic or metabotropic receptors results in antidepressant-like properties in animal models. Several glutamatergic modulators targeting various glutamate components are currently being studied in the treatment of mood disorders, including release inhibitors of glutamate, N-methyl-D-aspartate (NMDA) antagonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) throughput enhancers, and glutamate transporter enhancers. This paper reviews the currently available knowledge regarding the role of the glutamatergic system in the etiopathogenesis of mood disorders and putative glutamate modulators. PMID:19442176

Creative mood swings: divergent and convergent thinking affect mood in opposite ways.

PubMed

Akbari Chermahini, Soghra; Hommel, Bernhard

2012-09-01

Increasing evidence suggests that emotions affect cognitive processes. Recent approaches have also considered the opposite: that cognitive processes might affect people's mood. Here we show that performing and, to a lesser degree, preparing for a creative thinking task induce systematic mood swings: Divergent thinking led to a more positive mood, whereas convergent thinking had the opposite effect. This pattern suggests that thought processes and mood are systematically related but the type of relationship is process-specific.

Antipsychotic Medication Prescription Patterns in Adults with Developmental Disabilities Who Have Experienced Psychiatric Crisis

ERIC Educational Resources Information Center

Lunsky, Yona; Elserafi, Jonny

2012-01-01

Antipsychotic medication rates are high in adults with developmental disability. This study considered rates of antipsychotic use in 743 adults with developmental disability who had experienced a psychiatric crisis. Nearly half (49%) of these adults were prescribed antipsychotics. Polypharmacy was common with 22% of those prescribed antipsychotics…

Patient, Physician and Organizational Influences on Variation in Antipsychotic Prescribing Behavior

PubMed Central

Tang, Yan; Chang, Chung-Chou H.; Lave, Judith R.; Gellad, Walid F.; Huskamp, Haiden A.; Donohue, Julie M.

2016-01-01

Background Physicians face the choice of multiple ingredients when prescribing drugs in many therapeutic categories. For conditions with considerable patient heterogeneity in treatment response, customizing treatment to individual patient needs and preferences may improve outcomes. Aims of the Study To assess variation in the diversity of antipsychotic prescribing for mental health conditions, a necessary although not sufficient condition for personalizing treatment. To identify patient caseload, physician, and organizational factors associated with the diversity of antipsychotic prescribing. Methods Using 2011 data from Pennsylvania’s Medicaid program, IMS Health’s HCOS™ database, and the AMA Masterfile, we identified 764 psychiatrists who prescribed antipsychotics to ≥10 patients. We constructed three physician-level measures of diversity/concentration of antipsychotic prescribing: number of ingredients prescribed, share of prescriptions for most preferred ingredient, and Herfindahl-Hirschman index (HHI). We used multiple membership linear mixed models to examine patient caseload, physician, and healthcare organizational predictors of physician concentration of antipsychotic prescribing. Results There was substantial variability in antipsychotic prescribing concentration among psychiatrists, with number of ingredients ranging from 2-17, share for most preferred ingredient from 16%-85%, and HHI from 1,088-7,270. On average, psychiatrist prescribing behavior was relatively diversified; however, 11% of psychiatrists wrote an average of 55% of their prescriptions for their most preferred ingredient. Female prescribers and those with smaller shares of disabled or serious mental illness patients had more concentrated prescribing behavior on average. Discussion Antipsychotic prescribing by individual psychiatrists in a large state Medicaid program varied substantially across psychiatrists. Our findings illustrate the importance of understanding physicians�

Antipsychotic medications and dental caries in newly diagnosed schizophrenia: A nationwide cohort study.

PubMed

Hu, Kai-Fang; Chou, Yu-Hsiang; Wen, Yen-Hsia; Hsieh, Kun-Pin; Tsai, Jui-Hsiu; Yang, Pinchen; Yang, Yi-Hsin; Lin, Chun-Hung Richard

2016-11-30

We investigated the association between antipsychotic medications and the risk of dental caries in patients with schizophrenia. We enroled a nationwide cohort of patients with newly diagnosed schizophrenia within 1 year of dental caries development. Exposure to antipsychotics and other medications was categorised according to their type and duration, and the association between exposure and dental caries was assessed through logistic regressions. Of the 3610 patients with newly diagnosed schizophrenia, 2149 (59.5%) exhibited an incidence of treated dental caries. Logistic regression analysis identified a younger age, female sex, high income, a 2-year history of dental caries, and exposure to first-generation antipsychotics, and antihypertensives as independent risk factors for treated dental caries in patients with schizophrenia. Hyposalivation, the adverse effect of first-generation antipsychotics and antihypertensives, was associated with an increased risk of treated dental caries. However, hypersalivation from first-generation antipsychotics for dental caries was associated with a protective factor. These findings suggest that clinicians should pay attention to the aforementioned risk factors for dental caries in patients with schizophrenia, particularly while prescribing first-generation antipsychotics and antihypertensives to such patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sexual dysfunction with antihypertensive and antipsychotic agents.

PubMed

Smith, P J; Talbert, R L

1986-05-01

The physiology of the normal sexual response, epidemiology of sexual dysfunction, and the pharmacologic mechanisms involved in antihypertensive- and antipsychotic-induced problems with sexual function are discussed, with recommendations for patient management. The physiologic mechanisms involved in the normal sexual response include neurogenic, psychogenic, vascular, and hormonal factors that are coordinated by centers in the hypothalamus, limbic system, and cerebral cortex. Sexual dysfunction is frequently attributed to antihypertensive and antipsychotic agents and is a cause of noncompliance. Drug-induced effects include diminished libido, delayed orgasm, ejaculatory disturbances, gynecomastia, impotence, and priapism. The pharmacologic mechanisms proposed to account for these adverse effects include adrenergic inhibition, adrenergic-receptor blockade, anticholinergic properties, and endocrine and sedative effects. The most frequently reported adverse effect on sexual function with the antihypertensive agents is impotence. It is seen most often with methyldopa, guanethidine, clonidine, and propranolol. In contrast, the most common adverse effect on sexual function with the antipsychotic agents involves ejaculatory disturbances. Thioridazine, with its potent anticholinergic and alpha-blocking properties, is cited most often. Drug-induced sexual dysfunction may be alleviated by switching to agents with dissimilar mechanisms to alter the observed adverse effect while maintaining adequate control of the patient's disease state.

The role of NMDA receptors in the pathophysiology and treatment of mood disorders.

PubMed

Ghasemi, Mehdi; Phillips, Cristy; Trillo, Ludwig; De Miguel, Zurine; Das, Devsmita; Salehi, Ahmad

2014-11-01

Mood disorders such as major depressive disorder and bipolar disorder are chronic and recurrent illnesses that cause significant disability and affect approximately 350 million people worldwide. Currently available biogenic amine treatments provide relief for many and yet fail to ameliorate symptoms for others, highlighting the need to diversify the search for new therapeutic strategies. Here we present recent evidence implicating the role of N-methyl-D-aspartate receptor (NMDAR) signaling in the pathophysiology of mood disorders. The possible role of NMDARs in mood disorders has been supported by evidence demonstrating that: (i) both BPD and MDD are characterized by altered levels of central excitatory neurotransmitters; (ii) NMDAR expression, distribution, and function are atypical in patients with mood disorders; (iii) NMDAR modulators show positive therapeutic effects in BPD and MDD patients; and (iv) conventional antidepressants/mood stabilizers can modulate NMDAR function. Taken together, this evidence suggests the NMDAR system holds considerable promise as a therapeutic target for developing next generation drugs that may provide more rapid onset relief of symptoms. Identifying the subcircuits involved in mood and elucidating the role of NMDARs subtypes in specific brain circuits would constitute an important step toward the development of more effective therapies with fewer side effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mood and the market: can press reports of investors' mood predict stock prices?

PubMed

Cohen-Charash, Yochi; Scherbaum, Charles A; Kammeyer-Mueller, John D; Staw, Barry M

2013-01-01

We examined whether press reports on the collective mood of investors can predict changes in stock prices. We collected data on the use of emotion words in newspaper reports on traders' affect, coded these emotion words according to their location on an affective circumplex in terms of pleasantness and activation level, and created indices of collective mood for each trading day. Then, by using time series analyses, we examined whether these mood indices, depicting investors' emotion on a given trading day, could predict the next day's opening price of the stock market. The strongest findings showed that activated pleasant mood predicted increases in NASDAQ prices, while activated unpleasant mood predicted decreases in NASDAQ prices. We conclude that both valence and activation levels of collective mood are important in predicting trend continuation in stock prices.

Attitudes towards the administration of long-acting antipsychotics: a survey of physicians and nurses

PubMed Central

2013-01-01

Background Discontinuation of antipsychotic treatment for schizophrenia can interrupt improvement and exacerbate the illness. Reasons for discontinuing treatment are multifactorial and include adherence, efficacy and tolerability issues. Poor adherence may be addressed through non-pharmacological approaches as well as through pharmacological ones, ie ensured delivery of medication, such as that achieved with long-acting injectable (LAI) antipsychotics. However, attitudes of healthcare professionals (HCPs) towards LAI antipsychotics may influence their prescribing decisions and may influence medication choices offered to patients. We therefore conducted a survey to investigate factors driving LAI use as well as physician and nurse attitudes to LAI antipsychotics and to different injection sites. Methods An independent market research agency conducted the survey of HCPs across Europe. Participants were recruited by telephone and completed the survey online. Using conjoint analyses (a multivariate statistical technique analysing preferences on the basis of ranking a limited number of attributes which are presented repetitively), attitudes to oral versus LAI medication and gluteal versus deltoid injection routes were assessed. Results A total of 891 HCPs across Europe were surveyed. Of these, 40% would choose LAI antipsychotics for first episode patients whereas 90% would select LAI antipsychotics for chronic patients with two to five psychotic episodes. Dominant elements in antipsychotic choice were low sedation but no tardive dyskinesia, no or mild pain at injection and low risk of embarrassment or impact upon therapeutic alliance. Eighty-six per cent of respondents considered that having the choice of a deltoid as well as gluteal administration site was beneficial over not having that choice. Two thirds of respondents said they agreed that medication administration via the deltoid muscle may reduce social embarrassment associated with LAI antipsychotics and most

Ecological Momentary Assessment of Mood Disorders and Mood Dysregulation

ERIC Educational Resources Information Center

Ebner-Priemer, Ulrich W.; Trull, Timothy J.

2009-01-01

In this review, we discuss ecological momentary assessment (EMA) studies on mood disorders and mood dysregulation, illustrating 6 major benefits of the EMA approach to clinical assessment: (a) Real-time assessments increase accuracy and minimize retrospective bias; (b) repeated assessments can reveal dynamic processes; (c) multimodal assessments…

Therapeutic Potential of Mood Stabilizers Lithium and Valproic Acid: Beyond Bipolar Disorder

PubMed Central

Chiu, Chi-Tso; Wang, Zhifei; Hunsberger, Joshua G.

2013-01-01

The mood stabilizers lithium and valproic acid (VPA) are traditionally used to treat bipolar disorder (BD), a severe mental illness arising from complex interactions between genes and environment that drive deficits in cellular plasticity and resiliency. The therapeutic potential of these drugs in other central nervous system diseases is also gaining support. This article reviews the various mechanisms of action of lithium and VPA gleaned from cellular and animal models of neurologic, neurodegenerative, and neuropsychiatric disorders. Clinical evidence is included when available to provide a comprehensive perspective of the field and to acknowledge some of the limitations of these treatments. First, the review describes how action at these drugs’ primary targets—glycogen synthase kinase-3 for lithium and histone deacetylases for VPA—induces the transcription and expression of neurotrophic, angiogenic, and neuroprotective proteins. Cell survival signaling cascades, oxidative stress pathways, and protein quality control mechanisms may further underlie lithium and VPA’s beneficial actions. The ability of cotreatment to augment neuroprotection and enhance stem cell homing and migration is also discussed, as are microRNAs as new therapeutic targets. Finally, preclinical findings have shown that the neuroprotective benefits of these agents facilitate anti-inflammation, angiogenesis, neurogenesis, blood-brain barrier integrity, and disease-specific neuroprotection. These mechanisms can be compared with dysregulated disease mechanisms to suggest core cellular and molecular disturbances identifiable by specific risk biomarkers. Future clinical endeavors are warranted to determine the therapeutic potential of lithium and VPA across the spectrum of central nervous system diseases, with particular emphasis on a personalized medicine approach toward treating these disorders. PMID:23300133

Retrospective cohort study of diabetes mellitus and antipsychotic treatment in a geriatric population in the United States.

PubMed

Feldman, Peter D; Hay, Linda K; Deberdt, Walter; Kennedy, John S; Hutchins, David S; Hay, Donald P; Hardy, Thomas A; Hoffmann, Vicki P; Hornbuckle, Kenneth; Breier, Alan

2004-01-01

The objective of this study was to investigate risk of diabetes among elderly patients during treatment with antipsychotic medications. We conducted a longitudinal, retrospective study assessing the incidence of new prescription claims for antihyperglycemic agents during antipsychotic therapy. Prescription claims from the AdvancePCS claim database were followed for 6 to 9 months. Study participants consisted of patients in the United States aged 60+ and receiving antipsychotic monotherapy. The following cohorts were studied: an elderly reference population (no antipsychotics: n = 1,836,799), those receiving haloperidol (n = 6481) or thioridazine (n = 1658); all patients receiving any conventional antipsychotic monotherapy (n = 11,546), clozapine (n = 117), olanzapine (n = 5382), quetiapine (n = 1664), and risperidone (n = 12,244), and all patients receiving any atypical antipsychotic monotherapy (n = 19,407). We used Cox proportional hazards regression to determine the risk ratio of diabetes for antipsychotic cohorts relative to the reference population. Covariates included sex and exposure duration. New antihyperglycemic prescription rates were higher in each antipsychotic cohort than in the reference population. Overall rates were no different between atypical and conventional antipsychotic cohorts. Among individual antipsychotic cohorts, rates were highest among patients treated with thioridazine (95% confidence interval [CI], 3.1- 5.7), lowest with quetiapine (95% CI, 1.3-2.9), and intermediate with haloperidol, olanzapine, and risperidone. Among atypical cohorts, only risperidone users had a significantly higher risk (95% CI, 1.05-1.60; P = 0.016) than for haloperidol. Conclusions about clozapine were hampered by the low number of patients. These data suggest that diabetes risk is elevated among elderly patients receiving antipsychotic treatment. However, causality remains to be demonstrated. As a group, the risk for atypical antipsychotic users was not

Bipolar disorder recurrence prevention using self-monitoring daily mood charts: case reports from a 5 year period.

PubMed

Yasui-Furukori, Norio; Nakamura, Kazuhiko

2017-01-01

Mood symptoms in bipolar disorders are significantly related to psychosocial events, and the personalized identification of symptom triggers is important. Ecological momentary assessments have been used in paper-and-pencil form to explore emotional reactivity to daily life stress in patients with bipolar disorder. However, there are few data on long-term recurrence prevention effects using ecological momentary assessments. Subjects were three outpatients with bipolar disorder who had a history of at least one admission. They recorded self-monitoring daily mood charts using a 5-point Likert scale. Paper-and-pencil mood charts included mood, motivation, thinking speed, and impulsivity. Additionally, they recorded waking time, bedtime, and medication compliance. Fewer manic or depressive episodes including admissions occurred after self-monitoring daily mood charts compared to patients' admissions in the past 3 years. This study suggests that self-monitoring daily mood in addition to mood stabilizing medication has some effect on recurrence prevention in follow-up periods of at least 5 years. Further studies with rigorous designs and large sample sizes are needed.

Use of antipsychotics increases the risk of fracture: a systematic review and meta-analysis.

PubMed

Lee, S-H; Hsu, W-T; Lai, C-C; Esmaily-Fard, A; Tsai, Y-W; Chiu, C-C; Wang, J; Chang, S-S; Lee, C C

2017-04-01

Our systematic review and meta-analysis of observational studies indicated that the use of antipsychotics was associated with a nearly 1.5-fold increase in the risk of fracture. First-generation antipsychotics (FGAs) appeared to carry a higher risk of fracture than second-generation antipsychotics (SGAs). The risk of fractures associated with the use of antipsychotic medications has inconsistent evidence between different drug classes. A systematic review and meta-analysis was conducted to evaluate whether there is an association between the use of antipsychotic drugs and fractures. Searches were conducted through the PubMed and EMBASE databases to identify observational studies that had reported a quantitative estimate of the association between use of antipsychotics and fractures. The summary risk was derived from random effects meta-analysis. The search yielded 19 observational studies (n = 544,811 participants) with 80,835 fracture cases. Compared with nonuse, use of FGAs was associated with a significantly higher risk for hip fractures (OR 1.67, 95% CI, 1.45-1.93), and use of second generation antipsychotics (SGAs) was associated with an attenuated but still significant risk for hip fractures (OR 1.33, 95% CI, 1.11-1.58). The risk of fractures associated with individual classes of antipsychotic users was heterogeneous, and odds ratios ranged from 1.24 to 2.01. Chlorpromazine was associated with the highest risk (OR 2.01, 95% CI 1.43-2.83), while Risperidone was associated with the lowest risk of fracture (OR 1.24, 95% CI 0.95-1.83). FGA users were at a higher risk of hip fracture than SGA users. Both FGAs and SGAs were associated with an increased risk of fractures, especially among the older population. Therefore, the benefit of the off-label use of antipsychotics in elderly patients should be weighed against any risks for fracture.

Mood and the Market: Can Press Reports of Investors' Mood Predict Stock Prices?

PubMed Central

Scherbaum, Charles A.; Kammeyer-Mueller, John D.

2013-01-01

We examined whether press reports on the collective mood of investors can predict changes in stock prices. We collected data on the use of emotion words in newspaper reports on traders' affect, coded these emotion words according to their location on an affective circumplex in terms of pleasantness and activation level, and created indices of collective mood for each trading day. Then, by using time series analyses, we examined whether these mood indices, depicting investors' emotion on a given trading day, could predict the next day's opening price of the stock market. The strongest findings showed that activated pleasant mood predicted increases in NASDAQ prices, while activated unpleasant mood predicted decreases in NASDAQ prices. We conclude that both valence and activation levels of collective mood are important in predicting trend continuation in stock prices. PMID:24015202

The role of emotional engagement and mood valence in retrieval fluency of mood incongruent autobiographical memory

PubMed Central

Greenberg, Jonathan; Meiran, Nachshon

2014-01-01

Background: Retrieval of opposite mood autobiographical memories serves emotion regulation, yet the factors influencing this ability are poorly understood. Methods: Three studies examined the effect of mood valence (sad vs. happy) and degree of emotional engagement on fluency of mood incongruent retrieval by manipulating emotional engagement and examining the effect of emotional film clips on the Fluency of Autobiographical Memory task. Results: Following both sad and happy film clips, participants who received emotionally engaging instructions exhibited a greater recall latency of the first opposite mood memory, and had generated less such memories than those receiving emotionally disengaging instructions (Studies 1 and 2). A happy mood induction resulted in recollection of fewer mood incongruent memories compared to a sad mood induction. Providing emotionally engaging instructions was found to specifically hinder mood incongruent retrieval, without impairing mood congruent retrieval (Study 3). Conclusion: High emotional engagement seems to impair the retrieval of mood incongruent memories. Being in a happy mood may also partially impair such retrieval. Implications regarding emotional regulation are discussed. PMID:24570671

A note on age differences in mood-congruent vs. mood-incongruent emotion processing in faces.

PubMed

Voelkle, Manuel C; Ebner, Natalie C; Lindenberger, Ulman; Riediger, Michaela

2014-01-01

(1) Does experienced mood affect emotion perception in faces and is this perception mood-congruent or mood-incongruent?(2) Are there age-group differences in the interplay between experienced mood and emotion perception? (3) Does emotion perception in faces change as a function of the temporal sequence of study sessions and stimuli presentation, and (4) does emotion perception in faces serve a mood-regulatory function? One hundred fifty-four adults of three different age groups (younger: 20-31 years; middle-aged: 44-55 years; older adults: 70-81 years) were asked to provide multidimensional emotion ratings of a total of 1026 face pictures of younger, middle-aged, and older men and women, each displaying six different prototypical (primary) emotional expressions. By analyzing the likelihood of ascribing an additional emotional expression to a face whose primary emotion had been correctly recognized, the multidimensional rating approach permits the study of emotion perception while controlling for emotion recognition. Following up on previous research on mood responses to recurring unpleasant situations using the same dataset (Voelkle et al., 2013), crossed random effects analyses supported a mood-congruent relationship between experienced mood and perceived emotions in faces. In particular older adults were more likely to perceive happiness in faces when being in a positive mood and less likely to do so when being in a negative mood. This did not apply to younger adults. Temporal sequence of study sessions and stimuli presentation had a strong effect on the likelihood of ascribing an additional emotional expression. In contrast to previous findings, however, there was neither evidence for a change from mood-congruent to mood-incongruent responses over time nor evidence for a mood-regulatory effect.

Purinergic System Dysfunction in Mood Disorders: A Key Target for Developing Improved Therapeutics

PubMed Central

Ortiz, Robin; Ulrich, Henning; Zarate, Carlos A; Machado-Vieira, Rodrigo

2014-01-01

Uric acid and purines (such as adenosine) regulate mood, sleep, activity, appetite, cognition, memory, convulsive threshold, social interaction, drive, and impulsivity. A link between purinergic dysfunction and mood disorders was first proposed a century ago. Interestingly, a recent nationwide population-based study showed elevated risk of gout in subjects with bipolar disorder (BD), and a recent meta-analysis and systematic review of placebo-controlled trials of adjuvant purinergic modulators confirmed their benefits in bipolar mania. Uric acid may modulate energy and activity levels, with higher levels associated with higher energy and BD spectrum. Several recent genetic studies suggest that the purinergic system particularly the modulation of P1 and P2 receptor subtypes—plays a role in mood disorders, lending credence to this model. Nucleotide concentrations can be measured using brain spectroscopy, and ligands for in vivo positron emission tomography (PET) imaging of adenosine (P1) receptors have been developed, thus allowing potential target engagement studies. This review discusses the key role of the purinergic system in the pathophysiology of mood disorders. Focusing on this promising therapeutic target may lead to the development of therapies with antidepressant, mood stabilization, and cognitive effects. PMID:25445063

Trends in Antipsychotic Drug Use by Very Young, Privately Insured Children

ERIC Educational Resources Information Center

Olfson, Mark; Crystal, Stephen; Huang, Cecilia; Gerhard, Tobias

2010-01-01

Objective: This study describes recent trends and patterns in antipsychotic treatment of privately insured children aged 2 through 5 years. Method: A trend analysis is presented of antipsychotic medication use (1999-2001 versus 2007) stratified by patient characteristics. Data are analyzed from a large administrative database of privately insured…

Rhythm and mood: relationships between the circadian clock and mood-related behavior.

PubMed

Schnell, Anna; Albrecht, Urs; Sandrelli, Federica

2014-06-01

Mood disorders are multifactorial and heterogeneous diseases caused by the interplay of several genetic and environmental factors. In humans, mood disorders are often accompanied by abnormalities in the organization of the circadian system, which normally synchronizes activities and functions of cells and tissues. Studies on animal models suggest that the basic circadian clock mechanism, which runs in essentially all cells, is implicated in the modulation of biological phenomena regulating affective behaviors. In particular, recent findings highlight the importance of the circadian clock mechanisms in neurological pathways involved in mood, such as monoaminergic neurotransmission, hypothalamus-pituitary-adrenal axis regulation, suprachiasmatic nucleus and olfactory bulb activities, and neurogenesis. Defects at the level of both, the circadian clock mechanism and system, may contribute to the etiology of mood disorders. Modification of the circadian system using chronotherapy appears to be an effective treatment for mood disorders. Additionally, understanding the role of circadian clock mechanisms, which affect the regulation of different mood pathways, will open up the possibility for targeted pharmacological treatments. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Antipsychotic drug use since the FDA black box warning: survey of nursing home policies.

PubMed

Lester, Paula; Kohen, Izchak; Stefanacci, Richard G; Feuerman, Martin

2011-10-01

To use a nationwide survey to assess changes in antipsychotic utilization patterns and usage policies in nursing homes (NHs) in the United States since the introduction of the black box warning by the FDA. A survey was distributed online and was completed by 250 directors of nursing of NH. The directors of nursing answered questions concerning policies about and use of antipsychotic medications. The most commonly reported intervention to manage symptoms in residents with dementia since the black box warning was to lower doses of antipsychotics. Over half of facilities report obtaining more frequent psychiatry/psychology consults. One-hundred seven facilities have a policy regarding informing family members of residents about the black box warning. Most facilities (63.6%) with a policy require family to sign consent. In the NH setting, the presence or absence of a policy did not correlate with the reported change in use of antipsychotics or types of alternative interventions. Notably, a large number of NH facilities have policies regarding informed consent on the use of antipsychotics. However, in our study, the rate of use of antipsychotics did not change in many facilities since the black box warning. In addition, having a policy did not correlate with decreased antipsychotic use or with use of alternate agents or nonpharmacologic methods to address symptoms. The results of this survey suggest that NH administrators should worry less about the legal exposure of using antipsychotics and focus on actions that result in improved patient care. Copyright © 2011 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.

Maintenance therapy with second generation antipsychotics for bipolar disorder - A systematic review and meta-analysis.

PubMed

Lindström, Leif; Lindström, Eva; Nilsson, Mikael; Höistad, Malin

2017-04-15

Second generations antipsychotics (SGA) are frequently used for maintenance treatment in bipolar disorder. We systematically reviewed the efficacy and long-term effects of treatment with SGA, regardless of treatment strategy (SGA administered either as monotherapy or as adjunctive therapy), in comparison to placebo, lithium or valproate. Primary outcomes were relapses (mood episode recurrence) and discontinuation. Clinical studies were identified through database searching in PubMed, Embase, PsychInfo and Cochrane Library and critically appraised based on the Cochrane Handbook. Full data extraction of raw data was performed and analyzed with meta-analyses, and level of evidence graded using GRADE. Only randomized controlled studies (RCT) and observational studies were included, with a minimum follow-up of 6 months. Comparators used were restricted to placebo, lithium, valproate or other anti-epileptic drugs. We identified 15 RCTs on SGA in bipolar disorder with follow-up-time of 6 months up to 2 years, and one observational study reporting long-term effects of up to 4 years. A total of 6142 patients were included in the randomized trials. No long-term RCTs beyond 2 years follow-up was identified. All RCTs except for one included patients with bipolar disorder type I only. All RCTs except for two included patients pre-stabilized on the drug under investigation prior to randomization (enrichment design). For SGA as adjunctive therapy to lithium or valproate, meta-analyses showed that treatment with either aripiprazole (RR: 0.65, 95% CI 0.50-0.85), quetiapine (RR: 0.38, 95% CI 0.32-0.46) or ziprasidone (RR: 0.62, 95% CI 0.40-0.96) reduced the overall risk of relapses in patients that had responded during the stabilization phase. Adjunctive therapy with quetiapine was the only drug that reduced both manic and depressive episodes. For SGA as monotherapy, only quetiapine was shown to be better than lithium/ valproate for both manic and depressive relapses, but only for

Anticholinergics in the era of atypical antipsychotics: short-term or long-term treatment?

PubMed

Desmarais, Julie Eve; Beauclair, Linda; Margolese, Howard C

2012-09-01

Anticholinergic agents are usually prescribed to prevent or treat antipsychotic-induced extrapyramidal symptoms. Their long-term benefits are questionable and they carry diverse adverse effects, including cognitive impairment and worsening of tardive dyskinesia. This literature review explores the impact of anticholinergic medication discontinuation on movement disorders, cognition and psychopathology in patients receiving antipsychotics. Medline, Embase and PsycInfo were searched from 1950 to July 2011 using "cessation /withdrawal /discontinuation /stopping" with "anticholinergic*" or "antiparkinson*" and "neuroleptic*" or "antipsychotic*". Additional articles were obtained by searching the bibliographies of relevant references. Earlier studies of anticholinergic agent discontinuation in patients receiving first-generation antipsychotics reported relapse rates of extrapyramidal symptoms between 4% and 80%, reflecting the heterogeneity of the studies. Two recent studies of patients prescribed second-generation antipsychotics obtained relapse rates of 4% and 33%. Some studies suggest improvement in tardive dyskinesia with cessation of anticholinergics. Four studies examined the effects of anticholinergic agent discontinuation on cognition and all observed an improvement post-discontinuation. Changes in symptoms of schizophrenia with anticholinergic discontinuation are conflicting, with more recent studies suggesting an improvement. Given their questionable benefit with continued use, clinicians should consider a gradual withdrawal of anticholinergic agents in stable patients receiving antipsychotics.

Cerebrovascular accidents in elderly people treated with antipsychotic drugs: a systematic review.

PubMed

Sacchetti, Emilio; Turrina, Cesare; Valsecchi, Paolo

2010-04-01

After 2002, an association between stroke and antipsychotic use was reported in clinical trials and large database studies. This review considers previous quantitative reviews, newly published clinical trials, and recent observational cohort and case-control studies, and focuses on the clinical significance of the risk for stroke, the difference between typical and atypical antipsychotics, the possible at-risk patient profile and the timing of stroke after exposure. A search of MEDLINE covering the period from 1966 to June 2009 was carried out using selected keywords. Inclusion criteria were (i) quantitative reviews on stroke and antipsychotics; (ii) double-blind, placebo-controlled clinical trials involving patients with dementia treated with antipsychotics; and (iii) observational database cohort studies and observational case-control studies investigating the association between stroke and antipsychotics. Clinical trials were excluded if they were single-blind or if patients were affected by dementia and/or other neurological illnesses. Four reviews with aggregate data, 2 meta-analyses, 13 randomized, double-blind, controlled trials, 7 observational cohort studies and 4 observational case-control studies were selected and analysed. The incidence of cerebrovascular accidents (CVAs) was found to be very low in aggregate reviews and meta-analyses (2-4%). When the number collected was sufficiently high, or different drug treatments were grouped together, the higher rate in subjects exposed to antipsychotics was statistically significant. Inspection of other randomized controlled clinical trials, not included in aggregate reviews and meta-analyses, reported similar rates of CVAs. The majority of observational cohort studies compared typical and atypical antipsychotics and no significant class differences were found. A comparison with non-users was carried out in some cohort studies. In case-control studies, the probability of CVAs in users compared with non-users was

Mood Components in Cocoa and Chocolate: The Mood Pyramid.

PubMed

Tuenter, Emmy; Foubert, Kenn; Pieters, Luc

2018-03-14

Cocoa and chocolate, prepared from cocoa beans that originate from the fruits of the cocoa tree Theobroma cacao , have a long-standing reputation as healthy food, including mood-enhancing effects. In spite of many clinical trials with chocolate, cocoa, or its constituents, the mechanisms of action on mood and cognition remain unclear. More in particular, it is still controversial which constituents may contribute to the psychopharmacological activities, ranging from the major cacao flavanols and methylxanthines to the minor amines, amides, and alkaloids. In this review a critical appraisal is made of recent studies on mood and cognition, with a special emphasis on analytical characterization of the test samples. It is concluded that the mood and cognition-enhancing effects of cocoa and chocolate can be ranked from more general activities associated with flavanols and methylxanthines, to more specific activities related to minor constituents such as salsolinol, with on top the orosensory properties of chocolate. Therefore, the "mood pyramid" of cocoa and chocolate is proposed as a new concept. To understand the role and interactions of the different major and minor constituents of cocoa, it is recommended that all test samples used in future in vitro, in vivo , or human studies should be phytochemically characterized in much more detail than is common practice today. Georg Thieme Verlag KG Stuttgart · New York.

Pharmacogenetics of leptin in antipsychotic-associated weight gain and obesity-related complications

PubMed Central

Lee, Amy K; Bishop, Jefrey R

2013-01-01

Second-generation antipsychotics can greatly improve symptoms of psychosis-spectrum disorders. Unfortunately, these drugs are associated with weight gain, which increases a patient’s risk for developing chronic diseases including Type 2 diabetes, cardiovascular diseases or other obesity-related complications. There are interindividual differences in weight gain resulting from antipsychotic drug use that may be explained by pharmacodynamic characteristics of these agents as well as clinical factors. In addition, genetic variations in pathways associated with satiety are increasingly recognized as potential contributors to antipsychotic-associated weight gain. Polymorphisms in the leptin gene, as well as the leptin receptor gene, are potential pharmacogenetic markers associated with these outcomes. This article summarizes evidence for the associations of the leptin gene and the leptin receptor gene polymorphisms with antipsychotic-induced weight gain, potential mechanisms underlying these relationships, and discusses areas for future pharmacogenetic investigation. PMID:21787190

Antipsychotic dose modulates behavioral and neural responses to feedback during reinforcement learning in schizophrenia.

PubMed

Insel, Catherine; Reinen, Jenna; Weber, Jochen; Wager, Tor D; Jarskog, L Fredrik; Shohamy, Daphna; Smith, Edward E

2014-03-01

Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how treatment with antipsychotic medication impacts the behavioral and neural signatures of reinforcement learning in schizophrenia. The goal of this study was to examine whether antipsychotic medication modulates behavioral and neural responses to prediction error coding during reinforcement learning. Patients with schizophrenia completed a reinforcement learning task while undergoing functional magnetic resonance imaging. The task consisted of two separate conditions in which participants accumulated monetary gain or avoided monetary loss. Behavioral results indicated that antipsychotic medication dose was associated with altered behavioral approaches to learning, such that patients taking higher doses of medication showed increased sensitivity to negative reinforcement. Higher doses of antipsychotic medication were also associated with higher learning rates (LRs), suggesting that medication enhanced sensitivity to trial-by-trial feedback. Neuroimaging data demonstrated that antipsychotic dose was related to differences in neural signatures of feedback prediction error during the loss condition. Specifically, patients taking higher doses of medication showed attenuated prediction error responses in the striatum and the medial prefrontal cortex. These findings indicate that antipsychotic medication treatment may influence motivational processes in patients with schizophrenia.

A note on age differences in mood-congruent vs. mood-incongruent emotion processing in faces

PubMed Central

Voelkle, Manuel C.; Ebner, Natalie C.; Lindenberger, Ulman; Riediger, Michaela

2014-01-01

This article addresses four interrelated research questions: (1) Does experienced mood affect emotion perception in faces and is this perception mood-congruent or mood-incongruent?(2) Are there age-group differences in the interplay between experienced mood and emotion perception? (3) Does emotion perception in faces change as a function of the temporal sequence of study sessions and stimuli presentation, and (4) does emotion perception in faces serve a mood-regulatory function? One hundred fifty-four adults of three different age groups (younger: 20–31 years; middle-aged: 44–55 years; older adults: 70–81 years) were asked to provide multidimensional emotion ratings of a total of 1026 face pictures of younger, middle-aged, and older men and women, each displaying six different prototypical (primary) emotional expressions. By analyzing the likelihood of ascribing an additional emotional expression to a face whose primary emotion had been correctly recognized, the multidimensional rating approach permits the study of emotion perception while controlling for emotion recognition. Following up on previous research on mood responses to recurring unpleasant situations using the same dataset (Voelkle et al., 2013), crossed random effects analyses supported a mood-congruent relationship between experienced mood and perceived emotions in faces. In particular older adults were more likely to perceive happiness in faces when being in a positive mood and less likely to do so when being in a negative mood. This did not apply to younger adults. Temporal sequence of study sessions and stimuli presentation had a strong effect on the likelihood of ascribing an additional emotional expression. In contrast to previous findings, however, there was neither evidence for a change from mood-congruent to mood-incongruent responses over time nor evidence for a mood-regulatory effect. PMID:25018740

Bipolar disorder and the risk of fracture: A nationwide population-based cohort study.

PubMed

Su, Jian-An; Cheng, Bi-Hua; Huang, Yin-Cheng; Lee, Chuan-Pin; Yang, Yao-Hsu; Lu, Mong-Liang; Hsu, Chung-Yao; Lee, Yena; McIntyre, Roger S; Chin Lin, Tzu; Chin-Hung Chen, Vincent

2017-08-15

The co-primary aims are: 1) to compare the risk of fracture between adults with bipolar disorder and those without bipolar disorder; and 2) to assess whether lithium, anticonvulsants and antipsychotics reduce risk of fracture among individuals with bipolar disorder. The analysis herein is a population-based retrospective cohort study, utilizing the National Health Insurance (NHI) medical claims data collected between 1997 and 2013 in Taiwan. We identified 3705 cases with incident diagnoses of bipolar disorder during study period and 37,050 matched controls without bipolar diagnoses. Incident diagnosis of fracture was operationalized as any bone fracture after the diagnosis of bipolar disorder or after the matched index date for controls. Bipolar patients had significantly higher risk of facture when compared to matched controls (17.6% versus 11.7%, respectively p<0.001). The hazard ratio (HR) was 1.33 (95% confidence interval [CI]＝1.23-1.48, p<0.001) after adjusting for covariates. Persons with bipolar disorder and a prior history of psychiatric hospitalization were had higher risk for bone fracture than those without prior history of psychiatric hospitalization when compared to match controls. Higher cumulative dose of antipsychotics or mood stabilizers did not increase the risk of fracture. The diagnoses of bipolar disorder were not confirmed with structured clinical interview. Drug adherence, exact exposure dosage, smoking, lifestyle, nutrition and exercise habits were unable to be assessed in our dataset. Bipolar disorder is associated with increased risk of fracture, and higher cumulative dose of mood stabilizers and antipsychotics did not further increase the risk of fracture. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of Atypical Antipsychotics in Nursing Homes and Pharmaceutical Marketing

PubMed Central

Pimentel, Camilla B.; Donovan, Jennifer L.; Field, Terry S.; Gurwitz, Jerry H.; Harrold, Leslie R.; Kanaan, Abir O.; Lemay, Celeste A.; Mazor, Kathleen M.; Tjia, Jennifer; Briesacher, Becky A.

2014-01-01

BACKGROUND Many nursing home (NH) residents are prescribed atypical antipsychotics despite US Food and Drug Administration warnings of increased risk of death in older adults with dementia. Aggressive pharmaceutical marketing has been cited as a potential cause, although data are scarce. The objectives of this study were to describe the current extent and type of pharmaceutical marketing in NHs in one state, and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs. DESIGN Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial. SETTING 41 NHs in Connecticut. PARTICIPANTS NH administrators, directors of nursing and medical directors (n = 93, response rate 75.6%). MEASUREMENTS Quantitative data, including prescription drug dispensing data (September 2009–August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility-level prevalence of atypical antipsychotic use, facility-level characteristics, NH staffing and NH quality. Qualitative data, including semi-structured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing. RESULTS Leadership at 46.3% of NHs (19/41) reported pharmaceutical marketing encounters, consisting of educational training, written/Internet-based materials and/or sponsored training. No association was detected between the level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader. CONCLUSION NH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear. PMID:25688605

Food can lift mood by affecting mood-regulating neurocircuits via a serotonergic mechanism.

PubMed

Kroes, Marijn C W; van Wingen, Guido A; Wittwer, Jonas; Mohajeri, M Hasan; Kloek, Joris; Fernández, Guillén

2014-01-01

It is commonly assumed that food can affect mood. One prevalent notion is that food containing tryptophan increases serotonin levels in the brain and alters neural processing in mood-regulating neurocircuits. However, tryptophan competes with other long-neutral-amino-acids (LNAA) for transport across the blood-brain-barrier, a limitation that can be mitigated by increasing the tryptophan/LNAA ratio. We therefore tested in a double-blind, placebo-controlled crossover study (N=32) whether a drink with a favourable tryptophan/LNAA ratio improves mood and modulates specific brain processes as assessed by functional magnetic resonance imaging (fMRI). We show that one serving of this drink increases the tryptophan/LNAA ratio in blood plasma, lifts mood in healthy young women and alters task-specific and resting-state processing in brain regions implicated in mood regulation. Specifically, Test-drink consumption reduced neural responses of the dorsal caudate nucleus during reward anticipation, increased neural responses in the dorsal cingulate cortex during fear processing, and increased ventromedial prefrontal-lateral prefrontal connectivity under resting-state conditions. Our results suggest that increasing tryptophan/LNAA ratios can lift mood by affecting mood-regulating neurocircuits. © 2013 Elsevier Inc. All rights reserved.

Experimental treatment of antipsychotic-induced movement disorders

PubMed Central

Shireen, Erum

2016-01-01

Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314

Halting Antipsychotic Use in Long-Term care (HALT): a single-arm longitudinal study aiming to reduce inappropriate antipsychotic use in long-term care residents with behavioral and psychological symptoms of dementia.

PubMed

Jessop, Tiffany; Harrison, Fleur; Cations, Monica; Draper, Brian; Chenoweth, Lynn; Hilmer, Sarah; Westbury, Juanita; Low, Lee-Fay; Heffernan, Megan; Sachdev, Perminder; Close, Jacqueline; Blennerhassett, Jenny; Marinkovich, Millicent; Shell, Allan; Brodaty, Henry

2017-08-01

Inappropriate use of antipsychotic medications to manage Behavioral and Psychological Symptoms of Dementia (BPSD) continues despite revised guidelines and evidence for the associated risks and side effects. The aim of the Halting Antipsychotic Use in Long-Term care (HALT) project is to identify residents of long-term care (LTC) facilities on antipsychotic medications, and undertake an intervention to deprescribe (or cease) these medicines and improve non-pharmacological behavior management. LTC facilities will be recruited across Sydney, Australia. Resident inclusion criteria will be aged over 60 years, on regular antipsychotic medication, and without a primary psychotic illness or very severe BPSD, as measured using the Neuropsychiatric Inventory (NPI). Data collection will take place one month and one week prior to commencement of deprescribing; and 3, 6 and 12 months later. During the period prior to deprescribing, training will be provided for care staff on how to reduce and manage BPSD using person-centered approaches, and general practitioners of participants will be provided academic detailing. The primary outcome measure will be reduction of regular antipsychotic medication without use of substitute psychotropic medications. Secondary outcome measures will be NPI total and domain scores, Cohen-Mansfield Agitation Inventory scores and adverse events, including falls and hospitalizations. While previous studies have described strategies to minimize inappropriate use of antipsychotic medications in people with dementia living in long-term care, sustainability and a culture of prescribing for BPSD in aged care remain challenges. The HALT project aims to evaluate the feasibility of a multi-disciplinary approach for deprescribing antipsychotics in this population.

Positive mood can increase or decrease message scrutiny: the hedonic contingency view of mood and message processing.

PubMed

Wegener, D T; Petty, R E; Smith, S M

1995-07-01

Currently dominant explanations of mood effects on persuasive message processing (i.e., cognitive capacity and feelings as information) predict that happy moods lead to less message scrutiny than neutral or sad moods. The hedonic contingency view (D. T. Wegener & R. E. Petty, 1994) predicts that happy moods can sometimes be associated with greater message processing activity because people in a happy mood are more attentive than neutral or sad people to the hedonic consequences of their actions. Consistent with this view, Experiment 1 finds that a happy mood can lead to greater message scrutiny than a neutral mood when the message is not mood threatening. Experiment 2 finds that a happy mood leads to greater message scrutiny than a sad mood when an uplifting message is encountered, but to less message scrutiny when a depressing message is encountered.

Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review.

PubMed

Umar, Musa Usman; Abdullahi, Aminu Taura

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect.

Loxapine for Reversal of Antipsychotic-Induced Metabolic Disturbances: A Chart Review

ERIC Educational Resources Information Center

Jain, Seema; Andridge, Rebecca; Hellings, Jessica A.

2016-01-01

Loxapine substitution is a promising option for patients with autism spectrum disorder (ASD) who develop antipsychotic-induced metabolic illness. We performed a chart review of 15 adolescents and adults meeting DSM-IV-TR criteria for ASD, all with antipsychotic-associated weight gain, who received low dose loxapine in an attempt to taper or…

Asenapine, blonanserin, iloperidone, lurasidone, and sertindole: distinctive clinical characteristics of 5 novel atypical antipsychotics.

PubMed

Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un

2013-01-01

Schizophrenia is a serious, chronic, and devastating mental illness with a substantial impact on psychological, physical, social, and economical areas of an individual and society. To treat such critical mental illness, a number of first-generation (typical) and second-generation (atypical) antipsychotics are currently available in the market. Despite such treatment options, most of patients with schizophrenia have a poor treatment outcome and become treatment resistant, causing continual deterioration on positive, negative, and cognitive symptoms, resulting in impairment of socio-occupational functioning. Hence, additional novel antipsychotics with better efficacy, safety, and tolerability profiles are needed to enable clinicians to diversify treatment options to improve treatment of schizophrenia. Recently, the 3 antipsychotics, including iloperidone (2009), asenapine (2009), and lurasidone (2010), have been approved by the US Food and Drug Administration. Two other atypical antipsychotics, including sertindole and blonanserin, are approved and used outside the United States for treatment of schizophrenia. Sertindole, after it has been voluntarily suspended by the manufacturer in 1998 due to its potential risk in causing cardiovascular-related death, was relaunched to the European market in 2005. More recently, blonanserin was approved in Japan (2008) and in Korea (2009) for the management of schizophrenia. Individual antipsychotic may have differential pros and cons compared with other antipsychotic in terms of efficacy, safety, tolerability, restoration of functional capacity, and economic aspect reflecting relapse prevention. The purpose of this review was to provide distinctive clinical characteristics and up-to-date of clinical trial data of the 5 novel atypical antipsychotics for the management of schizophrenia, which may deliver clinicians better understanding in the use of such atypical antipsychotics for the treatment of schizophrenia in clinical

Impact of antipsychotic medication on transcranial direct current stimulation (tDCS) effects in schizophrenia patients.

PubMed

Agarwal, Sri Mahavir; Bose, Anushree; Shivakumar, Venkataram; Narayanaswamy, Janardhanan C; Chhabra, Harleen; Kalmady, Sunil V; Varambally, Shivarama; Nitsche, Michael A; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

2016-01-30

Transcranial direct current stimulation (tDCS) has generated interest as a treatment modality for schizophrenia. Dopamine, a critical pathogenetic link in schizophrenia, is also known to influence tDCS effects. We evaluated the influence of antipsychotic drug type (as defined by dopamine D2 receptor affinity) on the impact of tDCS in schizophrenia. DSM-IV-TR-diagnosed schizophrenia patients [N=36] with persistent auditory hallucinations despite adequate antipsychotic treatment were administered add-on tDCS. Patients were divided into three groups based on the antipsychotic's affinity to D2 receptors. An auditory hallucinations score (AHS) was measured using the auditory hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS). Add-on tDCS resulted in a significant reduction inAHS. Antipsychotic drug type had a significant effect on AHS reduction. Patients treated with high affinity antipsychotics showed significantly lesser improvement compared to patients on low affinity antipsychotics or a mixture of the two. Furthermore, a significant sex-by-group interaction occurred; type of medication had an impact on tDCS effects only in women. Improvement differences could be due to the larger availability of the dopamine receptor system in patients taking antipsychotics with low D2 affinity. Sex-specific differences suggest potential estrogen-mediated effects. This study reports a first-time observation on the clinical utility of antipsychotic drug type in predicting tDCS effects in schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mental disorder diagnoses among children and adolescents who use antipsychotic drugs.

PubMed

Nesvåg, Ragnar; Hartz, Ingeborg; Bramness, Jørgen G; Hjellvik, Vidar; Handal, Marte; Skurtveit, Svetlana

2016-09-01

Antipsychotic drugs are used increasingly by children and adolescents and there is concern about off-label use. We aimed to study which substances, and for which mental disorder diagnoses, antipsychotic drugs were prescribed to 0-18-year-old boys and girls in Norway. Linked data from the national health registry for prescription drugs in 2010 and mental disorder diagnoses in 2008-2012 were used to study the prevalence of antipsychotic drug use, the type of antipsychotic drug substances used, mental disorder diagnoses in users and distribution of drugs per diagnostic category across gender. In total, 0.18% of Norwegian children and adolescents were prescribed antipsychotic drugs during 2010, of which there were more boys (0.23%) than girls (0.13%). Risperidone was the most frequently used substance among boys (57.4%) and girls (32.3%), followed by aripiprazole (19.4%) in boys and quetiapine (27.4%) in girls. The most common mental disorder diagnoses among male users were hyperkinetic (49.9%) and autism spectrum disorder (27.1%), while anxiety disorders (41.5%) and depressive illness (33.6%) were most common among female users. A schizophrenia-like psychosis diagnosis was given to 11.1% of the male and 18.2% of the female users. A hyperkinetic disorder was diagnosed among 56.9% and 52.4% of the male risperidone and aripiprazole users, respectively. Among female quetiapine users, 57.1% were diagnosed with anxiety disorders and 52.4% with depressive illness. These results demonstrate that children and adolescents who use antipsychotic drugs are predominantly diagnosed with non-psychotic mental disorders such as hyperkinetic disorder among boys and anxiety disorder or depressive illness among girls. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review

PubMed Central

Umar, Musa Usman; Abdullahi, Aminu Taura

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect. PMID:27335511

AKT Kinase Activity Is Required for Lithium to Modulate Mood-Related Behaviors in Mice

PubMed Central

Pan, Jen Q; Lewis, Michael C; Ketterman, Josh K; Clore, Elizabeth L; Riley, Misha; Richards, Keenan R; Berry-Scott, Erin; Liu, Xiulin; Wagner, Florence F; Holson, Edward B; Neve, Rachael L; Biechele, Travis L; Moon, Randall T; Scolnick, Edward M; Petryshen, Tracey L; Haggarty, Stephen J

2011-01-01

Bipolar disorder (BP) is a debilitating psychiatric disorder, affecting ∼2% of the worldwide population, for which the etiological basis, pathogenesis, and neurocircuitry remain poorly understood. Individuals with BP suffer from recurrent episodes of mania and depression, which are commonly treated with the mood stabilizer lithium. However, nearly half of BP patients do not respond adequately to lithium therapy and the clinically relevant mechanisms of lithium for mood stabilization remain elusive. Here, we modeled lithium responsiveness using cellular assays of glycogen synthase kinase 3 (GSK-3) signaling and mood-related behavioral assays in inbred strains of mice that differ in their response to lithium. We found that activating AKT through phosphosrylation of a key regulatory site (Thr308) was associated with lithium response—activation of signaling pathways downstream of GSK-3 in cells and attenuation of mood-related behaviors in mice—and this response was attenuated by selective and direct inhibition of AKT kinase activity. Conversely, the expression of constitutively active AKT1 in both the cellular and behavioral assays conferred lithium sensitivity. In contrast, selective and direct GSK-3 inhibition by the ATP-competitive inhibitor CHIR99021 bypassed the requirement for AKT activation and modulated behavior in both lithium-responsive and non-responsive mouse strains. These results distinguish the mechanism of action of lithium from direct GSK-3 inhibition both in vivo and in vitro, and highlight the therapeutic potential for selective GSK-3 inhibitors in BP treatment. PMID:21389981

The impact of severe mental disorders and psychotropic medications on sexual health and its implications for clinical management

PubMed Central

Montejo, Angel L.; Montejo, Laura; Baldwin, David S.

2018-01-01

Sexual dysfunction often accompanies severe psychiatric illness and can be due to both the mental disorder itself and the use of psychotropic treatments. Many sexual symptoms resolve as the mental state improves, but treatment‐related sexual adverse events tend to persist over time, and are unfortunately under‐recognized by clinicians and scarcely investigated in clinical trials. Treatment‐emergent sexual dysfunction adversely affects quality of life and may contribute to reduce treatment adherence. There are important differences between the various compounds in the incidence of adverse sexual effects, associated with differences in mechanisms of action. Antidepressants with a predominantly serotonergic activity, antipsychotics likely to induce hyperprolactinaemia, and mood stabilizers with hormonal effects are often linked to moderate or severe sexual dysfunction, including decreased libido, delayed orgasm, anorgasmia, and sexual arousal difficulties. Severe mental disorders can interfere with sexual function and satisfaction, while patients wish to preserve a previously satisfactory sexual activity. In many patients, a lack of intimate relationships and chronic deterioration in mental and physical health can be accompanied by either a poor sexual life or a more frequent risky sexual behaviour than in the general population. Here we describe the influence of psychosis and antipsychotic medications, of depression and antidepressant drugs, and of bipolar disorder and mood stabilizers on sexual health, and the optimal management of patients with severe psychiatric illness and sexual dysfunction. PMID:29352532

Stress and Mood

MedlinePlus

... Relaxation Emotions & Relationships HealthyYouTXT Tools Home » Stress & Mood Stress & Mood Many people who go back to smoking ... story: Time Out Times 10 >> share What Causes Stress? Read full story: What Causes Stress? >> share The ...

LORETA functional imaging in antipsychotic-naive and olanzapine-, clozapine- and risperidone-treated patients with schizophrenia.

PubMed

Tislerova, Barbora; Brunovsky, Martin; Horacek, Jiri; Novak, Tomas; Kopecek, Miloslav; Mohr, Pavel; Krajca, Vladimír

2008-01-01

The aim of our study was to detect changes in the distribution of electrical brain activity in schizophrenic patients who were antipsychotic naive and those who received treatment with clozapine, olanzapine or risperidone. We included 41 subjects with schizophrenia (antipsychotic naive = 11; clozapine = 8; olanzapine = 10; risperidone = 12) and 20 healthy controls. Low-resolution brain electromagnetic tomography was computed from 19-channel electroencephalography for the frequency bands delta, theta, alpha-1, alpha-2, beta-1, beta-2 and beta-3. We compared antipsychotic-naive subjects with healthy controls and medicated patients. (1) Comparing antipsychotic-naive subjects and controls we found a general increase in the slow delta and theta frequencies over the fronto-temporo-occipital cortex, particularly in the temporolimbic structures, an increase in alpha-1 and alpha-2 in the temporal cortex and an increase in beta-1 and beta-2 in the temporo-occipital and posterior limbic structures. (2) Comparing patients who received clozapine and those who were antipsychotic naive, we found an increase in delta and theta frequencies in the anterior cingulate and medial frontal cortex, and a decrease in alpha-1 and beta-2 in the occipital structures. (3) Comparing patients taking olanzapine with those who were antipsychotic naive, there was an increase in theta frequencies in the anterior cingulum, a decrease in alpha-1, beta-2 and beta-3 in the occipital cortex and posterior limbic structures, and a decrease in beta-3 in the frontotemporal cortex and anterior cingulum. (4) In patients taking risperidone, we found no significant changes from those who were antipsychotic naive. Our results in antipsychotic-naive patients are in agreement with existing functional findings. Changes in those taking clozapine and olanzapine versus those who were antipsychotic naive suggest a compensatory mechanism in the neurobiological substrate for schizophrenia. The lack of difference in

Effectiveness and cost of atypical versus typical antipsychotic treatment for schizophrenia in routine care.

PubMed

Stargardt, Tom; Weinbrenner, Susanne; Busse, Reinhard; Juckel, Georg; Gericke, Christian A

2008-06-01

In two recent randomised clinical trials, a meta-analysis and in an effectiveness study analysing routine data from the U.S. Veterans Administration the superiority of the newer atypical drugs over typical antipsychotic drugs, concerning both their efficacy and their side-effect profile, has been questioned. To analyse the effectiveness and cost of atypical versus typical antipsychotic treatment for schizophrenia in routine care. Cohort study using routine care data from a statutory sickness fund with 5.4 million insured in Germany. To be included, patients had to be discharged with a diagnosis of schizophrenia in 2003 and fulfil membership criteria. Main outcome measures were rehospitalisation rates, mean hospital bed days, mean length of stay, cost of inpatient and pharmaceutical care to the sickness fund during follow-up and medication used to treat side-effects. 3121 patients were included into the study. There were no statistically significant differences in the effectiveness of atypical and typical antipsychotics on rehospitalisation during follow-up (rehospitalisation rate ratio 1.07, 95% confidence interval 0.86 to 1.33). However, there were consistent observations of atypical antipsychotics being more effective for severe cases of schizophrenia (14.6% of study population; >61 prior bed days per year in 2000-2002) in the follow-up period, whereas for the other severity strata typical antipsychotics seemed more effective in reducing various rehospitalisation outcomes. Patients treated with atypical antipsychotics received significantly less prescriptions for anticholinergics or tiaprid (relative risk 0.26, 95% confidence interval 0.18 to 0.38). The effectiveness of atypical antipsychotics for schizophrenia on rehospitalisation measures appeared similar to that of typical antipsychotics. With the exception of severe cases, the higher costs for atypical antipsychotics were not offset by savings from reduced inpatient care. Major limitations include the lack of

Impact of regulatory measures on antipsychotics drug consumption in Castilla y León, Spain.

PubMed

Martín Arias, L H; Treceño Lobato, C; Pérez García, S; García Ortega, P; Sáinz Gil, M; Sanz Fadrique, R; Carvajal García-Pando, A

2016-12-01

Antipsychotics are currently used to treat different diseases; even some off-labelled conditions are treated with this medication. Consumption and cost of antipsychotic drugs sharply increased in Spain after second-generation drugs were marketed; several regulatory measures were adopted to curb this trend. The aim of this study was to examine the impact of these measures upon the use and cost of antipsychotics. Study of drug use (SDU) from 1995 to 2012. Consumption and cost data were obtained from the CONCYLIA database; this database contains the retail community pharmacies sales of medicinal products reimbursed by the National Health System in Castilla y León (Spain). Data are presented as defined daily doses per 1000 inhabitants per day (DID) and day treatment cost (DTC). First-generation antipsychotics prescriptions gradually decreased from 3.0 to 1.8 DID; meanwhile, prescriptions for second-generation antipsychotics considerably increased from 0.3 to 9.9 DID. The use of risperidone dropped after the marketing of its structural derivative paliperidone with a similar efficacy but with a substantially higher cost per day. In 2011 and thereafter, patients in Spain began to pay a part of the medications cost, but this did not decrease antipsychotics consumption. Global cost of antipsychotics only began to fall after measures were adopted to lower the price of medicines because of the economic collapse in Spain after May 2010. Several health policy measures have tried to reduce antipsychotics consumption in Spain, special ways of dispensing, marketing of generic drugs and special economic measures for patients. These measures eventually failed to avoid the increase in antipsychotics use. The cost only dropped when lowering prescription drug prices took place. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Motivated prediction of future feelings: effects of negative mood and mood orientation on affective forecasts.

PubMed

Buehler, Roger; McFarland, Cathy; Spyropoulos, Vassili; Lam, Kent C H

2007-09-01

This article examines the role of motivational factors in affective forecasting. The primary hypothesis was that people predict positive emotional reactions to future events when they are motivated to enhance their current feelings. Three experiments manipulated participants' moods (negative vs. neutral) and orientation toward their moods (reflective vs. ruminative) and then assessed the positivity of their affective predictions for future events. As hypothesized, when participants adopted a reflective orientation, and thus should have been motivated to engage in mood-regulation processes, they predicted more positive feelings in the negative than in the neutral mood condition. This pattern of mood-incongruent affective prediction was not exhibited when participants adopted a ruminative orientation. Additionally, within the negative mood condition, generating affective forecasts had a more positive emotional impact on reflectors than on ruminators. The findings suggest that affective predictions are sometimes driven by mood-regulatory motives.

Movies and mood: an exploration of the critical variables related to mood states

Treesearch

Laura L. Payne; Tammie Shaw; Linda L. Caldwell

1998-01-01

The purpose of this study was to examine the relationship between movie viewing and mood, and to test the Pleasure Arousal Dominance (PAD) mood theory in a theater setting. The results of this exploratory study are presented here, challenging the PAD model, and providing suggestions for future research regarding the leisure and mood relationship.

Use of atypical antipsychotics in nursing homes and pharmaceutical marketing.

PubMed

Pimentel, Camilla B; Donovan, Jennifer L; Field, Terry S; Gurwitz, Jerry H; Harrold, Leslie R; Kanaan, Abir O; Lemay, Celeste A; Mazor, Kathleen M; Tjia, Jennifer; Briesacher, Becky A

2015-02-01

To describe the current extent and type of pharmaceutical marketing in nursing homes (NHs) in one state and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs. Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial. Forty-one NHs in Connecticut. NH administrators, directors of nursing, and medical directors (n = 93, response rate 75.6%). Quantitative data, including prescription drug dispensing data (September 2009-August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility-level prevalence of atypical antipsychotic use, facility-level characteristics, NH staffing, and NH quality. Qualitative data, including semistructured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing. Leadership at 46.3% of NHs (n = 19) reported pharmaceutical marketing encounters, consisting of educational training, written and Internet-based materials, and sponsored training. No association was detected between level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader. NH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Weight loss in overweight patients maintained on atypical antipsychotic agents.

PubMed

Centorrino, F; Wurtman, J J; Duca, K A; Fellman, V H; Fogarty, K V; Berry, J M; Guay, D M; Romeling, M; Kidwell, J; Cincotta, S L; Baldessarini, R J

2006-06-01

Weight gain and associated medical morbidity offset the reduction of extrapyramidal side effects associated with atypical antipsychotics. Efforts to control weight in antipsychotic-treated patients have yielded limited success. We studied the impact of an intensive 24-week program of diet, exercise, and counseling in 17 chronically psychotic patients (10 women, seven men) who entered at high average body weight (105.0+/-18.4 kg) and body mass index (BMI) (36.6+/-4.6 kg/m(2)). A total of 12 subjects who completed the initial 24 weeks elected to participate in an additional 24-week, less intensive extension phase. By 24 weeks, weight-loss/patient averaged 6.0 kg (5.7%) and BMI decreased to 34.5 (by 5.7%). Blood pressure decreased from 130/83 to 116/74 (11% improvement), pulse fell slightly, and serum cholesterol and triglyceride concentrations changed nonsignificantly. With less intensive management for another 24 weeks, subjects regained minimal weight (0.43 kg). These findings add to the emerging view that weight gain is a major health problem associated with modern antipsychotic drugs and that labor-intensive weight-control efforts in patients requiring antipsychotic treatment yield clinically promising benefits. Improved treatments without weight-gain risk are needed.

Utilization of antihypertensives, antidepressants, antipsychotics, and hormones in Alzheimer disease.

PubMed

Zhu, Carolyn W; Livote, Elayne E; Kahle-Wrobleski, Kristin; Scarmeas, Nikolaos; Albert, Marilyn; Brandt, Jason; Blacker, Deborah; Sano, Mary; Stern, Yaakov

2011-01-01

This study explores the longitudinal relationship between patient characteristics and use of 4 drug classes (antihypertensives, antidepressants, antipsychotics, and hormones) that showed significant changes in use rates over time in patients with Alzheimer disease. Patient/caregiver-reported prescription medication usage was categorized by drug class for 201 patients from the Predictors Study. Patient characteristics included use of cholinesterase inhibitors and/or memantine, function, cognition, living situation, baseline age, and sex. Assessment interval, year of study entry, and site were controlled for. Before adjusting for covariates, useage increased for antihypertensives (47.8% to 62.2%), antipsychotics (3.5% to 27.0%), and antidepressants (32.3% to 40.5%); use of hormones decreased (19.4% to 5.4%). After controlling for patient characteristics, effects of time on the use of antidepressants were no longer significant. Antihypertensive use was associated with poorer functioning, concurrent use of memantine, and older age. Antipsychotic use was associated with poorer functioning and poorer cognition. Antidepressant use was associated with younger age, poorer functioning, and concurrent use of cholinesterase inhibitors and memantine. Hormone use was associated with being female and younger age. Findings suggest accurate modeling of the Alzheimer disease treatment paradigm for certain subgroups of patients should include antihypertensives and antipsychotics in addition to cholinesterase inhibitors and memantine.

Antipsychotics and dementia in Canada: a retrospective cross-sectional study of four health sectors.

PubMed

Rios, Sebastian; Perlman, Christopher M; Costa, Andrew; Heckman, George; Hirdes, John P; Mitchell, Lori

2017-10-23

Antipsychotic medications are not recommended for the management of symptoms of dementia, particularly among persons with no behavioral or psychological symptoms. We examine patterns of antipsychotic medication use among persons with dementia across health sectors in Canada, with a focus on factors related to use among those without behavioral or psychotic symptoms. Using a retrospective cross-sectional design, this study examines antipsychotic use among adults aged 65 or older with dementia in home care (HC), complex continuing care (CCC), long-term care (LTC), and among alternate level care patients in acute hospitals (ALC). Using clinical data from January 1, 2009 to December 31, 2014, the prevalence of antipsychotic medication use was estimated by the presence of behavioral and psychotic symptoms. Logistic regression was used to identify sector specific factors associated with antipsychotic use in the absence of behavioral and psychotic symptoms. The total prevalence of antipsychotic use among older adults with dementia was 26% in HC, 54% in ALC, 41% in CCC, and 48% in LTC. This prevalence ranged from 38% (HC) to 73% (ALC) for those with both behavioral and psychotic symptoms and from 15% (HC) to 31% (ALC) among those with no symptoms. The regression models identified a number of variables were related to antipsychotic use in the absence of behavior or psychotic symptoms, such as bipolar disorder (OR = 6.63 in CCC; OR = 5.52 in LTC), anxious complaints (OR = 1.54 in LTC to 2.01 in CCC), and wandering (OR = 1.83 in ALC). Potentially inappropriate use of antipsychotic medications is prevalent among older adults with dementia across health sectors. The variations in prevalence observed from community to facility based care suggests that system issues may exist in appropriately managing persons with dementia.

A prescription survey of antipsychotic use in England and Wales following the introduction of NICE guidance.

PubMed

MacE, Shubhra; Taylor, David

2005-01-01

Objective : In the United Kingdom (UK) the National Institute for Clinical Excellence (NICE) has recommended the use of atypical antipsychotics for the treatment of schizophrenia. As part of its guidance it discourages the concurrent use of typical and atypical antipsychotics. In previous prescribing surveys antipsychotic polypharmacy has been noted to be widespread. We sought to evaluate atypical antipsychotic prescribing after the publication of NICE guidance. Method : We invited psychiatric centres in England and Wales to participate, in March 2004, in an atypical antipsychotic prescribing survey of hospital in-patients. Results : Thirty-six in-patient units submitted data for 2012 patients. After exclusions, 1092 patients were eligible. Of these, 28.6% (312) were prescribed a typical alongside an atypical antipsychotic and 19.3% (211) were prescribed high-dose antipsychotics. Co-prescription was more prevalent in patients aged 40 years and above (32.0 vs. 25.3%; P=0.018). It was also noted that in centres employing senior pharmacists, co-prescription was more common (28.6 vs. 14.3%; P=0.03). High-dose treatment was more commonly observed in patients of a white ethnic background (20.6 vs. 13.9%; P=0.02) as well as in patients aged 40 years and above (24.4 vs. 15.0%; P<0.001). Prescription of anticholinergics was significantly more prevalent in those receiving atypical and typical combinations than atypicals alone (26.0 vs. 12.0%; P<0.001). Conclusions : Antipsychotic polypharmacy remains commonplace. Similarly the prescription of high-dose antipsychotics is also widespread.

A critical assessment of antipsychotic drug monitoring.

PubMed

Waraska, J; Nagle, J D

1987-06-01

Analytic problems associated with monitoring antipsychotic drug levels have largely been resolved. Despite the establishment of target values for some drugs, the clinical utility of such levels remains to be determined.

Issues related to sex differences in antipsychotic treatment.

PubMed

Crawford, Mitchell B; DeLisi, Lynn E

2016-05-01

The effectiveness, side-effect profiles, and numerous other characteristics of antipsychotic medications have been extensively studied. However, the majority of publications do not address the many potential sex differences in efficacy and doses of medications, as well as other sex-specific considerations. Of studies that exist, some suggest that female patients respond to lower doses of antipsychotic medications than males and that side-effect profiles vary between the sexes. However, the majority of preclinical trials use only male laboratory animals, and human clinical trials consist of too few women to analyze their response as a separate group. Although changes in hormone production occurring at multiple stages throughout a women's life (such as during pregnancy, breast feeding, menopause, and postmenopausal) are presented as too complex to deal with in clinical trials, they could instead be embraced as clinical dilemmas that require additional study and consideration. We suggest that a focus should be made to reanalyze data from existing major treatment trials of antipsychotics to determine what medications specifically provide the most efficacy for female patients and at what dose range. In addition, new prospective studies are needed to specifically address appropriate adjustments in psychopharmacologic treatment for female patients during pregnancy, and when postmenopausal. More studies of the effects of antipsychotics on male and female fetuses in utero and during breast feeding are also needed to better manage women with schizophrenia and their offspring on a long-term basis in the community. There is currently too little known about sex differences in neuropharmacology. With the new USA National Institutes of Health policy to include sex in all new proposals, the time has come to close this gap in knowledge.

Pharmacogenetics and outcome with antipsychotic drugs.

PubMed

Pouget, Jennie G; Shams, Tahireh A; Tiwari, Arun K; Müller, Daniel J

2014-12-01

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.

Pharmacogenetics and outcome with antipsychotic drugs

PubMed Central

Pouget, Jennie G.; Shams, Tahireh A.; Tiwari, Arun K.; Müller, Daniel J.

2014-01-01

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h2~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future. PMID:25733959

Determinants of physical health parameters in individuals with intellectual disability who use long-term antipsychotics.

PubMed

de Kuijper, Gerda; Mulder, Hans; Evenhuis, Heleen; Scholte, Frans; Visser, Frank; Hoekstra, Pieter J

2013-09-01

Individuals with intellectual disability frequently use antipsychotics for many years. This may have detrimental health effects, including neurological symptoms and metabolic and hormonal dysregulation, the latter possibly affecting bone metabolism. There is large variability in the degree in which antipsychotic agents lead to these health problems. In the current study we investigated potential determinants of physical symptoms and biological parameters known to be associated with use of antipsychotics in a convenience sample of 99 individuals with intellectual disability who had used antipsychotics for more than one year for behavioural symptoms. We focused on extrapyramidal symptoms; on overweight and presence of components of the metabolic syndrome; and on elevated plasma prolactin and bone turnover parameters. As predictor variables, we used patient (sex, age, genetic polymorphisms, and severity of intellectual disability) and medication use (type and dosage) characteristics. We found extrapyramidal symptoms to be present in 53%, overweight or obesity in 46%, and the metabolic syndrome in 11% of participants. Hyperprolactineaemia and one or more elevated bone turnover markers were present in 17% and 25%, respectively. Higher age and more severe intellectual disability were associated with dyskinesia and a higher dosage of the antipsychotic drug was associated with parkinsonism. Less severe intellectual disability was related to higher Body Mass Index. Use of atypical antipsychotics was associated with higher diastolic blood pressure and elevated fasting glucose. Clinicians who prescribe antipsychotics in individuals with intellectual disability should carefully balance the potential benefits of prolonged treatment against the risk of health hazards associated with the use of antipsychotics. Copyright © 2013 Elsevier Ltd. All rights reserved.

Long-acting injectable antipsychotics update: lengthening the dosing interval and expanding the diagnostic indications.

PubMed

Citrome, Leslie

2017-10-01

Long-acting injectable (LAI) antipsychotics are a useful but underutilized option in the management of schizophrenia. Areas covered: This is a narrative review of newer LAI antipsychotics approved by the US Food and Drug Administration and is an update to a previously published review from 2013. Emphasized are new indications and new dosing intervals. Expert commentary: Ensuring that persons receiving oral antipsychotics are aware that LAI antipsychotics are available is important. The use of LAI antipsychotics can decrease the risk of relapse in both first-episode and chronic schizophrenia. Available treatments differ in terms of specific indications, approved injection sites, needle gauge, injection volume, injection interval, requirements for oral supplementation, availability of pre-filled syringes, storage needs, and post-injection observation period, as well as potential drug-drug interactions and commonly encountered adverse reactions. Approved indications have expanded beyond schizophrenia to also include bipolar maintenance (risperidone microspheres and aripiprazole monohydrate) and schizoaffective disorder (paliperidone palmitate monthly). Intervals between injections can be longer than one month (six-week or two-month aripiprazole lauroxil, and three-month paliperidone palmitate). After a review of the evidence-base, guidance is offered on the appropriate selection among the LAI formulations of both first and second-generation antipsychotics.

Antipsychotic-like vs cataleptogenic actions in mice of novel antipsychotics having D2 antagonist and 5-HT1A agonist properties.

PubMed

Bardin, Laurent; Kleven, Mark S; Barret-Grévoz, Catherine; Depoortère, Ronan; Newman-Tancredi, Adrian

2006-09-01

A new generation of proven or potential antipsychotics, including aripiprazole, bifeprunox, SSR181507 and SLV313, exhibit agonist actions at serotonin 5-HT1A receptors, but little comparative data are available on their pharmacological profiles. Here, we compared in mice the in vivo antipsychotic-like vs cataleptogenic activities of these compounds with those of drugs that exhibit little interaction at 5-HT1A receptors, such as haloperidol, olanzapine and risperidone. All the drugs dose-dependently reduced apomorphine-induced climbing or sniffing and, with the exception of ziprasidone, produced complete suppression of these responses. In the bar catalepsy test, when administered alone, haloperidol, olanzapine and risperidone produced marked catalepsy, whereas, at doses up to 40 mg/kg, aripiprazole, SLV313, SSR181507, and sarizotan produced little or no catalepsy. The latter compounds, therefore, displayed a large separation between doses with 'antipsychotic-like' and those with cataleptogenic actions. When 5-HT1A receptors were blocked by pretreatment with WAY100635 (2.5 mg/kg, s.c.), cataleptogenic properties of SSR181507 and sarizotan were unmasked, and the catalepsy induced by bifeprunox was enhanced. In the case of aripiprazole and SLV313, although WAY100635 produced upward shifts in their dose-response, the magnitude of catalepsy appeared to reach an asymptotic plateau, suggesting that other mechanisms may be involved in their low cataleptogenic liability. The present data confirm that 5-HT1A receptor activation reduces or even completely prevents the cataleptogenic potential of novel antipsychotic agents. Further, they indicate that the balance of affinity and/or efficacy between D2 and 5-HT1A receptors profoundly influences their pharmacological activities, and will likely impact their therapeutic profiles.

Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

PubMed Central

2012-01-01

Background Antipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1). Moreover, we account for similarities in brain changes between schizophrenia and overweight patients. Discussion Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogs used in the treatment of type 2 diabetes are associated with significant and sustained weight loss in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogs are discussed. Conclusions We propose that adjunctive treatment with GLP-1 analogs may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies in schizophrenia patients with antipsychotic-induced weight gain. Clinical research to support this idea is highly warranted. PMID:22891821

Comparative effect of antipsychotics on risk of self-harm among patients with schizophrenia.

PubMed

Ma, C-H; Chang, S-S; Tsai, H-J; Gau, S S-F; Chen, I-M; Liao, S-C; Chien, Y-L; Hsieh, M H; Wu, C-S

2018-04-01

To investigate the association of different antipsychotic treatments with hospitalization due to self-harm among patients with schizophrenia. This retrospective cohort study was based on Taiwan's universal health insurance database. Patients aged 15-45 years with a newly diagnosed schizophrenic disorder in 2001-2012 were included. The study outcome was the first hospitalization due to self-harm or undetermined injury after the diagnosis of schizophrenic disorders. The exposure status of antipsychotics was modeled as a time-dependent variable. The analyses were stratified by antipsychotic dosage based on defined daily dose (DDD). Among 70 380 patients with a follow-up of 500 355 person-years, 2272 self-harm hospitalization episodes were identified. Compared with none or former use, current use of several second-generation antipsychotics with a dose of one DDD or above, including amisulpride, aripiprazole, clozapine, risperidone, and sulpiride, was associated with decreased risk of self-harm hospitalization, with clozapine showing the strongest effect (adjusted rate ratio = 0.26, 95% confidence interval 0.15-0.47). The protective effect on self-harm may vary across different antipsychotics. Further studies are needed to replicate the findings. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Glutamatergic neurotransmission modulation and the mechanisms of antipsychotic atypicality.

PubMed

Heresco-Levy, Uriel

2003-10-01

The neurotransmission mediated by the excitatory amino acids (EAA) glutamate (GLU) and aspartate is of interest to the pharmacotherapy of psychosis due to its role in neurodevelopment and neurotoxicity, its complex interactions with dopaminergic and other neurotransmitter systems and its pivotal importance in recent models of schizophrenia. Accumulating evidence indicates that modulation of glutamatergic neurotransmission may play an important role in the mechanisms of action of atypical antipsychotic drugs. The principles of the phencyclidine (PCP) model of schizophrenia suggest that conventional neuroleptics cannot counteract all aspects of schizophrenia symptomatology, while a more favorable outcome, including anti-negative and cognitive symptoms effects, would be expected with the use of treatment modalities targeting glutamatergic neurotransmission. Clozapine and other presently used atypical antipsychotics differ from conventional neuroleptics in the way they affect various aspects of glutamatergic receptors function. In this context, a specific hypothesis suggesting an agonistic role of clozapine at the N-methyl-D-aspartate (NMDA) subtype of GLU receptors has been postulated. Furthermore, the results of the first generation of clinical trials with glycine (GLY) site agonists of the NMDA receptor in schizophrenia suggest that this type of compounds (1) have efficacy and side effects profiles different than those of conventional neuroleptics and (2) differ in their synergic effects when used in addition to conventional neuroleptics versus clozapine and possibly additional atypical antipsychotics. These findings (1) bring further support to the hypothesis that glutamatergic effects may play an important role in the mechanism of action of atypical antipsychotics, (2) help explain the unique clinical profile of clozapine, and (3) suggest that GLY site agonists of the NMDA receptor may represent a new class of atypical antipsychotic medication. Future research in

Using Mood Ratings and Mood Induction in Assessment and Intervention for Severe Problem Behavior.

ERIC Educational Resources Information Center

Carr, Edward G.; McLaughlin, Darlene Magito; Giacobbe-Grieco, Theresa; Smith, Christopher E.

2003-01-01

A study examined whether a correlation existed between mood ratings and subsequent display of problem behavior in eight adults with mental retardation. Results indicated that bad mood ratings were highly predictive of problem behavior. When an induction procedure to improve mood ratings was implemented, dramatic decreases in problem behaviors…

Depending on My Mood: Mood-Driven Influences on Text Comprehension

PubMed Central

Bohn-Gettler, Catherine M.; Rapp, David N.

2011-01-01

Reading comprehension is a critical component of success in educational settings. To date, research on text processing in educational and cognitive psychological domains has focused predominantly on cognitive influences on comprehension, and in particular, those influences that might be derived from particular tasks or strategies. However, there is growing interest in documenting the influences of emotional factors on the processes and products of text comprehension, because these factors are less likely to be associated with explicit reading strategies. The present study examines this issue by evaluating the degree to which mood can influence readers’ processing of text. Participants in control, happy-induced, or sad-induced groups thought aloud while reading expository texts. Happy, sad, and neutral moods influenced the degree to which readers engaged in particular types of coherence-building processes in the service of comprehension. Although reading strategies clearly influence processing, understudied factors that are less explicitly goal-driven, such as mood, can similarly impact comprehension activity. These findings have important implications for the role of mood on reading instruction and evaluation. PMID:21927504

Mood and threat to attitudinal freedom: delineating the role of mood congruency and hedonic contingency in counterattitudinal message processing.

PubMed

Ziegler, Rene; Schlett, Christian; Aydinli, Arzu

2013-08-01

The present research examined when happy individuals' processing of a counterattitudinal message is guided by mood-congruent expectancies versus hedonic considerations. Recipients in positive, neutral, or negative mood read a strong or weak counterattitudinal message which either contained a threat to attitudinal freedom or did not contain such a threat. As expected, a freedom-threatening counterattitudinal message was more mood threatening than a counterattitudinal message not threatening freedom. Furthermore, as predicted by the mood-congruent expectancies approach, people in positive mood processed a nonthreatening counterattitudinal message more thoroughly than people in negative mood. Message processing in neutral mood lay in between. In contrast, as predicted by the hedonic-contingency view, a threatening counterattitudinal message was processed less thoroughly in positive mood than in neutral mood. In negative mood, processing of a threatening counterattitudinal message was as low as in positive mood. These findings suggest that message processing is determined by mood congruency unless hedonic considerations override expectancy-based processing inclinations.

Brain structural changes associated with chronicity and antipsychotic treatment in schizophrenia.

PubMed

Tomelleri, Luisa; Jogia, Jigar; Perlini, Cinzia; Bellani, Marcella; Ferro, Adele; Rambaldelli, Gianluca; Tansella, Michele; Frangou, Sophia; Brambilla, Paolo

2009-12-01

Accumulating evidence suggest a life-long impact of disease related mechanisms on brain structure in schizophrenia which may be modified by antipsychotic treatment. The aim of the present study was to investigate in a large sample of patients with schizophrenia the effect of illness duration and antipsychotic treatment on brain structure. Seventy-one schizophrenic patients and 79 age and gender matched healthy participants underwent brain magnetic resonance imaging (MRI). All images were processed with voxel based morphometry, using SPM5. Compared to healthy participants, patients showed decrements in gray matter volume in the left medial and left inferior frontal gyrus. In addition, duration of illness was negatively associated with gray matter volume in prefrontal regions bilaterally, in the temporal pole on the left and the caudal superior temporal gyrus on the right. Cumulative exposure to antipsychotics correlated positively with gray matter volumes in the cingulate gyrus for typical agents and in the thalamus for atypical drugs. These findings (a) indicate that structural abnormalities in prefrontal and temporal cortices in schizophrenia are progressive and, (b) suggest that antipsychotic medication has a significant impact on brain morphology.

Type 2 Diabetes Mellitus in Youth Exposed to Antipsychotics: A Systematic Review and Meta-analysis.

PubMed

Galling, Britta; Roldán, Alexandra; Nielsen, René E; Nielsen, Jimmi; Gerhard, Tobias; Carbon, Maren; Stubbs, Brendon; Vancampfort, Davy; De Hert, Marc; Olfson, Mark; Kahl, Kai G; Martin, Andres; Guo, Jeff J; Lane, Hsien-Yuan; Sung, Fung-Chang; Liao, Chun-Hui; Arango, Celso; Correll, Christoph U

2016-03-01

Antipsychotics are used increasingly in youth for nonpsychotic and off-label indications, but cardiometabolic adverse effects and (especially) type 2 diabetes mellitus (T2DM) risk have raised additional concern. To assess T2DM risk associated with antipsychotic treatment in youth. Systematic literature search of PubMed and PsycINFO without language restrictions from database inception until May 4, 2015. Data analyses were performed in July 2015, and additional analyses were added in November 2015. Longitudinal studies reporting on T2DM incidence in youth 2 to 24 years old exposed to antipsychotics for at least 3 months. Two independent investigators extracted study-level data for a random-effects meta-analysis and meta-regression of T2DM risk. The coprimary outcomes were study-defined T2DM, expressed as cumulative T2DM risk or as T2DM incidence rate per patient-years. Secondary outcomes included the comparison of the coprimary outcomes in antipsychotic-treated youth with psychiatric controls not receiving antipsychotics or with healthy controls. Thirteen studies were included in the meta-analysis, including 185,105 youth exposed to antipsychotics and 310,438 patient-years. The mean (SD) age of patients was 14.1 (2.1) years, and 59.5% were male. The mean (SD) follow-up was 1.7 (2.3) years. Among them, 7 studies included psychiatric controls (1,342,121 patients and 2,071,135 patient-years), and 8 studies included healthy controls (298,803 patients and 463,084 patient-years). Antipsychotic-exposed youth had a cumulative T2DM risk of 5.72 (95% CI, 3.45-9.48; P < .001) per 1000 patients. The incidence rate was 3.09 (95% CI, 2.35-3.82; P < .001) cases per 1000 patient-years. Compared with healthy controls, cumulative T2DM risk (odds ratio [OR], 2.58; 95% CI, 1.56-4.24; P < .0001) and incidence rate ratio (IRR) (IRR, 3.02; 95% CI, 1.71-5.35; P < .0001) were significantly greater in antipsychotic-exposed youth. Similarly, compared with psychiatric controls

Adherence to depot versus oral antipsychotic medication in schizophrenic patients during the long-term therapy.

PubMed

Stanković, Zana; Ille, Tatjana

2013-03-01

There is a high rate of schizophrenic patients who do not adhere to their prescribed therapy, despite the implementation of antipsychotic long-acting injections and the introduction of atypical antipsychotics. The aim of this study was to investigate the differences in sociodemographic, clinical and medication adherence variables between the two groups of schizophrenic patients on maintenance therapy with depot antipsychotic fluphenazine decanoate and oral antipsychotics only as well as a correlation between the medication adherence and other examined variables. A total of 56 patients of both genders, aged < 60 years, with the diagnosis of schizophrenia (F20) (ICD-10, 1992) clinically stable for at least 6 months were introduced in this cross-sectional study. The patients from the depot group (n = 19) were on classical depot antipsychotic fluphenazine decanoate administering intramuscularly every 4 weeks (with or without oral antipsychotic augmentation) and the patients from the oral group (n = 37) were on oral therapy alone with classical or atypical antipsychotics, either as monotherapy or combined. The Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity. Item G12 of the PANSS was used to assess insight into the illness. The patients completed the Medical Adherence Rating Scale (MARS) was used to assess adherence to the therapy. A higher MARS score indicates behavior [Medical Adherence Questionnaire (MAQ subscale)] and attitudes toward medication [Drug Attitude Inventory (DAI subscale)] that are more consistent with treatment adherence. The exclusion criteria were determined. The Pearson's chi2 test was used to compare categorical variables, Student's t-test to compare continuous variables and Pearson's correlation to test the correlation significance; p = 0.05. Significant between-group differences in age, illness duration, chlorpromazine equivalents, PANSS score and DAI subscore were found. Item G12 of the PANSS subscore and MARS

Antipsychotic therapeutic drug monitoring: psychiatrists’ attitudes and factors predicting likely future use

PubMed Central

Law, Suzanne; Haddad, Peter M.; Chaudhry, Imran B.; Husain, Nusrat; Drake, Richard J.; Flanagan, Robert J.; David, Anthony S.

2015-01-01

Background: This study aimed to explore predictive factors for future use of therapeutic drug monitoring (TDM) and to further examine psychiatrists’ current prescribing practices and perspectives regarding antipsychotic TDM using plasma concentrations. Method: A cross-sectional study for consultant psychiatrists using a postal questionnaire was conducted in north-west England. Data were combined with those of a previous London-based study and principal axis factor analysis was conducted to identify predictors of future use of TDM. Results: Most of the 181 participants (82.9%, 95% confidence interval 76.7–87.7%) agreed that ‘if TDM for antipsychotics were readily available, I would use it’. Factor analysis identified five factors from the original 35 items regarding TDM. Four of the factors significantly predicted likely future use of antipsychotic TDM and together explained 40% of the variance in a multivariate linear regression model. Likely future use increased with positive attitudes and expectations, and decreased with potential barriers, negative attitudes and negative expectations. Scientific perspectives of TDM and psychiatrist characteristics were not significant predictors. Conclusion: Most senior psychiatrists indicated that they would use antipsychotic TDM if available. However, psychiatrists’ attitudes and expectations and the potential barriers need to be addressed, in addition to the scientific evidence, before widespread use of antipsychotic TDM is likely in clinical practice. PMID:26301077

Biases in medication prescribing: the case of second-generation antipsychotics.

PubMed

Makhinson, Michael

2010-01-01

The shift from first-generation antipsychotic medications to second-generation antipsychotic medications initially caused a wave of excitement about the potential for improved and broader efficacy of these medications concurrent with an improved side-effect profile. Recent data from high-quality research analyses have subsequently raised significant questions about these claims. This research evidence has, however, not altered prescribing behavior in a way that would be expected from fully rational evaluation of the evidence. Prescribing decisions represent poorly understood, complex behaviors influenced by a number of external and internal forces, some of which may be elucidated by advances in social and cognitive psychology. In this article, the decision to prescribe first- versus second-generation antipsychotic medications is examined, and specific social psychological biases and individual cognitive biases are hypothesized to be significant influences on clinicians. These biases may perpetuate disparity between research evidence and clinical practice.

Mood congruent tuning of reward expectation in positive mood: evidence from FRN and theta modulations

PubMed Central

Pourtois, Gilles

2017-01-01

Abstract Positive mood broadens attention and builds additional mental resources. However, its effect on performance monitoring and reward prediction errors remain unclear. To examine this issue, we used a standard mood induction procedure (based on guided imagery) and asked 45 participants to complete a gambling task suited to study reward prediction errors by means of the feedback-related negativity (FRN) and mid-frontal theta band power. Results showed a larger FRN for negative feedback as well as a lack of reward expectation modulation for positive feedback at the theta level with positive mood, relative to a neutral mood condition. A control analysis showed that this latter result could not be explained by the mere superposition of the event-related brain potential component on the theta oscillations. Moreover, these neurophysiological effects were evidenced in the absence of impairments at the behavioral level or increase in autonomic arousal with positive mood, suggesting that this mood state reliably altered brain mechanisms of reward prediction errors during performance monitoring. We interpret these new results as reflecting a genuine mood congruency effect, whereby reward is anticipated as the default outcome with positive mood and therefore processed as unsurprising (even when it is unlikely), while negative feedback is perceived as unexpected. PMID:28199707

Efficacy and safety of novel antipsychotics: a critical review.

PubMed

Balestrieri, Matteo; Vampini, Claudio; Bellantuono, Cesario

2000-10-01

Efficacy and safety of novel antipsychotic (AP) drugs (amisulpride, olanzapine, quetiapine, ziprasidone and zotepine) have been reviewed. Data on their antipsychotic efficacy and side effects profile have been evaluated only on the basis of controlled trials so far published. Overall, all these drugs have shown an antipsychotic efficacy on positive symptoms of schizophrenia similar to that of the conventional AP drugs. On negative symptoms, all novel AP drugs, except quetiapine and ziprasidone, demonstrated a better efficacy than haloperidol. Long-term efficacy of these AP drugs in the maintenance treatment of schizophrenia needs to be explored by further, better-designed, epidemiological studies. The safety profile shows that the novel AP drugs are generally well-tolerated and induce significantly less acute extrapyramidal side effects in comparison with haloperidol. Some methodological flaws in the experimental design of the clinical trials analysed are discussed. Although these novel AP drugs have potential clinical advantages, a number of relevant questions still remain to be addressed, in order to establish the impact of these drugs in the overall treatment of schizophrenia. Copyright 2000 John Wiley & Sons, Ltd.

Could cannabidiol be used as an alternative to antipsychotics?

PubMed

Fakhoury, Marc

2016-09-01

Schizophrenia is a mental disorder that affects close to 1% of the population. Individuals with this disorder often present signs such as hallucination, anxiety, reduced attention, and social withdrawal. Although antipsychotic drugs remain the cornerstone of schizophrenia treatment, they are associated with severe side effects. Recently, the endocannabinoid system (ECS) has emerged as a potential therapeutic target for pharmacotherapy that is involved in a wide range of disorders, including schizophrenia. Since its discovery, a lot of effort has been devoted to the study of compounds that can modulate its activity for therapeutic purposes. Among them, cannabidiol (CBD), a non-psychoactive component of cannabis, shows great promise for the treatment of psychosis, and is associated with fewer extrapyramidal side effects than conventional antipsychotic drugs. The overarching goal of this review is to provide current available knowledge on the role of the dopamine system and the ECS in schizophrenia, and to discuss key findings from animal studies and clinical trials investigating the antipsychotic potential of CBD. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Antipsychotic-induced weight gain--pharmacogenetic studies].

PubMed

Olajossy-Hilkesberger, Luiza; Godlewska, Beata; Marmurowska-Michałowskal, Halina; Olajossy, Marcin; Landowski, Jerzy

2006-01-01

Drug-naive patients with schizophrenia often present metabolic abnormalities and obesity. Weight gain may be the side effect of treatment with many antipsychotic drugs. Genetic effects, besides many other factors, are known to influence obesity in patients with schizophrenia treated with antipsychotics. Numerous studies of several genes' polymorphisms have been performed. -759C/T polymorphism of 5HT2C gene attracted most attention. In 5 independent studies of this polymorphism the association between T allele with the lower AP-induced weight gain was detected. No associations could be detected between weight gain and other polymorphisms of serotonergic system genes as well as histaminergic system genes. Studies of adrenergic and dopaminergic system have neither produced any unambiguous results. Analysis of the newest candidate genes (SAP-25, leptin gene) confirmed the role of genetic factors in AP-induced weight gain. It is worth emphasising, that the studies have been conducted in relatively small and heterogenic groups and that various treatment strategies were used.

Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats

PubMed Central

Bordia, Tanuja; McIntosh, J. Michael

2012-01-01

Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce tardive dyskinesia because nicotine attenuates other drug-induced abnormal movements. We used a well established model of tardive dyskinesia in which rats injected with the commonly used antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2 mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once daily. Nicotine treatment reduced haloperidol-induced VCMs by ∼20% after 5 weeks, with a significant ∼60% decline after 13 weeks. There was no worsening of haloperidol-induced catalepsy. To understand the molecular basis for this improvement, we measured the striatal dopamine transporter and nicotinic acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment decreased the transporter and α6β2* nAChRs (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex) when given alone, with no further decline with combined drug treatment. By contrast, nicotine alone increased, while haloperidol reduced α4β2* nAChRs in both vehicle and haloperidol-treated rats. These data suggest that molecular mechanisms other than those directly linked to the transporter and nAChRs underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats. The present results are the first to suggest that nicotine may be useful for improving the tardive dyskinesia associated with antipsychotic use. PMID:22144565

The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2006 update.

PubMed

Moore, Troy A; Buchanan, Robert W; Buckley, Peter F; Chiles, John A; Conley, Robert R; Crismon, M Lynn; Essock, Susan M; Finnerty, Molly; Marder, Stephen R; Miller, Del D; McEvoy, Joseph P; Robinson, Delbert G; Schooler, Nina R; Shon, Steven P; Stroup, T Scott; Miller, Alexander L

2007-11-01

A panel of academic psychiatrists and pharmacists, clinicians from the Texas public mental health system, advocates, and consumers met in June 2006 in Dallas, Tex., to review recent evidence in the pharmacologic treatment of schizophrenia. The goal of the consensus conference was to update and revise the Texas Medication Algorithm Project (TMAP) algorithm for schizophrenia used in the Texas Implementation of Medication Algorithms, a statewide quality assurance program for treatment of major psychiatric illness. Four questions were identified via premeeting teleconferences. (1) Should antipsychotic treatment of first-episode schizophrenia be different from that of multiepisode schizophrenia? (2) In which algorithm stages should first-generation antipsychotics (FGAs) be an option? (3) How many antipsychotic trials should precede a clozapine trial? (4) What is the status of augmentation strategies for clozapine? Subgroups reviewed the evidence in each area and presented their findings at the conference. The algorithm was updated to incorporate the following recommendations. (1) Persons with first-episode schizophrenia typically require lower antipsychotic doses and are more sensitive to side effects such as weight gain and extrapyramidal symptoms (group consensus). Second-generation antipsychotics (SGAs) are preferred for treatment of first-episode schizophrenia (majority opinion). (2) FGAs should be included in algorithm stages after first episode that include SGAs other than clozapine as options (group consensus). (3) The recommended number of trials of other antipsychotics that should precede a clozapine trial is 2, but earlier use of clozapine should be considered in the presence of persistent problems such as suicidality, comorbid violence, and substance abuse (group consensus). (4) Augmentation is reasonable for persons with inadequate response to clozapine, but published results on augmenting agents have not identified replicable positive results (group

Use of antipsychotic and antidepressant within the Psychiatric Disease Centre, Regional Health Service of Ferrara.

PubMed

Bianchi, Stefano; Bianchini, Erica; Scanavacca, Paola

2011-12-20

This study aimed at describing the type and dosage of psychopharmaceuticals dispensed to patients with psychiatric disorders and to assess the percentage of patients treated with antipsychotics and antidepressants, the associated therapies, treatment adherence, and dosages used in individuals registered at the Psychiatric Disease Center (PDC), Regional Health Service of Ferrara. The analysis focused on therapeutic programmes presented to the Department of Pharmacy of the University Hospital of Ferrara of 892 patients treated by the PDC (catchment area of 134605 inhabitants). All diagnoses were made according to International Classification of Diseases (ICD-9). The analysis focused on prescriptions from September 2007 to June 2009. Data on adherence to prescribed therapy have were processed by analysis of variance. Among the patients 63% were treated with antipsychotics and 40% with antidepressants. Among patients receiving antipsychotics 92% used second-generation antipsychotics (SGAs) whereas the remaining 8% used first generation antipsychotics (FGAs). Antipsychotic doses were lower than Daily Defined Dose (DDDs), and SGAs were often given with anticholinergics to decrease side effects. Mean adherence to antipsychotic therapy was 64%. Among antidepressants, selective serotonin reuptake inhibitors (SSRIs) were the most often prescribed, 55%. Dosages of these were within the limits indicated by the technical datasheet but higher than DDDs. Only 26% of patients underwent monotherapy. In antidepressants polytherapy, medication was associated with another antidepressant, 6% or with an antipsychotic, 51%. Mean adherence to the antidepressant therapy was 64%. Patients treated with antipsychotics tend to use doses lower than DDDs. The opposite tendency was noted in patients treated with antidepressants. Only a small percentage of patients (14%) modified their neuroleptic therapy by increasing the dosage. On the contrary, patients treated with antidepressants mainly

[Treatment-resistant mood disorders].

PubMed

Machado-Vieira, Rodrigo; Soares, Jair C

2007-10-01

Mood disorders are the most prevalent psychiatric disorders. Despite new insights and advances on the neurobiological basis and therapeutic approaches for bipolar disorders and recurrent depression, elevated prevalence of recurrence, persistent sub-syndromal symptoms and treatment resistance are challenging aspects and need to be urgently addressed. The objective of this literature review is to evaluate the current concepts of treatment resistance and refractoriness in mood disorders. Genetic factors, misdiagnosis, use of inappropriate pharmacological approaches, non-compliance and biological/psychosocial stressors account for dysfunctions in mood regulation, thus increasing the prevalence of refractory mood disorders. Regarding available treatments, the use of effective doses during an adequate period followed by augmentation with a second and/or third agent, and finally switching to other agent are steps frequently necessary to optimize efficacy. However, in the treatment-resistant paradigm, drugs mimicking standard strategies, which target preferentially the monoaminergic system, can present reduced therapeutic effects. Thus, the search for new effective treatments for mood disorders is critical to decreasing the overall morbidity secondary to treatment resistance. Emerging strategies targeting brain plasticity pathways or 'plasticity enhancers', including antiglutamatergic drugs, glucocorticoid receptor antagonists and neuropeptides, have been considered promising therapeutic options for difficult-to-treat mood disorders.

Persistence of Antipsychotic Treatment in Elderly Dementia Patients: A Retrospective, Population-Based Cohort Study.

PubMed

Mast, Gavin; Fernandes, Kimberly; Tadrous, Mina; Martins, Diana; Herrmann, Nathan; Gomes, Tara

2016-06-01

Antipsychotics are commonly used to manage behavioral and psychological symptoms of dementia. Concerns over their safety and efficacy in this role have resulted in antipsychotics typically being recommended for short-term usage only when used among dementia patients. However, there is little work examining the duration of antipsychotic treatment in the elderly dementia patient population. To determine the persistence of use of antipsychotics in elderly dementia patients and the role of dose on therapy duration. A retrospective, population-based cohort study using administrative data, including dispensing records from a provincial public drug program, from Ontario, Canada between 2009 and 2012. Elderly dementia patients newly initiated onto antipsychotics were followed until drug discontinuation, death, 2-year follow-up, or end of study. Competing risk analysis was performed to determine time to discontinuation, stratified by categories of initial dose. After 2 years 49.1 % of the cohort ( N  = 22,927 of 46,695) had discontinued treatment. When stratified by dose, the high-dose group (51.1 % discontinued) discontinued more frequently than the medium- (48.7 % discontinued) and low- (47.5 % discontinued) dose groups ( p  < 0.0001). Approximately half of elderly dementia patients treated with antipsychotics discontinue within 2 years, with those on higher doses more likely to discontinue. However, the number of patients remaining on therapy represents a serious public health concern.

Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence.

PubMed

Rohleder, Cathrin; Müller, Juliane K; Lange, Bettina; Leweke, F M

2016-01-01

There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ 9 -THC), cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although, results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in both rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. Although, a plethora of mechanisms of action has been suggested, their potential relevance for the antipsychotic effects of cannabidiol still needs to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol's antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials.

Antidepressant and antipsychotic medication errors reported to United States poison control centers.

PubMed

Kamboj, Alisha; Spiller, Henry A; Casavant, Marcel J; Chounthirath, Thitphalak; Hodges, Nichole L; Smith, Gary A

2018-05-08

To investigate unintentional therapeutic medication errors associated with antidepressant and antipsychotic medications in the United States and expand current knowledge on the types of errors commonly associated with these medications. A retrospective analysis of non-health care facility unintentional therapeutic errors associated with antidepressant and antipsychotic medications was conducted using data from the National Poison Data System. From 2000 to 2012, poison control centers received 207 670 calls reporting unintentional therapeutic errors associated with antidepressant or antipsychotic medications that occurred outside of a health care facility, averaging 15 975 errors annually. The rate of antidepressant-related errors increased by 50.6% from 2000 to 2004, decreased by 6.5% from 2004 to 2006, and then increased 13.0% from 2006 to 2012. The rate of errors related to antipsychotic medications increased by 99.7% from 2000 to 2004 and then increased by 8.8% from 2004 to 2012. Overall, 70.1% of reported errors occurred among adults, and 59.3% were among females. The medications most frequently associated with errors were selective serotonin reuptake inhibitors (30.3%), atypical antipsychotics (24.1%), and other types of antidepressants (21.5%). Most medication errors took place when an individual inadvertently took or was given a medication twice (41.0%), inadvertently took someone else's medication (15.6%), or took the wrong medication (15.6%). This study provides a comprehensive overview of non-health care facility unintentional therapeutic errors associated with antidepressant and antipsychotic medications. The frequency and rate of these errors increased significantly from 2000 to 2012. Given that use of these medications is increasing in the US, this study provides important information about the epidemiology of the associated medication errors. Copyright © 2018 John Wiley & Sons, Ltd.

The US Food and Drug Administration's Perspective on the New Antipsychotic Pimavanserin.

PubMed

Mathis, Mitchell V; Muoio, Brendan M; Andreason, Paul; Avila, Amy M; Farchione, Tiffany; Atrakchi, Aisar; Temple, Robert J

2017-06-01

To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. We describe the regulatory and clinical issues important to the FDA's approval of this New Drug Application, with special focus on the risk-benefit balance. We also describe a new labeling feature that presents additional efficacy data to clinicians. Data sets for all relevant clinical trials of pimavanserin and the Applicant's and FDA's analyses of these data were considered in this review. Data were available from 616 patients with Parkinson's disease with hallucinations and delusions who received at least 1 dose of pimavanserin, with a total exposure of 825 patient-years in the Parkinson's disease psychosis population. Pimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease. In the Applicant's single pivotal trial, 80.5% of pimavanserin patients experienced at least some improvement in symptoms compared to 58.1% of patients taking placebo. Pimavanserin did not worsen motor function, an adverse effect commonly observed with other antipsychotics, probably because of a lack of consequential dopamine binding. Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease. Although pimavanserin appears to have a pharmacologic mechanism that is different from other atypical antipsychotics, concern remained that the increased risk of death seen with antipsychotic use in elderly demented patients, and described in all approved antipsychotic labels, would also occur with pimavanserin. Pimavanserin bears the same boxed warning about the risk of death associated with antipsychotic use in elderly patients with dementia. © Copyright 2017 Physicians Postgraduate Press, Inc.

Investigation of air quality on mood

NASA Astrophysics Data System (ADS)

Isaac, L.

2017-12-01

My project evaluated the effect of air quality on mood. We quantified people's mood using an online survey and then looked at the relationship between mood and pm 2.5 and ozone concentrations. Mood was quantified using the Positive and Negative Affect Schedule (PANAS). I found that with increasing ozone AQI the positive score for mood decreased and the negative score for mood increased. The trend was not significant (p=0.414 for positive and p=0.158 for negative). I also found that the positive score decreased with increasing PM2.5 AQI (p=0.19); however there was no pattern between the negative scores and PM 2.5 AQI. In summary, air quality does look to have a negative effect on mood; however more data is needed to confirm this relationship.

Atypical antipsychotics, insulin resistance and weight; a meta-analysis of healthy volunteer studies.

PubMed

Burghardt, Kyle J; Seyoum, Berhane; Mallisho, Abdullah; Burghardt, Paul R; Kowluru, Renu A; Yi, Zhengping

2018-04-20

Atypical antipsychotics increase the risk of diabetes and cardiovascular disease through their side effects of insulin resistance and weight gain. The populations for which atypical antipsychotics are used carry a baseline risk of metabolic dysregulation prior to medication which has made it difficult to fully understand whether atypical antipsychotics cause insulin resistance and weight gain directly. The purpose of this work was to conduct a systematic review and meta-analysis of atypical antipsychotic trials in healthy volunteers to better understand their effects on insulin sensitivity and weight gain. Furthermore, we aimed to evaluate the occurrence of insulin resistance with or without weight gain and with treatment length by using subgroup and meta-regression techniques. Overall, the meta-analysis provides evidence that atypical antipsychotics decrease insulin sensitivity (standardized mean difference=-0.437, p<0.001) and increase weight (standardized mean difference=0.591, p<0.001) in healthy volunteers. It was found that decreases in insulin sensitivity were potentially dependent on treatment length but not weight gain. Decreases in insulin sensitivity occurred in multi-dose studies <13days while weight gain occurred in studies 14days and longer (max 28days). These findings provide preliminary evidence that atypical antipsychotics cause insulin resistance and weight gain directly, independent of psychiatric disease and may be associated with length of treatment. Further, well-designed studies to assess the co-occurrence of insulin resistance and weight gain and to understand the mechanisms and sequence by which they occur are required. Copyright © 2018 Elsevier Inc. All rights reserved.

Mood and birth experience.

PubMed

Crowther, Susan; Smythe, Liz; Spence, Deb

2014-03-01

Those at the birth of a baby sometimes speak of the experience as significant and meaningful; an experience in which there is an atmosphere or mood that surrounds the occasion. This paper explores this mood, its recognition, disclosure and how we attune or not to it. The paper is philosophically underpinned by hermeneutic phenomenology. The Heideggerian notion of "attunement to mood" is used to interpret this phenomenon. This paper describes how such a mood becomes visible. Using a hermeneutic phenomenological approach, 14 tape-recorded transcribed interviews, each about an hour long, were conducted over 8 months from mothers, birth partners, midwives and obstetricians. The stories crafted from these transcripts have been interpreted alongside my own preunderstandings and related literature. Appropriate ethical approval was gained. Analysis suggests that there is a positively construed mood of joy at birth that can be concealed when disrupted. Disturbing this mood has the effect of exposing the world of birth and its inherent activities and feelings revealing possible meanings inherent in the lived birth experiences. Disturbances at birth provide distinctions and tensions in which a concealed constitutive mood at birth can be seen. This paper provides insight towards a deeper appreciation into how the sacred joy of birth may be protected. The way in which we attune to birth may have consequences to birth outcomes and to the experience of childbirth. The consequences of these findings for those in the world of birth are discussed. Copyright © 2013 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sárvári, Anitta K., E-mail: anittasarvari@med.unideb.hu; Veréb, Zoltán, E-mail: jzvereb@gmail.com; Uray, Iván P., E-mail: ipuray@mdanderson.org

Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism andmore » proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones

Systematic review of the economic aspects of nonadherence to antipsychotic medication in patients with schizophrenia.

PubMed

Dilla, Tatiana; Ciudad, Antonio; Alvarez, María

2013-01-01

There is strong evidence supporting the link between nonadherence to antipsychotic medication and relapse of schizophrenia. However, less obvious are the economic consequences of nonadherence. The systematic review reported here evaluated the economic aspects of nonadherence to antipsychotic medication. A systematic review of scientific papers in the PubMed MEDLINE, Embase, PsychINFO, BIOSIS, and Evidence-Based Medicine Reviews databases was undertaken. Studies that measured adherence to antipsychotic medication and that provided comparative information on health care costs were included. Eight studies met the inclusion criteria. All were observational. Despite the differences between the studies in terms of design, adherence measures, and cost components analyzed, the results of this systematic review indicate that nonadherence to antipsychotic medication is associated with increased hospitalization rates and resource utilization, resulting in increased direct health care costs. Nonadherence to antipsychotic medication results in poor health and economic outcomes; therefore, the authors suggest endorsing interventions aimed at improving adherence because they can improve patient health without substantially increasing costs.

Movement Disorders Induced by the "Atypical" Antipsychotic Aripiprazole.

PubMed

Selfani, Karim; Soland, Valérie L; Chouinard, Sylvain; Huot, Philippe

2017-01-01

Aripiprazole is an antipsychotic that acts as a partial agonist at dopamine D2 receptors. Because of its partial agonist activity, it was believed that aripiprazole would be less susceptible than typical antipsychotics to induce extrapyramidal side effects. However, a few case-reports and case-series detailing aripiprazole-induced movement disorders have been published, suggesting that aripiprazole-induced movement disorders may arise. Here, we seek to report further cases of aripiprazole-induced movement disorders to raise the awareness of clinicians on this adverse effect. Patients referred to the André-Barbeau Movement Disorder clinic treated with aripiprazole were enrolled in this study. Their charts were retrospectively reviewed and data regarding past psychiatric history, past antipsychotic medication, duration of aripiprazole treatment, daily dose of aripiprazole administered, and resulting movement disorders were collected. We report 14 cases of parkinsonism, tardive dyskinesia and akathisia induced by aripiprazole. Some of these, mostly the parkinsonian phenotype, abated spontaneously following drug discontinuation, whereas others, mostly related to tardive phenomena, persisted after aripiprazole was discontinued, and required treatment. This case-series adds to the existing literature that suggests that movement disorders may arise following treatment with aripiprazole. Clinicians should be aware of this potential side effect when prescribing aripiprazole to patients.

Does changing from a first generation antipsychotic (perphenazin) to a second generation antipsychotic (risperidone) alter brain activation and motor activity? A case report

PubMed Central

2013-01-01

Background In patients with schizophrenia, altered brain activation and motor activity levels are central features, reflecting cognitive impairments and negative symptoms, respectively. Newer studies using nonlinear methods have addressed the severe disturbances in neurocognitive functioning that is regarded as one of the core features of schizophrenia. Our aim was to compare brain activation and motor activity in a patient during pharmacological treatment that was switched from a first- to a second-generation antipsychotic drug. We hypothesised that this change of medication would increase level of responding in both measures. Case presentation We present the case of a 53-year-old male with onset of severe mental illness in adolescence, ICD-10 diagnosed as schizophrenia of paranoid type, chronic form. We compared brain activation and motor activity in this patient during pharmacological treatment with a first-generation (perphenazin), and later switched to a second-generation (risperidone) antipsychotic drug. We used functional magnetic resonance imaging (fMRI) to measure brain activation and wrist worn actigraphy to measure motor activity. Conclusion Our study showed that brain activation decreased in areas critical for cognitive functioning in this patient, when changing from a first to a second generation antipsychotic drug. However the mean motor activity level was unchanged, although risperidone reduced variability, particularly short-term variability from minute to minute. Compared to the results from previous studies, the present findings indicate that changing to a second-generation antipsychotic alters variability measures towards that seen in a control group, but with reduced brain activation, which was an unexpected finding. PMID:23648137

Does changing from a first generation antipsychotic (perphenazin) to a second generation antipsychotic (risperidone) alter brain activation and motor activity? A case report.

PubMed

Berle, Jan Øystein; Løberg, Else-Marie; Fasmer, Ole Bernt

2013-05-06

In patients with schizophrenia, altered brain activation and motor activity levels are central features, reflecting cognitive impairments and negative symptoms, respectively. Newer studies using nonlinear methods have addressed the severe disturbances in neurocognitive functioning that is regarded as one of the core features of schizophrenia. Our aim was to compare brain activation and motor activity in a patient during pharmacological treatment that was switched from a first- to a second-generation antipsychotic drug. We hypothesised that this change of medication would increase level of responding in both measures. We present the case of a 53-year-old male with onset of severe mental illness in adolescence, ICD-10 diagnosed as schizophrenia of paranoid type, chronic form. We compared brain activation and motor activity in this patient during pharmacological treatment with a first-generation (perphenazin), and later switched to a second-generation (risperidone) antipsychotic drug. We used functional magnetic resonance imaging (fMRI) to measure brain activation and wrist worn actigraphy to measure motor activity. Our study showed that brain activation decreased in areas critical for cognitive functioning in this patient, when changing from a first to a second generation antipsychotic drug. However the mean motor activity level was unchanged, although risperidone reduced variability, particularly short-term variability from minute to minute. Compared to the results from previous studies, the present findings indicate that changing to a second-generation antipsychotic alters variability measures towards that seen in a control group, but with reduced brain activation, which was an unexpected finding.

Cannabidiol exhibits anxiolytic but not antipsychotic property evaluated in the social interaction test.

PubMed

Almeida, Valéria; Levin, Raquel; Peres, Fernanda Fiel; Niigaki, Suzy T; Calzavara, Mariana B; Zuardi, Antônio W; Hallak, Jaime E; Crippa, José A; Abílio, Vanessa C

2013-03-05

Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa, has been reported to have central therapeutic actions, such as antipsychotic and anxiolytic effects. We have recently reported that Spontaneously Hypertensive Rats (SHRs) present a deficit in social interaction that is ameliorated by atypical antipsychotics. In addition, SHRs present a hyperlocomotion that is reverted by typical and atypical antipsychotics, suggesting that this strain could be useful to study negative symptoms (modeled by a decrease in social interaction) and positive symptoms (modeled by hyperlocomotion) of schizophrenia as well as the effects of potential antipsychotics drugs. At the same time, an increase in social interaction in control animals similar to that induced by benzodiazepines is used to screen potential anxiolytic drugs. The aim of this study was to investigate the effects of CBD on social interaction presented by control animals (Wistar) and SHRs. The lowest dose of CBD (1mg/kg) increased passive and total social interaction of Wistar rats. However, the hyperlocomotion and the deficit in social interaction displayed by SHRs were not altered by any dose of CBD. Our results do not support an antipsychotic property of cannabidiol on symptoms-like behaviors in SHRs but reinforce the anxiolytic profile of this compound in control rats. Copyright © 2012 Elsevier Inc. All rights reserved.

The Effects of Antipsychotics on Prolactin Levels and Women's Menstruation

PubMed Central

Bargiota, S. I.; Bonotis, K. S.; Messinis, I. E.; Angelopoulos, N. V.

2013-01-01

Introduction. Typical and atypical antipsychotic agent is currently used for treatment in the majority of patients with psychotic disorders. The aim of this review is to assess antipsychotic induced hyperprolactinaemia and the following menstrual dysfunction that affects fertility, quality of life, and therapeutic compliance of women. Method. For this purpose, Medline, PsychInfo, Cochrane library, and Scopus databases were accessed, with a focus on the publication dates between 1954 and 2012. Research of references was also performed and 78 studies were retrieved and used for the needs of this review. Results. A summary of several antipsychotics as well as frequency rates and data on hyperprolactinaemia and menstrual disorders for different agent is presented. Conclusion. Diverse prevalence rates of hyperprolactinaemia and menstrual abnormalities have been found about each medication among different studies. Menstruation plays an important role for women, thus, understanding, careful assessment, and management of hyperprolactinaemia could enhance their lives, especially when dealing with women that suffer from a psychotic disorder. PMID:24490071

Antipsychotic treatment in schizophrenia: the role of computerized neuropsychological assessment.

PubMed

Kertzman, Semion; Reznik, Ilya; Grinspan, Haim; Weizman, Abraham; Kotler, Moshe

2008-01-01

The present study analyzes the role of neurocognitive assessment instruments in the detection of the contribution of antipsychotic treatment to cognitive functioning. Recently, a panel of experts suggested six main domains (working memory; attention/vigilance; verbal/visual learning and memory; reasoning and problem solving; speed of processing) implicated in schizophrenia-related cognitive deficits, which serve as a theoretical base for creation of real-time computerized neurocognitive batteries. The high sensitivity of computerized neuropsychological testing is based on their ability to adopt the reaction time (RT) paradigm for the assessment of brain function in a real-time regime. This testing is highly relevant for the monitoring of the cognitive effects of antipsychotics. Computerized assessment assists in the identification of state- and trait-related cognitive impairments. The optimal real-time computerized neurocognitive battery should composite balance between broad and narrow coverage of cognitive domains relevant to the beneficial effects of antipsychotics and will enable better planning of treatment and rehabilitation programs.

Paralytic ileus requiring hospitalization secondary to high-dose antipsychotic polypharmacy and benztropine.

PubMed

Kwiatkowski, Mercedes; Denka, Zachary D; White, Christopher C

2011-01-01

Ileus can result from the combined activity of antipsychotic and anticholinergic medications. Despite frequent use, case reports in the literature are sparse. We present a patient who developed a paralytic ileus requiring extended hospitalization. Providers should minimize antipsychotic and concurrent anticholinergic medications, consider prophylactic bowel regimens and monitor for constipation. Copyright © 2011 Elsevier Inc. All rights reserved.

Mood lability and psychopathology in youth.

PubMed

Stringaris, A; Goodman, R

2009-08-01

Mood lability is a concept widely used. However, data on its prevalence and morbid associations are scarce. We sought to establish the occurrence and importance of mood lability in a large community sample of children and adolescents by testing a priori hypotheses. Cross-sectional data were taken from a national mental health survey including 5326 subjects aged 8-19 years in the UK. The outcomes were prevalence and characteristics of mood lability and its associations with psychopathology and overall impairment. Mood lability occurred in more than 5% of the population of children and adolescents, both by parent and self-report. Mood lability was strongly associated with a wide range of psychopathology and was linked to significant impairment even in the absence of psychiatric disorders. Mood lability was particularly strongly associated with co-morbidity between internalizing and externalizing disorders, even when adjusting for the association with individual disorders. The pattern of results did not change after excluding youth with bipolar disorder or with episodes of elated mood. Clinically significant mood lability is relatively common in the community. Our findings indicate that mood lability is not a mere consequence of other psychopathology in that it is associated with significant impairment even in the absence of psychiatric diagnoses. Moreover, the pattern of association of mood lability with co-morbidity suggests that it could be a risk factor shared by both internalizing and externalizing disorders. Our data point to the need for greater awareness of mood lability and its implications for treatment.

Medication and aggressiveness in real-world schizophrenia. Results from the FACE-SZ dataset.

PubMed

Fond, G; Boyer, L; Favez, M; Brunel, L; Aouizerate, B; Berna, F; Capdevielle, D; Chereau, I; Dorey, J M; Dubertret, C; Dubreucq; Faget, C; Gabayet, F; Laouamri, H; Lancon, C; Le Strat, Y; Misdrahi, D; Rey, R; Passerieux, C; Schandrin, A; Schurhoff, F; Tronche, A M; Urbach, M; Vidalhet, P; Llorca, P M; Pelissolo, A

2016-02-01

The primary objective of this study was to determine if second-generation antipsychotic (SGA) administration was associated with lower aggressiveness scores compared to first-generation (FGA) in schizophrenia (SZ). The secondary objective was to determine if antidepressants, mood stabilizers, and benzodiazepines administration were respectively associated with lower aggressiveness scores compared to patients who were not administered these medications. Three hundred thirty-one patients with schizophrenia (N = 255) or schizoaffective disorder (N = 76) (mean age = 32.5 years, 75.5 % male gender) were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with the structured clinical interview for DSM-IV Axis I disorders and validated scales for psychotic symptomatology, insight, and compliance. Aggressiveness was measured by the Buss-Perry Aggression Questionnaire (BPAQ) score. Ongoing psychotropic treatment was recorded. Patients who received SGA had lower BPAQ scores than patients who did not (p = 0.01). More specifically, these patients had lower physical and verbal aggression scores. On the contrary, patients who received benzodiazepines had higher BPAQ scores than patients who did not (p = 0.04). No significant difference was found between BPAQ scores of patients respectively being administered mood stabilizers (including valproate), antidepressant, and the patients who were not. These results were found independently of socio-demographical variables, psychotic symptomatology, insight, compliance into treatment, daily-administered antipsychotic dose, the way of antipsychotic administration (oral vs long acting), current alcohol disorder, and daily cannabis consumption. The results of the present study are in favor of the choice of SGA in SZ patients with aggressiveness, but these results need further investigation in longitudinal studies. Given the potent side effects of benzodiazepines

Psychological factors related to nurses' intentions to initiate an antipsychotic or psychosocial intervention with nursing home residents.

PubMed

Ludwin, Brian M; Meeks, Suzanne

2018-05-03

This study examined the validity of a psychological model for understanding nursing home providers' treatment choices when managing challenging dementia-related behaviors. Ninety-nine nurses from 26 long-term care facilities responded to a case study with their intentions to initiate an antipsychotic or psychosocial intervention and completed self-report measures of their attitudes, descriptive norms, self-efficacy, and outcome expectancies. The multi-level modeling results demonstrated that nurses with more positive outcome expectancies for the effect of an antipsychotic on resident behavior, and those with more positive attitudes towards antipsychotics, had greater intentions to initiate an antipsychotic. Intentions to initiate a psychosocial intervention were greater when nurses perceived a lower prevalence of antipsychotics and in facilities with nurses who collectively had higher self-efficacy to implement such interventions. The findings offer partial support for the proposed model and possible intervention targets to improve psychosocial intervention use and antipsychotic prescribing. Published by Elsevier Inc.

PPAR-γ agonism as a modulator of mood: proof-of-concept for pioglitazone in bipolar depression.

PubMed

Kemp, David E; Schinagle, Martha; Gao, Keming; Conroy, Carla; Ganocy, Stephen J; Ismail-Beigi, Faramarz; Calabrese, Joseph R

2014-06-01

Insulin resistance and other cardio-metabolic risk factors predict increased risk of depression and decreased response to antidepressant and mood stabilizer treatments. This proof-of-concept study tested whether administration of an insulin-sensitizing peroxisome proliferator-activated receptor (PPAR)-γ agonist could reduce bipolar depression symptom severity. A secondary objective was to determine whether levels of highly sensitive C-reactive protein and interleukin (IL)-6 predicted treatment outcome. Patients (n = 34) with bipolar disorder (I, II, or not otherwise specified) and metabolic syndrome/insulin resistance who were currently depressed (Quick Inventory of Depressive Symptoms [QIDS] total score ≥11) despite an adequate trial of a mood stabilizer received open-label, adjunctive treatment with the PPAR-γ agonist pioglitazone (15-30 mg/day) for 8 weeks. The majority of participants (76 %, n = 26) were experiencing treatment-resistant bipolar depression, having already failed two mood stabilizers or the combination of a mood stabilizer and a conventional antidepressant. Supporting an association between insulin sensitization and depression severity, pioglitazone treatment was associated with a decrease in the total Inventory of Depressive Symptomatology (IDS-C30) score from 38.7 ± 8.2 at baseline to 21.2 ± 9.2 at week 8 (p < 0.001). Self-reported depressive symptom severity and clinician-rated anxiety symptom severity significantly improved over 8 weeks as measured by the QIDS (p < 0.001) and Structured Interview Guide for the Hamilton Anxiety Scale (p < 0.001), respectively. Functional improvement also occurred as measured by the change in total score on the Sheehan Disability Scale (-17.9 ± 3.6; p < 0.001). Insulin sensitivity increased from baseline to week 8 as measured by the Insulin Sensitivity Index derived from an oral glucose tolerance test (0.98 ± 0.3; p < 0.001). Higher baseline levels of IL-6 were associated with greater decrease in

Impact of side-effects of atypical antipsychotics on non-compliance, relapse and cost.

PubMed

Mortimer, A; Williams, P; Meddis, D

2003-01-01

Atypical antipsychotics generally have milder side-effects than conventional antipsychotics, but also differ among themselves in this respect. This study aimed to compare the impact of different side-effect profiles of individual atypical antipsychotics on non-compliance, relapse and cost in schizophrenia. A state-transition model was built using literature data supplemented by expert opinion. The model found that quetiapine and ziprasidone were similar in estimated non-compliance and relapse rates. Olanzapine and risperidone had higher estimated non-compliance and relapse rates, and incremental, 1-year, per-patient direct costs, using US-based cost data, of approximately $530 (95% confidence interval [CI] approximately $275, $800), and approximately $485 (95% CI approximately $235, $800), respectively, compared with quetiapine. Incremental costs attributable to different side-effect profiles were highly significant. This study shows that differing side-effect profiles of the newer antipsychotic agents are likely to lead to different compliance rates, and consequent variation in relapse rates. The cost implications of these heterogenous clinical outcomes are substantial.

Antipsychotic treatment leading to dopamine supersensitivity persistently alters nucleus accumbens function.

PubMed

El Hage, Cynthia; Bédard, Anne-Marie; Samaha, Anne-Noël

2015-12-01

Chronic exposure to some antipsychotic medications can induce supersensitivity to dopamine receptor stimulation. This is linked to a worsening of clinical outcome and to antipsychotic treatment failure. Here we investigated the role of striatal subregions [nucleus accumbens (NAc) and caudate-putamen (CPu)] in the expression of antipsychotic-induced dopamine supersensitivity. We treated rats with haloperidol (HAL) or olanzapine (OLZ), using regimens that achieve clinically relevant kinetics of striatal D2 receptor occupancy. Under these conditions, HAL produces dopamine supersensitivity whereas OLZ does not. We then assessed behaviors evoked by the dopamine agonist amphetamine (AMPH). We either injected AMPH into the striatum or inhibited striatal function with microinjections of GABA receptor agonists prior to injecting AMPH systemically. HAL-treated rats were dopamine supersensitive, as indicated by sensitization to systemic AMPH-induced potentiation of both locomotor activity and operant responding for a conditioned reward (CR). Intra-CPu injections of AMPH had no effect on these behaviors, in any group. Intra-NAc injections of AMPH enhanced operant responding for CR in OLZ-treated and control rats, but not in HAL-treated rats. In HAL-treated rats, inhibition of the NAc also failed to disrupt systemic AMPH-induced potentiation of operant responding for CR. Furthermore, while intra-NAc AMPH enhanced locomotion in both HAL-treated and control animals, inhibition of the NAc disrupted systemic AMPH-induced locomotion only in control rats. Thus, antipsychotic-induced dopamine supersensitivity persistently disrupts NAc function, such that some behaviors that normally depend upon NAc dopamine no longer do so. This has implications for understanding dysfunctions in dopamine-mediated behaviors in patients undergoing chronic antipsychotic treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Mood induction procedures: a critical review].

PubMed

Gilet, A-L

2008-06-01

For a long period in the history of psychological research, emotion and cognition have been studied independently, as if one were irrelevant to the other. The renewed interest of researchers for the study of the relations between cognition and emotion has led to the development of a range of laboratory methods for inducing temporary mood states. This paper aims to review the main mood induction procedures allowing the induction of a negative mood as well as a positive mood, developed since the pioneer study of Schachter and Singer [Psychol Rev 69 (1962) 379-399] and to account for the usefulness and problems related to the use of such techniques. The first part of this paper deals with the detailed presentation of some of the most popular mood induction procedures according to their type: simple (use of only one mood induction technique) or combined (association of two or more techniques at once). The earliest of the modern techniques is the Velten Mood Induction Procedure [Behav Res Ther 6 (1968) 473-482], which involves reading aloud sixty self-referent statements progressing from relative neutral mood to negative mood or dysphoria. Some researchers have varied the procedure slightly by changing the number of the statements [Behav Res Ther 21 (1983) 233-239, Br J Clin Psychol 21 (1982) 111-117, J Pers Soc Psychol 35 (1977) 625-636]. Various other mood induction procedures have been developed including music induction [Cogn Emotion 11 (1997) 403-432, Br J Med Psychol 55 (1982) 127-138], film clip induction [J Pers Soc Psychol 20 (1971) 37-43, Cogn Emotion 7 (1993) 171-193, Rottenberg J, Ray RR, Gross JJ. Emotion elicitation using films. In: Coan JA, Allen JJB, editors. The handbook of emotion elicitation and assessment. New York: Oxford University Press, 2007], autobiographical recall [J Clin Psychol 36 (1980) 215-226, Jallais C. Effets des humeurs positives et négatives sur les structures de connaissances de type script. Thèse de doctorat non publi

Antipsychotic medication and long-term mortality risk in patients with schizophrenia; a systematic review and meta-analysis.

PubMed

Vermeulen, J; van Rooijen, G; Doedens, P; Numminen, E; van Tricht, M; de Haan, L

2017-10-01

Patients with schizophrenia have a higher mortality risk than patients suffering from any other psychiatric disorder. Previous research is inconclusive regarding the association of antipsychotic treatment with long-term mortality risk. To this aim, we systematically reviewed the literature and performed a meta-analysis on the relationship between long-term mortality and exposure to antipsychotic medication in patients with schizophrenia. The objectives were to (i) determine long-term mortality rates in patients with schizophrenia using any antipsychotic medication; (ii) compare these with mortality rates of patients using no antipsychotics; (iii) explore the relationship between cumulative exposure and mortality; and (iv) assess causes of death. We systematically searched the EMBASE, MEDLINE and PsycINFO databases for studies that reported on mortality and antipsychotic medication and that included adults with schizophrenia using a follow-up design of more than 1 year. A total of 20 studies fulfilled our inclusion criteria. These studies reported 23,353 deaths during 821,347 patient years in 133,929 unique patients. Mortality rates varied widely per study. Meta-analysis on a subgroup of four studies showed a consistent trend of an increased long-term mortality risk in schizophrenia patients who did not use antipsychotic medication during follow-up. We found a pooled risk ratio of 0.57 (LL:0.46 UL:0.76 p value <0.001) favouring any exposure to antipsychotics. Statiscal heterogeneity was found to be high (Q = 39.31, I 2 = 92.37%, p value < 0.001). Reasons for the increased risk of death for patients with schizophrenia without antipsychotic medication require further research. Prospective validation studies, uniform measures of antipsychotic exposure and classified causes of death are commendable.

Demand Characteristics, Moods, and Helping

ERIC Educational Resources Information Center

Wispe, Lauren; And Others

1977-01-01

Procedures used in empathy-helping studies suggest results may be due to demand characteristics. Two studies were run to investigate especially the mood induction process. One reproduced the Aderman-Berkowitz main mood effects. Another showed that after seeing a help-non-help incident, mood effects were demonstrated only when Ss knew the research…

Brain volume changes over the first year of treatment in schizophrenia: relationships to antipsychotic treatment.

PubMed

Emsley, R; Asmal, L; du Plessis, S; Chiliza, B; Phahladira, L; Kilian, S

2017-09-01

Progressive brain volume reductions have been described in schizophrenia, and an association with antipsychotic exposure has been reported. We compared percentage changes in grey and white matter volume from baseline to month 12 in 23 previously antipsychotic-naïve patients with a first episode of schizophrenia or schizophreniform disorder who were treated with the lowest effective dose of flupenthixol decanoate depot formulation, with 53 matched healthy individuals. Total antipsychotic dose was precisely calculated and its relationship with brain volume changes investigated. Relationships between volumetric changes and treatment were further investigated in terms of treatment response (changes in psychopathology and functionality) and treatment-related adverse-events (extrapyramidal symptoms and weight gain). Excessive cortical volume reductions were observed in patients [-4.6 (6.6)%] v. controls [-1.12 (4.0)%] (p = 0.009), with no significant group differences for changes in subcortical grey matter and white matter volumes. In a multiple regression model, the only significant predictor of cortical volume change was total antipsychotic dose received (p = 0.04). Cortical volume change was not significantly associated with the changes in psychopathology, functionality, extrapyramidal symptoms and body mass index or age, gender and duration of untreated psychosis. Brain volume reductions associated with antipsychotic treatment are not restricted to poor outcome patients and occur even with the lowest effective dose of antipsychotic. The lack of an association with poor treatment response or treatment-related adverse effects counts against cortical volume reductions reflecting neurotoxicity, at least in the short term. On the other hand, the volume reductions were not linked to the therapeutic benefits of antipsychotics.

Antipsychotic medication and remission of psychotic symptoms 10years after a first-episode psychosis.

PubMed

Wils, Regitze Sølling; Gotfredsen, Ditte Resendal; Hjorthøj, Carsten; Austin, Stephen F; Albert, Nikolai; Secher, Rikke Gry; Thorup, Anne Amalie Elgaard; Mors, Ole; Nordentoft, Merete

2017-04-01

Several national guidelines recommend continuous use of antipsychotic medication after a psychotic episode in order to minimize the risk of relapse. However some studies have identified a subgroup of patients who obtain remission of psychotic symptoms while not being on antipsychotic medication for a period of time. This study investigated the long-term outcome and characteristics of patients in remission of psychotic symptoms with no use of antipsychotic medication at the 10-year follow-up. The study was a cohort study including 496 patients diagnosed with schizophrenia spectrum disorders (ICD 10: F20 and F22-29). Patients were included in the Danish OPUS Trial and followed up 10years after inclusion, where patient data was collected on socio-demographic factors, psychopathology, level of functioning and medication. 61% of the patients from the original cohort attended the 10-year follow up and 30% of these had remission of psychotic symptoms at the time of the 10-year follow up with no current use of antipsychotic medication. This outcome was associated with female gender, high GAF-F score, participation in the labour market and absence of substance abuse. Our results describe a subgroup of patients who obtained remission while not being on antipsychotic medication at the 10-year follow-up. The finding calls for further investigation on a more individualized approach to long-term treatment with antipsychotic medication. Copyright © 2016 Elsevier B.V. All rights reserved.

Preconditioning mesenchymal stem cells with the mood stabilizers lithium and valproic acid enhances therapeutic efficacy in a mouse model of Huntington's disease.

PubMed

Linares, Gabriel R; Chiu, Chi-Tso; Scheuing, Lisa; Leng, Yan; Liao, Hsiao-Mei; Maric, Dragan; Chuang, De-Maw

2016-07-01

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by CAG repeat expansions in the huntingtin gene. Although, stem cell-based therapy has emerged as a potential treatment for neurodegenerative diseases, limitations remain, including optimizing delivery to the brain and donor cell loss after transplantation. One strategy to boost cell survival and efficacy is to precondition cells before transplantation. Because the neuroprotective actions of the mood stabilizers lithium and valproic acid (VPA) induce multiple pro-survival signaling pathways, we hypothesized that preconditioning bone marrow-derived mesenchymal stem cells (MSCs) with lithium and VPA prior to intranasal delivery to the brain would enhance their therapeutic efficacy, and thereby facilitate functional recovery in N171-82Q HD transgenic mice. MSCs were treated in the presence or absence of combined lithium and VPA, and were then delivered by brain-targeted single intranasal administration to eight-week old HD mice. Histological analysis confirmed the presence of MSCs in the brain. Open-field test revealed that ambulatory distance and mean velocity were significantly improved in HD mice that received preconditioned MSCs, compared to HD vehicle-control and HD mice transplanted with non-preconditioned MSCs. Greater benefits on motor function were observed in HD mice given preconditioned MSCs, while HD mice treated with non-preconditioned MSCs showed no functional benefits. Moreover, preconditioned MSCs reduced striatal neuronal loss and huntingtin aggregates in HD mice. Gene expression profiling of preconditioned MSCs revealed a robust increase in expression of genes involved in trophic effects, antioxidant, anti-apoptosis, cytokine/chemokine receptor, migration, mitochondrial energy metabolism, and stress response signaling pathways. Consistent with this finding, preconditioned MSCs demonstrated increased survival after transplantation into the brain compared to non-preconditioned cells

[Atypical antipsychotics and sexual dysfunction: five case-reports associated with risperidone].

PubMed

Haefliger, T; Bonsack, C

2006-01-01

Sexual and reproductive function side effects of atypical antipsychotics are frequent, often underestimated and badly tolerated. They contribute to the 50% rate of non-compliance reported for treated patients. Prevalence of sexual dysfunction associated with atypical antipsychotic treatment is high, varying from 18 to 96%. Atypical antipsychotics aren't, as a group, much better than typical antipsychotics, and among them, risperidone seems to induce more and quetiapine less sexual dysfunction. Most atypicals are non-selective, and have actions on multiple central and peripheral receptors. Among these, dopaminergic blockade could have a direct - altering motivation (desire) and reward (orgasm) - and an indirect negative influence on sexuality. Actually, the secondary hyperprolactinemia induced by some antipsychotics (typical antipsychotics, risperidone and amisulpiride), is dose-dependent, more pronounced for female patients, and may have a detrimental effect on sexual function. It also may result in hypogonadism, particularly for female patients. The long-term consequences of this secondary hypogonadism are subject to debate but potentially severe. Furthermore, the blocking and/or modulating actions of atypical antipsychotics on adrenaline, serotonine, histamine or acetyl-choline receptors all have the potential to contribute to secondary sexual problems. The pharmacological profile of risperidone, characterized by a strong affinity for D2 and alpha1 receptors, correlates with his tendency to significantly elevate prolactin levels and to produce ejaculatory disturbances. FIVE CASE-REPORTS: We describe five case-reports of sexual or hormonal disturbances associated with risperidone treatment: two cases of ejaculatory disturbance, one case of galactorrhea and two cases of amenorrhea. Alberto and David are two young male schizophrenic patients, treated with risperidone, and complaining of a total absence of ejaculation despite a preserved orgasm. Many recent case

Mood effects of antiepileptic drugs.

PubMed

Reijs, Rianne; Aldenkamp, Albert P; De Krom, Marc

2004-02-01

This article reviews our knowledge about a specific subgroup of chronic CNS-related side effects of antiepileptic drugs (AED) treatment, i.e., the effects of AEDs on mood. In line with a recent hypothesis, using the experience of AED treatment in psychiatry, we examined whether mood effects are related to the known anticonvulsant mechanisms of action of the AEDs. Specifically we examined whether AEDs, acting through potentiation of GABAergic neurotransmitter release, have "sedating" effects on mood, whereas AEDs that act through the reduction of excitatory glutamate neurotransmitter release have "activating" effects on mood. The results of this review yield evidence that there are relationships between the known anticonvulsant mechanisms of action of the AEDs and mood effects. Mood effects occur especially when the drugs have a sustained effect on neuronal mechanisms, in particular when the inhibitory or excitatory neurotransmitter release is altered. Drugs with "use-dependent" impact on sodium or calcium channels probably have a more transient impact and do not lead to interictal stable mood effects. Drugs with multiple mechanisms of action seem to combine a favorable efficacy profile with an increased risk of severe mood problems. The quality of the evidence, however, is not conclusive and there are many paradoxical results. One reason for this lack of "fit" may be the use in this review of a simplified classification, based only on the predominant mechanism of action to classify a drug. Only a limited number of AEDs (ethosuximide, tiagabine) are characterized by a single anticonvulsant mechanism of action. Probably more detailed coupling of mechanisms of action (e.g., inspecting the type and route of impact on GABA release) and mood effects may give less confusing results. The use of magnetic resonance imaging techniques such as spectroscopy may provide interesting results.

Individual Differences in the Effects of Mood on Sexuality: The Revised Mood and Sexuality Questionnaire (MSQ-R)

PubMed Central

Janssen, Erick; Macapagal, Kathryn R.; Mustanski, Brian

2013-01-01

Previous research using the Mood and Sexuality Questionnaire (MSQ) has revealed substantial variability in how negative mood impacts sexual response and behavior. However, the MSQ does not address differences between desire for solo or partnered sexual activity, examine the effects of sexual activity on mood, or assess the effects of positive mood. This paper presents the development and factor structure of the Revised Mood and Sexuality Questionnaire (MSQ-R). An exploratory factor analysis in a sample of heterosexual men, homosexual men, and heterosexual women (N = 1983) produced 8 factors. Considerable variability was found in how moods influence sexual desire and arousal, in the effects of mood on sexual behavior, and in the reciprocal effects of sexual activity on mood. Among other findings, heterosexual women were less likely than heterosexual and homosexual men to experience increased sexual desire and arousal when anxious or stressed, whereas homosexual men and heterosexual women were less likely than heterosexual men to experience increased desire when sad or depressed. Heterosexual men and women were more likely than homosexual men to report increased desire when in a positive mood. Intercorrelations and correlations with various sexual behaviors varied by group. Limitations and implications of the findings are discussed. PMID:22963331

Trends in the Use of Typical and Atypical Antipsychotics in Children and Adolescents.

ERIC Educational Resources Information Center

Patel, Nick C.; Crismon, M. Lynn; Hoagwood, Kimberly; Johnsrud, Michael T.; Rascati, Karen L.; Wilson, James P.; Jensen, Peter S.

2005-01-01

Objective: To estimate prevalence rates of antipsychotic use in children and adolescents from 1996 to 2001 in three state Medicaid programs (midwestern [MM], southern [SM], and western [WM]) and one private managed care organization (MCO). Method: Prescription claims were used to evaluate antipsychotic prevalence, defined as the number of children…

Acute Antipsychotic Treatment of Children and Adolescents With Schizophrenia-Spectrum Disorders: A Systematic Review and Network Meta-Analysis.

PubMed

Pagsberg, Anne Katrine; Tarp, Simon; Glintborg, Dorte; Stenstrøm, Anne Dorte; Fink-Jensen, Anders; Correll, Christoph Ulrich; Christensen, Robin

2017-03-01

To determine the comparative efficacy and safety of antipsychotics for youth with early-onset schizophrenia using network meta-analytic methods combining direct and indirect trial data. The authors systematically searched MEDLINE, the Cochrane Library, and clinicaltrials.gov and selected randomized controlled trials allocating youth with schizophrenia spectrum disorders to a (non-clozapine) antipsychotic versus placebo or another antipsychotic. Major efficacy outcomes were Positive and Negative Syndrome Scale (PANSS) total and positive symptoms. Major safety outcomes were weight, plasma triglyceride levels, extrapyramidal symptoms, akathisia, and all-cause discontinuation. Sixteen additional outcomes were analyzed. A random-effects arm-based network meta-analysis was applied, and consistency was assessed by pairwise meta-analysis. Confidence in PANSS total estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Twelve 6- to 12-week trials (N = 2,158; 8-19 years old; 61% boys) involving 8 antipsychotics (aripiprazole, asenapine, paliperidone, risperidone, quetiapine, olanzapine, molindone, and ziprasidone) were analyzed. PANSS total symptom change was comparable among antipsychotics (low- to moderate-quality evidence), except ziprasidone (very low- to low-quality evidence), and all antipsychotics were superior to placebo (low- to high-quality evidence), except ziprasidone and asenapine (low- to moderate-quality evidence). PANSS positive changes and additional efficacy outcomes were comparable among antipsychotics. Weight gain was primarily associated with olanzapine; extrapyramidal symptoms and akathisia were associated with molindone; and prolactin increased with risperidone, paliperidone, and olanzapine. Serious adverse events, discontinuation of treatment, sedation, insomnia, or change in triglycerides did not differ among antipsychotics. This network meta-analysis showed comparable efficacy

Computerized Self-Administered Measures of Mood and Appetite for Older Adults: The Novel Assessment of Nutrition and Ageing Toolkit.

PubMed

Brown, Laura J E; Adlam, Tim; Hwang, Faustina; Khadra, Hassan; Maclean, Linda M; Rudd, Bridey; Smith, Tom; Timon, Claire; Williams, Elizabeth A; Astell, Arlene J

2018-02-01

The "Novel Assessment of Nutrition and Ageing" (NANA) toolkit is a computerized system for collecting longitudinal information about older adults' health and behavior. Here, we describe the validation of six items for measuring older adults' self-reported mood and appetite as part of the NANA system. In Study 1, 48 community-living older adults (aged 65-89 years) completed NANA measures of their current mood and appetite alongside standard paper measures, on three occasions, in a laboratory setting. In Study 2, 40 community-living older adults (aged 64-88 years) completed daily NANA measures of momentary mood and appetite in their own homes, unsupervised, alongside additional measures of health and behavior, over three 7-day periods. The NANA measures were significantly correlated with standard measures of mood and appetite, and showed stability over time. They show utility for tracking mood and appetite longitudinally, and for better understanding links with other aspects of health and behavior.

Antipsychotics increase vesicular glutamate transporter 2 (VGLUT2) expression in thalamolimbic pathways.

PubMed

Moutsimilli, Larissa; Farley, Severine; El Khoury, Marie-Anne; Chamot, Christophe; Sibarita, Jean-Baptiste; Racine, Victor; El Mestikawy, Salah; Mathieu, Flavie; Dumas, Sylvie; Giros, Bruno; Tzavara, Eleni T

2008-03-01

Recently the two vesicular-glutamate-transporters VGLUT1 and VGLUT2 have been cloned and characterized. VGLUT1 and VGLUT2 together label all glutamatergic neurons, but because of their distinct expression patterns in the brain they facilitate our ability to define between a VGLUT1-positive cortical and a VGLUT2-positive subcortical glutamatergic systems. We have previously demonstrated an increased cortical VGLUT1 expression as marker of antidepressant activity. Here, we assessed the effects of different psychotropic drugs on brain VGLUT2 mRNA and protein expression. The typical antipsychotic haloperidol, and the atypicals clozapine and risperidone increased VGLUT2 mRNA selectively in the central medial/medial parafascicular, paraventricular and intermediodorsal thalamic nuclei; VGLUT2 protein was accordingly amplified in paraventricular and ventral striatum and in prefrontal cortex. The antidepressants fluoxetine and desipramine and the sedative anxiolytic diazepam had no effect. These results highlight the implication of thalamo-limbic glutamatergic pathways in the action of antipsychotics. Increased VGLUT2 expression in these neurons might constitute a marker for antipsychotic activity and subcortical glutamate neurotransmission might be a possible novel target for future generation antipsychotics.

Antipsychotic polypharmacy prescribing patterns and costs in the Florida adult and child Medicaid populations.

PubMed

Becker, Edmund R; Constantine, Robert J; McPherson, Marie A; Jones, Mary Elizabeth

2013-01-01

The rapid growth in the use of antipsychotic medications and their related costs have resulted in states developing programs to measure, monitor, and insure their beneficial relevance to public program populations. One such program developed in the state of Florida has adopted an evidence-based approach to identify prescribers with unusual psychotherapeutic prescription patterns and track their utilization and costs among Florida Medicaid patients. This study reports on the prescriber prescription and cost patterns for adults and children using three measures of unusual antipsychotic prescribing patterns: (1) two antipsychotics for 60 days (2AP60), (2) three antipsychotics for 60 days (3AP60), and (2) two antipsychotics for 90 or more days (2AP90). We find that over the four-year study period there were substantial increases in several aspects of the Florida Medicaid behavioral drug program. Overall, for adults and children, patient participation increased by 29 percent, the number of prescriptions grew by 30 percent, and the number of prescribers that wrote at least one prescription grew 48.5 percent, while Medicaid costs for behavioral drugs increased by 32 percent. But the results are highly skewed. We find that a relatively small number of prescribers account for a disproportionately large share of prescriptions and costs of the unusual antipsychotic prescriptions. In general, the top 350 Medicaid prescribers accounted for more than 70 percent of the unusual antipsychotic prescriptions, and we find that this disparity in unusual prescribing patterns appears to be substantially more pronounced in adults than in children prescribers. For just the top 13 adult and children prescribers, their practice patterns accounted for 11 percent to 21 percent of the unusual prescribing activity and, overall, these 13 top prescribers accounted for 13 percent of the total spent on antipsychotics by the Florida Medicaid program and 9.3 percent of the total expenditure by the

Physicians' reasons not to discontinue long-term used off-label antipsychotic drugs in people with intellectual disability.

PubMed

de Kuijper, G M; Hoekstra, P J

2017-10-01

People with intellectual disability (ID) frequently use antipsychotic drugs on an off-label base, often for many years. Physicians' decisions to discontinue these drugs not only depend on patient characteristics, like the presence of mental or behavioural disorders, but also on environmental factors, such as inappropriate living circumstances, and on attitudes, knowledge and beliefs of staff, clients and their representatives towards the effects of antipsychotic drug use. In this study, we therefore investigated the influence of participant and setting-related factors on decisions of physicians not to discontinue off-label prescribed antipsychotics. The study took place in living facilities of six service providers for people with ID spread over the Netherlands and staffed with support professionals, nurses, behavioural scientist and physicians and was part of an antipsychotics discontinuation trial. ID physicians had to decide whether the off-label use of antipsychotics could be discontinued. Medical and pharmaceutical records were used to establish the prevalence of antipsychotic drug use in the study population, along with duration of use and whether the use was off-label. Reasons of physicians not to discontinue the prescription of antipsychotics in those participants who used off-label antipsychotics for more than a year were collected and categorised as related to participant or setting characteristics, including lack of consent to discontinue, and staff members, participants or their legal representatives. Of the 3299 clients of the service providers, 977 used one or more antipsychotic drugs. The prevalence of antipsychotic drug use was 30%. Reasons for use were in 5% of cases, a chronic psychotic disorder classified according to Diagnostic System Mental Disorders, Fourth Edition, criteria, in 25%, present or past (suspected) non-schizophrenia-related psychotic symptoms and in 69%, challenging behaviours. Overall, physicians were willing to discontinue their

Identifying fallacious arguments in a qualitative study of antipsychotic prescribing in dementia.

PubMed

Donyai, Parastou

2017-10-01

Dementia can result in cognitive, noncognitive and behavioural symptoms which are difficult to manage. Formal guidelines for the care and management of dementia in the UK state that antipsychotics should only be prescribed where fully justified. This is because inappropriate use, particularly problematic in care-home settings, can produce severe side effects including death. The aim of this study was to explore the use of fallacious arguments in professionals' deliberations about antipsychotic prescribing in dementia in care-home settings. Fallacious arguments have the potential to become unremarkable discourses that construct and validate practices which are counter to guidelines. This qualitative study involved interviews with 28 care-home managers and health professionals involved in caring for patients with dementia. Potentially fallacious arguments were identified using qualitative content analysis and a coding framework constructed from existing explanatory models of fallacious reasoning. Fallacious arguments were identified in a range of explanations and reasons that participants gave for in answer to questions about initiating, reducing doses of and stopping antipsychotics in dementia. The dominant fallacy was false dichotomy. Appeal to popularity, tradition, consequence, emotion, or fear, and the slippery slope argument was also identified. Fallacious arguments were often formulated to present convincing cases whereby prescribing antipsychotics or maintaining existing doses (versus not starting medication or reducing the dose, for example) appeared as the only acceptable decision but this is not always the case. The findings could help health professionals to recognise and mitigate the effect of logic-based errors in decisions about the prescribing of antipsychotics in dementia. © 2016 Royal Pharmaceutical Society.

Stress-related Clinical Pain and Mood in Women with Chronic Pain: Moderating Effects of Depression and Positive Mood Induction

PubMed Central

Davis, Mary C.; Thummala, Kirti; Zautra, Alex J.

2014-01-01

Background Chronic pain with co-morbid depression is characterized by poor mood regulation and stress-related pain. Purpose Compare depressed and non-depressed pain patients in mood and pain stress reactivity and recovery, and test whether a post-stress positive mood induction moderates pain recovery. Methods Women with fibromyalgia and/or osteoarthritis (N=110) underwent interpersonal stress and were then randomly assigned by pain condition and depression status, assessed via the Center for Epidemiological Studies-Depression scale, to positive versus neutral mood induction. Results Depression did not predict stress-related reactivity in despondency, joviality, or clinical pain. However, depression X mood condition predicted recovery in joviality and clinical pain; depressed women recovered only in the positive mood condition, whereas non-depressed women recovered in both mood conditions. Conclusions Depression does not alter pain and mood stress reactivity, but does impair recovery. Boosting post-stress jovial mood ameliorates pain recovery deficits in depressed patients, a finding relevant to chronic pain interventions. PMID:24532393

Stress-related clinical pain and mood in women with chronic pain: moderating effects of depression and positive mood induction.

PubMed

Davis, Mary C; Thummala, Kirti; Zautra, Alex J

2014-08-01

Chronic pain with comorbid depression is characterized by poor mood regulation and stress-related pain. This study aims to compare depressed and non-depressed pain patients in mood and pain stress reactivity and recovery, and test whether a post-stress positive mood induction moderates pain recovery. Women with fibromyalgia and/or osteoarthritis (N = 110) underwent interpersonal stress and were then randomly assigned by pain condition and depression status, assessed via the Center for Epidemiological Studies-Depression scale, to positive versus neutral mood induction. Depression did not predict stress-related reactivity in despondency, joviality, or clinical pain. However, depression × mood condition predicted recovery in joviality and clinical pain; depressed women recovered only in the positive mood condition, whereas non-depressed women recovered in both mood conditions. Depression does not alter pain and mood stress reactivity, but does impair recovery. Boosting post-stress jovial mood ameliorates pain recovery deficits in depressed patients, a finding relevant to chronic pain interventions.

Mood-dependent integration in discourse comprehension: happy and sad moods affect consistency processing via different brain networks.

PubMed

Egidi, Giovanna; Caramazza, Alfonso

2014-12-01

According to recent research on language comprehension, the semantic features of a text are not the only determinants of whether incoming information is understood as consistent. Listeners' pre-existing affective states play a crucial role as well. The current fMRI experiment examines the effects of happy and sad moods during comprehension of consistent and inconsistent story endings, focusing on brain regions previously linked to two integration processes: inconsistency detection, evident in stronger responses to inconsistent endings, and fluent processing (accumulation), evident in stronger responses to consistent endings. The analysis evaluated whether differences in the BOLD response for consistent and inconsistent story endings correlated with self-reported mood scores after a mood induction procedure. Mood strongly affected regions previously associated with inconsistency detection. Happy mood increased sensitivity to inconsistency in regions specific for inconsistency detection (e.g., left IFG, left STS), whereas sad mood increased sensitivity to inconsistency in regions less specific for language processing (e.g., right med FG, right SFG). Mood affected more weakly regions involved in accumulation of information. These results show that mood can influence activity in areas mediating well-defined language processes, and highlight that integration is the result of context-dependent mechanisms. The finding that language comprehension can involve different networks depending on people's mood highlights the brain's ability to reorganize its functions. Copyright © 2014 Elsevier Inc. All rights reserved.

A Multimodal, Nonpharmacologic Intervention Improves Mood and Cognitive Function in People with Multiple Sclerosis.

PubMed

Lee, Jennifer E; Bisht, Babita; Hall, Michael J; Rubenstein, Linda M; Louison, Rebecca; Klein, Danielle T; Wahls, Terry L

2017-01-01

The objective of this study was to examine whether participation in a 12-month multimodal intervention would improve mood and cognitive function in adults with progressive multiple sclerosis (MS). In this one-arm, open-label feasibility trial, participants were prescribed a home-based multimodal intervention, including (1) a modified Paleolithic diet; (2) an exercise program (stretching and strengthening of the trunk and lower limb muscles); (3) neuromuscular electrical stimulation (EStim) of trunk and lower limb muscles; and (4) stress management (meditation and self-massage). Individuals completed measures of mood (Beck Anxiety and Depression Inventories) and cognitive (Cognitive Stability Index, Cognitive Screening Test, Delis-Kaplan Executive Function System) and executive function (Wechsler Adult Intelligence Scale) at baseline and 3, 6, 9, and 12 months after the start of the intervention. Dosage of the multimodal intervention was assessed at 3, 6, 9, and 12 months. The more individuals participated in the intervention activities, the greater improvements they had from baseline to 12 months on self-report measures of anxiety (Beck Anxiety Inventory [BAI]; ps = 0.001 to 0.02), depression (Beck Depression Inventory [BDI]; ps = <0.0001 to 0.09), cognitive function (Cognitive Stability Index [CSI/T], Delis-Kaplan Executive Function System [DKEFS]; ps = 0.001 to 0.06), and executive function (Wechsler Adult Intelligence Scale [WAIS]; ps = <0.0001 to 0.09). Mood and cognitive improvements were more closely related to a higher intake of the modified Paleolithic diet than to exercise and stress management dosage. Anxiety and depression changes were evident after just a few months, whereas changes in cognitive function were generally not observed until later in the intervention period. Mood and cognitive function changes from baseline to 12 months were significantly associated with fatigue improvements (ps = <0.0001 to 0.03). A modified Paleolithic diet, exercise

Reduction or discontinuation of antipsychotics for challenging behaviour in adults with intellectual disability: a systematic review.

PubMed

Sheehan, Rory; Hassiotis, Angela

2017-03-01

The use of antipsychotics to manage challenging behaviour in adults with intellectual disability is widespread but controversial, and evidence is scarce. There is a perception that antipsychotics used in this context can be reduced or discontinued, and this has been a major focus of recent national policy. However, such an intervention risks harm as well as having potential benefits. We reviewed the available evidence and found that antipsychotics can be reduced or discontinued in a substantial proportion of adults who use them for challenging behaviour, although not always without adverse effects. There is a group which displays behavioural deterioration on antipsychotic reduction that prevents discontinuation; predictors of poor response could not be reliably identified. In view of the relatively scarce data and methodological limitations of the available studies, we cannot draw firm conclusions to inform a population level approach to this issue. Antipsychotic medication used for behaviour should be reviewed regularly and an individualised approach taken to treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of physical restraints and antipsychotic medications in nursing homes: a cross-national study

PubMed Central

Feng, Zhanlian; Hirdes, John P.; Smith, Trevor F.; Finne-Soveri, Harriet; Chi, Iris; Pasquier, Jean-Noel Du; Gilgen, Ruedi; Ikegami, Naoki; Mor, Vincent

2013-01-01

SUMMARY Objectives This study compares inter- and intra-country differences in the prevalence of physical restraints and antipsychotic medications in nursing homes, and examines aggregated resident conditions and organizational characteristics correlated with these treatments. Methods Population-based, cross-sectional data were collected using a standardized Resident Assessment Instrument (RAI) from 14,504 long-term care facilities providing nursing home level services in five countries participating in the interRAI consortium, including Canada, Finland, Hong Kong (Special Administrative Region, China), Switzerland, and the United States. Facility-level prevalence rates of physical restraints and antipsychotic use were examined both between and within the study countries. Results The prevalence of physical restraint use varied more than five-fold across the study countries, from an average 6% in Switzerland, 9% in the US, 20% in Hong Kong, 28% in Finland, and over 31% in Canada. The prevalence of antipsychotic use ranged from 11% in Hong Kong, between 26–27% in Canada and the US, 34% in Switzerland, and nearly 38% in Finland. Within each country, substantial variations existed across facilities in both physical restraint and antipsychotic use rates. In all countries, neither facility case mix nor organizational characteristics were particularly predictive of the prevalence of either treatment. Conclusions There exists large, unexplained variability in the prevalence of physical restraint and antipsychotic use in nursing home facilities both between and within countries. Since restraints and antipsychotics are associated with adverse outcomes, it is important to understand the idiosyncratic factors specific to each country that contribute to variation in use rates. PMID:19280680

Use of physical restraints and antipsychotic medications in nursing homes: a cross-national study.

PubMed

Feng, Zhanlian; Hirdes, John P; Smith, Trevor F; Finne-Soveri, Harriet; Chi, Iris; Du Pasquier, Jean-Noel; Gilgen, Ruedi; Ikegami, Naoki; Mor, Vincent

2009-10-01

This study compares inter- and intra-country differences in the prevalence of physical restraints and antipsychotic medications in nursing homes, and examines aggregated resident conditions and organizational characteristics correlated with these treatments. Population-based, cross-sectional data were collected using a standardized Resident Assessment Instrument (RAI) from 14,504 long-term care facilities providing nursing home level services in five countries participating in the interRAI consortium, including Canada, Finland, Hong Kong (Special Administrative Region, China), Switzerland, and the United States. Facility-level prevalence rates of physical restraints and antipsychotic use were examined both between and within the study countries. The prevalence of physical restraint use varied more than five-fold across the study countries, from an average 6% in Switzerland, 9% in the US, 20% in Hong Kong, 28% in Finland, and over 31% in Canada. The prevalence of antipsychotic use ranged from 11% in Hong Kong, between 26-27% in Canada and the US, 34% in Switzerland, and nearly 38% in Finland. Within each country, substantial variations existed across facilities in both physical restraint and antipsychotic use rates. In all countries, neither facility case mix nor organizational characteristics were particularly predictive of the prevalence of either treatment. There exists large, unexplained variability in the prevalence of physical restraint and antipsychotic use in nursing home facilities both between and within countries. Since restraints and antipsychotics are associated with adverse outcomes, it is important to understand the idiosyncratic factors specific to each country that contribute to variation in use rates. Copyright (c) 2009 John Wiley & Sons, Ltd.

Second-generation antipsychotics and risk of cerebrovascular accidents in the elderly.

PubMed

Percudani, Mauro; Barbui, Corrado; Fortino, Ida; Tansella, Michele; Petrovich, Lorenzo

2005-10-01

Concern has been recently raised for risperidone and olanzapine, possibly associated with cerebrovascular events in placebo-controlled trials conducted in elderly subjects with dementia. We investigated the relationship between exposure to second-generation antipsychotics (SGAs) and occurrence of cerebrovascular accidents in the elderly. From the regional database of hospital admissions of Lombardy, Italy, we extracted all patients aged 65 or older with cerebrovascular-related outcomes for the year 2002. From the regional database of prescriptions reimbursed by the National Health Service, we extracted all patients aged 65 or older who received antipsychotic prescriptions during 2001. The 2 databases were linked anonymously using the individual patient code. The proportions of cerebrovascular accidents were 3.31% (95% confidence interval, 2.95-3.69) in elderly subjects exclusively exposed to SGAs and 2.37% (95% confidence interval, 2.19-2.57) in elderly subjects exclusively exposed to first-generation antipsychotics. After background group differences were controlled for, exposure to SGAs significantly increased the risk of accidents. The analysis of cerebrovascular events in elderly subjects exposed to each individual SGA, in comparison with exposure to haloperidol, showed a significantly increased risk for risperidone only (adjusted odds ratio, 1.43; 95% confidence interval, 1.12-1.93). These data provide preliminary epidemiological evidence that exposure to SGAs, in comparison with exposure to first-generation antipsychotics, significantly increased the risk of cerebrovascular accidents in the elderly.

Brain site- and transmitter-dependent actions of methamphetamine, morphine and antipsychotics.

PubMed

Mori, Tomohisa; Iwase, Yoshiyuki; Murata, Asami; Iwata, Noriyuki; Suzuki, Tsutomu

2016-06-01

While several methamphetamine- and morphine-induced psychotic states are ordinarily treated by antipsychotics, the therapeutic mechanisms of antipsychotic drugs have yet been elucidated. The present study was designed to investigate the mechanisms how antipsychotic drugs suppress the behavioral changes induced by psychoactive drugs in mice. Low to medium doses of methamphetamine produced hyperlocomotion, whereas high dose of methamphetamine induced hypolocomotion. Hyperlocomotion induced by methamphetamine was potently suppressed by clozapine and 5-HT2 receptor antagonists, but not by the intra-accumbens injection of haloperidol. On the other hand, microinjection of haloperidol into the ventrolateral striatum increased locomotor activity with high dose of methamphetamine. In contrast, morphine-induced hyperlocomotion was suppressed by systemic as well as intra-accumbens injection of haloperidol, whereas relatively resistant to clozapine, compared to its effects in the case of methamphetamine. It has been widely believed that methamphetamine-induced psychosis is an animal model of schizophrenia, which is mediated by activation of accumbal dopamine receptors. Our findings suggest that methamphetamine differentially regulate monoaminergic systems (e.g., dopaminergic vs. 5-HTnergic), and accumbal dopamine receptors are not involved in methamphetamine-induced hyperlocomotion in mice. Thus, our findings may lead to a better understanding of the therapeutic mechanisms that underlie the effects of antipsychotic drugs and behavioral effects of methamphetamine and morphine. Copyright © 2016 Elsevier B.V. All rights reserved.

Antipsychotics side effects' influence on stigma of mental illness: focus group study results.

PubMed

Novak, Lan; Svab, Vesna

2009-03-01

Little research was done on the influence of antipsychotics' side effects on stigma of mental illness. An overview of studies shows that people with mental illness state that because of medication side effects they feel discriminated in the field of employment, observe worsening of family relations and tend to skip or discontinue their regular medication. It is difficult to discriminate between stigmatizing effects of antipsychotics and other stigma related factors such as illness symptoms. A focus group of ten patients with schizophrenia or schizoaffective disorder with severe and remitting mental illness treated with antipsychotic medication was conducted to obtain their personal views on how side effects of antipsychotic drugs affect their everyday lives and contribute to the stigmatization because of mental illness. The patients felt most stigmatized in areas of employment and occupation. They repeatedly skipped or discontinued regular medication due to side effects. Their families supported them throughout treatment and recovery despite problems associated with psychotropic medication. Medication induced stigma affects patients' lives in substantial ways and therefore merits further research, part of which is the patients' personal experience.

The association between dyslipidaemia and types of antipsychotic medications among patients with chronic schizophrenia.

PubMed

Ruzanna, Z Z; Ong, L Y; Cheah, Y C; Fairuz, A; Marhani, M

2012-02-01

This cross sectional study aimed to explore the association between dyslipidaemia and types of antipsychotics in 100 patients with chronic schizophrenia. Lipid profile, weight, height and waist circumference together with other relevant factors were measured. We found there was a high rate of dyslipidaemia among patients with chronic schizophrenia treated with antipsychotics (66%), however there was no significant difference found between typical or atypical antipsychotics (OR=1). All sociodemographic and clinical factors were not significantly associated with dyslipidaemia. Only non-Malays were found to have significant dyslipidaemia (p<0.1). Effective management is needed to deal with the dyslipidaemia in this group.

Impact of Modafinil Add-on with Atypical Anti-psychotics on Excessive Daytime Drowsiness

PubMed Central

Prasuna, P Lakshmi; Sudhakar, TP

2015-01-01

Background: Atypical antipsychotic drugs are known to cause many side effects which include daytime drowsiness. So many add on drugs are tried to reduce the same. Materials and Methods: 72 patients who were on atypical antipsychotic drugs were randomly assigned to either Modafinil or placebo and were followed for a period of 12 weeks. Daytime drowsiness, was taken at baseline, week 3, and at week 12 by using VAS, EDD scales. Results: The results were analyzed and showed that the Modafinil add on therapy significantly reduced the daytime Drowsiness. Conclusions: Modafinil could be a potential candidate in selected group of patients to decrease some of the unwanted adverse events like daytime drowsiness produced by atypical antipsychotics. PMID:26702168

Comparison of Sexual Function and Hormonal Parameters Between Mood Stabilizer Treatment Modalities in Bipolar Disorder

PubMed Central

KESEBİR, Sermin; TOPRAK, Burak; BAYKARAN, Burak; HARİRİ, Aytül; BİLİCİ, Mustafa

2014-01-01

Introduction The aim of this study was to determine the differences between lithium and atypical antipsychotics (quetiapine and olanzapine) with regard to their effects on sexual functions and hormonal variables and to assess the findings in term of gender differences, in patients with bipolar disorder. Method 28 female and 29 male patients diagnosed as having bipolar disorder type I according to the DSM-IV, using lithium or quetiapine and quetiapine+lithium or olanzapine and olanzapine+lithium were evaluated consecutively. Being in remission period and given informed consent were set as inclusion criteria in these cases. Interviews with the patients were carried out using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and SKIP-TURK. Sexual functions and satisfaction were evaluated with the Arizona Sexual Experiences Scale (ASEX) and the Golombok Rust Inventory of Sexual Satisfaction (GRISS). Blood samples of the patients were taken in order to determine prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and free testosterone (T) levels. Results GRISS scores in male patients were higher than in female patients (p=.001). The number of manic, depressive and total episodes, and functionality levels were similar between the treatment groups, both in female and male patients. No differences were found between treatment modalities in terms of hormone levels both in female and male patients. Among females, ASEX scores of the patients treated with lithium monotherapy were less than the ones treated with quetiapine and olanzapine. Among patients with quetiapine monotherapy, GRISS scores in male patients were higher than in female patients. Conclusion There are some evidences showing gender-based differences in the side effects of atypical antipsychotic drugs. Future studies with a specific focus on this topic are needed in order to have a better understanding of the basic mechanisms of gender differences

Switching and augmentation strategies for antipsychotic medications in acute-phase schizophrenia: latest evidence and place in therapy

PubMed Central

Hatta, Kotaro; Sugiyama, Naoya; Ito, Hiroto

2018-01-01

In terms of effectiveness of antipsychotics in schizophrenia, discrepancy often exists between results from double-blind randomized controlled trials and observations in emergency or acute-phase clinical practice. For instance, the antipsychotic switching strategy is not always applicable in emergency or acute-phase situations, and augmentation of another antipsychotic is occasionally done instead. In this review, we discuss strategies for early nonresponse to an antipsychotic drug such as switching and augmentation from the perspective of emergency and acute-phase treatment. We searched PubMed for the latest evidence on switching and augmentation strategies of antipsychotics for an emergency or acute-phase period. For risperidone and olanzapine, there is some evidence on switching and augmentation strategies in the management of acute-phase schizophrenia. There may be responders to olanzapine alone among early nonresponders to risperidone, whereas there may be few responders to risperidone alone among early nonresponders to olanzapine. However, there is still insufficient evidence at this time for application of these findings to routine clinical practice. For other antipsychotics, there is little evidence for their augmentation in acute-phase practice. We should be wary of polypharmacy, as multiple agents are too often prescribed by clinicians when not warranted. Considering current evidence, we propose how to switch antipsychotics in the acute phase of schizophrenia in routine practice. PMID:29854396

Brief Report: Metformin for Antipsychotic-Induced Weight Gain in Youth with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Wink, Logan K.; Adams, Ryan; Pedapati, Ernest V.; Dominick, Kelli C.; Fox, Emma; Buck, Catherine; Erickson, Craig A.

2017-01-01

Antipsychotic treatment in youth with autism spectrum disorder (ASD) is becoming increasingly common, placing individuals at risk for antipsychotic-induced weight gain and associated complications. Metformin hydrochloride, a biguanide medication FDA-approved for treatment of type-2 diabetes in youth, may hold promise for treatment of…

Diagnosis of Mood Disorders.

ERIC Educational Resources Information Center

Seligman, Linda; Moore, Bonita Marcus

1995-01-01

Provides an overview of mood disorders according to Diagnostic and Statistical Manual (fourth edition) criteria and other relevant information. Differential diagnosis is facilitated through discussion of differences and similarities among mental disorders, age and gender-related patterns of mood disorders, and useful diagnostic tools. (Author)

Bipolar disorder in adults with Asperger׳s Syndrome: a systematic review.

PubMed

Vannucchi, Giulia; Masi, Gabriele; Toni, Cristina; Dell'Osso, Liliana; Erfurth, Andreas; Perugi, Giulio

2014-10-01

Asperger׳s Syndrome (AS) is a neurodevelopmental disorder included in the Autism Spectrum (ASD). The current literature shows growing evidence of a high rate of comorbidity between AS and other psychiatric disorders, particularly Bipolar Disorder (BD). We reviewed available epidemiological and clinical data on BD-AS comorbidity and its diagnostic and therapeutic implications A systematic review of the literature was conducted through PubMed, Scopus and Psych-Info using combinations of the following search terms: Asperger׳s Syndrome, Bipolar Disorder, depression, mood disorder, psychiatric comorbidity, treatment, mood stabilizers, anticonvulsants, antipsychotics, and antidepressants. BD prevalence in adults with AS ranges from 6% to 21.4% of the cases. Relatives of patients with AS showed a doubled risk of being affected by BD and a BD prevalence near to 10%. When comorbid with AS, BD assumes peculiar features which might shape its under-recognition or misdiagnosis (especially schizophrenia when psychotic symptoms are prominent). Although controlled data on pharmacological treatments in BD-AS comorbidity are substantially lacking, information is derived by open observations, case series and chart reviews. Mood stabilizers should be considered the first choice, and antipsychotics, especially second generation drugs (SGA) with 5-HT2a antagonism, have been shown useful in controlling psychotic and behavioral symptoms and improving social withdrawal. Some evidence of efficacy for the treatment of anxiety, obsessive-compulsive symptoms and depression is reported for SSRI antidepressants. The use of these drugs should be carefully monitored, because activation with hypomanic or manic switches is reported up to 54% of the treated subjects. BD in AS patients is frequent, usually it onsets during adolescence and is often characterized by atypical presentation, making its correct identification particularly difficult. A correct diagnosis of BD in AS individuals has relevant

Terminal illness and the increased mortality risk of conventional antipsychotics in observational studies: a systematic review.

PubMed

Luijendijk, Hendrika J; de Bruin, Niels C; Hulshof, Tessa A; Koolman, Xander

2016-02-01

Numerous large observational studies have shown an increased risk of mortality in elderly users of conventional antipsychotics. Health authorities have warned against use of these drugs. However, terminal illness is a potentially strong confounder of the observational findings. So, the objective of this study was to systematically assess whether terminal illness may have biased the observational association between conventional antipsychotics and risk of mortality in elderly patients. Studies were searched in PubMed, CINAHL, Embase, the references of selected studies and articles referring to selected studies (Web of Science). Inclusion criteria were (i) observational studies that estimated (ii) the risk of all-cause mortality in (iii) new elderly users of (iv) conventional antipsychotics compared with atypical antipsychotics or no use. Two investigators assessed the characteristics of the exposure and reference groups, main results, measured confounders and methods used to adjust for unmeasured confounders. We identified 21 studies. All studies were based on administrative medical and pharmaceutical databases. Sicker and older patients received conventional antipsychotics more often than new antipsychotics. The risk of dying was especially high in the first month of use, and when haloperidol was administered per injection or in high doses. Terminal illness was not measured in any study. Instrumental variables that were used were also confounded by terminal illness. We conclude that terminal illness has not been adjusted for in observational studies that reported an increased risk of mortality risk in elderly users of conventional antipsychotics. As the validity of the evidence is questionable, so is the warning based on it. Copyright © 2015 John Wiley & Sons, Ltd.

Revisiting Antipsychotic-induced Akathisia: Current Issues and Prospective Challenges

PubMed Central

Salem, Haitham; Nagpal, Caesa; Pigott, Teresa; Teixeira, Antonio Lucio

2017-01-01

Background: Akathisia continues to be a significant challenge in current neurological and psychiatric practice. Prompt and accurate detection is often difficult and there is a lack of consensus concerning the neurobiological basis of akathisia. No definitive treatment has been established for akathisia despite numerous preclinical and clinical studies. Method: We reviewed antipsychotic-induced akathisia including its clinical presentation, proposed underlying pathophysiology, current and under investigation therapeutic strategies. Conclusion: Despite the initial promise that second generation antipsychotics would be devoid of akathisia effects, this has not been confirmed. Currently, there are limited therapeutic options for the clinical practice and the evidence supporting the most widely used treatments (beta blockers, anticholinergic drugs) is still absent or inconsistent. PMID:27928948

Chronobiology of mood disorders.

PubMed

Malhi, G S; Kuiper, S

2013-01-01

As part of a series of papers examining chronobiology ['Getting depression clinical guidelines right: time for change?' Kuiper et al. Acta Psychiatr Scand 2013;128(Suppl. 444):24-30; and 'Manipulating melatonin in managing mood' Boyce & Hopwood. ActaPsychiatrScand 2013;128(Suppl. 444):16-23], in this article, we review and synthesise the extant literature pertaining to the chronobiology of depression and provide a preliminary model for understanding the neural systems involved. A selective literature search was conducted using search engines such as MEDLINE/PubMed, combining terms associated with chronobiology and mood disorders. We propose that understanding of sleep-wake function and mood can be enhanced by simultaneously considering the circadian system, the sleep homoeostat and the core stress system, all of which are likely to be simultaneously disrupted in major mood disorders. This integrative approach is likely to allow flexible modelling of a much broader range of mood disorder presentations and phenomenology. A preliminary multifaceted model is presented, which will require further development and testing. Future depression research should aim to examine multiple systems concurrently in order to derive a more sophisticated understanding of the underlying neurobiology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The art and science of switching antipsychotic medications, part 2.

PubMed

Weiden, Peter J; Miller, Alexander L; Lambert, Tim J; Buckley, Peter F

2007-01-01

In the presentation "Switching and Metabolic Syndrome," Weiden summarizes reasons to switch antipsychotics, highlighting weight gain and other metabolic adverse events as recent treatment targets. In "Texas Medication Algorithm Project (TMAP)," Miller reviews the TMAP study design, discusses results related to the algorithm versus treatment as usual, and concludes with the implications of the study. Lambert's presentation, "Dosing and Titration Strategies to Optimize Patient Outcome When Switching Antipsychotic Therapy," reviews the decision-making process when switching patients' medication, addresses dosing and titration strategies to effectively transition between medications, and examines other factors to consider when switching pharmacotherapy.

Bioactivity guided isolation of antipsychotic constituents from the leaves of Rauwolfia tetraphylla L.

PubMed

Gupta, Shikha; Khanna, Vinay Kumar; Maurya, Anupam; Bawankule, Dnyaneshwar Umrao; Shukla, Rajendra Kumar; Pal, Anirban; Srivastava, Santosh Kumar

2012-09-01

This study was undertaken to ascertain the antipsychotic properties of Rauwolfia tetraphylla L. leaves and to isolate and characterize the antipsychotic constituents. Among the MeOH extract and some alkaloidal fractions at different pHs, the alkaloidal CHCl(3) fraction at pH-9 (2C) showed the highest antipsychotic activity against dopaminergic (DA-D(2)) and serotonergic (5-HT(2A)) receptors in-vitro and amphetamine induced hyperactive mouse model in-vivo. The activity guided isolation of CHCl(3) fraction (2C) afforded six indole alkaloids: 10-methoxytetrahydroalstonine (1), isoreserpiline (2), an isomeric mixture of 11-demethoxyreserpiline (3) and 10-demethoxyreserpiline (4), α-yohimbine (5) and reserpiline (6). Given orally, alkaloids 3-6 showed significant antipsychotic activity in a dose dependent manner. None of the extract, alkaloidal fractions or alkaloids showed any extra pyramidal symptoms at the tested doses. It was also observed that MeOH extract was behaving similar to other clinically used novel atypical antipsychotics in having 5-HT(2A) occupancy greater than the DA-D(2) receptor at the tested doses. Further toxicity and safety evaluation studies of MeOH extracts of R. tetraphylla leaves at different doses (10, 100, 300 and 2000 mg/kg) on female Swiss albino mice showed that MeOH extract is non toxic. The isolated alkaloids, 3-6 could serve as a promising lead structure for drug development of treating psychotic conditions in human. Copyright © 2012 Elsevier B.V. All rights reserved.

Induced mood and selective attention.

PubMed

Brand, N; Verspui, L; Oving, A

1997-04-01

Subjects (N = 60) were randomly assigned to an elated, depressed, or neutral mood-induction condition to assess the effect of mood state on cognitive functioning. In the elated condition film fragments expressing happiness and euphoria were shown. In the depressed condition some frightening and distressing film fragments were presented. The neutral group watched no film. Mood states were measured using the Profile of Mood States, and a Stroop task assessed selective attention. Both were presented by computer. The induction groups differed significantly in the expected direction on the mood subscales Anger, Tension, Depression, Vigour, and Fatigue, and also in the mean scale response times, i.e., slower responses for the depressed condition and faster for the elated one. Differences between conditions were found in the errors on the Stroop: in the depressed condition were the fewest errors and significantly longer error reaction times. Speed of error was associated with self-reported fatigue.

Adherence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia.

PubMed

Gilmer, Todd P; Dolder, Christian R; Lacro, Jonathan P; Folsom, David P; Lindamer, Laurie; Garcia, Piedad; Jeste, Dilip V

2004-04-01

The authors' goal was to evaluate the relationship between adherence to treatment with antipsychotic medication and health expenditures. A secondary objective was to identify risk factors predictive of nonadherence. Data included Medicaid eligibility and claims data from 1998 to 2000 for San Diego County, Calif. Pharmacy records were used to assess adherence to treatment with antipsychotic medication according to the cumulative possession ratio (the number of days medications were available for consumption divided by the number of days subjects were eligible for Medi-Cal). Regression models were used to examine risk factors, hospitalizations, and costs associated with nonadherence, partial adherence, adherence, and excess fills of antipsychotic medication. Forty-one percent of Medicaid beneficiaries with schizophrenia were found to be adherent to treatment with their antipsychotic medications: 24% were nonadherent, 16% were partially adherent, and 19% were excess fillers. Rates of psychiatric hospitalization were lower for those who were adherent (14%) than for those who were nonadherent (35%), partially adherent (24%), or had excess fills (25%). Rates of medical hospitalization were lower for those who were adherent (7%) than for those who were nonadherent (13%) or had excess fills (12%). Those who were adherent had significantly lower hospital costs than the other groups; pharmacy costs were higher among those who were adherent than among those who were nonadherent or partially adherent and were highest for excess fillers. Total costs for excess fillers (14,044 US dollars) were substantially higher than total costs for any other group. Despite the widespread use of atypical antipsychotic medications, alarmingly high rates of both underuse and excessive filling of antipsychotic prescriptions were found in Medicaid beneficiaries with schizophrenia. The high rates of antipsychotic nonadherence and associated negative consequences suggest interventions on multiple

Design and in vivo evaluation of solid lipid nanoparticulate systems of Olanzapine for acute phase schizophrenia treatment: Investigations on antipsychotic potential and adverse effects.

PubMed

Joseph, Emil; Reddi, Satish; Rinwa, Vibhu; Balwani, Garima; Saha, Ranendra

2017-06-15

The present paper discusses the design, characterization and in vivo evaluation of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic drug for acute schizophrenia treatment, during which hospitalization is mandatory and adverse effects are at its peak. The solid lipid nanoparticulate system was obtained by emulsification-ultra sonication technique wherein three factors such as solid lipid content, concentration of surfactant and drug: solid lipid ratio were selected at three different levels in order to study their influence on significant characteristic responses such as particle size, encapsulation efficiency and drug content. A Box Behnken design with 17 runs involving whole factors at three levels was employed for the study. The optimized formulation was further coated with Polysorbate 80 in order to enhance its brain targeting potential through endocytosis transport process via blood brain barrier. The designed formulations were pre-clinically tested successfully in Wistar rat model for in vivo antipsychotic efficacy (apomorphine induced psychosis) and adverse effects (weight gain study for 28days). The results obtained indicated that solid lipid nanoparticles had very narrow size distribution (151.29±3.36nm) with very high encapsulation efficiency (74.51±1.75%). Morphological studies by SEM have shown that solid lipid nanoparticles were spherical in shape with smooth surface. Olanzapine-loaded nanoparticles prepared from solid lipid, extended the release of drug for 48h, as found by the in vitro release studies. The formulations also exhibited high redispersibility after freeze-drying and stability study results demonstrated good stability, with no significant change for a period of 6months. In vivo evaluation and adverse effects studies of Olanzapine-loaded nanoparticulate systems in animal model have demonstrated an improved therapeutic efficacy than pure Olanzapine. The antipsychotic effect of drug loaded nanoparticulate systems

Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida).

PubMed

Linck, Viviane M; Ganzella, Marcelo; Herrmann, Ana P; Okunji, Christopher O; Souza, Diogo O; Antonelli, Marta C; Elisabetsky, Elaine

2015-01-15

Alstonine is the major component of plant based remedies that traditional psychiatrists use in Nigeria. Alstonine is an indole alkaloid that has an antipsychotic experimental profile comparable with that of clozapine and is compatible with the alleged effects in mental patients. Representing a desirable innovation in the pharmacodynamics of antipsychotic medications, the evidence indicates that alstonine does not bind to D2 dopamine receptors (D2R) and differentially regulates dopamine in the cortical and limbic areas. The purpose of this study was to further investigate the effects of alstonine on D2R binding in specific brain regions using quantitative autoradiography (QAR) and its effects on dopamine (DA) uptake in mouse striatal synaptosomes. The effects of alstonine on D2R binding were determined in the nucleus accumbens and caudate-putamen using QAR in mice treated with alstonine doses that have antipsychotic effects. The effects of alstonine [3H]DA uptake were assessed in synaptosomes prepared from striatal tissue obtained from mice treated acutely or for 7 days with alstonine. Alstonine did not change the D2R binding densities in the studied regions. DA uptake was increased after acute (but not after 7 days) treatment with alstonine. Consistent with the alstonine behavioral profile, these results indicate that alstonine indirectly modulates DA receptors, specifically by modulating DA uptake. This unique mechanism for DA transmission modulation contributes to the antipsychotic-like effects of alstonine and is compatible with its behavioral profile in mice and alleged effects in patients. These results may represent an innovation in the antipsychotic development field. Copyright © 2014 Elsevier GmbH. All rights reserved.

A Pharmacovigilance Study in First Episode of Psychosis: Psychopharmacological Interventions and Safety Profiles in the PEPs Project

PubMed Central

Bioque, Miquel; Llerena, Adrián; Cabrera, Bibiana; Mezquida, Gisela; Lobo, Antonio; González-Pinto, Ana; Díaz-Caneja, Covadonga M.; Corripio, Iluminada; Aguilar, Eduardo J.; Bulbena, Antoni; Castro-Fornieles, Josefina; Vieta, Eduard; Lafuente, Amàlia; Mas, Sergi; Parellada, Mara; Saiz-Ruiz, Jerónimo; Cuesta, Manuel J.

2016-01-01

Background: The characterization of the first episode of psychosis and how it should be treated are principal issues in actual research. Realistic, naturalistic studies are necessary to represent the entire population of first episode of psychosis attended in daily practice. Methods: Sixteen participating centers from the PEPs project recruited 335 first episode of psychosis patients, aged 7 to 35 years. This article describes and discusses the psychopharmacological interventions and safety profiles at baseline and during a 60-day pharmacovigilance period. Results: The majority of first episode of psychosis patients received a second-generation antipsychotic (96.3%), orally (95%), and in adjusted doses according to the product specifications (87.2%). A total of 24% were receiving an antipsychotic polytherapy pattern at baseline, frequently associated with lower or higher doses of antipsychotics than the recommended ones. Eight patients were taking clozapine, all in monotherapy. Males received higher doses of antipsychotic (P=.043). A total of 5.2% of the patients were being treated with long-acting injectable antipsychotics; 12.2% of the patients received anticholinergic drugs, 12.2% antidepressants, and 13.7% mood stabilizers, while almost 40% received benzodiazepines; and 35.52% reported at least one adverse drug reaction during the pharmacovigilance period, more frequently associated with higher antipsychotic doses and antipsychotic polytherapy (85.2% vs 45.5%, P<.001). Conclusions: These data indicate that the overall pharmacologic prescription for treating a first episode of psychosis in Spain follows the clinical practice guideline recommendations, and, together with security issues, support future research of determinate pharmacological strategies for the treatment of early phases of psychosis, such as the role of clozapine, long-acting injectable antipsychotics, antipsychotic combination, and the use of benzodiazepines. PMID:26506856

Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro.

PubMed

Sárvári, Anitta K; Veréb, Zoltán; Uray, Iván P; Fésüs, László; Balajthy, Zoltán

2014-08-08

Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin and adiponectin, suggesting that both glucose and fat metabolism may be affected by these drugs. These data further suggest that antipsychotic treatments in patients alter the gene expression patterns in adipocytes in a coordinated fashion and priming them for a low-level inflammatory state. Copyright © 2014 Elsevier Inc. All rights reserved.

Antipsychotic treatment and the Rorschach Perceptual Thinking Index (PTI) in psychotic disorder patients: Effects of treatment.

PubMed

Biagiarelli, Mario; Curto, Martina; Di Pomponio, Ileana; Comparelli, Anna; Baldessarini, Ross J; Ferracuti, Stefano

2017-05-01

The Rorschach-based Perceptual Thinking Index (PTI) is used to identify and rate features of psychotic disorders, but effects of antipsychotic treatment on such ratings is not clear. Accordingly, we examined potential effects of antipsychotic drugs on PTI measures in 114 patients with a psychotic or bipolar-I disorder. Use and doses of antipsychotic drugs (as chlorpromazine-equivalent [CPZ-eq] mg/day) were unrelated to PTI total or subscale scores in any diagnostic group. PTI scores were independently and significantly associated with psychotic symptomatic severity (PANSS score) and less with female sex. These findings support the validity and value of the PTI in identifying features of psychosis even in the presence of antipsychotic treatment. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Antipsychotic treatment and the risk of hip fracture in subjects with schizophrenia: a 10-year population-based case-control study.

PubMed

Wu, Chi-Shin; Chang, Chia-Ming; Tsai, Yu-Ting; Huang, Ya-Wen; Tsai, Hui-Ju

2015-09-01

To investigate the association between antipsychotic treatment and risk of hip fracture in subjects with schizophrenia. Among patients with schizophrenia (ICD-9-CM code 295), 605 cases with hip fracture and 2,828 matched controls were identified from 2002 to 2011 using the National Health Insurance Research Database in Taiwan. The authors conducted a nested case-control study to investigate the association between antipsychotic treatment and risk of hip fracture in subjects with schizophrenia. The modifiable effects of age and gender were evaluated by stratified analysis. In addition, the effects of antipsychotic use, antipsychotic classes, and receptor-binding profiles of antipsychotics, individually, on hip fracture were estimated, and potential confounding factors were adjusted in subsequent analysis. Conditional logistic regressions were applied to determine the effect of antipsychotic treatment on hip fracture. Current antipsychotic use was associated with an increased risk for hip fracture (adjusted odds ratio [AOR] = 1.61; 95% CI, 1.24-2.10). Among current users, new users had a higher risk of hip fracture (AOR = 4.28; 95% CI, 1.76-10.36) than past users (AOR = 1.11; 95% CI, 0.79-1.56). In addition, a significant increased risk of hip fracture was noted in schizophrenia subjects with first-generation antipsychotic use (AOR = 1.59; 95%CI, 1.15-2.20) but not in those with second-generation antipsychotic use (AOR = 1.16; 95% CI, 0.91-1.48). These results extend previous findings and demonstrate an increased risk of hip fracture associated with antipsychotic use in schizophrenia subjects. Further investigation is needed to dissect the underlying mechanisms related to the effect of antipsychotic use on hip fracture in subjects at risk. © Copyright 2015 Physicians Postgraduate Press, Inc.

Delirium and Antipsychotics: A Systematic Review of Epidemiology and Somatic Treatment Options

PubMed Central

2008-01-01

Delirium is a very common medical condition encountered throughout the world and, undoubtedly, is one of the most frequent reasons psychiatrists are consulted by primary care physicians. Recognizing delirium and treating the underlying medical cause are the first steps in the management of this potentially fatal syndrome. The selection of an appropriate medication to target the perceptual, behavioral, and cognitive abnormalities is crucial. In addition to several of the older, typical antipsychotics, which have been found to be effective for the treatment of delirium, some of the newer, atypical antipsychotic agents have been demonstrated to be efficacious. This paper will review both the typical and atypical antipsychotics with the best evidence for efficacy and safety in the treatment of delirium. Finally, environmental treatments are discussed to present the full armamentarium of therapeutic options available to the practicing clinician. PMID:19724721

Binge eating in adults with mood disorders: Results from the International Mood Disorders Collaborative Project.

PubMed

Woldeyohannes, Hanna O; Soczynska, Joanna K; Maruschak, Nadia A; Syeda, Kahlood; Wium-Andersen, Ida K; Lee, Yena; Cha, Danielle S; Xiao, Holly X; Gallaugher, Laura A; Dale, Roman M; Alsuwaidan, Mohammad T; Mansur, Rodrigo B; Muzina, David J; Carvalho, Andre F; Jerrell, Jeanette; Kennedy, Sidney; McIntyre, Roger S

A post hoc analysis was conducted using data from participants (N=631) with a DSM-IV-TR defined diagnosis of major depressive disorder (MDD) or bipolar disorder (BD) who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. It was determined that 20.6% of adults with mood disorders as part of the IMDCP fulfilled criteria for binge eating behaviour (BE). A higher percentage of individuals with BD met criteria for BE when compared to MDD (25.4% vs. 16%; p=0.004) Univariate analyses indicated that individuals with a mood disorder (i.e., MDD or BD) and BE had greater scores on measures of anxiety severity (p=0.013) and higher rates of lifetime and current substance dependence, lifetime alcohol abuse (p=0.007, p=0.006, and p=0.015, respectively), Attention Deficit Hyperactivity Disorder (ADHD) (p=0.018) and measures of neuroticism (p=0.019). Individuals with a mood disorder and concurrent BE had lower scores on measures of conscientiousness (p=0.019). Individuals meeting criteria for BE were also significantly more likely to be obese (i.e., BMI≥30kg/m 2 ) (50% vs. 25.5%; p<0.001). Binge eating is common amongst adults utilising tertiary care services principally for a mood disorder. The presence of BE identifies a subset of adults with mood disorders who have greater illness complexity as evidenced by course of illness variables and comorbidity. Screening for BE amongst individuals with mood disorders is warranted; parsing neurobiological substrates subserving non-homeostatic eating behaviour amongst individuals with mood disorders is a future research vista. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

The Effect of Mental Progression on Mood

ERIC Educational Resources Information Center

Mason, Malia F.; Bar, Moshe

2012-01-01

Mood affects the way people think. But can the way people think affect their mood? In the present investigation, we examined this promising link by testing whether mood is influenced by the presence or absence of associative progression by manipulating the scope of participants' information processing and measuring their subsequent mood. In…

Nature and Quality of Antipsychotic Prescribing Practice in UK Psychiatry of Intellectual Disability Services

ERIC Educational Resources Information Center

Paton, C.; Flynn, A.; Shingleton-Smith, A.; McIntyre, S.; Bhaumik, S.; Rasmussen, J.; Hardy, S.; Barnes, T.

2011-01-01

Background: Antipsychotics are perceived to be over-used in the management of behavioural problems in people with an intellectual disability (ID). Published guidelines have set good practice standards for the use of these drugs for behavioural indications. We sought to identify the range of indications for which antipsychotic drugs are prescribed…

Increased use of antipsychotic long-acting injections with community treatment orders.

PubMed

Patel, Maxine X; Matonhodze, Jane; Baig, Mirza K; Gilleen, James; Boydell, Jane; Holloway, Frank; Taylor, David; Szmukler, George; Lambert, Tim; David, Anthony S

2011-04-01

Community treatment orders (CTOs) are increasingly being used, despite a weak evidence base, and problems continue regarding Second Opinion Appointed Doctor (SOAD) certification of medication. The aim of the current study was to describe current CTO usage regarding patient characteristics, prescribed medication and CTO conditions. A 1-year prospective cohort study with consecutive sampling was conducted for all patients whose CTO was registered in a large mental health trust. Only the first CTO for each patient was included. Measures included sociodemographic variables, psychiatric diagnosis, CTO date of initiation and conditions, psychotropic medication and date of SOAD certification for medication. This study was conducted in the first year of CTO legislation in England and Wales. A total of195 patients were sampled (mean age 40.6 years, 65% male, 52% black ethnic origin). There was significant geographical variability in rates of CTO use (χ(2) = 11.3, p = 0.012). A total of 53% had their place of residence specified as a condition and 29% were required to allow access into their homes. Of those with schizophrenia, 64% were prescribed an antipsychotic long-acting injection (LAI). Of the total group, 7% received high-dose antipsychotics, 10% were prescribed two antipsychotics and only 15% received SOAD certification in time. There was geographical and ethnic variation in CTO use but higher rates of hospital detention in minority ethnic groups may be contributory. Most patients were prescribed antipsychotic LAIs and CTO conditions may not follow the least restrictive principle.

Exercise enhances creativity independently of mood

PubMed Central

Steinberg, Hannah; Sykes, Elizabeth A; Moss, Tim; Lowery, Susan; LeBoutillier, Nick; Dewey, Alison

1997-01-01

Objectives It has been widely accepted in the literature that various forms of physical exercise, even in a single session, enhance positive mood. It has also been shown that physical exercise may sometimes enhance creative thinking, but the evidence is inconclusive. Positive moods can favour creative thinking, but the opposite has also been reported and these relations are unclear. There is a large anecdotal literature suggesting that creative people sometimes use bodily movement to help overcome “blocks”. The aim of this study was to establish whether post-exercise creative thinking was attributable to improved mood. Methods The responses of 63 participants to an exercise (aerobic workout or aerobic dance) and a “neutral” video watching condition were compared. Mood was measured using an adjective list, and creative thinking was tested by three measures of the Torrance test. Results Analysis of variance showed a large and significant increase in positive mood after exercise (P<0.001) and a significant decrease in positive mood after video watching (P<0.001). A significant increase between the creative thinking scores of the two conditions was found on the flexibility (variety of responses) measure (P<0.05). A multifactorial analysis of all data failed to show a significant covariance of creative thinking with the two measures of mood (P>0.05). Conclusions These results suggest that mood and creativity were improved by physical exercise independently of each other. ImagesFigure 1Figure 2 PMID:9298561

Glucometabolic hormones and cardiovascular risk markers in antipsychotic-treated patients.

PubMed

Ebdrup, Bjørn H; Knop, Filip K; Madsen, Anna; Mortensen, Henrik B; Søgaard, Birgitte; Holst, Jens J; Szecsi, Pal B; Lublin, Henrik

2014-09-01

Treatment with antipsychotic drugs is widely associated with metabolic side effects such as weight gain and disturbed glucose metabolism, but the pathophysiologic mechanisms are unclear. Fifty nondiabetic (fasting plasma glucose ≤ 7.0 mmol/L), antipsychotic-treated male patients (ICD-10 diagnosis code F20, F21, F22, F25, F28, or F60; mean ± SD age = 33.0 ± 6.7 years; body mass index [BMI; kg/m²] = 26.0 ± 4.7; waist circumference = 95.9 ± 13.3 cm; glycated hemoglobin A1c [HbA1c] = 5.7% ± 0.3%) and 93 age- and waist circumference-matched healthy male controls (age = 33 ± 7.3 years; BMI = 26.1 ± 3.9; waist circumference = 94.6 ± 11.9 cm; HbA1c = 5.7% ± 0.3%) participated in this cross-sectional study. Blood was sampled in the fasting state and 90 minutes after ingestion of a standardized liquid meal (2,268 kJ). The primary outcomes were glucometabolic hormones and cardiovascular risk markers. Data were collected between March 2008 and February 2010. Compared to healthy controls, patients were characterized by elevated fasting levels of proinsulin, C-peptide, and glucose-dependent insulinotropic polypeptide (GIP) (P < .05) and higher postprandial levels of insulin, proinsulin, C-peptide, and GIP (P ≤ .02). Also, patients exhibited elevated plasma levels of C-reactive protein and signs of dyslipidemia. Fasting plasma levels of insulin, glucagon, glucagon-like peptide-1 (GLP-1), ghrelin, leptin, adiponectin, tumor necrosis factor-α, plasminogen activator inhibitor-1, and interleukin-6 and postprandial levels of glucagon, GLP-1, ghrelin, leptin, and adiponectin did not differ between groups. Presenting with an insulin resistant-like pattern, including beta cell hypersecretion and elevated GIP levels, nondiabetic antipsychotic-treated patients display emerging signs of dysmetabolism and a compromised cardiovascular risk profile. The appetite-regulating hormones GLP-1 and ghrelin appear not to be influenced by antipsychotic treatment. Our findings provide new

Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach

PubMed Central

Ruderfer, Douglas M; Charney, Alexander W; Readhead, Ben; Kidd, Brian A; Kähler, Anna K; Kenny, Paul J; Keiser, Michael J; Moran, Jennifer L; Hultman, Christina M; Scott, Stuart A; Sullivan, Patrick F; Purcell, Shaun M; Dudley, Joel T; Sklar, Pamela

2016-01-01

Summary Background Therapeutic treatments for schizophrenia do not alleviate symptoms for all patients and efficacy is limited by common, often severe, side-effects. Genetic studies of disease can identify novel drug targets, and drugs for which the mechanism has direct genetic support have increased likelihood of clinical success. Large-scale genetic studies of schizophrenia have increased the number of genes and gene sets associated with risk. We aimed to examine the overlap between schizophrenia risk loci and gene targets of a comprehensive set of medications to potentially inform and improve treatment of schizophrenia. Methods We defined schizophrenia risk loci as genomic regions reaching genome-wide significance in the latest Psychiatric Genomics Consortium schizophrenia genome-wide association study (GWAS) of 36 989 cases and 113 075 controls and loss of function variants observed only once among 5079 individuals in an exome-sequencing study of 2536 schizophrenia cases and 2543 controls (Swedish Schizophrenia Study). Using two large and orthogonally created databases, we collated drug targets into 167 gene sets targeted by pharmacologically similar drugs and examined enrichment of schizophrenia risk loci in these sets. We further linked the exome-sequenced data with a national drug registry (the Swedish Prescribed Drug Register) to assess the contribution of rare variants to treatment response, using clozapine prescription as a proxy for treatment resistance. Findings We combined results from testing rare and common variation and, after correction for multiple testing, two gene sets were associated with schizophrenia risk: agents against amoebiasis and other protozoal diseases (106 genes, p=0·00046, pcorrected =0·024) and antipsychotics (347 genes, p=0·00078, pcorrected=0·046). Further analysis pointed to antipsychotics as having independent enrichment after removing genes that overlapped these two target sets. We noted significant enrichment both in

Association between community pharmacy loyalty and persistence and implementation of antipsychotic treatment among individuals with schizophrenia.

PubMed

Zongo, Frank E; Moisan, Jocelyne; Grégoire, Jean-Pierre; Lesage, Alain; Dossa, Anara Richi; Lauzier, Sophie

2018-01-01

Non-adherence is a major obstacle to optimal treatment of schizophrenia. Community pharmacists are in a key position to detect non-adherence and put in place interventions. Their role is likely to be more efficient when individuals are loyal to a single pharmacy. To assess the association between the level of community pharmacy loyalty and persistence with and implementation of antipsychotic drug treatment among individuals with schizophrenia. A cohort study using databases from the Quebec health insurance board (Canada) was conducted among new antipsychotic users insured by Quebec's public drug plan. Level of community pharmacy loyalty was assessed as the number of pharmacies visited in the year after antipsychotics initiation. Persistence was defined as having an antipsychotic supply in the user's possession on the 730 th day after its initiation and implementation as having antipsychotics in the user's possession for ≥80% of the days in the second year after antipsychotics initiation (among persistent only). Generalized linear models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (95%CI). 6,251 individuals were included in the cohort and 54.1% had their drug prescriptions filled in >1 pharmacy. When compared to those who had their prescriptions filled in a single pharmacy, those who had their prescriptions filled in ≥4 different pharmacies were 22% more likely to be non-persistent (aPR = 1.22; 95%CI = 1.10-1.37) and 49% more likely to have an antipsychotic for <80% of the days (aPR = 1.49; 95%IC = 1.28-1.74). This first exploration of community pharmacy loyalty in the context of severe mental illness indicates that this healthcare organisation factor might be associated with antipsychotics persistence and implementation. Identification of individuals with low community pharmacy loyalty and initiatives to optimize community pharmacy loyalty could contribute to enhanced persistence and implementation. Copyright �

Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People With Parkinson Disease Psychosis.

PubMed

Ballard, Clive; Isaacson, Stuart; Mills, Roger; Williams, Hilde; Corbett, Anne; Coate, Bruce; Pahwa, Rajesh; Rascol, Olivier; Burn, David J

2015-10-01

To establish the mortality risk and adverse events associated with the use of atypical antipsychotic medications in people with Parkinson disease psychosis (PDP) in a clinically defined trial cohort. Post hoc analysis of data from a multicenter, open-label extension study of pimavanserin comparing people taking and not taking current antipsychotics. Primary and secondary care medical centers in the United States, Canada, Europe, and India. A total of 459 people with PDP enrolled in the extension study. Participants were between ages 30 and 80 years, and had an established diagnosis of idiopathic Parkinson disease and moderate to severe psychosis. Participants were categorized into 2 groups: those receiving concomitant antipsychotic medications ("concurrent APD") and those who did not take antipsychotic medications at any time during the study ("no APD"). Participants were receiving 40 mg pimavanserin daily in addition to concurrent antipsychotics and Parkinson disease medications. Safety assessments at 2 weeks; 1, 3, 6, 9, and 12 months; and every 6 months thereafter, including evaluation of adverse events (AEs), vital signs, weight, physical examinations, 12-lead electrocardiograms, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and the Unified Parkinson's Disease Rating Scale Parts II and III (UPDRS-II+III, activities of daily living and motor impairment, respectively). Differences between participants taking and not taking current antipsychotics were evaluated using incidence rate ratios (IRRs) with 95% confidence intervals (CIs). There was significant increase in the mortality rate for participants taking concurrent antipsychotics compared with the group not taking antipsychotic medications (IRR 4.20, 95% CI 2.13-7.96). Participants who received a concurrent antipsychotic were also significantly more likely to experience overall a serious AE (IRR 2.95, 95% CI 2.02-4.24), any antipsychotic-related event (IRR 1.66, 95% CI 1

Antipsychotic drugs prevent the motor hyperactivity induced by psychotomimetic MK-801 in zebrafish (Danio rerio).

PubMed

Seibt, Kelly Juliana; Oliveira, Renata da Luz; Zimmermann, Fernanda Francine; Capiotti, Katiúcia Marques; Bogo, Maurício Reis; Ghisleni, Gabriele; Bonan, Carla Denise

2010-12-25

Glutamate N-methyl-d-aspartate (NMDA) receptor antagonists, such as dizocilpine (MK-801), elicit schizophrenia-like symptoms in humans and a behavioral syndrome in rodents, characterized by hyperlocomotion and stereotyped actions, which is antagonized by antipsychotic drugs. Animal models of schizophrenia have been established and used for the development of new antipsychotic drugs. In this work we characterized the behavioral effects of MK-801 and investigated the effect of typical and atypical antipsychotic treatments on locomotor activity as well on the hyperlocomotion induced by MK-801 in zebrafish. MK-801 (20 microM) increased the locomotor behavior as measured by the number of line crossings, distance traveled, and the mean speed in the tank test after 15, 30, and 60 min of exposure. All tested antipsychotics counteracted MK-801-induced hyperactivity on all parameters analyzed and at doses that, given alone, had no effect on spontaneous locomotor activity. The results suggest a similar profile between typical and atypical antipsychotics in the reversal of locomotor disorders induced by MK-801. Moreover, an anxiolytic effect was verified at 30 and 60 min of MK-801 exposure, which was not reversed by antipsychotics tested in this work. In addition, olanzapine, which alone caused an anxiolytic response, when given with MK-801 potentiated the latter's effect on anxiety. In this work we demonstrated the value of the zebrafish, a simple to use animal model, in developing some behavioral features observed in schizophrenia, which may indicate a new approach for drug screening. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Antipsychotic treatment dosing profile in patients with schizophrenia evaluated with electronic monitoring (MEMS®).

PubMed

Acosta, Francisco J; Ramallo-Fariña, Yolanda; Bosch, Esperanza; Mayans, Teresa; Rodríguez, Carlos J; Caravaca, Ana

2013-05-01

Although the Medication Event Monitoring System (MEMS®) device offers accurate information on treatment dosing profile, such profile has never been studied in patients with schizophrenia. Enhancing our knowledge on this issue would help in developing intervention strategies to improve adherence to antipsychotic treatment in these patients. 74 outpatients with schizophrenia were monitored with the MEMS device for a 3-month period, for evaluation of antipsychotic treatment dosing profile, possible influence of medication schedule-related variables, adherence to treatment--considering dose intake within prescribed timeframes--and possible Hawthorne's effect of using the MEMS device. Dose-omission gaps occurred in 18.7% of monitoring days, most frequently during weekends, almost significantly. Almost one-third of prescribed doses were taken out of prescribed time. Neither the prescribed number of daily doses nor the indicated time of the day for dose intake (breakfast, dinner), were associated with correct antipsychotic dosing. Excess-dose was rare in general, and more frequent out of prescribed dose timeframe. No Hawthorne's effect was found for the MEMS device. Adherence reached only 35% according to a definition that included dose intake within prescribed timeframes. Antipsychotic treatment dosing was considerably irregular among patients with schizophrenia. Strategies to reduce dose-omission gaps and increase dosing within prescribed timeframes seem to be necessary. Gaining knowledge on precise oral antipsychotic dosing profiles or the influence of schedule-related variables may be useful to design strategies towards enhancing adherence. There appears to be no Hawthorne's effect associated with the use of MEMS devices in outpatients with schizophrenia. Copyright © 2013 Elsevier B.V. All rights reserved.

Continuous, but not intermittent, antipsychotic drug delivery intensifies the pursuit of reward cues.

PubMed

Bédard, Anne-Marie; Maheux, Jérôme; Lévesque, Daniel; Samaha, Anne-Noël

2011-05-01

Chronic exposure to antipsychotic medications can persistently change brain dopamine systems. Most studies on the functional significance of these neural changes have focused on motor behavior and few have addressed how long-term antipsychotic treatment might influence dopamine-mediated reward function. We asked, therefore, whether a clinically relevant antipsychotic treatment regimen would alter the incentive motivational properties of a reward cue. We assessed the ability of a Pavlovian-conditioned stimulus to function as a conditioned reward, as well as to elicit approach behavior in rats treated with haloperidol, either continuously (achieved via subcutaneous osmotic minipump) or intermittently (achieved via daily subcutaneous injections). Continuous, but not intermittent, treatment enhanced the ability of amphetamine to potentiate the conditioned reinforcing effects of a cue associated with water. This effect was not related to differences in the ability to attribute predictive value to a conditioned stimulus (as measured by conditioned approach behavior), but was potentially linked to the development of behavioral supersensitivity to amphetamine and to augmented amphetamine-induced immediate early-gene expression (c-fos and Nur77) in dorsal striatopallidal and striatonigral cells. By enhancing the ability of reward cues to control behavior and by intensifying dopamine-mediated striatopallidal and striatonigral cell activity, standard (ie, continuous) antipsychotic treatment regimens might exacerbate drug-seeking and drug-taking behavior in schizophrenia. Achieving regular but transiently high antipsychotic levels in the brain (as modeled in the intermittent condition) might be a viable option to prevent these changes. This possibility should be explored in the clinic.

The Effect of Observers’ Mood on the Local Processing of Emotional Faces: Evidence from Short-Lived and Prolonged Mood States

PubMed Central

Mokhtari, Setareh; Buttle, Heather

2015-01-01

We examined the effect of induced mood, varying in valence and longevity, on local processing of emotional faces. It was found that negative facial expression conveyed by the global level of the face interferes with efficient processing of the local features. The results also showed that the duration of involvement with a mood influenced the local processing. We observed that attending to the local level of faces is not different in short-lived happy and sad mood states. However, as the mood state is experienced for a longer period, local processing was impaired in happy mood compared to sad mood. Taken together, we concluded that both facial expressions and affective states influence processing of the local parts of faces. Moreover, we suggest that mediating factors like the duration of involvement with the mood play a role in the interrelation between mood, attention, and perception. PMID:25883696

Mood instability: significance, definition and measurement.

PubMed

Broome, M R; Saunders, K E A; Harrison, P J; Marwaha, S

2015-10-01

Mood instability is common, and an important feature of several psychiatric disorders. We discuss the definition and measurement of mood instability, and review its prevalence, characteristics, neurobiological correlates and clinical implications. We suggest that mood instability has underappreciated transdiagnostic potential as an investigational and therapeutic target. © The Royal College of Psychiatrists 2015.

Clinical risk factors for the development of tardive dyskinesia.

PubMed

Solmi, Marco; Pigato, Giorgio; Kane, John M; Correll, Christoph U

2018-06-15

Tardive dyskinesia (TD) is a severe condition that can affect almost 1 out of 4 patients on current or previous antipsychotic treatment, including both first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs). While two novel vesicular monoamine transporter inhibitors, deutetrabenazine and valbenazine, have shown acute efficacy for TD, the majority of patients do not remit, and TD appears to recur once treatment is withdrawn. Hence, prevention of TD remains a crucial goal. We provide a clinically oriented overview of risk factors for TD, dividing them into patient-, illness- and treatment-related variables, as well as nonmodifiable and modifiable factors. Unmodifiable patient-related and illness-related risk factors for TD include older age, female sex, white and African descent, longer illness duration, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related and treatment-related factors include diabetes, smoking, and alcohol and substance abuse, FGA vs SGA treatment, higher cumulative and current antipsychotic dose or antipsychotic plasma levels, early parkinsonian side effects, anticholinergic co-treatment, akathisia, and emergent dyskinesia. Clinicians using dopamine antagonists need to consider risk factors for TD to minimize TD and its consequences. Copyright © 2018 Elsevier B.V. All rights reserved.

Responses to depressed mood and suicide attempt in young adults with a history of childhood-onset mood disorder.

PubMed

Liu, Xianchen; Gentzler, Amy L; George, Charles J; Kovacs, Maria

2009-05-01

Although individuals' responses to their depressed mood are hypothesized to play an important role in the development and maintenance of depression, how these responses might impact the likelihood of suicidal behavior in mood disorders remains largely unexplored. The goal of the current study was to examine whether maladaptive responses to depressed mood are associated with suicide attempts in adults with a history of childhood-onset mood disorder (COMD). Participants included 223 young adult probands with COMD meeting DSM-III or DSM-IV criteria for major depressive disorder or bipolar disorder and 112 controls without a history of psychiatric disorders. All participants were recruited between 1996 and 2004. Probands were followed for 6 to 99 months (median = 32 months). The Responses Styles Questionnaire was used to assess 2 adaptive (distraction and problem solving) and 2 maladaptive (dangerous activity and rumination) ways of coping with depressed mood. Compared to controls, COMD probands scored significantly higher on maladaptive response styles and lower on adaptive styles. Compared to their COMD peers, probands with a history of suicide attempt were less likely to report using distracting activities to manage their depressed mood. However, COMD probands who engaged in dangerous activities in response to depressed mood were more likely to attempt suicide during the follow-up period (hazard ratio = 1.8, 95% CI = 1.2 to 2.8). One of the pathways to suicide attempt in mood disorders may involve maladaptive responses to depressed mood. The assessment of how depressed individuals manage their dysphoric moods, therefore, should be considered an important aspect of treatment and prevention of suicidal behavior. Copyright 2009 Physicians Postgraduate Press, Inc.

Cognitive Function and Depression in Symptom Resolution in Schizophrenia Patients Treated with an Atypical Antipsychotic

ERIC Educational Resources Information Center

Stip, Emmanuel; Mancini-Marie, Adham

2004-01-01

Objective: To investigate which cognitive and affective features contribute most to responder/non-responder group separation during a switching trial with atypical antipsychotic. Design: A prospective open trial with an atypical antipsychotic (olanzapine). Patients: One hundred and thirty-four patients meeting diagnostic criteria for…

A cognitive neuroscience hypothesis of mood and depression

PubMed Central

Bar, Moshe

2009-01-01

Although mood has a direct impact on mental and physical health, our understanding of the mechanisms underlying mood regulation is limited. I propose here that there is a direct, reciprocal relation between the cortical activation of associations and mood regulation, whereby positive mood promotes associative processing, and associative processing promotes positive mood. This relation might stem from an evolutionary pressure for learning and predicting. Along these lines, one can think of mood as a reward mechanism that guides us to use our brains in the most productive manner. The proposed framework has many implications, most notably for diagnosing and treating mood disorders such as depression, for elucidating the role of inhibition in the regulation of mood, for contextualizing adult hippocampal neurogenesis, and for a general, non-invasive improvement of well-being. PMID:19819753

Perceived emotional intelligence in nursing: psychometric properties of the Trait Meta-Mood Scale.

PubMed

Aradilla-Herrero, Amor; Tomás-Sábado, Joaquín; Gómez-Benito, Juana

2014-04-01

To examine the psychometric properties of the Trait Meta-Mood Scale in the nursing context and to determine the relationships between emotional intelligence, self-esteem, alexithymia and death anxiety. The Trait Meta-Mood Scale is one of the most widely used self-report measures for assessing perceived emotional intelligence. However, in the nursing context, no extensive analysis has been conducted to examine its psychometric properties. Cross-sectional and observational study. A total of 1417 subjects participated in the study (1208 nursing students and 209 hospital nurses). The Trait Meta-Mood Scale, the Toronto Alexithymia Scale, the Rosenberg Self-Esteem Scale and the Death Anxiety Inventory were all applied to half of the sample (n = 707). A confirmatory factor analysis was carried out, and statistical analyses examined the internal consistency and test-retest reliability of the Trait Meta-Mood Scale, as well as its relationship with relevant variables. Confirmatory factor analysis confirmed the three dimensions of the original scale (Attention, Clarity and Repair). The instrument showed adequate internal consistency and temporal stability. Correlational results indicated that nurses with high scores on emotional Attention experience more death anxiety, report greater difficulties identifying feelings and have less self-esteem. By contrast, nurses with high levels of emotional Clarity and Repair showed less death anxiety and higher levels of self-esteem. The Trait Meta-Mood Scale is an effective, valid and reliable tool for measuring perceived emotional intelligence in the nursing context. Training programmes should seek to promote emotional abilities among nurses. Use of the Trait Meta-Mood Scale in the nursing context would provide information about nurses' perceived abilities to interpret and manage emotions when interacting with patients. © 2013 John Wiley & Sons Ltd.

Effects of antipsychotics and reference monoaminergic ligands on marble burying behavior in mice.

PubMed

Bruins Slot, Liesbeth A; Bardin, Laurent; Auclair, Agnès L; Depoortere, Ronan; Newman-Tancredi, Adrian

2008-03-01

Antipsychotics constitute efficacious augmenting agents in the treatment of anxiety disorders, including refractory obsessive-compulsive disorder. We examined the effects of 36 compounds, including typical, atypical and novel antipsychotics with dual dopamine D2/5-hydroxytryptamine 1A (D2/5-HT1A) actions on marble burying behavior in mice, a putative preclinical test for anxiety disorders. One hour after drug administration, male NMRI mice were placed individually in cages containing 20 marbles, and the total number of marbles buried after 30 min was counted. The selective serotonin reuptake inhibitors, citalopram (2.5-40 mg/kg), fluoxetine (2.5-10 mg/kg) and the benzodiazepine diazepam (2.5-10 mg/kg), reduced the number of buried marbles. The atypical antipsychotic, clozapine (0.16-10 mg/kg), but not its congener olanzapine, was effective in this test. Haloperidol, a typical antipsychotic, also reduced the number of buried marbles, albeit not in a dose-dependent manner. The atypical risperidone was partially active (0.16-0.63 mg/kg), as was the benzamide derivative, amisulpride, albeit at high (10-40 mg/kg) doses. Among the 'third-generation' antipsychotics possessing combined D2/5-HT1A properties, bifeprunox was active at 0.0025 mg/kg, whereas SLV313 and aripiprazole were active only at the highest doses (2.5 and 10 mg/kg, respectively). SSR181507, F15063 and the antidyskinetic agent, sarizotan, were without any effect. Among a series of receptor subtype-selective ligands, only the 5-HT1A agonist, (+)-8-OH-DPAT (0.63-2.5 mg/kg) and the 5-HT2A/2B/2C antagonist, ritanserin (0.63-2.5 mg/kg) were active. Among novel antipsychotics with dual D2/5-HT1A properties, only bifeprunox was able to potently reduce the number of buried marbles. Inhibition of marble burying behavior may result from the interplay of several receptor systems, including 5-HT2 receptor blockade, dopamine D2 partial agonism and serotonin 5-HT1A agonism.

Antipsychotics and mortality: adjusting for mortality risk scores to address confounding by terminal illness.

PubMed

Park, Yoonyoung; Franklin, Jessica M; Schneeweiss, Sebastian; Levin, Raisa; Crystal, Stephen; Gerhard, Tobias; Huybrechts, Krista F

2015-03-01

To determine whether adjustment for prognostic indices specifically developed for nursing home (NH) populations affect the magnitude of previously observed associations between mortality and conventional and atypical antipsychotics. Cohort study. A merged data set of Medicaid, Medicare, Minimum Data Set (MDS), Online Survey Certification and Reporting system, and National Death Index for 2001 to 2005. Dual-eligible individuals aged 65 and older who initiated antipsychotic treatment in a NH (N=75,445). Three mortality risk scores (Mortality Risk Index Score, Revised MDS Mortality Risk Index, Advanced Dementia Prognostic Tool) were derived for each participant using baseline MDS data, and their performance was assessed using c-statistics and goodness-of-fit tests. The effect of adjusting for these indices in addition to propensity scores (PSs) on the association between antipsychotic medication and mortality was evaluated using Cox models with and without adjustment for risk scores. Each risk score showed moderate discrimination for 6-month mortality, with c-statistics ranging from 0.61 to 0.63. There was no evidence of lack of fit. Imbalances in risk scores between conventional and atypical antipsychotic users, suggesting potential confounding, were much lower within PS deciles than the imbalances in the full cohort. Accounting for each score in the Cox model did not change the relative risk estimates: 2.24 with PS-only adjustment versus 2.20, 2.20, and 2.22 after further adjustment for the three risk scores. Although causality cannot be proven based on nonrandomized studies, this study adds to the body of evidence rejecting explanations other than causality for the greater mortality risk associated with conventional antipsychotics than with atypical antipsychotics. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Evaluation of the antipsychotic medication review process at four long-term facilities in Alberta.

PubMed

Birney, Arden; Charland, Paola; Cole, Mollie; Aslam Arain, Mubashir

2016-01-01

The goal of this evaluation was to understand how four long-term care (LTC) facilities in Alberta have implemented medication reviews for the Appropriate Use of Antipsychotics (AUA) initiative. We aimed to determine how interprofessional (IP) collaboration was incorporated in the antipsychotic medication reviews and how the reviews had been sustained. Four LTC facilities in Alberta participated in this evaluation. We conducted semistructured interviews with 18 facility staff and observed one antipsychotic medication review at each facility. We analyzed data according to the following key components that we identified as relevant to the antipsychotic medication reviews: the structure of the reviews, IP interactions between the staff members, and strategies for sustaining the reviews. The duration of antipsychotic medication reviews ranged from 1 to 1.5 hours. The number of professions in attendance ranged from 3 to 9; a pharmacist led the review at two sites, while a registered nurse led the review at one site and a nurse practitioner at the remaining site. The number of residents discussed during the review ranged from 6 to 20. The process at some facilities was highly IP, demonstrating each of the six IP competencies. Other facilities conducted the review in a less IP manner due to challenges of physician involvement and staff workload, particularly of health care aides. Facilities that had an nurse practitioner on site were more efficient with the process of implementing recommendations resulting from the medication reviews. The LTC facilities were successful in implementing the medication review process and the process seemed to be sustainable. A few challenges were observed in the implementation process at two facilities. IP practice moved forward the goals of the AUA initiative to reduce the inappropriate use of antipsychotics.

The Impact of Coverage Restrictions on Antipsychotic Utilization Among Low-Income Medicare Part D Enrollees.

PubMed

Roberto, Pamela N; Brandt, Nicole; Onukwugha, Eberechukwu; Perfetto, Eleanor; Powers, Christopher; Stuart, Bruce

2017-11-01

Prior research demonstrates substantial access problems associated with utilization management and formulary exclusions for antipsychotics in Medicaid, but the use and impact of coverage restrictions for these medications in Medicare Part D remains unknown. We assess the effect of coverage restrictions on antipsychotic utilization in Part D by exploiting a unique natural experiment in which low-income beneficiaries are randomly assigned to prescription drug plans with varying levels of formulary generosity. Despite considerable variation in use of coverage restrictions across Part D plans, we find no evidence that these restrictions significantly deter utilization or reduce access to antipsychotics for low-income beneficiaries.

ADRA1A gene is associated with BMI in chronic schizophrenia patients exposed to antipsychotics.

PubMed

Liu, Y-R; Loh, E-W; Lan, T-H; Chen, S-F; Yu, Y-H; Chang, Y-H; Huang, C-J; Hu, T-M; Lin, K-M; Yao, Y-T; Chiu, H-J

2010-02-01

Noradrenaline and adrenaline are neurotransmitters of the sympathetic nervous system that interact with various adrenergic receptor (ADR) subtypes, and this regulates the basal metabolic rate, thermogenesis and efficiency of energy utilization. We examined a possible role of the gene coding for ADRA1A receptor in weight gain in schizophrenia subjects exposed to antipsychotics. A total of 401 schizophrenia in-patients treated with antipsychotics for >2 years were recruited and a final 394 DNA samples were genotyped. Their body mass indexes (BMIs) were recorded for 12 months and parameterized to be correlated in regression. Among the 58 single-nucleotide polymorphisms (SNPs) genotyped, 44 valid SNPs, which had minor allele frequency > or =0.03, were analyzed in statistics. Linear regression model with age, gender, diabetes, use of typical antipsychotics and use of atypical antipsychotics as covariates, with or without gender interaction, showed evidence of associations between the ADRA1A gene and BMI. Most of the SNPs associated with BMI are located in the promoter and intron regions, and being female appeared to enhance the gene effect. Our study suggests that the ADRA1A gene is involved in weight gain among schizophrenia patients treated with antipsychotics. Further molecular dissection of the ADRA1A gene warrants better understanding on weight gain mechanisms in schizophrenia.

Effects of controlled discontinuation of long-term used antipsychotics on weight and metabolic parameters in individuals with intellectual disability.

PubMed

de Kuijper, Gerda; Mulder, Hans; Evenhuis, Heleen; Visser, Frank; Hoekstra, Pieter J

2013-08-01

Antipsychotics are frequently prescribed agents in individuals with intellectual disability, often for behavioral symptoms. Efficacy of antipsychotics for this is ambiguous, so discontinuation should be considered. Weight gain and metabolic dysregulation are well-known adverse effects of antipsychotics which increase the risk of the metabolic syndrome. We performed a discontinuation study in 99 adults with intellectual disability, living in residential facilities who used antipsychotics for behavioral symptoms for more than 1 year. The aim of the present study was to investigate the effects of discontinuation of long-term used antipsychotics on weight, body mass index (BMI), and parameters of the metabolic syndrome and to investigate the influence of genetic polymorphisms and medication factors on these outcomes. Discontinuation of antipsychotics led to a mean decrease of 4 cm waist circumference, of 3.5 kg weight, 1.4 kg/m2 BMI, and 7.1 mm Hg systolic blood pressure. In those participants who had not completely discontinued use of antipsychotics we found a decrease in weight and BMI and an increase in fasting glucose. The presence of the C-allele of serotonin 5-hydroxytryptamine receptor polymorphism rs141334 was associated with higher waist circumference and higher plasma levels of triglycerides and lower levels of high-density lipoprotein. Achievement of complete discontinuation predicted a larger decrease in waist circumference and BMI. In conclusion, results of the study show the beneficial effects of discontinuation of long-term used antipsychotics on metabolic outcomes.

Psychopharmacology of aggression in children and adolescents with primary neuropsychiatric disorders: a review of current and potentially promising treatment options.

PubMed

Nevels, Robert M; Dehon, Erin E; Alexander, Katrina; Gontkovsky, Samuel T

2010-04-01

Research examining the role of pharmacological therapy in the treatment of children and adolescents with clinical disorders is growing. Clinical disorders that present with comorbid aggression can add a challenge to treatment. Child and adolescent neuropsychiatric disorders associated with aggression include attention-deficit hyperactivity disorder, various mood disorders and in particular bipolar disorders/pediatric mania, schizophrenia, mental retardation, oppositional defiant disorder, conduct disorder, and autism spectrum disorders. This review describes the psychopharmacy to treat these disorders and the aggression that often appears comorbidly. Existing literature regarding the efficacy and safety of psychotropics for youth with neuropsychiatric disorders also is discussed. In addition, general guidelines for psychopharmacy of aggression in children and adolescents are presented. Studies reviewed in this article provide evidence for the use of psychostimulants, alpha-2 agonists, beta blockers, lithium, anticonvulsant mood-stabilizers, atypical antipsychotics, traditional antipsychotics, and selective serotonin reuptake inhibitors in treating pediatric aggression with the choice of medication dependent on symptomology. Despite increased support for pediatric psychotropic use, there is a need for more long-term safety and efficacy studies of existing medications and newer, safer, and more effective agents with fewer side effects for the pharmacological treatment of all childhood disorders in which aggression is prominent. 2010 APA, all rights reserved

Stability of the Positive Mood Effect on Creativity When Task Switching, Practice Effect, and Test Item Differences Are Taken into Consideration

ERIC Educational Resources Information Center

Tan, Chee-Seng; Qu, Li

2015-01-01

Although experimentally induced positive mood can generally last for 20 min and the induced mood is conducive to creative performance, it is still unclear whether the facilitation effect is stable during these 20 min. Two studies were conducted to examine this issue while controlling for the impacts of task switching, practice effect, and test…

Sleep, daily activity rhythms and postpartum mood: A longitudinal study across the perinatal period.

PubMed

Krawczak, Elizabeth M; Minuzzi, Luciano; Simpson, William; Hidalgo, Maria Paz; Frey, Benicio N

2016-01-01

Women with a diagnosis of bipolar and major depressive disorders are at higher risk to develop postpartum depression. The primary objective of this longitudinal study was to determine whether daily activity rhythms and sleep parameters differ between women with and without a history of a mood disorder across the perinatal period. A secondary objective was to determine whether changes in these parameters were associated with postpartum mood. In total, 33 women were included in this study, 15 of which had a history of a mood disorder (high-risk group) and 18 who did not (low-risk group). Sleep and daily rhythms were assessed subjectively and objectively during the third trimester (≥26 weeks gestation) and again at 6-12 weeks postpartum. Mood was also assessed at both time points. Women in the high-risk group showed greater subjective daily rhythms and sleep disturbances across the perinatal period. Objective sleep efficiency was worse in the high-risk group in the postpartum period. Changes in both subjective daily rhythms and objective sleep efficiency were predictive of changes in depressive symptoms across the perinatal period. These findings encourage the development of preventative therapeutics to ensure circadian rhythm and sleep stability throughout the perinatal period.

Risk of Adverse Outcomes for Older People with Dementia Prescribed Antipsychotic Medication: A Population Based e-Cohort Study.

PubMed

Dennis, Michael; Shine, Laura; John, Ann; Marchant, Amanda; McGregor, Joanna; Lyons, Ronan A; Brophy, Sinead

2017-06-01

Over recent years there has been growing evidence of increased risk of mortality associated with antipsychotic use in older people with dementia. Although this concern combined with limited evidence of efficacy has informed guidelines restricting antipsychotic prescription in this population, the use of antipsycotics remains common. Many published studies only report short-term outcomes, are restricted to examining mortality and stroke risk or have other limitations. The aim of this study was to assess adverse outcomes associated with the use of antipsychotics in older people living with dementia in Wales (UK). This was a retrospective study of a population-based dementia cohort using the Welsh Secure Anonymised Information Linkage databank. The prior event rate ratio (PERR) was used to estimate the influence of exposure to antipsychotic medication on acute cardiac events, venous thromboembolism, stroke and hip fracture, and adjusted Cox proportional hazard models were used to compare all-cause mortality. A total of 10,339 people aged ≥65 years were identified with newly diagnosed dementia. After excluding those who did not meet the inclusion criteria, 9674 people remained in the main cohort of whom 3735 were exposed to antipsychotic medication. An increased risk of a venous thromboembolic episode [PERR 1.95, 95% confidence interval (CI) 1.83-2.0], stroke (PERR 1.41, 95% CI 1.4-1.46) and hip fracture (PERR 1.62, 95% CI 1.59-1.65) was associated with antipsychotic use. However, there was no long-term increased mortality in people exposed to antipsychotics (adjusted hazard ratio 1.06, 95% CI 0.99-1.13). The increase in adverse medical events supports guidelines restricting antipsychotic use in this population.

[Prevention and Treatment of Common Acute Adverse Effects With Antipsychotic Use in Adults With Schizophrenia Diagnosis].

PubMed

Arenas Borrero, Álvaro Enrique; Gómez Restrepo, Carlos; Bohórquez Peñaranda, Adriana Patricia; Vélez Traslaviña, Ángela; Castro Díaz, Sergio Mario; Jaramillo González, Luis Eduardo; García Valencia, Jenny

2014-01-01

To determine the most adequate strategies for the prevention and treatment of the acute adverse effects of the use of antipsychotics. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. A systematic literature search was carried out. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. The non-pharmacological interventions such as nutritional counseling by a nutritionist, exercise and psychotherapy are effective in preventing weight gain with the use of antipsychotics. (Kg Weight reduction in DM of -3.05 (-4.16, -1.94)). The antipsychotic change from olanzapine to aripiprazole showed weight loss and decreased BMI (decreased weight in KG DM -3.21 (-9.03, -2.61). The use of beta blockers was ineffective in reducing akathisia induced by antipsychotic; using as outcome the 50% reduction of symptoms of akathisia comparing beta-blockers with placebo RR was 1.4 (0.59, 1.83). It is recommended to make psychotherapeutic accompaniment and nutrition management of overweight for patients with weight gain. If these alternatives are ineffective is suggested to change the antipsychotic or consider starting metformin. For the management of drug-induced akathisia it is recommended to decrease the dose of the drug and the addition of lorazepam. It is recommended using 5mg biperiden IM or trihexyphenidyl 5mg orally in case of secondary acute dystonia and for the treatment of antipsychotic-induced parkinsonism to decrease the dose of antipsychotic or consider using 2 - 4mg/day of biperiden or diphenhydramine 50mg once daily. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Vitamin E for antipsychotic-induced tardive dyskinesia.

PubMed

Soares-Weiser, Karla; Maayan, Nicola; Bergman, Hanna

2018-01-17

Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. Vitamin E has been proposed as a treatment to prevent or decrease TD. The primary objective was to determine the clinical effects of vitamin E in people with schizophrenia or other chronic mental illness who had developed antipsychotic-induced TD.The secondary objectives were:1. to examine whether the effect of vitamin E was maintained as duration of follow-up increased;2. to test the hypothesis that the use of vitamin E is most effective for those with early onset TD (less than five years) SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. We included reports if they were controlled trials dealing with people with antipsychotic-induced TD and schizophrenia who remained on their antipsychotic medication and had been randomly allocated to either vitamin E or to a placebo, no intervention, or any other intervention. We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assumed that people who left early had no improvement. We assessed risk of bias and created a 'Summary of findings' table using GRADE. The review now includes 13 poorly reported randomised trials (total 478 people), all participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. There was no clear difference between vitamin E and placebo for the outcome of TD: not improved to a clinically important extent (6 RCTs, N = 264, RR 0.95, 95% CI 0.89 to 1.01, low-quality evidence

Antipsychotics promote GABAergic interneuron genesis in the adult rat brain: Role of heat-shock protein production.

PubMed

Kaneta, Hiroo; Ukai, Wataru; Tsujino, Hanako; Furuse, Kengo; Kigawa, Yoshiyasu; Tayama, Masaya; Ishii, Takao; Hashimoto, Eri; Kawanishi, Chiaki

2017-09-01

Current antipsychotics reduce positive symptoms and reverse negative symptoms in conjunction with cognitive behavioral issues with the goal of restoring impaired occupational and social functioning. However, limited information is available on their influence on gliogenesis or their neurogenic properties in adult schizophrenia brains, particularly on GABAergic interneuron production. In the present study, we used young adult subventricular zone (SVZ)-derived progenitor cells expressing proteoglycan NG2 cultures to examine the oligodendrocyte and GABAergic interneuron genesis effects of several kinds of antipsychotics on changes in differentiation function induced by exposure to the NMDA receptor antagonist MK-801. We herein demonstrated that antipsychotics promoted or restored changes in the oligodendrocyte/GABAergic interneuron differentiation functions of NG2(+) cells induced by the exposure to MK-801, which was considered to be one of the drug-induced schizophrenia model. We also demonstrated that antipsychotics restored heat-shock protein (HSP) production in NG2(+) cells with differentiation impairment. The antipsychotics olanzapine, aripiprazole, and blonanserin, but not haloperidol increased HSP90 levels, which were reduced by the exposure to MK-801. Our results showed that antipsychotics, particularly those recently synthesized, exerted similar GABAergic interneuron genesis effects on NG2(+) neuronal/glial progenitor cells in the adult rat brain by increasing cellular HSP production, and also suggest that HSP90 may play a crucial role in the pathophysiology of schizophrenia and is a key target for next drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mood alterations during deanol therapy.

PubMed

Casey, D E

1979-04-11

An imbalance between central cholinergic and adrenergic influences may affect mood disorders. Of 38 patients taking high doses of deanol, a putative acetylcholine precursor, eight developed changes in mood: five became depressed and three became hypomanic. A predisposition is suggested as seven of these eight patients had histories of affective symptoms. There was no relationship between the changes in dyskinesias and mood. These observations have both practical and heuristic implications for the management of patients and for further research into the pharmacology of affective disorders and deanol.

Morbidity and mortality of women and men with intellectual and developmental disabilities newly initiating antipsychotic drugs.

PubMed

Vigod, Simone N; Lunsky, Yona; Cobigo, Virginie; Wilton, Andrew S; Somerton, Sarah; Seitz, Dallas P

2016-03-01

While up to 45% of individuals with intellectual and developmental disabilities (IDD) have a comorbid psychiatric disorder, and antipsychotics are commonly prescribed, gender differences in the safety of antipsychotics have rarely been studied in this population. To compare men and women with IDD on medical outcomes after antipsychotic initiation. Our population-based study in Ontario, Canada, compared 1457 women and 1951 men with IDD newly initiating antipsychotic medication on risk for diabetes mellitus, hypertension, venous thromboembolism, myocardial infarction, stroke and death, with up to 4 years of follow-up. Women were older and more medically complex at baseline. Women had higher risks for venous thromboembolism (HR 1.72, 95% CI 1.15-2.59) and death (HR 1.46, 95% CI 1.02-2.10) in crude analyses; but only thromboembolism risk was greater for women after covariate adjustment (aHR 1.58, 95% CI 1.05-2.38). Gender should be considered in decision-making around antipsychotic medications for individuals with IDD. None. © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Antipsychotic Prescriptions Among Adults With Major Depressive Disorder in Office-Based Outpatient Settings: National Trends From 2006 to 2015.

PubMed

Rhee, Taeho Greg; Mohamed, Somaia; Rosenheck, Robert A

A recent moderately long-term study found an antipsychotic to be more effective than an antidepressant as the next-step treatment of unresponsive major depressive disorder (MDD). It is thus timely to examine recent trends in the pharmacoepidemiology of antipsychotic treatment of MDD. Data from the 2006-2015 National Ambulatory Medical Care Survey, nationally representative samples of office-based outpatient visits in adults with MDD (ICD-9-CM codes 296.20-296.26 and 296.30-296.36) (n = 4,044 unweighted), were used to estimate rates of antipsychotic prescribing over these 10 years. Multivariable logistic regression analysis identified demographic and clinical factors independently associated with antipsychotic use in MDD. Antipsychotic prescribing for MDD increased from 18.5% in 2006-2007 to 24.9% in 2008-2009 and then declined to 18.9% in 2014-2015. Visits with adults 75 years or older showed the greatest decline from 27.0% in 2006-2007 to 10.7% in 2014-2015 (OR for overall trend = 0.73; 95% CI, 0.56-0.95). The most commonly prescribed antipsychotic agents were aripiprazole, olanzapine, quetiapine, and risperidone. Antipsychotic prescription was associated with being black or Hispanic, having Medicare among adults under 65 years or Medicaid as a primary source of payment, and receiving mental health counseling, 3 or more concomitant medications, and diagnosis of cannabis use disorder (P < .01). Antipsychotics, prescribed for about one-fifth of adults with MDD, increased and then declined from 2006 to 2015, reflecting, first, FDA approval and then concern about adverse effects in the elderly. Future research should track evolving trends following the publication of evidence of greater long-term effectiveness of antipsychotic than antidepressant next-step therapy in adults with MDD. © Copyright 2018 Physicians Postgraduate Press, Inc.

Atypical antipsychotic properties of AD-6048, a primary metabolite of blonanserin.

PubMed

Tatara, Ayaka; Shimizu, Saki; Masui, Atsushi; Tamura, Miyuki; Minamimoto, Shoko; Mizuguchi, Yuto; Ochiai, Midori; Mizobe, Yusuke; Ohno, Yukihiro

2015-11-01

Blonanserin is a new atypical antipsychotic drug that shows high affinities to dopamine D2 and 5-HT2 receptors; however, the mechanisms underlying its atypicality are not fully understood. In this study, we evaluated the antipsychotic properties of AD-6048, a primary metabolite of blonanserin, to determine if it contributes to the atypicality of blonanserin. Subcutaneous administration of AD-6048 (0.3-1mg/kg) significantly inhibited apomorphine (APO)-induced climbing behavior with an ED50 value of 0.200mg/kg, the potency being 1/3-1/5 times that of haloperidol (HAL). AD-6048 did not cause extrapyramidal side effects (EPS) even at high doses (up to 10mg/kg, s.c.), whereas HAL at doses of 0.1-3mg/kg (s.c.) significantly induced bradykinesia and catalepsy in a dose-dependent manner. Thus, the therapeutic index (potency ratios of anti-APO action to that of EPS induction) of AD-6048 was much higher than that of haloperidol, illustrating that AD-6048 per se possesses atypical antipsychotic properties. In addition, immunohistochemical analysis of Fos protein expression revealed that both AD-6048 and HAL significantly increased Fos expression in the shell part of the nucleus accumbens and the striatum. However, in contrast to HAL which preferentially enhanced striatal Fos expression, AD-6048 showed a preferential action to the nucleus accumbens. These results indicate that AD-6048 acts as an atypical antipsychotic, which seems to at least partly contribute to the atypicality of blonanserin. Copyright © 2015 Elsevier Inc. All rights reserved.

Schizophrenia: multi-attribute utility theory approach to selection of atypical antipsychotics.

PubMed

Bettinger, Tawny L; Shuler, Garyn; Jones, Donnamaria R; Wilson, James P

2007-02-01

Current guidelines/algorithms recommend atypical antipsychotics as first-line agents for the treatment of schizophrenia. Because there are extensive healthcare costs associated with the treatment of schizophrenia, many institutions and health systems are faced with making restrictive formulary decisions regarding the use of atypical antipsychotics. Often, medication acquisition costs are the driving force behind formulary decisions, while other treatment factors are not considered. To apply a multi-attribute utility theory (MAUT) analysis to aid in the selection of a preferred agent among the atypical antipsychotics for the treatment of schizophrenia. Five atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole) were selected as the alternative agents to be included in the MAUT analysis. The attributes identified for inclusion in the analysis were efficacy, adverse effects, cost, and adherence, with relative weights of 35%, 35%, 20%, and 10%, respectively. For each agent, attribute scores were calculated, weighted, and then summed to generate a total utility score. The agent with the highest total utility score was considered the preferred agent. Aripiprazole, with a total utility score of 75.8, was the alternative agent with the highest total utility score in this model. This was followed by ziprasidone, risperidone, and quetiapine, with total utility scores of 71.8, 69.0, and 65.9, respectively. Olanzapine received the lowest total utility score. A sensitivity analysis was performed and failed to displace aripiprazole as the agent with the highest total utility score. This model suggests that aripiprazole should be considered a preferred agent for the treatment of schizophrenia unless found to be otherwise inappropriate.

Insight into illness and its relationship to illness severity, cognition and estimated antipsychotic dopamine receptor occupancy in schizophrenia: An antipsychotic dose reduction study.

PubMed

Gerretsen, Philip; Takeuchi, Hiroyoshi; Ozzoude, Miracle; Graff-Guerrero, Ariel; Uchida, Hiroyuki

2017-05-01

Little is known about the influence of D 2 receptor occupancy on impaired insight into illness (III)-a core feature of schizophrenia. III is associated with illness severity and cognitive dysfunction. Comparably, supratherapeutic D 2 receptor occupancy can impair cognition. However, it is unclear how illness severity, cognition, and D 2 receptor occupancy interact to influence III in schizophrenia. The aim of this study was to explore the influence of antipsychotic dose reduction on the relationships of illness severity and cognition to III. III was assessed at baseline and 28 weeks post-antipsychotic dose reduction in 16 participants with schizophrenia and plasma antipsychotic concentrations. III was assessed primarily with the Schedule for the Assessment of Insight-Japanese version, and secondarily with the Positive and Negative Syndrome Scale item G12. Correlation and regression analyses were performed to explore III's relationship to illness severity, cognition, and estimated D 2 receptor occupancy (Est.D 2 ). Cognition and Est.D 2 predicted III at baseline. At 28 weeks post-reduction, illness severity and Est.D 2 predicted III. Our findings suggest a complex relationship may exist among III, illness severity, cognition and Est.D 2 . At higher D 2 receptor occupancies, III is influenced by cognitive dysfunction, whereas, at lower occupancies, illness severity has a stronger effect on III. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Antipsychotic Use and Hospitalization Among Older Assisted Living Residents: Does Risk Vary by Frailty Status?

PubMed

Stock, Kathryn J; Hogan, David B; Lapane, Kate; Amuah, Joseph E; Tyas, Suzanne L; Bronskill, Susan E; Morris, Andrew M; Bell, Chaim M; Jeffs, Lianne; Maxwell, Colleen J

2017-07-01

To examine associations between baseline frailty measures, antipsychotic use, and hospitalization over 1 year and whether hospitalization risk associated with antipsychotic use varies by frailty level. In this prospective cohort study of 1,066 residents (mean age: 85 years; 77% women) from the Alberta Continuing Care Epidemiological Studies, trained research nurses conducted comprehensive resident assessments at baseline (2006-2007) for sociodemographic characteristics, health conditions, frailty status, behavioral problems, and all medications consumed during the past 3 days. Two separate measures of frailty were assessed, the Cardiovascular Health Study (CHS) phenotype and an 86-item Frailty Index (FI). Time to first hospitalization during follow-up was determined via linkage with the Alberta Inpatient Discharge Abstract Database. Baseline frailty status (both measures), but not antipsychotic use, was significantly associated with hospitalization over 1 year. When stratified by frailty, FI-defined frail residents using antipsychotics showed a significantly increased risk for hospitalization (adjusted HR: 1.54; 95% CI: 1.01-2.36) compared with frail nonusers. CHS-defined frail antipsychotic users versus frail nonusers also showed an elevated risk (adjusted HR: 1.67; 95% CI: 0.96-2.88). Nonfrail residents using antipsychotics were significantly less likely to be hospitalized compared with nonfrail nonusers whether defined by the FI (adjusted HR: 0.62; 95% CI: 0.39-0.99) or CHS criteria (adjusted HR: 0.62; 95% CI: 0.40-0.96). Frailty measures may be helpful in identifying those who are particularly vulnerable to adverse effects and those who may experience benefit with treatment. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Emotion word processing: does mood make a difference?

PubMed Central

Sereno, Sara C.; Scott, Graham G.; Yao, Bo; Thaden, Elske J.; O'Donnell, Patrick J.

2015-01-01

Visual emotion word processing has been in the focus of recent psycholinguistic research. In general, emotion words provoke differential responses in comparison to neutral words. However, words are typically processed within a context rather than in isolation. For instance, how does one's inner emotional state influence the comprehension of emotion words? To address this question, the current study examined lexical decision responses to emotionally positive, negative, and neutral words as a function of induced mood as well as their word frequency. Mood was manipulated by exposing participants to different types of music. Participants were randomly assigned to one of three conditions—no music, positive music, and negative music. Participants' moods were assessed during the experiment to confirm the mood induction manipulation. Reaction time results confirmed prior demonstrations of an interaction between a word's emotionality and its frequency. Results also showed a significant interaction between participant mood and word emotionality. However, the pattern of results was not consistent with mood-congruency effects. Although positive and negative mood facilitated responses overall in comparison to the control group, neither positive nor negative mood appeared to additionally facilitate responses to mood-congruent words. Instead, the pattern of findings seemed to be the consequence of attentional effects arising from induced mood. Positive mood broadens attention to a global level, eliminating the category distinction of positive-negative valence but leaving the high-low arousal dimension intact. In contrast, negative mood narrows attention to a local level, enhancing within-category distinctions, in particular, for negative words, resulting in less effective facilitation. PMID:26379570

Emotion word processing: does mood make a difference?

PubMed

Sereno, Sara C; Scott, Graham G; Yao, Bo; Thaden, Elske J; O'Donnell, Patrick J

2015-01-01

Visual emotion word processing has been in the focus of recent psycholinguistic research. In general, emotion words provoke differential responses in comparison to neutral words. However, words are typically processed within a context rather than in isolation. For instance, how does one's inner emotional state influence the comprehension of emotion words? To address this question, the current study examined lexical decision responses to emotionally positive, negative, and neutral words as a function of induced mood as well as their word frequency. Mood was manipulated by exposing participants to different types of music. Participants were randomly assigned to one of three conditions-no music, positive music, and negative music. Participants' moods were assessed during the experiment to confirm the mood induction manipulation. Reaction time results confirmed prior demonstrations of an interaction between a word's emotionality and its frequency. Results also showed a significant interaction between participant mood and word emotionality. However, the pattern of results was not consistent with mood-congruency effects. Although positive and negative mood facilitated responses overall in comparison to the control group, neither positive nor negative mood appeared to additionally facilitate responses to mood-congruent words. Instead, the pattern of findings seemed to be the consequence of attentional effects arising from induced mood. Positive mood broadens attention to a global level, eliminating the category distinction of positive-negative valence but leaving the high-low arousal dimension intact. In contrast, negative mood narrows attention to a local level, enhancing within-category distinctions, in particular, for negative words, resulting in less effective facilitation.

[Maintenance Treatment With Antipsychotics for Adult Patients Diagnosed With Schizophrenia].

PubMed

Gómez-Restrepo, Carlos; Bohórquez Peñaranda, Adriana Patricia; de la Hoz Bradford, Ana María; Tamayo Martínez, Nathalie; García Valencia, Jenny; Jaramillo González, Luis Eduardo

2014-01-01

To determine the effectiveness and security of the antipsychotics available for the management of adult patients with schizophrenia in the maintenance phase. To develop recommendations of treatment for the maintenance phase of the disease. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. 18 studies were included to evaluate the effectiveness and / or safety of different antipsychotic drugs first and second generation. Overall, antipsychotics (AP) showed superiority over placebo in relapse rate over 12 months (RR 0.59 95% CI 0.42, 0.82) and hospitalization rate over 24 months of follow-up (RR 0.38 95% 0.27, 0.55); its use is associated with increased risk of treatment dropout (RR 0.53 95% CI 0.46, 0.61) and adverse events such as weight gain, dystonia, extrapyramidal symptoms and sedation. There was no difference in the outcome of re hospitalizations, comparisons on quality of life, negative symptoms or weight gain between AP first and second generation. Continuous or standard dose regimens appear to be superior to intermittent or low doses in reducing the risk of abandonment of treatment regimes. Adult patients diagnosed with schizophrenia should receive maintenance treatment with antipsychotics. The medication of choice will depend on the management of the acute phase, the patient's tolerance to it and the presentation of adverse events. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Tolerability of outpatient antipsychotic treatment: 36-month results from the European Schizophrenia Outpatient Health Outcomes (SOHO) study.

PubMed

Novick, Diego; Haro, Josep Maria; Perrin, Elena; Suarez, David; Texeira, João Marques

2009-08-01

SOHO is a 3-year, prospective, observational study of schizophrenia patients who started a new antipsychotic in 10 European countries. Cohorts of patients were defined according to the antipsychotic started at baseline: olanzapine, risperidone, quetiapine, amisulpride, clozapine, oral typical and depot typical antipsychotics. Tolerability in terms of rates of extrapyramidal symptoms (EPS), tardive dyskinesia (TD), anticholinergic use, loss of libido/impotence, amenorrhoea/galactorrhoea/gynaecomastia, and weight change was assessed in 4939 patients who started monotherapy. Logistic regression models related medication initiated at study entry to adverse events over follow-up, adjusting by baseline differences among treatment cohorts. Patients taking typical antipsychotics or risperidone were more likely to experience EPS and TD during follow-up than patients taking olanzapine. Patients taking olanzapine were less likely to have loss of libido/impotence during follow-up than patients in the risperidone, amisulpride, clozapine, oral typical and depot typical cohorts. Weight gain occurred in all groups, but was greater with olanzapine. In conclusion, antipsychotics have different tolerability profiles in terms of the adverse events we monitored. Results should be interpreted conservatively due to the observational study design.

Anxious mood narrows attention in feature space.

PubMed

Wegbreit, Ezra; Franconeri, Steven; Beeman, Mark

2015-01-01

Spatial attention can operate like a spotlight whose scope can vary depending on task demands. Emotional states contribute to the spatial extent of attentional selection, with the spotlight focused more narrowly during anxious moods and more broadly during happy moods. In addition to visual space, attention can also operate over features, and we show here that mood states may also influence attentional scope in feature space. After anxious or happy mood inductions, participants focused their attention to identify a central target while ignoring flanking items. Flankers were sometimes coloured differently than targets, so focusing attention on target colour should lead to relatively less interference. Compared to happy and neutral moods, when anxious, participants showed reduced interference when colour isolated targets from flankers, but showed more interference when flankers and targets were the same colour. This pattern reveals that the anxious mood caused these individuals to attend to the irrelevant feature in both cases, regardless of its benefit or detriment. In contrast, participants showed no effect of colour on interference when happy, suggesting that positive mood did not influence attention in feature space. These mood effects on feature-based attention provide a theoretical bridge between previous findings concerning spatial and conceptual attention.

The risks and benefits of switching patients with schizophrenia or schizoaffective disorder from two to one antipsychotic medication: a randomized controlled trial.

PubMed

Constantine, Robert J; Andel, Ross; McPherson, Marie; Tandon, Rajiv

2015-08-01

Despite little evidence to support its use and practice guidelines discouraging the practice, antipsychotic polypharmacy is widely prevalent in schizophrenia. This randomized controlled trial studied the effects of switching patients stable on two antipsychotic medications to one antipsychotic medication. 104 adult outpatients with schizophrenia from 7 community mental health centers clinically stable on concurrent treatment with 2 antipsychotics were randomly assigned to stay on polypharmacy or to switch to antipsychotic monotherapy. Participants were followed for 1-year with assessments of symptoms and side effects occurring every 60days (7 total assessments). We examined differences in time trajectories in symptoms (PANSS, CGI) and side effects (EPS, metabolic, other) as a function of group assignment (switch vs. stay) and time, using intention-to-treat analysis. Participants who switched to antipsychotic monotherapy experienced greater increases in symptoms than stay patients. These differences emerged in the second 6months of the trial. All-cause discontinuation rates over the 1-year trial were higher in the switch-to-monotherapy group than in the stay-on-polypharmacy group (42% vs. 13%; p<0.01). There were no differences in change over time in any of the side effect measures, except that stay patients experienced a greater decrease in Simpson Angus total scores than switch patients. Clinicians should be cautious in switching patients with chronic schizophrenia who are stable on 2 antipsychotics to one antipsychotic. Given the challenges in discontinuing antipsychotic polypharmacy, adequate trials of evidence-based treatments such as clozapine and long-acting injectable antipsychotics should be undertaken in inadequately responsive schizophrenia patients before moving to antipsychotic polypharmacy. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of prenatal exposure to atypical antipsychotics on postnatal development and growth of infants: a case-controlled, prospective study.

PubMed

Peng, Mei; Gao, Keming; Ding, Yiling; Ou, Jianjun; Calabrese, Joseph R; Wu, Renrong; Zhao, Jingping

2013-08-01

This study aims to investigate the developmental effects of atypical antipsychotics on infants who were born to mothers taking an atypical antipsychotic throughout pregnancy. The developmental progress of 76 infants who experienced fetal exposure to atypical antipsychotics was compared to that of 76 matched control infants who had no fetal exposure to any antipsychotics. Planned assessment included Apgar score, body weight, height, and the cognitive, language, motor, social-emotional, and adaptive behavior composite scores of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III). Student's t test and Chi-square analysis were used as appropriate. Repeated measurements were evaluated by analysis of covariance. At 2 months of age, the mean composite scores of cognitive, motor, social-emotional, and adaptive behavior of BSID-III were significantly lower in atypical antipsychotic-exposed infants than the controls. More atypical antipsychotic-exposed infants had delayed development in cognitive, motor, social-emotional, and adaptive behavior domains as defined by the composite score of <85 in these subscales of BSID-III. At 12 months of age, there were no significant differences between the two groups in all mean composite scores of BSID-III. More atypical antipsychotic-exposed infants had low birth weight than the controls (13.2 vs. 2.6 %, P = 0.031), although there were no significant difference in mean birth weight and height between the two groups. Fetal exposure to atypical antipsychotics may cause short-term delayed development in cognitive, motor, social-emotional, and adaptive behavior, but not in language, body weight, or height.

Adverse mood symptoms with oral contraceptives.

PubMed

Poromaa, Inger Sundström; Segebladh, Birgitta

2012-04-01

In spite of combined oral contraceptives (COCs) having been available for more than 50 years, surprisingly little is known about the prevalence of truly COC-related adverse mood symptoms and about the underlying biological mechanisms of proposed changes in mood and affect. Precise estimates of COC-related adverse mood symptoms are not available due to the lack of placebo-controlled trials. In prospective trials the frequency of women who report deteriorated mood or deteriorated emotional well-being varies between 4 and 10%, but it can be assumed that the causal relation in these prevalence rates is overestimated. Adverse mood symptoms and somatic symptoms are most pronounced during the pill-free interval of the treatment cycles, but whether extended COC regimens would be more favorable in this respect is not known. COCs with anti-androgenic progestagens, such as drospirenone and desogestrel, appear more favorable in terms of mood symptoms than progestagens with a more androgenic profile. Available data suggest that lower doses of ethinylestradiol could be beneficial. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Diagnoses associated with use of atypical antipsychotics in a commercial health plan: a claims database analysis.

PubMed

Citrome, Leslie; Kalsekar, Iftekhar; Guo, Zhenchao; Laubmeier, Kimberly; Hebden, Tony

2013-12-01

Atypical antipsychotics are indicated for specific psychiatric conditions; however, they are frequently used for US Food and Drug Administration-nonapproved indications. This study assessed the types of medical diagnoses associated with atypical antipsychotic prescriptions in commercial health care plans. This retrospective cohort study used the OptumInsight commercial data set from January 2008 to June 2011. The index date was defined as the earliest date of prescription for the atypical antipsychotics aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone, from January 1, 2009, through June 30, 2010. Medical claims during a 2-year period (12 months before and 12 months after the index date) were used to identify relevant diagnostic codes from the International Classification of Diseases, Ninth Edition, Clinical Modification associated with the antipsychotic prescription. A logistic regression analysis was conducted to examine the predictors of use of atypical antipsychotics without a relevant diagnosis, that is, schizophrenia, bipolar, or major depressive disorder (MDD). Of 18,352 patients included in the analysis, 3593 (19.5%) who filled a prescription for atypical antipsychotics did not have an approved diagnosis. Off-label utilization varied, with approximately a quarter of patients with prescriptions for quetiapine (24.1%), risperidone (23.1%), or olanzapine (21.8%) being without a relevant diagnostic code, whereas proportions were lower for patients prescribed aripiprazole (14.0%) or ziprasidone (13.1%). Of those with a psychiatric disorder other than schizophrenia, bipolar disorder, or MDD, approximately a third of prescriptions were for anxiety disorders, with similar proportions across all atypical antipsychotics. Patients were often prescribed quetiapine for substance abuse (22.7%), whereas patients with "other psychiatric conditions" were prescribed risperidone (26.3%) or ziprasidone (25.0%). The logistic regression analysis indicated that

A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation.

PubMed

Zuardi, Antonio Waldo; Crippa, Jose Alexandre S; Hallak, Jaime E C; Bhattacharyya, Sagnik; Atakan, Zerrin; Martin-Santos, Rocio; McGuire, Philip K; Guimarães, Francisco Silveira

2012-01-01

Δ(9)-tetrahydrocannabinol (Δ(9)-THC) is the main compound of the Cannabis Sativa responsible for most of the effects of the plant. Another major constituent is cannabidiol (CBD), formerly regarded to be devoid of pharmacological activity. However, laboratory rodents and human studies have shown that this cannabinoid is able to prevent psychotic-like symptoms induced by high doses of Δ(9)- THC. Subsequent studies have demonstrated that CBD has antipsychotic effects as observed using animal models and in healthy volunteers. Thus, this article provides a critical review of the research evaluating antipsychotic potential of this cannabinoid. CBD appears to have pharmacological profile similar to that of atypical antipsychotic drugs as seem using behavioral and neurochemical techniques in animal models. Additionally, CBD prevented human experimental psychosis and was effective in open case reports and clinical trials in patients with schizophrenia with a remarkable safety profile. Moreover, fMRI results strongly suggest that the antipsychotic effects of CBD in relation to the psychotomimetic effects of Δ(9)-THC involve the striatum and temporal cortex that have been traditionally associated with psychosis. Although the mechanisms of the antipsychotic properties are still not fully understood, we propose a hypothesis that could have a heuristic value to inspire new studies. These results support the idea that CBD may be a future therapeutic option in psychosis, in general and in schizophrenia, in particular.

Mood and Performance in Young Malaysian Karateka

PubMed Central

Wong, Rebecca S. K.; Thung, Jin Seng; Pieter, Willy

2006-01-01

In an attempt to test the conceptual model by Lane and Terry, the purposes of this study were 1) to assess mood states in non-depressed and depressed young karate athletes; 2) to assess mood states in relation to performance in young karate athletes. The participants were recruited from the 2004 Malaysian Games (72 males, 19.20 ± 1.16 years; 37 females, 18.78 ± 0.88 years). The athletes were divided into winners (medalists) and losers. The Brunel Mood Scale (BRUMS) was administered prior to the start of competition. MANOVA was employed to treat the data, while Pearson correlations were calculated for mood states in each depressed mood group and by gender. In terms of non-depressed and depressed mood, tension in the females was higher in the depressed group (5.61 ± 3.02 vs. 3.11 ± 1.90, p = 0.026, eta2 = 0.133), as was fatigue (3.64 ± 2.61 vs. 0.89 ± 1.69, p = 0.006, eta2 = 0.199). Tension in the males was higher in the depressed group (4.41 ± 2.52 vs. 1.50 ± 1.55, p < 0.001, eta2 = 0.215), as was anger (1.43 ± 1.88 vs. 0.25 ± 1.00, p = 0.019, eta2 = 0.076). The highest associations among mood subscales were between anger and depression (r = 0.57), and between depression and fatigue ( r = 0.55) in depressed males. The female winning karateka scored higher on anger (3.08 ± 2.96 vs. 1.29 ± 2.24, p = 0.046, eta2 = 0.109). The highest correlations between mood dimensions in depressed females were between depression and anger (r = 0.85) and between depression and confusion (r = 0.85). Contrary to previous research on the influence of depression on anger, only the female winners scored higher on anger. Several negative mood dimensions were higher in both male and female depressed groups, lending some support to the conceptual model advanced by Lane and Terry. Key Points To date, there is no information about the relationship between mood and martial arts performance in Malaysian athletes. There might be cultural differences in the way Malaysian athletes

Potential antipsychotic properties of central cannabinoid (CB1) receptor antagonists.

PubMed

Roser, Patrik; Vollenweider, Franz X; Kawohl, Wolfram

2010-03-01

Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the principal psychoactive constituent of the Cannabis sativa plant, and other agonists at the central cannabinoid (CB(1)) receptor may induce characteristic psychomotor effects, psychotic reactions and cognitive impairment resembling schizophrenia. These effects of Delta(9)-THC can be reduced in animal and human models of psychopathology by two exogenous cannabinoids, cannabidiol (CBD) and SR141716. CBD is the second most abundant constituent of Cannabis sativa that has weak partial antagonistic properties at the CB(1) receptor. CBD inhibits the reuptake and hydrolysis of anandamide, the most important endogenous CB(1) receptor agonist, and exhibits neuroprotective antioxidant activity. SR141716 is a potent and selective CB(1) receptor antagonist. Since both CBD and SR141716 can reverse many of the biochemical, physiological and behavioural effects of CB(1) receptor agonists, it has been proposed that both CBD and SR141716 have antipsychotic properties. Various experimental studies in animals, healthy human volunteers, and schizophrenic patients support this notion. Moreover, recent studies suggest that cannabinoids such as CBD and SR141716 have a pharmacological profile similar to that of atypical antipsychotic drugs. In this review, both preclinical and clinical studies investigating the potential antipsychotic effects of both CBD and SR141716 are presented together with the possible underlying mechanisms of action.