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Sample records for ongoing pharmacological treatment

  1. Pharmacologic treatment of paraphilias.

    PubMed

    Assumpção, Alessandra Almeida; Garcia, Frederico Duarte; Garcia, Heloise Delavenne; Bradford, John M W; Thibaut, Florence

    2014-06-01

    The treatment of paraphilias remains a challenge in the mental health field. Combined pharmacologic and psychotherapeutic treatment is associated with better efficacy. The gold standard treatment of severe paraphilias in adult males is antiandrogen treatment with cognitive behavioral therapy. Selective serotonin reuptake inhibitors have been used in mild types of paraphilia and in cases of sexual compulsions and juvenile paraphilias. Antiandrogen treatments seem to be effective in severe paraphilic subjects committing sexual offenses. In particular, gonadotropin-releasing hormone analogs have shown high efficacy working in a similar way to physical castration but being reversible at any time. Treatment recommendations, side effects, and contraindications are discussed. PMID:24877704

  2. Pharmacological treatment of vertigo.

    PubMed

    Hain, Timothy C; Uddin, Mohammed

    2003-01-01

    This review discusses the physiology and pharmacological treatment of vertigo and related disorders. Classes of medications useful in the treatment of vertigo include anticholinergics, antihistamines, benzodiazepines, calcium channel antagonists and dopamine receptor antagonists. These medications often have multiple actions. They may modify the intensity of symptoms (e.g. vestibular suppressants) or they may affect the underlying disease process (e.g. calcium channel antagonists in the case of vestibular migraine). Most of these agents, particularly those that are sedating, also have a potential to modulate the rate of compensation for vestibular damage. This consideration has become more relevant in recent years, as vestibular rehabilitation physical therapy is now often recommended in an attempt to promote compensation. Accordingly, therapy of vertigo is optimised when the prescriber has detailed knowledge of the pharmacology of medications being administered as well as the precise actions being sought. There are four broad causes of vertigo, for which specific regimens of drug therapy can be tailored. Otological vertigo includes disorders of the inner ear such as Ménière's disease, vestibular neuritis, benign paroxysmal positional vertigo (BPPV) and bilateral vestibular paresis. In both Ménière's disease and vestibular neuritis, vestibular suppressants such as anticholinergics and benzodiazepines are used. In Ménière's disease, salt restriction and diuretics are used in an attempt to prevent flare-ups. In vestibular neuritis, only brief use of vestibular suppressants is now recommended. Drug treatments are not presently recommended for BPPV and bilateral vestibular paresis, but physical therapy treatment can be very useful in both. Central vertigo includes entities such as vertigo associated with migraine and certain strokes. Prophylactic agents (L-channel calcium channel antagonists, tricyclic antidepressants, beta-blockers) are the mainstay of treatment

  3. Pharmacologic treatment of osteoarthritis.

    PubMed

    Pinals, R S

    1992-01-01

    Current pharmacotherapy for osteoarthritis (OA) is aimed at relief of pain and functional disability. Although an inflammatory component may be found in some cases, there is little evidence that anti-inflammatory drugs commonly used in the treatment of OA provide more relief than simple analgesics. A growing body of knowledge about the pathophysiology of OA now offers opportunities to develop interventions aimed at retarding the progressive degeneration of articular cartilage. This is a function of an imbalance between cartilage matrix synthesis and breakdown. New and experimental treatments include oral, parenteral, and intra-articular agents, some of which are chemicals and others biological products. Their modes of action have generally not been established in humans, but may be inferred from in vitro culture systems and animal models. These mechanisms include inhibition of synovial cell-derived cytokines and chondrocyte-derived degradative enzymes, inactivation of superoxide free radicals, stimulation of matrix synthesis, and enhancement of synovial fluid lubrication. Many of these treatments have been shown to provide short- or long-term symptomatic improvement in clinical trials. Protection of cartilage or promotion of repair has been demonstrated in animal studies, but not convincingly in human OA studies. PMID:1386287

  4. Pharmacologic treatment of pediatric insomnia.

    PubMed

    Owens, Judith A; Moturi, Sricharan

    2009-10-01

    Pediatric insomnia is common in children and adolescents, particularly in children who have comorbid medical, psychiatric, and neurodevelopmental disorders, and may be associated with cognitive, emotional, and psychosocial impairments that often result in significant caregiver burden. Although several behavioral interventions for pediatric insomnia are effective, there is a relative paucity of empiric evidence supporting the use of pharmacologic treatment. Sedative/hypnotic drugs are frequently used in clinical practice to treat pediatric insomnia, and guidelines for the use of these medications in general as well as for specific medications have been developed. This review presents expert consensus guidelines for the use of these medications in clinical practice, with a focus on the different classes of pharmacologic agents that are most commonly prescribed. PMID:19836701

  5. Pharmacological treatment of epilepsy today.

    PubMed

    Benna, P; Bergamasco, B

    1986-01-01

    The pharmacological treatment of epilepsy has not gone through remarkable changes in recent years. Treatment is based on few first choice drugs, the mechanism of action of which we do not yet know exactly. These include: phenobarbital, primidone, phenytoin, carbamazepine, valproic acid, ethosuximide, clonazepam. Choice of drug is determined by the kind of seizures presented by the patient, while successful treatment is determined by the kind of epilepsy. The present trend is the use of first line drugs in monotherapy, fixing individually the dosage according to the plasma levels. The results obtained with the GABA-agonists (progabide, gamma-vinyl GABA) and with some of the calcium-antagonists (flunarizine) seem promising. PMID:2886407

  6. Pharmacological Treatment of Uterine Fibroids

    PubMed Central

    Moroni, RM; Vieira, CS; Ferriani, RA; Candido-dos-Reis, FJ; Brito, LGO

    2014-01-01

    Uterine fibroids (UF) are common, benign gynecologic tumors, affecting one in three to four women, with estimates of up to 80%, depending on the population studied. Their etiology is not well established, but it is under the influence of several risk factors, such as early menarche, nulliparity and family history. More than 50% of affected women are asymptomatic, but the lesions may be related to bothersome symptoms, such as abnormal uterine bleeding, pelvic pain and bloating or urinary symptoms. The treatment of UF is classically surgical; however, various medical options are available, providing symptom control while minimizing risks and complications. A large number of clinical trials have evaluated commonly used medical treatments and potentially effective new ones. Through a comprehensive literature search using PubMed, EMBASE, CENTRAL, Scopus and Google Scholar databases, through which we included 41 studies out of 7658 results, we thoroughly explored the different pharmacological options available for management of UF, their indications, advantages and disadvantages. PMID:25364587

  7. Pharmacologic Treatment for Temporomandibular Disorders.

    PubMed

    Dym, Harry; Bowler, Dustin; Zeidan, Joseph

    2016-04-01

    Pharmacologic agents play an integral role in the overall management of temporomandibular joint disorder. The general dentist should be familiar with the different classes of drugs currently in use for dealing with this often complex medical/dental problem. PMID:27040290

  8. Treatment of Pancreatic Cancer with Pharmacological Ascorbate

    PubMed Central

    Cieslak, John A.; Cullen, Joseph J.

    2016-01-01

    The prognosis for patients diagnosed with pancreatic cancer remains dismal, with less than 3% survival at 5 years. Recent studies have demonstrated that high-dose, intravenous pharmacological ascorbate (ascorbic acid, vitamin C) induces cytotoxicity and oxidative stress selectively in pancreatic cancer cells vs. normal cells, suggesting a promising new role of ascorbate as a therapeutic agent. At physiologic concentrations, ascorbate functions as a reducing agent and antioxidant. However, when pharmacological ascorbate is given intravenously, it is possible to achieve millimolar plasma concentration. At these pharmacological levels, and in the presence of catalytic metal ions, ascorbate can induce oxidative stress through the generation of hydrogen peroxide (H2O2). Recent in vitro and in vivo studies have demonstrated ascorbate oxidation occurs extracellularly, generating H2O2 flux into cells resulting in oxidative stress. Pharmacologic ascorbate also inhibits the growth of pancreatic tumor xenografts and displays synergistic cytotoxic effects when combined with gemcitabine in pancreatic cancer. Phase I trials of pharmacological ascorbate in pancreatic cancer patients have demonstrated safety and potential efficacy. In this chapter, we will review the mechanism of ascorbate-induced cytotoxicity, examine the use of pharmacological ascorbate in treatment and assess the current data supporting its potential as an adjuvant in pancreatic cancer. PMID:26201606

  9. New approaches to pharmacological treatment of osteoporosis.

    PubMed Central

    Akesson, Kristina

    2003-01-01

    Osteoporosis has been recognized as a major public health problem for less than two decades. The increasing incidence of fragility fractures, such as vertebral, hip, and wrist fractures, first became apparent from epidemiological studies in the early and mid-1980s, when effective treatment was virtually unavailable. Pharmacological therapies that effectively reduce the number of fractures by improving bone mass are now available widely in countries around the world. Most current agents inhibit bone loss by reducing bone resorption, but emerging therapies may increase bone mass by directly promoting bone formation--as is the case with parathyroid hormone. Current treatment alternatives include bisphosphonates, calcitonin, and selective estrogen receptor modulators, but sufficient calcium and vitamin D are a prerequisite. The availability of evidence-based data that show reductions in the incidence of fractures of 30-50% during treatment has been a major step forward in the pharmacological prevention of fractures. With all agents, fracture reduction is most pronounced for vertebral fracture in high-risk individuals; alendronate and risedronate also may protect against hip fracture in the elderly. New approaches to pharmacological treatment will include further development of existing drugs, especially with regard to tolerance and frequency of dosing. New avenues for targeting the condition will emerge as our knowledge of the regulatory mechanisms of bone remodelling increases, although issues of tissue specificity may be difficult to solve. In the long term, information gained through knowledge of bone genetics may be used to adapt pharmacological treatments more precisely to each individual. PMID:14710507

  10. Pharmacological Treatment Effects on Eye Movement Control

    ERIC Educational Resources Information Center

    Reilly, James L.; Lencer, Rebekka; Bishop, Jeffrey R.; Keedy, Sarah; Sweeney, John A.

    2008-01-01

    The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to…

  11. Pharmacological treatment of cannabis dependence.

    PubMed

    Weinstein, A M; Gorelick, David A

    2011-01-01

    Cannabis is the most frequently used illegal psychoactive substance in the world. There is a significant increase in the number of treatment admissions for cannabis use disorders in the past few years, and the majority of cannabis-dependent individuals who enter treatment have difficulty in achieving and maintaining abstinence. Thus, there is increased need for medications that can be used to treat this population. So far, no medication has been shown broadly and consistently effective; none has been approved by any national regulatory authority. Medications studied have included those that alleviate symptoms of cannabis withdrawal (e.g., dysphoric mood, irritability),those that directly affect endogenous cannabinoid receptor function, and those that have shown efficacy in treatment of other drugs of abuse or psychiatric conditions. Buspirone is the only medication to date that has shown efficacy for cannabis dependence in a controlled clinical trial. Results from controlled human laboratory studies and small open-label clinical trials suggest that dronabinol, the COMT inhibitor entacapone, and lithium may warrant further study. Recent pre-clinical studies suggest the potential of fatty acid amide hydrolase (FAAH) inhibitors such as URB597, endocannabinoid-metabolizing enzymes, and nicotinic alpha 7 receptor antagonists such as methyllycaconitine (MLA).Controlled clinical trials are needed to evaluate the clinical efficacy of these medications and to validate the laboratory models being used to study candidate medications. PMID:21524266

  12. Pharmacological Treatment of Cannabis Dependence

    PubMed Central

    Weinstein, A.M.; Gorelick, David A.

    2011-01-01

    Cannabis is the most frequently used illegal psychoactive substance in the world. There is a significant increase in the number of treatment admissions for cannabis use disorders in the past few years, and the majority of cannabis-dependent individuals who enter treatment have difficulty in achieving and maintaining abstinence. Thus, there is increased need for medications that can be used to treat this population. So far, no medication has been shown broadly and consistently effective; none has been approved by any national regulatory authority. Medications studied have included those that alleviate symptoms of cannabis withdrawal (e.g., dysphoric mood, irritability), those that directly affect endogenous cannabinoid receptor function, and those that have shown efficacy in treatment of other drugs of abuse or psychiatric conditions. Buspirone is the only medication to date that has shown efficacy for cannabis dependence in a controlled clinical trial. Results from controlled human laboratory studies and small open-label clinical trials suggest that dronabinol, the COMT inhibitor entacapone, and lithium may warrant further study. Recent pre-clinical studies suggest the potential of fatty acid amide hydrolase (FAAH) inhibitors such as URB597, endocannabinoid-metabolizing enzymes, and nicotinic alpha7 receptor antagonists such as methyllycaconitine (MLA). Controlled clinical trials are needed to evaluate the clinical efficacy of these medications and to validate the laboratory models being used to study candidate medications. PMID:21524266

  13. Effectiveness of Psychological and Pharmacological Treatments for Nocturnal Enuresis.

    ERIC Educational Resources Information Center

    Houts, Arthur C.; And Others

    1994-01-01

    Assesses overall effectiveness of psychological and pharmacological treatments, relative effectiveness of specific treatments, and moderators of treatment effectiveness for nocturnal enuretic children via quantitative integration of research. Findings confirm that more children benefit from psychological than from pharmacological interventions and…

  14. Pharmacological treatment of exercise dyspnoea.

    PubMed

    Grazzini, M; Stendardi, L; Rosi, E; Scano, G

    2001-02-01

    A better understanding of the mechanisms of dyspnoea improves the clinician's ability to treat patients with shortness of breath. Any intervention that: 1) reduces ventilatory demands; 2) reduces ventilatory impedance; or 3) improves inspiratory muscle function, may relieve dyspnoea. Reduced ventilatory demand may be obtained by reducing metabolic load. Supplemental oxygen during exercise reduces exertional breathlessness and improves exercise tolerance, the decrease in dyspnoea being proportional to decrease in minute ventilation. Reduced ventilatory demand may also be obtained by decreasing the central drive. Opiates have been shown to decrease minute ventilation at rest and during submaximal exercise. They can alter the central processing of neural signals within the central nervous system to reduce sensations associated with breathing. Contrastingly, no consistent improvement in dyspnoea (versus placebo) has been shown with anxolytics. Decreasing central drive may also be obtained by altering pulmonary afferent information. Interventions that alter transmittal of afferent information to the central controller, potentially reduce dyspnoea. Reduction of ventilatory impedance is obtained by administering B2, anticholinergics or theophylline. B2 and anticholinergics act by modulating the increase in operational lung volumes and the inspiratory muscle effort during exercise. The mechanism by which theophylline relieves dyspnoea is probably related to a mechanism other than its bronchodilation alone. Alterations in respiratory muscle function are currently being detected in patients with chronic obstructive pulmonary disease, due to alteration in respiratory muscle energy balance. Nutritional repletion may improve respiratory muscle function but uncertainty remains as to whether nutritional repletion may relieve dyspnoea. The cumulative benefit of interventions targeting the pathophysiologic mechanism of dyspnoea must be identified for optimum treatment of patients

  15. Pharmacological Treatment of PTSD – Established and New Approaches

    PubMed Central

    Steckler, Thomas; Risbrough, Victoria

    2011-01-01

    A large proportion of humans will experience a traumatic event at least once in their lifetime, with up to 10% then going on to developing post-traumatic stress disorder (PTSD). In this review we will discuss established pharmacological interventions for PTSD as well as highlight novel therapeutic strategies undergoing extensive preclinical research as well as ongoing clinical research. Such strategies include prophylactic treatments and use of pharmacotherapy as adjunctive treatment with established trauma-focused psychological therapies. These potential treatment approaches include modulation of stress effects on memory consolidation after trauma (e.g. glucocorticoid, corticotropin releasing factor and norepinephrine signalling modulators), as well as putative cognitive enhancers that target mechanisms of conditioned fear extinction and reconsolidation (e.g. glucocorticoid receptor modulators and modulators of glutamate signalling such as positive allosteric modulators of glutamate receptors, glycine transporter inhibitors, glycine agonists, autoreceptor antagonists). We will discuss evidence for and against these potential novel treatment strategies and their limitations. PMID:21736888

  16. Pharmacological treatment of chronic obstructive pulmonary disease

    PubMed Central

    Montuschi, Paolo

    2006-01-01

    None of the drugs currently available for chronic obstructive pulmonary disease (COPD) are able to reduce the progressive decline in lung function which is the hallmark of this disease. Smoking cessation is the only intervention that has proved effective. The current pharmacological treatment of COPD is symptomatic and is mainly based on bronchodilators, such as selective β2-adrenergic agonists (short- and long-acting), anticholinergics, theophylline, or a combination of these drugs. Glucocorticoids are not generally recommended for patients with stable mild to moderate COPD due to their lack of efficacy, side effects, and high costs. However, glucocorticoids are recommended for severe COPD and frequent exacerbations of COPD. New pharmacological strategies for COPD need to be developed because the current treatment is inadequate. PMID:18044097

  17. New pharmacological treatment strategies for relapse prevention.

    PubMed

    Spanagel, Rainer; Vengeliene, Valentina

    2013-01-01

    Here we discuss treatment strategies that are based on pharmacological interventions to reduce craving and relapse in alcohol-dependent patients. We will first provide a historical overview about relapse prevention strategies. We will then review the development of disulfiram, naltrexone, acamprosate, and nalmefene and discuss their neurobiological modes of action. Then the concept of convergent genomic analysis will be introduced for the discovery of new molecular treatment targets. Finally, we will provide convincing evidence for the use of N-methyl-D-aspartate (NMDA) receptor channel blockers as substitution drugs. Important conclusions of this review are: (i) learning from other addictive substances is very helpful-e.g., substitution therapies as applied to opiate addiction for decades could also be translated to alcoholics, (ii) the glutamate theory of alcohol addiction provides a convincing framework for the use of NMDA receptor antagonists as substitution drugs for alcohol-dependent patients, (iii) a combination of behavioral and pharmacological therapies may be the optimal approach for future treatment strategies-one promising example concerns the pharmacological disruption of reconsolidation processes of alcohol cue memories, (iv) given that many neurotransmitter systems are affected by chronic alcohol consumption, numerous druggable targets have been identified; consequently, a "cocktail" of different compounds will further improve the treatment situation, (v) in silico psychopharmacology, such as drug repurposing will yield new medications, and finally, (vi) the whole organism has to be taken into consideration to provide the best therapy for our patients. In summary, there is no other field in psychiatric research that has, in recent years, yielded so many novel, druggable targets and innovative treatment strategies than for alcohol addiction. However, it will still be several years before the majority of the "treatment-seeking population" will benefit

  18. Emerging pharmacologic targets and treatments for myocarditis.

    PubMed

    Jensen, Lionel D; Marchant, David J

    2016-05-01

    Myocarditis is a heterogeneous group of disorders defined by inflammation of the heart muscle. The primary clinical manifestations of myocarditis are heart failure and sudden death in children and young adults. Numerous interventions have been investigated for the treatment of myocarditis, including broad spectrum alteration of the immune response and antiviral treatments; however, success has been limited. Since the myocarditis treatment trials in the 1990s there has been an improved understanding of disease progression and new facets of the immune response have been discovered. This new information provides fresh opportunities to develop therapeutics to treat myocarditis. This review analyzes previous pharmacologic approaches including immunosuppression, high dose intravenous immunoglobulin treatment, immunoadsorption and antiviral treatments, and looks forward toward recently identified immune factors that can be exploited as targets for new treatments. Such strategies include bolstering beneficial regulatory T cells or mitigating the detrimental Th17 T cells which can drive autoimmunity in the heart. The surging interest of the application of humanized monoclonal antibodies makes targeting deleterious arms of the immune response like Th17 cells a tangible goal in the near future. Promising constituents of herbal remedies have also been identified that may hold potential as new pharmacological treatments for myocarditis, however, significant work remains to elucidate the pharmacokinetics and side-effects of these compounds. Finally, advances in our understanding of the function of Matrix Metalloproteinases yield another target for altering disease progression given their role in the development of fibrosis during Dilated Cardiomyopathy. In bringing to light the various new targets and treatments available since the last myocarditis treatment trials, the aim of this review is to explore the new treatments that are possible in new myocarditis treatment trials

  19. Pharmacologic Strategies for Treatment of Poisonings.

    PubMed

    Roberts, Eric; Gooch, Michael D

    2016-03-01

    Poisoning is the leading cause of injury-related mortality in the United States. Data suggest that nonmedical use of pharmaceuticals is increasing, along with a proportional increase in subsequent adverse events. The widespread use of illegal drugs contributes to the challenge, because these drugs may produce a wide array of clinical presentations that warrant time-critical recognition and treatment. Common legal and illegal poisonings highlighting clinical presentations in terms of toxidromes as a means of categorically recognizing these emergencies is the focus of this article. To optimize outcomes for situations such as these, pharmacologic considerations are discussed and explored. PMID:26897424

  20. Review of pharmacologic treatment of tinnitus.

    PubMed

    Murai, K; Tyler, R S; Harker, L A; Stouffer, J L

    1992-09-01

    Recent research on the pharmacologic treatment of tinnitus is reviewed, emphasizing studies in which controls have been used. Several double-blind cross-over studies have found that lidocaine can reduce tinnitus in about 50 to 75 percent of subjects. Unfortunately, it cannot be used clinically because it must be administered intravenously and its effects are very brief. Other drugs have been much less successful. A few controlled studies have found success rates between 33 and 56 percent using oxazepam, clonazepam, sodium amylobarbitone, flunarizine, and eperisone hydrochloride. None of these studies have been replicated, however. Closely controlled studies using specified etiologic subgroups with subjective and objective psychophysical measurements are needed. PMID:1359790

  1. Pharmacologic treatment of depression in late life

    PubMed Central

    Flint, A J

    1997-01-01

    A number of age-related factors, including changes in pharmacokinetics and pharmacodynamics, medical comorbidity and an increased risk of drug-drug interaction, can complicate the pharmacologic management of depression in late life. Nevertheless, over 80% of elderly depressed patients will eventually respond to vigorous treatment and, when treated over 2 years, up to 75% of those will not have a relapse or recurrence of depression. This article reviews a number of issues relating to the pharmacotherapy of depression in elderly people. In particular, it discusses the similarities and differences between various antidepressant medications, issues pertaining to dosing and length of treatment, and management of the patient who does not respond to first-line treatment. The author emphasizes that, because of the high risk of relapse and recurrence, a long-term collaboration between the patient and the physician is required to successfully manage depression in late life. PMID:9347777

  2. Pharmacological treatment of obsessive-compulsive disorder

    PubMed Central

    Bloch, Michael H.

    2014-01-01

    Synopsis Obsessive-compulsive disorder (OCD) affects up to 2.5% of the population of the course of a lifetime and produces substantial morbidity. Approximately 70% of patients can experience significant symptomatic relief with appropriate pharmacotherapy. The selective serotonin reuptake inhibitors (SSRIs) are the main stay of pharmacological treatment. These are typically used at higher doses and for longer periods than in depression. Remission is, unfortunately, uncommon. Proven second-line treatments include the tricyclic clomipramine and the addition of low-dose neuroleptic medications. Other augmentation strategies have been explored for patients refractory to proven interventions, but they are not as of yet robustly supported by controlled studies. The combination of medication with psychotherapy is often used, though careful studies have not documented synergistic benefit in adult patients. OCD refractory to available treatments remains a profound clinical challenge. PMID:25150568

  3. Pharmacologic treatment of hypertensive disorders during pregnancy.

    PubMed

    Yankowitz, Jerome

    2004-01-01

    Pregnancy complicated by hypertension is a common problem faced by clinicians. It can lead to substantial maternal and/or fetal/neonatal morbidity and mortality. There are a variety of medications that can be used during pregnancy either for treatment of significant chronic hypertension or in cases of acute severe hypertension. Most antihypertensive drugs have been shown to be safe for use in pregnancy. A variety of medications are available to treat more severe hypertension, although the use of pharmacologic therapy to treat mild chronic hypertension during pregnancy has not been supported in the literature. The data are more limited concerning drugs that would be used in the event of hypertensive emergencies or in an intensive care setting; however, in such a situation, maternal health and life become paramount and, despite lack of good studies, appropriate treatment should be rendered. PMID:15478474

  4. [Pharmacological treatment of the premature ejaculation].

    PubMed

    Jurado López, A R

    2014-07-01

    Biomedical approach to premature ejaculation (PE) has permited a better phisiopatologycal knowledge and so the use of pharmacological agents for the treatment of this sexual dysfuncion. Most of the studies to evaluate the eficacy of these drugs were not carried at all the parameters which actually define PE: intravaginal ejaculatory latencie time (IELT) tested with watch, ejaculation control self perception cuantification (questionaries) and cuantification of generated consequences in patient and partner, if it existes. For this reason, it is difficult to analyse the scientific evidence and we use medicines with no approved indication for PE ("off label"). This text is a review of pharmacologycal agents with no approved indication (PDE type 5 inhibitors, α-blockers, tramadol, SSRI, clomipramine), and pharmacologycal agents developed to be used in the treatment of PE and having got indication in this sexual dysfunction or "on label" drugs (topic anesthesics, dapoxetine). PMID:25953037

  5. [Non pharmacologic treatment of neuropathic pain].

    PubMed

    Guastella, Virginie; Mick, Gérard; Laurent, Bernard

    2008-02-01

    Nondrug treatments of neuropathic pain should always begin at the same time as pharmacologic treatment. There are three types of nondrug treatment for neuropathic pain: physical, surgical, and "psychocorporal" and psychotherapeutic treatment. Transcutaneous electrical nerve stimulation (TENS) is a simple physical treatment that strengthens local inhibitory controls and is indicated in focal neuropathic pain when upstream stimulation is possible for a superficial sensitive nerve trunk. Destructive surgery is represented today by "DREZotomy", destruction of nociceptive fibers and their dorsal root entry zones. It is indicated essentially in intractable pain due to plexus avulsion. Functional surgery is implanted electric stimulation--either spinal or central (encephalic)--of structures that exert inhibitory control on the pain pathways. Spinal stimulation is performed at the level of the posterior spinal cord and is indicated essentially in segmental mononeuropathies refractory to drug treatment. Central stimulation is performed at the motor cortex and is indicated for refractory central pain. "Psychocorporal" techniques (relaxation, sophrology, hypnosis) are useful to reduce anxiety and neurovegetative hypertonicity, both factors that aggravate neuropathic pain. PMID:18191370

  6. Pharmacology for the treatment of premature ejaculation.

    PubMed

    Giuliano, François; Clèment, Pierre

    2012-07-01

    Male sexual response comprises four phases: excitement, including erection; plateau; ejaculation, usually accompanied by orgasm; and resolution. Ejaculation is a complex sexual response involving a sequential process consisting of two phases: emission and expulsion. Ejaculation, which is basically a spinal reflex, requires a tight coordination between sympathetic, parasympathetic, and somatic efferent pathways originating from different segments and area in the spinal cord and innervating pelvi-perineal anatomical structures. A major relaying and synchronizing role is played by a group of lumbar neurons described as the spinal generator of ejaculation. Excitatory and inhibitory influences from sensory genital and cerebral stimuli are integrated and processed in the spinal cord. Premature ejaculation (PE) can be defined by ≤1-min ejaculatory latency, an inability to delay ejaculation, and negative personal consequences. Because there is no physiological impairment in PE, any pharmacological agent with central or peripheral mechanism of action that is delaying the ejaculation is a drug candidate for the treatment of PE. Ejaculation is centrally mediated by a variety of neurotransmitter systems, involving especially serotonin and serotonergic pathways but also dopaminergic and oxytocinergic systems. Pharmacological delay of ejaculation can be achieved either by inhibiting excitatory or reinforcing inhibitory pathways from the brain or the periphery to the spinal cord. PE can be treated with long-term use of selective serotonin-reuptake inhibitors (SSRIs) or tricyclic antidepressants. Dapoxetine, a short-acting SSRI, is the first treatment registered for the on-demand treatment of PE. Anesthetics applied on the glans penis have the ability to lengthen the time to ejaculation. Targeting oxytocinergic, neurokinin-1, dopaminergic, and opioid receptors represent future avenues to delaying ejaculation. PMID:22679220

  7. Pharmacological maintenance treatments of opiate addiction

    PubMed Central

    Bell, James

    2014-01-01

    For people seeking treatment, the course of heroin addiction tends to be chronic and relapsing, and longer duration of treatment is associated with better outcomes. Heroin addiction is strongly associated with deviant behaviour and crime, and the objectives in treating heroin addiction have been a blend of humane support, rehabilitation, public health intervention and crime control. Reduction in street heroin use is the foundation on which all these outcomes are based. The pharmacological basis of maintenance treatment of dependent individuals is to minimize withdrawal symptoms and attenuate the reinforcing effects of street heroin, leading to reduction or cessation of street heroin use. Opioid maintenance treatment can be moderately effective in suppressing heroin use, although deviations from evidence-based approaches, particularly the use of suboptimal doses, have meant that treatment as delivered in practice may have resulted in poorer outcomes than predicted by research. Methadone treatment has been ‘programmatic’, with a one-size-fits-all approach that in part reflects the perceived need to impose discipline on deviant individuals. However, differences in pharmacokinetics and in side-effects mean that many patients do not respond optimally to methadone. Injectable diamorphine (heroin) provides a more reinforcing medication for some ‘nonresponders’ and can be a valuable option in the rehabilitation of demoralized, socially excluded individuals. Buprenorphine, a partial agonist, is a less reinforcing medication with different side-effects and less risk of overdose. Not only is it a different medication, but also it can be used in a different paradigm of treatment, office-based opioid treatment, with less structure and offering greater patient autonomy. PMID:23210630

  8. Advances in pharmacological treatment of migraine.

    PubMed

    Diener, H C; Limmroth, V

    2001-10-01

    Migraine is a paroxysmal disorder with attacks of headache, nausea, vomiting, photo- and phonophobia and malaise. This review summarises new treatment options both for the therapy of the acute attack as well as for migraine prophylaxis. Analgesics like aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) are effective in treating migraine attacks. Few controlled trials were performed for the use of ergotamine or dihydroergotamine. These trials indicate inferior efficacy compared with serotonin (5-HT(1B/D)) agonists (triptans). The triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan), are highly effective. They improve headache as well as nausea, photo- and phonophobia. The different triptans show only minor differences in efficacy, headache recurrence and adverse effects. The knowledge of their different pharmacological profile allows a more specific treatment of the individual migraine characteristics. Migraine prophylaxis is recommended, when more than three attacks occur per month, if attacks do not respond to acute treatment or if side effects of acute treatment are severe. Substances with proven efficacy include the beta-blockers metoprolol and propranolol, the calcium channel blocker flunarizine, several 5-HT antagonists and amitriptyline. Recently anti-epileptic drugs (valproic acid, gabapentin, topiramate) were evaluated for the prophylaxis of migraine. The use of botulinum toxin is under investigation. PMID:11772289

  9. [Pharmacological treatment of benign prostatic hyperplasia].

    PubMed

    Oelke, M; Martinelli, E

    2016-01-01

    The pharmacological treatment of benign prostatic hyperplasia (BPH) is indicated when men suffer from lower urinary tract symptoms (LUTS) but there are no absolute indications for prostate surgery or severe bladder outlet obstruction. Phytotherapy can be used in men with mild to moderate LUTS and alpha-blockers can quickly and effectively decrease the LUTS and symptomatic disease progression. Phosphodiesterase type 5 inhibitors (PDE5-I) are an alternative to alpha-blockers when men experience bothersome side effects from alpha-blockers or erectile dysfunction. If patients predominantly have bladder storage symptoms and a small prostate, muscarinic receptor antagonists are a viable treatment option. The combination of alpha-blocker plus muscarinic receptor antagonist is more efficacious in reducing LUTS than the single drugs alone. The 5 alpha-reductase inhibitors (5ARI) can significantly decrease LUTS and disease progression (e.g. acute urinary retention and need for prostate surgery) in men with larger prostates (> 30-40 ml). The combination of 5ARI plus alpha-blocker can reduce LUTS and disease progression more effectively than drug monotherapy. Combination therapy with PDE5-I (tadalafil) plus 5ARI (finasteride) reduces LUTS more substantially than 5ARI alone and, additionally, PDE5-Is reduce the sexual side effects during 5ARI treatment. PMID:26676726

  10. Pharmacological and non-pharmacological treatments for nightmare disorder.

    PubMed

    Nadorff, Michael R; Lambdin, Karen K; Germain, Anne

    2014-04-01

    Interest in the treatment of nightmares has greatly increased over the last several years as research has demonstrated the clinical significance of nightmare disorder. This paper provides an overview of nightmare disorder, its clinical relevance, and the leading treatments that are available. In particular, the paper defines nightmare disorder and then summarize the recent literature examining the clinical relevance of nightmare disorder, including its relation to post-traumatic stress disorder and other psychiatric conditions. The relation between nightmares and suicidality is also discussed. Recent findings on the treatment of nightmare with imagery rehearsal therapy and prazosin are then summarized. Lastly, the paper comments on potential future uses of nightmare treatment including using imagery rehearsal therapy or prazosin as a first-line intervention for post-traumatic stress disorder and using these treatments as an adjunctive therapy to reduce suicide risk in those at risk of suicide with nightmares. PMID:24892897

  11. Cerebral Vasospasm Pharmacological Treatment: An Update

    PubMed Central

    Siasios, Ioannis; Kapsalaki, Eftychia Z.; Fountas, Kostas N.

    2013-01-01

    Aneurysmal subarachnoid hemorrhage- (aSAH-) associated vasospasm constitutes a clinicopathological entity, in which reversible vasculopathy, impaired autoregulatory function, and hypovolemia take place, and lead to the reduction of cerebral perfusion and finally ischemia. Cerebral vasospasm begins most often on the third day after the ictal event and reaches the maximum on the 5th–7th postictal days. Several therapeutic modalities have been employed for preventing or reversing cerebral vasospasm. Triple “H” therapy, balloon and chemical angioplasty with superselective intra-arterial injection of vasodilators, administration of substances like magnesium sulfate, statins, fasudil hydrochloride, erythropoietin, endothelin-1 antagonists, nitric oxide progenitors, and sildenafil, are some of the therapeutic protocols, which are currently employed for managing patients with aSAH. Intense pathophysiological mechanism research has led to the identification of various mediators of cerebral vasospasm, such as endothelium-derived, vascular smooth muscle-derived, proinflammatory mediators, cytokines and adhesion molecules, stress-induced gene activation, and platelet-derived growth factors. Oral, intravenous, or intra-arterial administration of antagonists of these mediators has been suggested for treating patients suffering a-SAH vasospam. In our current study, we attempt to summate all the available pharmacological treatment modalities for managing vasospasm. PMID:23431440

  12. Pharmacology.

    PubMed

    Bolay, Hayrunnisa; Durham, Paul

    2010-01-01

    Headache treatment has been based primarily on experiences with non-specific drugs such as analgesics, non-steroidal anti-inflammatory drugs, or drugs that were originally developed to treat other diseases, such as beta-blockers and anticonvulsant medications. A better understanding of the basic pathophysiological mechanisms of migraine and other types of headache has led to the development over the past two decades of more target-specific drugs. Since activation of the trigeminovascular system and neurogenic inflammation are thought to play important roles in migraine pathophysiology, experimental studies modeling those events successfully predicted targets for selective development of pharmacological agents to treat migraine. Basically, there are two fundamental strategies for the treatment of migraine, abortive or preventive, based to a large degree on the frequency of attacks. The triptans, which exhibit potency towards selective serotonin (5-hydroxytryptamine, 5-HT) receptors expressed on trigeminal nerves, remain the most effective drugs for the abortive treatment of migraine. However, numerous preventive medications are currently available that modulate the excitability of the nervous system, particularly the cerebral cortex. In this chapter, the pharmacology of commercially available medications as well as drugs in development that prevent or abort headache attacks will be discussed. PMID:20816410

  13. Pharmacologic approaches to the treatment of cocaine dependence.

    PubMed Central

    Taylor, W A; Gold, M S

    1990-01-01

    When pharmacologic agents are considered in the treatment of cocaine addiction, the objective of such treatment--sustained abstinence--must be considered. Medication and medical approaches have been disappointing in the treatment of cocaine overdose. The central neurobiologic mechanism(s) involved in cocaine toxicity are poorly understood. Without a cocaine antagonist, pharmacologic approaches have been less than promising in preventing relapse. Various psychoactive medications have been tried in early cocaine abstinence, with some success. PMID:1971975

  14. [Review of current pharmacologic treatment of pain].

    PubMed

    Brasseur, L

    1997-01-01

    Pain is the main reason prompting patients to consult their physicians. In acute conditions, pain has a very particular significance as a warning sign, enabling the physician to attempt a diagnosis. Nevertheless, its detrimental effect upon the individual (even in the case of acute pain) and its cost to society are now widely acknowledged. There can be no doubt about the physical component of pain, but the psychological and social aspects should not be ignored, particularly in the case of chronic pain. There is no single therapeutic approach to pain and, more often than not, successful treatment comprises a combination of several. Pharmacological treatments are undeniably the most common approach. In clinical practice, recent advances have been based upon an improved understanding of 'old' substances such as morphine and, at the same time, research continues in the hope of finding the 'ideal' analgesic-effective in most situations but without adverse effects: this appears to be a somewhat utopian arm at present, considering the number of different causes of pain. An improved understanding of the physiological mechanisms of pain has led, within the field of clinical practice, to several methods of differentiating pain. These depend on whether or not pain responds to morphine, or on the type of pain: pain due to an excess of nociception, pain resulting from deafferentation (caused by damage to nerve pathways) in the central or peripheral nervous system and psychogenic (idiopathic) pain. Likewise, there are several different ways of classifying analgesic treatments: according to the intensity of pain, as with use of the WHO ladder (which is based on the notion of steps) for the treatment of cancer pain; according to the presumed physiopathological mechanism and, in particular, the response to morphine, and according to the presumed central or peripheral mechanism of the drugs. In reality, peripherally acting drugs can also have a central mechanism of action, just as

  15. Non-pharmacological treatments for COPD.

    PubMed

    Mulhall, Patrick; Criner, Gerard

    2016-07-01

    Chronic obstructive pulmonary disease (COPD) affects roughly 10% of the global population and is growing in prevalence annually. COPD is characterized by progressive non-reversible narrowing of airways mainly due to cigarette smoking. Therapeutic interventions aimed at altering this progressive disease course can largely be grouped into pharmacological or non-pharmacological therapies. The focus of this paper is on the non-pharmacological aspects of COPD management, reviewing the current literature to provide an evidence-based management approach. Non-pharmacological therapies reviewed in this article include the implementation of comprehensive care models utilizing a coordinated multidisciplinary team, tele-monitoring and patient-centred approach to optimize COPD care and improve compliance. Preventing progression of COPD via smoking cessation remains of paramount importance, and newer therapeutic options including electronic cigarettes show promise in small studies as cessation aids. COPD has systemic manifestations that can be ameliorated with the enrollment in pulmonary rehabilitation programmes, which focus on exercise endurance to improve dyspnoea and quality of life. Advanced therapeutics for COPD includes lung volume reduction surgery for a pre-specified cohort and minimally invasive bronchoscopic valves that in recent reviews show promise. Lastly, patients on maximal COPD therapy with progressive disease can be referred for lung transplantation; however, this often requires a highly selected and motivated patient and care team. Survival rates for lung transplantation are improving; thus, this procedure remains a viable option as more expertise and experience are gained. PMID:27099216

  16. Non-Pharmacological Treatments of Allergic Rhinitis (Neglected Treatments)

    PubMed Central

    Zohalinezhad, Mohammad Ebrahim; Zarshenas, Mohammad M.

    2016-01-01

    Background: Allergic rhinitis is the most common diseases affecting people in industrialized society. However, this is not a new disease and it was clinically described and treated for the first time by Rhazes (865-925 CE). The disease was also mentioned in “The Canon of Medicine” by Avicenna (980–1037). Methods: We searched in Scopus, Web of Science, and PubMed for “allergic rhinitis”, “interactions”, “non-prescription”, “prescription”, and in electronic copies of ITM sources the “canon” and “Al-Havi”. Results: Both Persian pioneers of Medicine recommended non-pharmacologic management as an important phase of the therapy. Their recommendations consisted of avoiding overeating and polydipsia, massage of the lower extremities, adjusting the duration and time of sleep, sleeping in the supine position, avoiding exposure of the head to cold air and taking a shower early in the morning. Conclusion: Although some aspects of their recommendations, such as massage of the lower extremities, avoiding of overeating and adjusting of sleep pattern were approved, but further cross-sectional and prospective studies are needed to confirm other non-pharmacological treatments.

  17. Pharmacology of anticoagulants used in the treatment of venous thromboembolism.

    PubMed

    Nutescu, Edith A; Burnett, Allison; Fanikos, John; Spinler, Sarah; Wittkowsky, Ann

    2016-01-01

    Anticoagulant drugs are the foundation of therapy for patients with VTE. While effective therapeutic agents, anticoagulants can also result in hemorrhage and other side effects. Thus, anticoagulant therapy selection should be guided by the risks, benefits and pharmacologic characteristics of each agent for each patient. Safe use of anticoagulants requires not only an in-depth knowledge of their pharmacologic properties but also a comprehensive approach to patient management and education. This paper will summarize the key pharmacologic properties of the anticoagulant agents used in the treatment of patients with VTE. PMID:26780737

  18. Pharmacologic Approaches to the Treatment of Obstructive Sleep Apnea.

    PubMed

    White, David P

    2016-06-01

    The concept of pharmacologic therapy for obstructive sleep apnea (OSA) treatment has always been considered but no agent has had a large enough effect size to drive substantial adoption. A new construct of the pathophysiology of OSA is that there are 4 primary physiologic traits that dictate who develops OSA. These traits vary substantially between patients, meaning OSA may develop for quite different reasons. This encourages new thinking regarding pharmacologic therapy and continued attempts to find the ideal or acceptable drug. PMID:27236057

  19. Neuroscience of behavioral and pharmacological treatments for addictions

    PubMed Central

    Potenza, Marc N.; Sofuoglu, Mehmet; Carroll, Kathleen M.; Rounsaville, Bruce J.

    2011-01-01

    Summary Although substantial advances have been made in behavioral and pharmacological treatments for addictions, moving treatment development to the next stage may require novel ways of approaching addictions, particularly those derived from new findings regarding of the neurobiological underpinnings of addictions, while assimilating and incorporating relevant information from earlier approaches. In this review, we first briefly review theoretical and biological models of addiction and then describe existing behavioral and pharmacologic therapies for the addictions within this framework. We then propose new directions for treatment development and targets that are informed by recent evidence regarding the heterogeneity of addictions and the neurobiological contributions to these disorders. PMID:21338880

  20. [Pharmacological treatment of COPD. Where are we now?].

    PubMed

    Calle Rubio, Myriam; Pinedo Sierra, Celia; Rodríguez Hermosa, Juan Luis

    2010-12-01

    Current clinical guidelines recommend a step-wise approach to the pharmacological treatment of chronic obstructive pulmonary disease (COPD), with drugs being added according to the severity of airflow obstruction, symptoms, and the number of acute exacerbations in patients with severe disease. However, greater knowledge of the physiopathogenesis of this disease has led to COPD being considered a heterogeneous process in which therapeutic decisions should not be based exclusively on the results of spirometry. Treatment is increasingly individualized according to the patient's characteristics. The present article reviews the scientific evidence on the aims of treatment in COPD and the benefits achieved by the various pharmacological options available. PMID:21316549

  1. A Review of Pharmacologic Treatment for Compulsive Buying Disorder.

    PubMed

    Soares, Célia; Fernandes, Natália; Morgado, Pedro

    2016-04-01

    At present, no treatment recommendations can be made for compulsive buying disorder. Recent studies have found evidence for the efficacy of psychotherapeutic options, but less is known regarding the best pharmacologic treatment. The purpose of this review is to present and analyze the available published evidence on the pharmacological treatment of compulsive buying disorder. To achieve this, we conducted a review of studies focusing on the pharmacological treatment of compulsive buying by searching the PubMed/MEDLINE database. Selection criteria were applied, and 21 studies were identified. Pharmacological classes reported included antidepressants, mood stabilizers, opioid antagonists, second-generation antipsychotics, and N-methyl-D-aspartate receptor antagonists. We found only placebo-controlled trials for fluvoxamine; none showed effectiveness against placebo. Three open-label trials reported clinical improvement with citalopram; one was followed by a double-blind discontinuation. Escitalopram was effective in an open-label trial but did not show efficacy in the double-blind phase. Memantine was identified as effective in a pilot open-label study. Fluoxetine, bupropion, nortriptyline, clomipramine, topiramate and naltrexone were only reported to be effective in clinical cases. According to the available literature, there is no evidence to propose a specific pharmacologic agent for compulsive buying disorder. Future research is required for a better understanding of both pathogenesis and treatment of this disorder. PMID:27067344

  2. [Pharmacology].

    PubMed

    González, José; Orero, Ana; Olmo, Vicente; Martínez, David; Prieto, José; Bahlsen, Jose Antonio; Zaragozá, Francisco; Honorato, Jesús

    2011-06-01

    Two of the main characteristics of western societies in the last fifty years have been the medicalization of the human life and the environmental degradation. The first one has forced human being to consider medicines use related to what would be rational, reasonable and well-reasoned. The second one brought us to a new ecologist conscience. In relation to the "human social system", the effects of medication can be considered very positive as a whole, particularly those related to the amazing increase of expectative and quality of life. But, along with those unquestionable beneficial effects, medicines have also caused some negative effects for other biotic and abiotic systems, such as microbian alterations and their undesirable consequences which have involved the massive use of antibiotics in medicine and veterinary, the uncontrolled elimination of millions of doses of all kind of drugs, additives and excipients, etc., as well as atmospheric contamination and degradation of forests and deep oceans which can have been caused by investigation and production of determinated drugs. In this context Pharmacology appears as a scientific discipline that studies the research (R), development (D), production (P), and utilization (U) of drugs and medical substances in relation to the environment. From a farmaecologic perspective the drugs utilization has its development in three main contexts, all of them closely related: prescription quality, farmaceutical care, and patient's active participation in his own disease and treatment. PMID:21666997

  3. [Pharmacological treatment of syndromes of aggressivity].

    PubMed

    Itil, T M

    1978-01-01

    In the treatment of violent-aggressive behavior, four major groups of drugs emerged: 1. Major tranquilizers in the treatment of aggressive-violent behavior associated with psychotic syndromes. 2. Anti-epileptic drugs such as diphenylhydantoin and barbiturates in the treatment of aggressive-violent behavior within the epileptic syndrome. 3. Psychostimulants in the treatment of aggressive behavior of adolescents and children within behavior disturbances. 4. Anti-male hormones such as cyproterone acetate in the treatment of violent-aggressive behavior associated with pathological sexual hyperactivity. Whereas each category of drug is predominantly effective in one type of aggressive syndrome, it may also be effective in other conditions as well. Aggression as a result of a personality disorder is most difficult to treat with drugs. PMID:34189

  4. Pharmacological and Non-pharmacological Treatment Options for Depression and Depressive Symptoms in Hemodialysis Patients

    PubMed Central

    Grigoriou, Stefania S.; Karatzaferi, Christina; Sakkas, Giorgos K.

    2015-01-01

    Depression is a mental disorder with a high prevalence among patients with end stage renal disease (ESRD). It is reported that depression afflicts approximately 20-30% of this patient population, being associated, amongst other, with high mortality rate, low adherence to medication and low perceived quality of life. There is a variety of medications known to be effective for the treatment of depression but due to poor adherence to treatment as well as due to the high need for medications addressing other ESRD comorbidities, depression often remains untreated. According to the literature, depression is under-diagnosed and undertreated in the majority of the patients with chronic kidney disease. In the current review the main pharmacological and non-pharmacological approaches and research outcomes for the management of depressive symptoms in hemodialysis patients are discussed. PMID:26973957

  5. Pharmacologic treatments for pulmonary hypertension: exploring pharmacogenomics

    PubMed Central

    Duarte, Julio D; Hanson, Rebekah L; Machado, Roberto F

    2013-01-01

    Pulmonary hypertension (PH) is a disease with multiple etiologies and is categorized into five broad groups. Of these groups, pulmonary arterial hypertension (PAH) is the most studied and, therefore, all of the currently available drug classes (prostacyclin analogs, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors) were developed to treat PAH. Thus, limited treatment data exist for the less-studied non-PAH forms of PH. Pharmacogenomics can be a tool to better understand the pathways involved in PH, as well as to improve personalization of therapy. However, little pharmacogenomic research has been carried out on this disease. New treatments for PH are on the horizon, deriving from both repurposed currently available drugs and novel therapeutics. PMID:23668740

  6. Non-pharmacological treatment of Helicobacter pylori

    PubMed Central

    Shmuely, Haim; Domniz, Noam; Yahav, Jacob

    2016-01-01

    Many food and plant extracts have shown in vitro anti-Helicobacter pylori (H. pylori) activity, but are less effective in vivo. The anti-H. pylori effects of these extracts are mainly permeabilitization of the membrane, anti-adhesion, inhibition of bacterial enzymes and bacterial grown. We, herein, review treatment effects of cranberry, garlic, curcumin, ginger and pistacia gum against H. pylori in both in vitro, animal studies and in vivo studies. PMID:27158532

  7. Non-pharmacological treatment of Helicobacter pylori.

    PubMed

    Shmuely, Haim; Domniz, Noam; Yahav, Jacob

    2016-05-01

    Many food and plant extracts have shown in vitro anti-Helicobacter pylori (H. pylori) activity, but are less effective in vivo. The anti-H. pylori effects of these extracts are mainly permeabilitization of the membrane, anti-adhesion, inhibition of bacterial enzymes and bacterial grown. We, herein, review treatment effects of cranberry, garlic, curcumin, ginger and pistacia gum against H. pylori in both in vitro, animal studies and in vivo studies. PMID:27158532

  8. Pharmacological treatment of cardiac glycoside poisoning.

    PubMed

    Roberts, Darren M; Gallapatthy, Gamini; Dunuwille, Asunga; Chan, Betty S

    2016-03-01

    Cardiac glycosides are an important cause of poisoning, reflecting their widespread clinical usage and presence in natural sources. Poisoning can manifest as varying degrees of toxicity. Predominant clinical features include gastrointestinal signs, bradycardia and heart block. Death occurs from ventricular fibrillation or tachycardia. A wide range of treatments have been used, the more common including activated charcoal, atropine, β-adrenoceptor agonists, temporary pacing, anti-digoxin Fab and magnesium, and more novel agents include fructose-1,6-diphosphate (clinical trial in progress) and anticalin. However, even in the case of those treatments that have been in use for decades, there is debate regarding their efficacy, the indications and dosage that optimizes outcomes. This contributes to variability in use across the world. Another factor influencing usage is access. Barriers to access include the requirement for transfer to a specialized centre (for example, to receive temporary pacing) or financial resources (for example, anti-digoxin Fab in resource poor countries). Recent data suggest that existing methods for calculating the dose of anti-digoxin Fab in digoxin poisoning overstate the dose required, and that its efficacy may be minimal in patients with chronic digoxin poisoning. Cheaper and effective medicines are required, in particular for the treatment of yellow oleander poisoning which is problematic in resource poor countries. PMID:26505271

  9. Acid peptic diseases: pharmacological approach to treatment

    PubMed Central

    Mejia, Alex; Kraft, Walter K

    2011-01-01

    Acid peptic disorders are the result of distinctive, but overlapping pathogenic mechanisms leading to either excessive acid secretion or diminished mucosal defense. They are common entities present in daily clinical practice that, owing to their chronicity, represent a significant cost to healthcare. Key elements in the success of controlling these entities have been the development of potent and safe drugs based on physiological targets. The histamine-2 receptor antagonists revolutionized the treatment of acid peptic disorders owing to their safety and efficacy profile. The proton-pump inhibitors (PPIs) represent a further therapeutic advance due to more potent inhibition of acid secretion. Ample data from clinical trials and observational experience have confirmed the utility of these agents in the treatment of acid peptic diseases, with differential efficacy and safety characteristics between and within drug classes. Paradigms in their speed and duration of action have underscored the need for new chemical entities that, from a single dose, would provide reliable duration of acid control, particularly at night. Moreover, PPIs reduce, but do not eliminate, the risk of ulcers in patients taking NSAIDs, reflecting untargeted physiopathologic pathways and a breach in the ability to sustain an intragastric pH of more than 4. This review provides an assessment of the current understanding of the physiology of acid production, a discussion of medications targeting gastric acid production and a review of efficacy in specific acid peptic diseases, as well as current challenges and future directions in the treatment of acid-mediated diseases. PMID:21822447

  10. Evidence-Based Pharmacologic Treatment of Pediatric Bipolar Disorder.

    PubMed

    Findling, Robert L

    2016-01-01

    Pharmacotherapy is an important component of treatment for children and adolescents with bipolar disorder. The body of evidence supporting safe and effective treatments in this population is growing. Available data provide information on the risks and benefits of pharmacologic agents used for acute manic, mixed, and depressive episodes as well as for maintenance treatment. Lithium, anticonvulsants, and antipsychotics comprise the armamentarium for treating pediatric bipolar disorder. When selecting treatment, clinicians must consider the efficacy and side effect profile of potential pharmacotherapies, as well as the patient's history, including the presence of comorbidities, in order to develop a treatment plan that will ensure optimal outcomes. PMID:27570928

  11. Pharmacologic Options for the Treatment of Sarcopenia.

    PubMed

    Morley, John E

    2016-04-01

    Sarcopenia is now clinically defined as a loss of muscle mass coupled with functional deterioration (either walking speed or distance or grip strength). Based on the FRAX studies suggesting that the questions without bone mineral density can be used to screen for osteoporosis, there is now a valid simple questionnaire to screen for sarcopenia, i.e., the SARC-F. Numerous factors have been implicated in the pathophysiology of sarcopenia. These include genetic factors, mitochondrial defects, decreased anabolic hormones (e.g., testosterone, vitamin D, growth hormone and insulin growth hormone-1), inflammatory cytokine excess, insulin resistance, decreased protein intake and activity, poor blood flow to muscle and deficiency of growth derived factor-11. Over the last decade, there has been a remarkable increase in our understanding of the molecular biology of muscle, resulting in a marked increase in potential future targets for the treatment of sarcopenia. At present, resistance exercise, protein supplementation, and vitamin D have been established as the basic treatment of sarcopenia. High-dose testosterone increases muscle power and function, but has a number of potentially limiting side effects. Other drugs in clinical development include selective androgen receptor molecules, ghrelin agonists, myostatin antibodies, activin IIR antagonists, angiotensin converting enzyme inhibitors, beta antagonists, and fast skeletal muscle troponin activators. As sarcopenia is a major predictor of frailty, hip fracture, disability, and mortality in older persons, the development of drugs to treat it is eagerly awaited. PMID:26100650

  12. [Treatment of generalized anxiety: new pharmacologic approaches].

    PubMed

    Boulenger, J P

    1995-01-01

    First defined as a residual diagnostic category in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM), Generalized Anxiety Disorder (GAD) was until recently one of the least studied and least clearly conceptualized of the anxiety disorders. The clinical definition of GAD has however improved up to the fourth edition of the DSM where the disorder is now characterized as a chronic state of apprehensive expectation and uncontrollable worry concerning multiple daily life events or activities and accompanied with at least 3 symptoms belonging to a list of six common manifestations of psychic or motor tension. Clinical research demonstrating the stability and the specificity of somatic symptoms clearly support the validity of the diagnosis of GAD despite possible difficulties in the differential diagnosis with other chronic conditions or axis II disorders such as dysthymia or mixed anxiety-depressive disorder. After benzodiazepines (BZD) and 5-HT1A agonists like buspirone, several other types of new anxiolytic drugs have been developed for the treatment of GAD. Partial agonists at GABA-BZD receptor sites may offer the advantage of a better efficacy vs side-effects ratio over classical BZDs; however, systematic comparative clinical trials will have to demonstrate the clinical relevance of the encouraging results obtained with these drugs, at the experimental level, during studies in healthy volunteers and during the first placebo-controlled trials. Furthermore, the recent description of GABA-receptor's subunits clearly suggest that the development of drugs acting at this level and devoided of psychomotor or withdrawal side-effects is a target that is worth pursuing. On the other hand, the development of 5-HT2 and 5-HT3 antagonists is also of interest for the treatment of GAD since it could provide new anxiolytic drugs without these side-effects and thus easier to administer on a long-term basis corresponding to the chronicity of GAD

  13. Migraine: pathophysiology, pharmacology, treatment and future trends.

    PubMed

    Villalón, Carlos M; Centurión, David; Valdivia, Luis Felipe; de Vries, Peter; Saxena, Pramod R

    2003-03-01

    Migraine treatment has evolved into the scientific arena, but it seems still controversial whether migraine is primarily a vascular or a neurological dysfunction. Irrespective of this controversy, the levels of serotonin (5-hydroxytryptamine; 5-HT), a vasoconstrictor and a central neurotransmitter, seem to decrease during migraine (with associated carotid vasodilatation) whereas an i.v. infusion of 5-HT can abort migraine. In fact, 5-HT as well as ergotamine, dihydroergotamine and other antimigraine agents invariably produce vasoconstriction in the external carotid circulation. The last decade has witnessed the advent of sumatriptan and second generation triptans (e.g. zolmitriptan, rizatriptan, naratriptan), which belong to a new class of drugs, the 5-HT1B/1D/1F receptor agonists. Compared to sumatriptan, the second-generation triptans have a higher oral bioavailability and longer plasma half-life. In line with the vascular and neurogenic theories of migraine, all triptans produce selective carotid vasoconstriction (via 5-HT1B receptors) and presynaptic inhibition of the trigeminovascular inflammatory responses implicated in migraine (via 5-HT1D/5-ht1F receptors). Moreover, selective agonists at 5-HT1D (PNU-142633) and 5-ht1F (LY344864) receptors inhibit the trigeminovascular system without producing vasoconstriction. Nevertheless, PNU-142633 proved to be ineffective in the acute treatment of migraine, whilst LY344864 did show some efficacy when used in doses which interact with 5-HT1B receptors. Finally, although the triptans are effective antimigraine agents producing selective cranial vasoconstriction, efforts are being made to develop other effective antimigraine alternatives acting via the direct blockade of vasodilator mechanisms (e.g. antagonists at CGRP receptors, antagonists at 5-HT7 receptors, inhibitors of nitric oxide biosynthesis, etc). These alternatives will hopefully lead to fewer side effects. PMID:15320857

  14. [Non pharmacological treatment for bipolar disorder].

    PubMed

    Mirabel-Sarron, Christine; Giachetti, Raphaël

    2012-12-01

    Bipolar disorder is a chronic and recurring disorder associated with significant psychosocial impairment. A number of psychosocial interventions have been developed to address impairment. The consensus makes mood stabilizer the treatment of bipolar disorder. However, numerous patients are not in complete remission despite a controlled observance. Every patient can follow a psycho educational program. What this paper adds. The review identifies that a range of interventions have demonstrated efficacy in extended periods of euthymia, improved social and occupational functioning and alleviation of subsyndromal symptoms. Adjunctive, short-term psychotherapies have been shown to offer fairly consistent benefits to bipolar disorder patients. Cognitive-behavioural therapy, family-focused therapy, and psychoeducation offer the most robust efficacy in regard to relapse prevention. The most complex situations including comorbidities can be helped by behavioral and cognitive therapy for bipolar disorder. Evaluations emphasize positive impact. The psychosocial interventions reviewed provide mental health nurses with evidence-based approaches to improving mental health care for patients with bipolar disorder. There is a need for mental health nurses to conduct high quality trials of the clinical effectiveness of these interventions. PMID:23395231

  15. Music therapy as a non-pharmacological treatment for epilepsy.

    PubMed

    Liao, Huan; Jiang, Guohui; Wang, Xuefeng

    2015-01-01

    Epilepsy is one of the most common neurological diseases. Currently, the primary methods of treatment include pharmacological and surgical treatment. However, approximately one-third of patients exhibit refractory epilepsy. Therefore, a novel approach to epilepsy treatment is necessary. Several studies have confirmed that music therapy can be effective at reducing seizures and epileptiform discharges, thus providing a new option for clinicians in the treatment of epilepsy. Although the underlying mechanism of music therapy is unknown, it may be related to resonance, mirror neurons, dopamine pathways and parasympathetic activation. Large sample, multicenter, randomized double-blind and more effectively designed studies are needed for future music therapy studies. PMID:26196169

  16. Neuroimaging correlates of pharmacological and psychological treatments for specific phobia.

    PubMed

    Linares, Ila M; Chags, Marcos H N; Machado-de-Sousa, João P; Crippa, José A S; Hallak, Jaime E C

    2014-01-01

    Specific phobia is an anxiety disorder characterized by irrational fear and avoidance of specific things or situations, interfering significantly with the patients' daily life. Treatment for the disorder consists of both pharmacological and psychological approaches, mainly cognitive behavioral therapy (CBT). Neuroimaging techniques have been used in an attempt to improve our understanding of the neurobiology of SP and of the effects of treatment options available. This review describes the design and results of eight articles investigating the neuroimaging correlates of pharmacological and psychological treatments for SP. The studies show that CBT is effective in SP, leading to a reduction of anxiety symptoms that is accompanied by functional alterations in the brain. The results of pharmacological interventions for SP are less uniform, but suggest that the partial agonist of the NMDA (N-methyl D-aspartate) receptor DCS (D-cycloserine) can be used in combination with psychotherapy techniques for the achievement of quicker treatment response and that DCS modulates the function of structures implicated in the neurobiology of SP. Further research should explore the augmentation of CBT treatment with DCS in controlled trials. PMID:24923351

  17. Pharmacologic Treatment Strategies in Children with Type 2 Diabetes Mellitus

    PubMed Central

    Urakami, Tatsuhiko; Kuwabara, Remi; Habu, Masako; Yoshida, Ayako; Okuno, Misako; Suzuki, Junichi; Takahashi, Shori; Mugishima, Hideo

    2013-01-01

    We treated 80 obese and 28 nonobese children diagnosed as having type 2 diabetes mellitus (T2DM). Among these patients, 26 obese and 23 nonobese children were assigned to pharmacologic therapies during the course of diabetes. Pharmacologic therapies were started if the HbA1c (NGSP) value exceeded 7.0% despite dietary and exercise management. For the 26 obese patients, metformin alone or in combination with an additional medication was frequently used. Only 2 patients independently received sulfonylureas (SUs) in the form of glimepiride. In addition, 9 patients were treated with basal insulin supported with oral hypoglycemic drugs (OHDs) or biphasic premix insulin. On the other hand, the 23 nonobese patients were frequently treated with insulin alone or in combination with an additional medication followed by SUs. The nonobese patients tended to require pharmacologic therapies, in particular insulin, at an earlier stage of diabetes as compared with the obese patients. New antidiabetic drugs, DPP-4 inhibitors and GLP-1 receptor agonists, seemed to exert positive effects on glycemic control without occurrence of hypoglycemic episodes in some patients regardless of the type of diabetes. These results suggest that pharmacologic treatment strategies in childhood T2DM should be tailored to individual patient characteristics. PMID:23966754

  18. Treatment de-escalation in HPV-positive oropharyngeal carcinoma: ongoing trials, critical issues and perspectives.

    PubMed

    Mirghani, H; Amen, F; Blanchard, P; Moreau, F; Guigay, J; Hartl, D M; Lacau St Guily, J

    2015-04-01

    Due to the generally poor prognosis of head and neck squamous cell carcinoma (HNSCC), treatment has been intensified, these last decades, leading to an increase of serious side effects. High-risk human papillomavirus (HR-HPV) infection has been recently etiologically linked to a subset of oropharyngeal squamous cell carcinoma (OPSCC), which is on the increase. These tumors are different, at the clinical and molecular level, when compared to tumors caused by traditional risk factors. Additionally, their prognosis is much more favorable which has led the medical community to consider new treatment strategies. Indeed, it is possible that less intensive treatment regimens could achieve similar efficacy with less toxicity and improved quality of life. Several clinical trials, investigating different ways to de-escalate treatment, are currently ongoing. In this article, we review these main approaches, discuss the rationale behind them and the issues raised by treatment de-escalation in HPV-positive OPSCC. PMID:24622970

  19. Integrating electrodermal biofeedback into pharmacologic treatment of grand mal seizures

    PubMed Central

    Scrimali, Tullio; Tomasello, Damiana; Sciuto, Massimo

    2015-01-01

    Electrodermal activity (EDA) and electrodermal biofeedback, when integrated with pharmacologic treatments, indicate promising methods for the treatment of grand mal seizures. They can be used to monitor patient arousal and help patients learn new strategies to better cope with stress and anxiety. Our proposed method can possibly reduce the number of crises for patients who are dependent on pharmacologic therapy and can improve their quality of life. This article describes the scientific background of electrodermal monitoring and electrodermal biofeedback for patients affected by grand mal seizures. In this study, we have reported a clinical case study. The patient was treated for 2 years with electrodermal biofeedback to augment pharmacologic treatments. The trial has been designed in accordance with “n = 1 case study research”. Our results have shown that our methods could achieve a significant reduction in grand mal seizures and sympathetic arousal when applied. The patient under consideration was also relaxed and exhibited greater competency to cope with stress. Additionally, the patient’s sense of mastery and self-efficacy was enhanced. PMID:26029078

  20. Integrating electrodermal biofeedback into pharmacologic treatment of grand mal seizures.

    PubMed

    Scrimali, Tullio; Tomasello, Damiana; Sciuto, Massimo

    2015-01-01

    Electrodermal activity (EDA) and electrodermal biofeedback, when integrated with pharmacologic treatments, indicate promising methods for the treatment of grand mal seizures. They can be used to monitor patient arousal and help patients learn new strategies to better cope with stress and anxiety. Our proposed method can possibly reduce the number of crises for patients who are dependent on pharmacologic therapy and can improve their quality of life. This article describes the scientific background of electrodermal monitoring and electrodermal biofeedback for patients affected by grand mal seizures. In this study, we have reported a clinical case study. The patient was treated for 2 years with electrodermal biofeedback to augment pharmacologic treatments. The trial has been designed in accordance with "n = 1 case study research". Our results have shown that our methods could achieve a significant reduction in grand mal seizures and sympathetic arousal when applied. The patient under consideration was also relaxed and exhibited greater competency to cope with stress. Additionally, the patient's sense of mastery and self-efficacy was enhanced. PMID:26029078

  1. Pharmacologic treatment to improve venous leg ulcer healing.

    PubMed

    Raffetto, Joseph D; Eberhardt, Robert T; Dean, Steven M; Ligi, Daniela; Mannello, Ferdinando

    2016-07-01

    Pharmacologic treatment for venous leg ulcers (VLUs) is an adjuvant treatment to compression therapy. It encompasses a variety of plant-derived and synthetic compounds with properties that alter venous microcirculation, endothelial function, and leukocyte activity to promote VLU healing. These compounds are often referred to as venotonics or venoactive drugs but have also been referred to as edema-protective agents, phlebotonics, vasoprotectors, phlebotropics, and venotropics. The exact mechanism of their ability to heal VLUs is not known; however, clinical trials support their efficacy. This evidence-based review assesses randomized clinical trials and meta-analyses with the objective of determining the effectiveness of venotonics to promote VLU healing. PMID:27318060

  2. [Dual diagnosis in anxiety disorders: pharmacologic treatment recommendations].

    PubMed

    Sáiz Martínez, Pilar Alejandra; Jimenez Treviño, Luis; Díaz Mesa, Eva M; García-Portilla González, M Paz; Marina González, Pedro; Al-Halabí, Susana; Szerman, Néstor; Bobes García, Julio; Ruiz, Pedro

    2014-01-01

    Anxiety disorders and substance use disorders are highly comorbid (between 18% and 37%), and such comorbidity complicates treatment and worsens prognosis (including higher suicide risk). There are not many research works on the specific pharmacologic treatment of dual comorbid anxiety disorders. Most authors recommend a simultaneous approach of both, anxiety and substance use, disorders. Research data on pharmacotherapy suggest that psychotropics used in the treatment of anxiety disorders are also effective in dual diagnosis. SSRIs are considered first-line therapy in the treatment of dual anxiety while benzodiacepines should be avoided. New generation antiepileptic have shown efficacy in case series and open label studies in the latest years, thus being a promising treatment option for dual comorbid anxiety disorders, specially pregabalin in generalized anxiety disorder. PMID:25314041

  3. [The pharmacological treatment of obesity: past, present and future].

    PubMed

    Simonyi, Gábor; Pados, Gyula; Medvegy, Mihály; Bedros, J Róbert

    2012-03-11

    Currently, obesity presents one of the biggest health problems. Management strategies for weight reduction in obese individuals include changes in life style such as exercise and diet, behavioral therapy, and pharmacological treatment, and in certain cases surgical intervention. Diet and exercise are best for both prevention and treatment, but both require much discipline and are difficult to maintain. Drug treatment of obesity offer a possible adjunct, but it may only have modest results, limited by side effects; furthermore, the weight lowering effects last only as long as the drug is being taken and, unfortunately, as soon as the administration is stopped, the weight is regained. These strategies should be used in a combination for higher efficacy. Drugs used to induce weight loss have various effects: they increase satiety, reduce the absorption of nutrients or make metabolism faster; but their effect is usually moderate. In the past, several drugs were used in the pharmacological therapy of weight reduction including thyroid hormone, dinitrophenol, amphetamines and their analogues, e.g. fenfluramine, At present, only orlistat is available in the long term treatment (≥ 24 weeks) of obesity as sibutramine and rimonabant were withdrawn form the market. Several new anti-obesity drugs are being tested at present, and liraglutide, a GLP-1 analogue (incretin mimetic), is the most promising one. PMID:22370224

  4. Pharmacologic treatment of hand-, knee- and hip-osteoarthritis.

    PubMed

    Bobacz, Klaus

    2013-05-01

    Osteoarthritis (OA) is a joint disease of high prevalence and affects > 90 % of the population, depending on several risk factors. Symptomatic OA is less frequent, but requires an individually tailored therapeutic regimen consisting of non-pharmacological and pharmacological treatment modalities. Pharmacologic therapy, however, is mainly limited to analgetic and anti-inflammatory agents; structure modifying remedies do not exist. The therapeutic approach to hand-, knee- and hip-OA is basically similar and differs only at some minor points. Generally, topical agents or paracetamol are recommended as first-line agents. If unsuccessful oral non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2-selctive inhibitors should be introduced. Tramadol is an option in the case patients will not respond satisfactorily to NSAIDs. Glucosamine and chondroitine sulphate are no longer recommended in knee and hip OA, but chondroitine might be efficient in treating hand OA. Oral NSAIDs should be prescribed with caution due to potential side effects. Opioids are not recommended as their benefits are outweighed by an increased risk for serious adverse events. PMID:23715933

  5. Pharmacologic approaches for the treatment of chronic insomnia.

    PubMed

    Neubauer, David N

    2003-01-01

    Insomnia is a common problem that for many sufferers persists chronically and may result from a wide range of causes. Specific treatments address particular underlying medical disorders. General therapeutic approaches, including pharmacologic and behavioral strategies, may have broad applicability to insomnia patients. Many different medications and substances have been used in an attempt to improve sleep. This article reviews the advantages and disadvantages of medications and other substances employed to promote improved sleep. Special emphasis is given to the use of the newer-generation benzodiazepine receptor agonist hypnotics. PMID:14626538

  6. Childhood depression: pharmacological therapy/treatment (pharmacotherapy of childhood depression).

    PubMed

    Wagner, K D; Ambrosini, P J

    2001-03-01

    Critiqued the published double-blind, placebo-controlled studies of antidepressant pharmacotherapy in child and adolescent major depressive disorder to assess their overall efficacy. The pharmacological mechanism of antidepressant action also was discussed. At best, antidepressant treatment for depressed youths is only modestly effective. In particular, the tricyclic antidepressants are not superior to placebo; however, early evidence with the selective serotonin reuptake inhibitors is more encouraging. The theoretical basis for this response pattern is discussed from a methodological perspective, from a neurodevelopmental status, and from a biological viewpoint. Study modifications are suggested which could improve some of the methodological limitations apparent in previous clinical drug trials. PMID:11294082

  7. Cardiac Remodeling: Concepts, Clinical Impact, Pathophysiological Mechanisms and Pharmacologic Treatment

    PubMed Central

    Azevedo, Paula S.; Polegato, Bertha F.; Minicucci, Marcos F.; Paiva, Sergio A. R.; Zornoff, Leonardo A. M.

    2016-01-01

    Cardiac remodeling is defined as a group of molecular, cellular and interstitial changes that manifest clinically as changes in size, mass, geometry and function of the heart after injury. The process results in poor prognosis because of its association with ventricular dysfunction and malignant arrhythmias. Here, we discuss the concepts and clinical implications of cardiac remodeling, and the pathophysiological role of different factors, including cell death, energy metabolism, oxidative stress, inflammation, collagen, contractile proteins, calcium transport, geometry and neurohormonal activation. Finally, the article describes the pharmacological treatment of cardiac remodeling, which can be divided into three different stages of strategies: consolidated, promising and potential strategies. PMID:26647721

  8. Adding a treatment arm to an ongoing clinical trial: a review of methodology and practice.

    PubMed

    Cohen, Dena R; Todd, Susan; Gregory, Walter M; Brown, Julia M

    2015-01-01

    Incorporating an emerging therapy as a new randomisation arm in a clinical trial that is open to recruitment would be desirable to researchers, regulators and patients to ensure that the trial remains current, new treatments are evaluated as quickly as possible, and the time and cost for determining optimal therapies is minimised. It may take many years to run a clinical trial from concept to reporting within a rapidly changing drug development environment; hence, in order for trials to be most useful to inform policy and practice, it is advantageous for them to be able to adapt to emerging therapeutic developments. This paper reports a comprehensive literature review on methodologies for, and practical examples of, amending an ongoing clinical trial by adding a new treatment arm. Relevant methodological literature describing statistical considerations required when making this specific type of amendment is identified, and the key statistical concepts when planning the addition of a new treatment arm are extracted, assessed and summarised. For completeness, this includes an assessment of statistical recommendations within general adaptive design guidance documents. Examples of confirmatory ongoing trials designed within the frequentist framework that have added an arm in practice are reported; and the details of the amendment are reviewed. An assessment is made as to how well the relevant statistical considerations were addressed in practice, and the related implications. The literature review confirmed that there is currently no clear methodological guidance on this topic, but that guidance would be advantageous to help this efficient design amendment to be used more frequently and appropriately in practice. Eight confirmatory trials were identified to have added a treatment arm, suggesting that trials can benefit from this amendment and that it can be practically feasible; however, the trials were not always able to address the key statistical considerations

  9. [Statement about diagnosis assessment ano non pharmacological treatment of obesity].

    PubMed

    Manrique E, Mónica; de la Maza, María Pía; Carrasco, Fernando; Moreno, Manuel; Albala, Cecilia; García, Jaime; Díaz, Jaime; Liberman, Claudio

    2009-07-01

    The risk of complications of obesity is proportional to body mass index and is higher in severe or morbid obesities and when abdominal or visceral fat is predominant. In Chile the prevalence of obesity is increasing. According to the World Health Organization, obese subjects must reduce at least a 5% of their weight to reduce the risk of complications. Although this amount of reduction is seldom achieved with non pharmacological treatments, better results are obtained with multidisciplinary/ approaches that include a medical, psychosocial and laboratory assessment, to determine obesity level and different factors involved and the associated complications. In a second stage, goals of treatment are set and a personalized treatment is designed including dietary changes and physical activity. The aim is to obtain perdurable lifestyles modifications. PMID:19802427

  10. Use of quantitative pharmacology tools to improve malaria treatments.

    PubMed

    Davis, Timothy M E; Moore, Brioni R; Salman, Sam; Page-Sharp, Madhu; Batty, Kevin T; Manning, Laurens

    2016-01-01

    The use of pharmacokinetic (PK) and pharmacodynamic (PD) data to inform antimalarial treatment regimens has accelerated in the past few decades, due in no small part to the stimulus provided by progressive development of parasite resistance to most of the currently available drugs. An understanding of the disposition, interactions, efficacy and toxicity of the mainstay of contemporary antimalarial treatment, artemisinin combination therapy (ACT), has been facilitated by PK/PD studies which have been used to refine treatment regimens across the spectrum of disease, especially in special groups including young children and pregnant women. The present review highlights recent clinically-important examples of the ways in which these quantitative pharmacology tools have been applied to improve ACT, as well as 8-aminoquinoline use and the characterisation of novel antimalarial therapies such as the spiroindolones. PMID:26652110

  11. The evidence-based pharmacological treatment of social anxiety disorder.

    PubMed

    Blanco, Carlos; Raza, Muhammad S; Schneier, Franklin R; Liebowitz, Michael R

    2003-12-01

    Social anxiety disorder (SAD) is a highly prevalent and often disabling disorder. This paper reviews the pharmacological treatment of SAD based on published placebo-controlled studies and published meta-analyses. It addresses three specific questions: What is the first-line treatment of SAD? How long should treatment last? What should be the management of treatment-resistant cases? Based on their efficacy for SAD and common comorbid disorders, tolerability, and safety, SSRIs should be considered as the first-line treatment for most patients. Less information is available regarding the optimal length of treatment, although individuals who discontinue treatment after 12-20 wk appear more likely to relapse than those who continue on medication. Even less empirical evidence is available to support strategies for treatment-resistant cases. Clinical experience suggests that SSRI non-responders may benefit from augmentation with benzodiazepines or gabapentin, or from switching to MAOIs, RIMAs, benzodiazepines or gabapentin. Cognitive-behavioural therapy may also be a helpful adjunct or alternative. PMID:14609440

  12. Pharmacologic Treatment for Pediatric Gastroparesis: A Review of the Literature.

    PubMed

    Tillman, Emma M; Smetana, Keaton S; Bantu, Likeselam; Buckley, Merrion G

    2016-01-01

    There have been a number of agents that have been tried for treatment of gastroparesis over the past 3 decades, with varying levels of success. Guidelines exist for the management of gastroparesis in adults; however, even though the cause of gastroparesis in children is similar to that in adults, no guidelines exist for treating pediatric gastroparesis as studies on the topic are limited. With what little information we have on pediatric gastroparesis, medications used in children's studies do not seem to demonstrate the same results as in adult patients with gastroparesis; thus, future studies of whether certain medications are effective for treating pediatric gastroparesis and at what dose still need to be conducted. Pharmacological treatment options for pediatric gastroparesis do not show a clear correlation of resolving or even maintaining gastroparesis-associated symptoms or disease state. This article reviews the available studies of drugs that have shown some efficacy, with an emphasis on pediatric studies. PMID:27199619

  13. Non-pharmacologic treatment of insomnia in persons with dementia.

    PubMed

    Shub, Denis; Darvishi, Roham; Kunik, Mark E

    2009-02-01

    The prevalence of insomnia increases with age and affects up to 35% of community-dwelling adults with dementia. Sleep disturbances and associated cognitive and behavioral symptoms in this patient population can be a significant contributor to morbidity, mortality, and caregiver burden. Despite the frequency with which sleep disorders are encountered in primary care, few evidence-based guidelines are available to guide physician treatment plans. Sedative-hypnotic medications are commonly prescribed but are associated with significant adverse effects and have limited efficacy data. Non-pharmacologic treatments can be safe and effective adjuncts or alternatives to medications but are often underused in clinical practice. This article reviews practical applications of modalities such as light therapy, exercise, and sleep-hygiene modification in treating insomnia in persons with dementia. PMID:19256583

  14. Pharmacologic Treatment for Pediatric Gastroparesis: A Review of the Literature

    PubMed Central

    Smetana, Keaton S.; Bantu, Likeselam; Buckley, Merrion G.

    2016-01-01

    There have been a number of agents that have been tried for treatment of gastroparesis over the past 3 decades, with varying levels of success. Guidelines exist for the management of gastroparesis in adults; however, even though the cause of gastroparesis in children is similar to that in adults, no guidelines exist for treating pediatric gastroparesis as studies on the topic are limited. With what little information we have on pediatric gastroparesis, medications used in children's studies do not seem to demonstrate the same results as in adult patients with gastroparesis; thus, future studies of whether certain medications are effective for treating pediatric gastroparesis and at what dose still need to be conducted. Pharmacological treatment options for pediatric gastroparesis do not show a clear correlation of resolving or even maintaining gastroparesis-associated symptoms or disease state. This article reviews the available studies of drugs that have shown some efficacy, with an emphasis on pediatric studies. PMID:27199619

  15. [Indications and future perspectives in the pharmacological treatment of hypercortisolism].

    PubMed

    Stigliano, Antonio; Toscano, Vincenzo

    2016-03-01

    The hypercortisolism is a rare endocrine disease characterized by an autonomous steroid secretion or excessive adrenal stimulation by ACTH. the Surgical removal of the lesion directly responsible hypercortisolism represents the treatment of choice. When neurosurgery for pituitary adenoma is contraindicated, radiotherapy is candidate as the second line of therapy. Currently, the recent advances in medical therapy provide a viable alternative to surgery and radiotherapy, when these are not feasible or followed by relapses (present in more than one third of cases) of the underlying disease. Recently, also in Italy, are available pharmacological agents with central activity (pasireotide) specifically indicated for treating Cushing's disease together with peripherally acting drugs (metyrapone and ketoconazole) that are used in a broader spectrum of hypercortisolemic clinical pictures. In addition, drugs active in the inhibition of steroidogenesis provide a valid support to the patient's surgical preparation allowing the reduction or normalization of plasma cortisol levels. PMID:27030224

  16. Current challenges and pitfalls in the pharmacological treatment of depression

    PubMed Central

    Popa-Velea, O; Gheorghe, IR; Truţescu, CI; Purcărea, VL

    2015-01-01

    The multifactorial etiology of depression obliges needs an individual assessment, the psychopharmacological approach involving a biopsychosocial analysis for each individual case. The rebalancing of the depressive patient, seen as a return to a normal level of psychosocial functioning and reduced risk of relapse is achieved with a prompt and constant support of specialized teams. Treatment should include psychopharmacological and psychosocial approaches, the results being interrelated and contributing to the prognosis of the disorder. Progress in clinical and pharmacological research, vivid dynamics of socio-economic environment, the complexity of diagnostic evaluation and the need for an interdisciplinary approach may cause difficulties in addressing the depressive patient and the ethical controversies. The aim of this paper is to present a brief analysis of challenges encountered in the present psychiatric practice, starting from the heterogeneity of depressive manifestations and finishing with the prioritization of interventional forms. PMID:25866576

  17. Alternative pharmacological strategies for adult ADHD treatment: a systematic review.

    PubMed

    Buoli, Massimiliano; Serati, Marta; Cahn, Wiepke

    2016-01-01

    Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard pharmacotherapy (methylphenidate and atomoxetine) improves ADHD symptoms in the short-term, but poor data were published about long-term treatment. In addition a number of patients present partial or no response to methylphenidate and atomoxetine. Research into the main database sources has been conducted to obtain an overview of alternative pharmacological approaches in adult ADHD patients. Among alternative compounds, amphetamines (mixed amphetamine salts and lisdexamfetamine) have the most robust evidence of efficacy, but they may be associated with serious side effects (e.g. psychotic symptoms or hypertension). Antidepressants, particularly those acting as noradrenaline or dopamine enhancers, have evidence of efficacy, but they should be avoided in patients with comorbid bipolar disorder. Finally metadoxine and lithium may be particularly suitable in case of comorbid alcohol misuse or bipolar disorder. PMID:26693882

  18. Current challenges and pitfalls in the pharmacological treatment of depression.

    PubMed

    Popa-Velea, O; Gheorghe, I R; Truţescu, C I; Purcărea, V L

    2015-01-01

    The multifactorial etiology of depression obliges needs an individual assessment, the psychopharmacological approach involving a biopsychosocial analysis for each individual case. The rebalancing of the depressive patient, seen as a return to a normal level of psychosocial functioning and reduced risk of relapse is achieved with a prompt and constant support of specialized teams. Treatment should include psychopharmacological and psychosocial approaches, the results being interrelated and contributing to the prognosis of the disorder. Progress in clinical and pharmacological research, vivid dynamics of socio-economic environment, the complexity of diagnostic evaluation and the need for an interdisciplinary approach may cause difficulties in addressing the depressive patient and the ethical controversies. The aim of this paper is to present a brief analysis of challenges encountered in the present psychiatric practice, starting from the heterogeneity of depressive manifestations and finishing with the prioritization of interventional forms. PMID:25866576

  19. Optimal Pharmacologic Treatment Strategies in Obesity and Type 2 Diabetes

    PubMed Central

    Goswami, Gayotri; Shinkazh, Nataliya; Davis, Nichola

    2014-01-01

    The prevalence of obesity has increased to pandemic levels worldwide and is related to increased risk of morbidity and mortality. Metabolic comorbidities are commonly associated with obesity and include metabolic syndrome, pre-diabetes, and type 2 diabetes. Even if the prevalence of obesity remains stable until 2030, the anticipated numbers of people with diabetes will more than double as a consequence of population aging and urbanization. Weight reduction is integral in the prevention of diabetes among obese adults with pre-diabetes. Lifestyle intervention and weight reduction are also key in the management of type 2 diabetes. Weight loss is challenging for most obese patients, but for those with diabetes, it can pose an even greater challenge due to the weight gain associated with many treatment regimens. This article will review optimal treatment strategies for patients with comorbid obesity and type 2 diabetes. The role of anti-obesity agents in diabetes will also be reviewed. This literature review will provide readers with current strategies for the pharmacologic treatment of obesity and diabetes with a focus on the weight outcomes related to diabetes treatments. PMID:26237392

  20. Treatment Approaches for Self-Injurious Behavior in Individuals with Autism: Behavioral and Pharmacological Methods

    ERIC Educational Resources Information Center

    Mahatmya, Duhita; Zobel, Alicia; Valdovinos, Maria G.

    2008-01-01

    This paper reviews behavioral and pharmacological approaches to the treatment of self-injurious behavior in autism. Both behavioral and pharmacological approaches offer a multitude of treatment options which we hope to elucidate. In providing this review, the goal is to provide an awareness of the treatment options available and to prompt further…

  1. Pharmacology of opioids in the treatment of chronic pain syndromes.

    PubMed

    Vallejo, Ricardo; Barkin, Robert L; Wang, Victor C

    2011-01-01

    The perpetual pursuit of pain elimination has been constant throughout human history and pervades human cultures. In some ways it is as old as medicine itself. Cultures throughout history have practiced the art of pain management through remedies such as oral ingestion of herbs or techniques believed to have special properties. In fact, even Hippocrates wrote about the practice of trepanation, the cutting of holes in the body to release pain. Current therapies for management of pain include the pervasive utilization of opioids, which have an extensive history, spanning centuries. There is general agreement about the appropriateness of opioids for the treatment of acute and cancer pain, but the long-term use of these drugs for treatment of chronic non-malignant pain remains controversial. The pros and cons regarding these issues are beyond the scope of this review. Instead, the purpose of this review will be directed towards the pharmacology of commonly prescribed opioids in the treatment of various chronic pain syndromes. Opium, derived from the Greek word for "juice," is extracted from the latex sap of the opium poppy (Papaverum somniferum). The juice of the poppy is the source of some 20 different alkaloids of opium. These alkaloids of opioids can be divided into 2 chemical classes: phenanthrenes (morphine, codeine, and thebaine) and benzylisoquinolines (agents that do not interact with opioid receptors). PMID:21785485

  2. Suppression of ongoing experimental myasthenia by oral treatment with an acetylcholine receptor recombinant fragment

    PubMed Central

    Im, Sin-Hyeog; Barchan, Dora; Fuchs, Sara; Souroujon, Miriam C.

    1999-01-01

    Myasthenia gravis (MG) is an autoimmune disorder in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. In an attempt to develop an antigen-specific therapy for MG, we administered a nonmyasthenogenic recombinant fragment of AChR orally to rats. This fragment, corresponding to the extracellular domain of the human AChR α-subunit (Hα1-205), protected rats from subsequently induced experimental autoimmune myasthenia gravis (EAMG) and suppressed ongoing EAMG when treatment was initiated during either the acute or chronic phases of disease. Prevention and suppression of EAMG were accompanied by a significant decrease in AChR-specific humoral and cellular responses. The underlying mechanism for the Hα1-205–induced oral tolerance seems to be active suppression, mediated by a shift from a T-helper 1 (Th1) to a Th2/Th3 response. This shift was assessed by changes in the cytokine profile, a deviation of anti-AChR IgG isotypes from IgG2 to IgG1, and a suppressed AChR-specific delayed-type hypersensitivity response. Our results in experimental myasthenia suggest that oral administration of AChR-specific recombinant fragments may be considered for antigen-specific immunotherapy of myasthenia gravis. J. Clin. Invest. 104:1723–1730 (1999). PMID:10606626

  3. Suppression of ongoing experimental myasthenia by oral treatment with an acetylcholine receptor recombinant fragment.

    PubMed

    Im, S H; Barchan, D; Fuchs, S; Souroujon, M C

    1999-12-01

    Myasthenia gravis (MG) is an autoimmune disorder in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. In an attempt to develop an antigen-specific therapy for MG, we administered a nonmyasthenogenic recombinant fragment of AChR orally to rats. This fragment, corresponding to the extracellular domain of the human AChR alpha-subunit (Halpha1-205), protected rats from subsequently induced experimental autoimmune myasthenia gravis (EAMG) and suppressed ongoing EAMG when treatment was initiated during either the acute or chronic phases of disease. Prevention and suppression of EAMG were accompanied by a significant decrease in AChR-specific humoral and cellular responses. The underlying mechanism for the Halpha1-205-induced oral tolerance seems to be active suppression, mediated by a shift from a T-helper 1 (Th1) to a Th2/Th3 response. This shift was assessed by changes in the cytokine profile, a deviation of anti-AChR IgG isotypes from IgG2 to IgG1, and a suppressed AChR-specific delayed-type hypersensitivity response. Our results in experimental myasthenia suggest that oral administration of AChR-specific recombinant fragments may be considered for antigen-specific immunotherapy of myasthenia gravis. PMID:10606626

  4. Treatment of schizophrenia and comorbid substance abuse: pharmacologic approaches.

    PubMed

    Green, Alan I

    2006-01-01

    Co-occurring substance use disorder is common among patients with schizophrenia, and its presence greatly worsens the course of schizophrenia. A number of theories have been introduced to explain the increased rate of substance use disorder in these patients. These theories include the notion that substance use could trigger psychotic symptoms in vulnerable individuals and the idea that the substances are used to self-medicate symptoms of schizophrenia. Our group and others have advanced a neurobiological hypothesis to explain this comorbidity-that a mesocorticolimbic brain reward circuit underlies the substance use disorder in patients with schizophrenia. Treatment of substance use disorder in these patients is best done with integrated treatment programs that combine psychosocial interventions with pharmacotherapy. Recent data suggest that the atypical antipsychotic clozapine and perhaps other atypical agents may lessen substance use in patients with schizophrenia. My colleagues and I have proposed that clozapine's effect in these patients may be related to its ability to decrease the brain reward circuit dysfunction. Research is continuing on the use of atypical antipsychotics in patients with schizophrenia and comorbid substance abuse. The adjunctive use of naltrexone or other agents also may be helpful. Further research on the optimal pharmacologic approach to patients with dual diagnosis is needed. PMID:16961422

  5. Non-pharmacological approaches to the treatment of narcolepsy.

    PubMed

    Garma, L; Marchand, F

    1994-12-01

    A way of evaluating the part played by non-drug treatments is to study cases of patients who discontinued stimulant medications but still came back for follow-up visits. Out of 40 patients with narcolepsy-cataplexy, three refused medication because their work was compatible with a regimen of naps (follow-up 1 year), and 10 stopped taking drugs when they could adapt nap therapy to a new life-style (follow-up 6.9 +/- 5 years). Three interrelated levels of non-pharmacological treatments of narcolepsy were examined: 1) Behavioral management, which includes: (A) structured sleep schedules: literature shows that a single long afternoon nap proffered greatest performance benefits in reaction time, significantly increased over a no-nap control condition, with no evidence of sleep inertia. The placement of this nap might yield better results if scheduled 1 hour before that of a normal subject. (B) Dietary factors: little is known about the effects of diet in narcoleptics; however, avoiding simple sugars will improve alertness in some patients. 2) Medical and psychiatric aspects of care. 3) Social factors as an interface between the patients and their environment. PMID:7701208

  6. Update on the Pharmacological Treatment of Alzheimer’s Disease

    PubMed Central

    Massoud, Fadi; Gauthier, Serge

    2010-01-01

    Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Worldwide prevalence of the disease is estimated at more than 24 million cases. With aging of populations, this number will likely increase to more than 80 million cases by the year 2040. The annual incidence worldwide is estimated at 4.6 million cases which is the equivalent of one new case every seven seconds! The pathophysiology of AD is complex and largely misunderstood. It is thought to start with the accumulation of beta-amyloid (Aβ) that leads to deposition of insoluble neuritic or senile plaques. Secondary events in this “amyloid cascade” include hyperphosphorylation of the protein tau into neurofibrillary tangles, inflammation, oxidation, and excitotoxicity that eventually cause activation of apoptotis, cell death and neurotransmitter deficits. This review will briefly summarize recent advances in the pathophysiology of AD and focus on the pharmacological treatment of the cognitive and functional symptoms of AD. It will discuss the roles of vascular prevention, cholinesterase inhibitors and an NMDA-antagonist in the management of AD. It will address the issues thought to be related to the lack of persistence or discontinuation of therapy with cholinesterase inhibitors shown in recent studies and some of the solutions proposed. These include setting realistic expectations in light of a neurodegenerative condition and available symptomatic treatments, slowly titrating medications, and using alternate routes of administration. Finally, it will introduce future therapeutic options currently under study. PMID:20808547

  7. Recent advances in pharmacological treatment of irritable bowel syndrome

    PubMed Central

    Lazaraki, Georgia; Chatzimavroudis, Grigoris; Katsinelos, Panagiotis

    2014-01-01

    Irritable bowel syndrome (IBS) is a highly prevalent functional disorder that reduces patients’ quality of life. It is a chronic disorder characterized by abdominal pain or discomfort associated with disordered defecation in the absence of identifiable structural or biochemical abnormalities. IBS imposes a significant economic burden to the healthcare system. Alteration in neurohumoral mechanisms and psychological factors, bacterial overgrowth, genetic factors, gut motility, visceral hypersensitivity, and immune system factors are currently believed to influence the pathogenesis of IBS. It is possible that there is an interaction of one or more of these etiologic factors leading to heterogeneous symptoms of IBS. IBS treatment is predicated upon the patient’s most bothersome symptoms. Despite the wide range of medications and the high prevalence of the disease, to date no completely effective remedy is available. This article reviews the literature from January 2008 to July 2013 on the subject of IBS peripherally acting pharmacological treatment. Drugs are categorized according to their administration for IBS-C, IBS-D or abdominal pain predominant IBS. PMID:25083060

  8. Pharmacological treatment of acute migraine in adolescents and children.

    PubMed

    Wöber-Bingöl, Çiçek

    2013-06-01

    Migraine is a common disease in children and adolescents. The incidence of migraine has increased alarmingly in the general population during recent decades. Migraine causes considerable individual suffering and impaired quality of life. Therefore, appropriate management is essential. In this article, the treatment of acute migraine in children and adolescents will be reviewed. Only a few randomized controlled studies have been published and high placebo rates are a major problem for proving superiority of active drugs. Generally, acetaminophen (paracetamol) and ibuprofen are accepted as drugs of first choice, even though the evidence is poor for the former and limited for latter. Among 14 studies on triptans in adolescents, 9 showed some superiority over placebo with respect to pain relief and pain freedom, and among 6 studies in children, 5 suggest some superiority over placebo. Sumatriptan nasal spray and zolmitriptan nasal spray have been approved for adolescents in Europe; almotriptan has been approved for adolescents in the USA, as has rizatriptan for patients aged 6-17 years. A recent study demonstrated the efficacy of a fixed combination of sumatriptan and naproxen in adolescents with migraine. In conclusion, evidence for the pharmacological treatment of acute migraine in children is very poor and evidence for adolescents is better but still limited. PMID:23575981

  9. Pharmacologic approaches to treatment resistant depression: Evidences and personal experience

    PubMed Central

    Tundo, Antonio; de Filippis, Rocco; Proietti, Luca

    2015-01-01

    AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression (TRD) and to discuss them according to personal clinical experience. METHODS: Original studies, clinical trials, systematic reviews, and meta-analyses addressing pharmacological treatment for TRD in adult patients published from 1990 to 2013 were identified by data base queries (PubMed, Google Scholar e Quertle Searches) using terms: “treatment resistant depression”, “treatment refractory depression”, “partial response depression”, “non responder depression”, “optimization strategy”, “switching strategy”, “combination strategy”, “augmentation strategy”, selective serotonin reuptake inhibitors antidepressants (SSRI), tricyclic antidepressants (TCA), serotonin norepinephrine reuptake inhibitors antidepressants, mirtazapine, mianserine, bupropione, monoamine oxidase inhibitor antidepressant (MAOI), lithium, thyroid hormones, second generation antipsychotics (SGA), dopamine agonists, lamotrigine, psychostimulants, dextromethorphan, dextrorphan, ketamine, omega-3 fatty acids, S-adenosil-L-metionine, methylfolat, pindolol, sex steroids, glucocorticoid agents. Other citations of interest were further identified from references reported in the accessed articles. Selected publications were grouped by treatment strategy: (1) switching from an ineffective antidepressant (AD) to a new AD from a similar or different class; (2) combining the current AD regimen with a second AD from a different class; and (3) augmenting the current AD regimen with a second agent not thought to be an antidepressant itself. RESULTS: Switching from a TCA to another TCA provides only a modest advantage (response rate 9%-27%), while switching from a SSRI to another SSRI is more advantageous (response rate up to 75%). Evidence supports the usefulness of switching from SSRI to venlafaxine (5 positive trials out 6), TCA (2 positive trials out 3), and MAOI (2 positive trials out

  10. Fish oil–based lipid emulsions in the treatment of parenteral nutrition-associated liver disease: An ongoing positive experience

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously reported the beneficial effect of fish oil-based lipid emulsions (FOLEs) as monotherapy in the treatment of parenteral nutrition-associated liver disease (PNALD). In this report, we share our ongoing experience at Texas Children's Hospital, Houston, in the use of FOLE in treatment of P...

  11. Non-pharmacological medical treatment in pediatric epilepsies.

    PubMed

    Auvin, S

    2016-03-01

    The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet that has been employed as a non-pharmacologic therapy for refractory epilepsy. Several multicenter and two randomized studies have demonstrated the efficacy of the ketogenic diet and the modified Atkins diet for children and adolescent with pharmacoresitant epilepsy. In order to facilitate patient tolerability and palatability, the diet protocols are gradually modified including changes in ratios of the fat versus non-fat components and the initiation of the diet with or without fasting. The modified Atkins diet is now used as an alternative diet. A randomized trial establishing the efficacy of the modified Atkins diet is now available. More recently, the low glycemic index diet seems to be used successfully for pharmacoresistant epilepsy but there are currently only open studies. Looking at the clinical efficacy of dietary treatments, the studies usually report a greater than 50% reduction in seizure frequency in about half of patients at 3 months under diet. Most of the patients who are responders to the ketogenic diet exhibited a decrease in seizure frequency within two months of treatment onset. Efficacy of the ketogenic diet has also been reported for teenager and adult patients. Dietary treatment of epilepsy should not be considered as a last chance treatment. It can be used during the investigation for epilepsy surgery even in case of structural abnormalities. In some epilepsy syndromes such as infantile spasms, myoclonic-astatic epilepsy and refractory status epilepticus, an early use seems helpful. The exact underlying mechanisms are unknown and remain a topic of active research. PMID:26993568

  12. New pharmacologic horizons in the treatment of Parkinson disease.

    PubMed

    Bonuccelli, Ubaldo; Del Dotto, Paolo

    2006-10-10

    Many of the motoric features that define Parkinson's disease (PD) result primarily from the loss of dopaminergic neurons of the substantia nigra. l-dopa remains at present the most powerful symptomatic drug for the treatment of this condition. However, motor complications of chronic l-dopa treatment have emerged as a major limitation of this therapy. Slowing or delaying the progression of the disease with neuroprotective therapies may delay the need for l-dopa. In the past few years, novel insight into the pathogenetic mechanisms of neurodegeneration in PD has been provided. Mitochondrial function deficiency, increased oxidative stress, apoptosis, excitotoxicity, and inflammation are part of the processes that ultimately result in neurodegeneration. Drugs that are now under clinical scrutiny as neuroprotectant include molecules that combine one or more of the following properties: (1) monoamine oxidase inhibition (rasagiline, safinamide); (2) mitochondrial enhancement (coenzyme Q10, creatine); (3) antiapoptotic activity; (4) anti-inflammatory activity; (5) protein aggregation inhibition; (6) neurotrophic activity. In advanced Parkinson's disease, the combination of disease progression and l-dopa therapy leads to the development of motor response complications, particularly wearing off, on off, dyskinesias and dystonias. The nonphysiologic pulsatile stimulation of striatal dopamine receptors, produced by the currently available dopaminergic drugs, may trigger a dysregulation of many neurotransmitter systems within the basal ganglia, mainly localized on medium spiny striatal neurons. These include alterations of glutamatergic, serotonergic, adrenergic and adenosine A(2A) receptors. Novel strategies for pharmacological intervention with nondopaminergic treatments hold the promise of providing effective control or reversal of motor response complications. Of particular interest are NMDA and AMPA antagonists or drugs acting on 5-HT subtype 2A, alpha2-adrenergic, and

  13. Lithium in the treatment of bipolar disorder: pharmacology and pharmacogenetics.

    PubMed

    Alda, M

    2015-06-01

    After decades of research, the mechanism of action of lithium in preventing recurrences of bipolar disorder remains only partially understood. Lithium research is complicated by the absence of suitable animal models of bipolar disorder and by having to rely on in vitro studies of peripheral tissues. A number of distinct hypotheses emerged over the years, but none has been conclusively supported or rejected. The common theme emerging from pharmacological and genetic studies is that lithium affects multiple steps in cellular signaling, usually enhancing basal and inhibiting stimulated activities. Some of the key nodes of these regulatory networks include GSK3 (glycogen synthase kinase 3), CREB (cAMP response element-binding protein) and Na(+)-K(+) ATPase. Genetic and pharmacogenetic studies are starting to generate promising findings, but remain limited by small sample sizes. As full responders to lithium seem to represent a unique clinical population, there is inherent value and need for studies of lithium responders. Such studies will be an opportunity to uncover specific effects of lithium in those individuals who clearly benefit from the treatment. PMID:25687772

  14. Emerging pharmacologic treatment options for fragile X syndrome

    PubMed Central

    Schaefer, Tori L; Davenport, Matthew H; Erickson, Craig A

    2015-01-01

    Fragile X syndrome (FXS) is the most common single gene cause of intellectual disability and autism spectrum disorder. Caused by a silenced fragile X mental retardation 1 gene and the subsequent deficiency in fragile X mental retardation protein, patients with FXS experience a range of physical, behavioral, and intellectual debilitations. The FXS field, as a whole, has recently met with some challenges, as several targeted clinical trials with high expectations of success have failed to elucidate significant improvements in a variety of symptom domains. As new clinical trials in FXS are planned, there has been much discussion about the use of the commonly used clinical outcome measures, as well as study design considerations, patient stratification, and optimal age range for treatment. The evidence that modification of these drug targets and use of these failed compounds would prove to be efficacious in human clinical study were rooted in years of basic and translational research. There are questions arising as to the use of the mouse models for studying FXS treatment development. This issue is twofold: many of the symptom domains and molecular and biochemical changes assessed and indicative of efficacy in mouse model study are not easily amenable to clinical trials in people with FXS because of the intolerability of the testing paradigm or a lack of noninvasive techniques (prepulse inhibition, sensory hypersensitivity, startle reactivity, or electrophysiologic, biochemical, or structural changes in the brain); and capturing subtle yet meaningful changes in symptom domains such as sociability, anxiety, and hyperactivity in human FXS clinical trials is challenging with the currently used measures (typically parent/caregiver rating scales). Clinicians, researchers, and the pharmaceutical industry have all had to take a step back and critically evaluate the way we think about how to best optimize future investigations into pharmacologic FXS treatments. As new clinical

  15. Pharmacologic Treatment of Dimensional Anxious Depression: A Review

    PubMed Central

    Niciu, Mark J.; Richards, Erica M.; Zarate, Carlos A.

    2014-01-01

    Objective: To review the pharmacologic treatment of dimensionally defined anxious depression. Data Sources: English-language, adult human research articles published between 1949 and February 2013 were identified via PUBMED and EMBASE. The search term was treatment of anxious depression. Study Selection: We identified and reviewed 304 original articles. Of these, 31 studies of patients with anxious depression, who were treated with an antidepressant or antipsychotic, are included in this review. Data Extraction: All studies explicitly used a dimensional definition of anxious depression. All patients were treated with either antidepressants or antipsychotic medications. Results: Of the 31 relevant psychopharmacologic studies identified, 7 examined patients receiving only 1 medication, 2 studied cotherapeutic strategies, 1 examined antipsychotic augmentation, and 21 compared multiple medications. Eleven were pooled analyses from several studies. All studies were of adults (18–92 years old). The Hamilton Depression Rating Scale Anxiety/Somatization Factor Score was used to define anxious depression in 71% of the studies, and 77.4% were post hoc analyses of previous datasets. Seventeen studies found selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and/or tricyclic antidepressants (TCAs) to be useful for successfully treating anxious depression. However, patients with anxious depression were less likely to experience sustained response or remission. Furthermore, baseline anxious depression puts patients at greater risk for side effect burden. Conclusions: Despite achieving response with SSRIs, SNRIs, and TCAs, patients with dimensionally defined anxious depression do not maintain response or remission and often report a larger burden of side effects compared to nonanxious depressive patients, suggesting that it is a harder-to-treat subtype of major depressive disorder. PMID:25317369

  16. Children with schizophrenia: clinical picture and pharmacological treatment.

    PubMed

    Masi, Gabriele; Mucci, Maria; Pari, Cinzia

    2006-01-01

    these clinical patterns, such as multidimensionally impaired disorder and multiple complex developmental disorder. In the context of a multimodal approach, including behavioral, social, scholastic and familial interventions, a pharmacological treatment is usually the core treatment. Available experience from the few controlled studies, open studies and case reports on pharmacotherapy in children with schizophrenia aged <12 years is critically analysed in this review, with particular reference to the use of atypical antipsychotics in clinical practice. To date, the major evidence supports the efficacy of risperidone and olanzapine, while clozapine seems an effective option in treatment-refractory cases. Published experience with newer atypical antipsychotics (quetiapine, ziprasidone, aripiprazole) is still lacking in this age range. Safety data (namely extrapyramidal symptoms, weight gain, hyperprolactinaemia, haematological adverse effects, seizures, hepatotoxicity, metabolic effects, neuroleptic malignant syndrome and cardiovascular effects) are reviewed and discussed, along with strategies for management. PMID:16999454

  17. The effect of pharmacological treatment on gait biomechanics in peripheral arterial disease patients

    PubMed Central

    2010-01-01

    Background Pharmacological treatment has been advocated as a first line therapy for Peripheral Arterial Disease (PAD) patients suffering from intermittent claudication. Previous studies document the ability of pharmacological treatment to increase walking distances. However, the effect of pharmacological treatment on gait biomechanics in PAD patients has not been objectively evaluated as is common with other gait abnormalities. Methods Sixteen patients were prescribed an FDA approved drug (Pentoxifylline or Cilostazol) for the treatment of symptomatic PAD. Patients underwent baseline gait testing prior to medication use which consisted of acquisition of ground reaction forces and kinematics while walking in a pain free state. After three months of treatment, patients underwent repeat gait testing. Results Patients with symptomatic PAD had significant gait abnormalities at baseline during pain free walking as compared to healthy controls. However, pharmacological treatment did not produce any identifiable alterations on the biomechanics of gait of the PAD patients as revealed by the statistical comparisons performed between pre and post-treatment and between post-treatment and the healthy controls. Conclusions Pharmacological treatment did not result in statistically significant improvements in the gait biomechanics of patients with symptomatic PAD. Future studies will need to further explore different cohorts of patients that have shown to improve significantly their claudication distances and/or their muscle fiber morphology with the use of pharmacological treatment and determine if this is associated with an improvement in gait biomechanics. Using these methods we may distinguish the patients who benefit from pharmacotherapy and those who do not. PMID:20529284

  18. Pharmacologic and surgical treatment of dyslipidemic children and adolescents.

    PubMed

    Hoeg, J M

    1991-01-01

    A wide variety of treatment modalities have been used in children with dyslipidemias to reduce the concentrations of atherogenic lipoprotein particles. Most of the published experience has focused upon children with familial hypercholesterolemia (FH). A variety of pharmacologic regimens have been utilized with variable degrees of success. The bile acid sequestrants colestipol and cholestyramine, lovastatin, pantethine, paraminosalicylic acid, and fenofibrate have all been successful in reducing total blood cholesterol concentrations by 18-24% in hypercholesterolemic children. Of these medications, only the bile acid sequestrants are not absorbed into the circulation. This theoretic advantage is paralled by long-term safety studies which indicate the absence of serious adverse effects with bile acid sequestrant therapy. Therefore, the bile acid sequestrants represent the drugs of choice in treating severely dyslipidemic children. In selected cases of profoundly dyslipidemic children, other therapeutic strategies have been utilized. Most of these efforts have been directed in the treatment of the child homozygous for FH. Despite the lipid lowering effects of partial ileal bypass surgery in hypercholesterolemic adults, homozygous familial hypercholesterolemic children are not adequately treated by this approach. Portacaval shunt has reduced the total cholesterol concentrations by 20-35% in homozygous FH children without having a negative impact on growth and development. These children have, however, gone on to develop atherosclerotic cardiovascular disease despite therapy. Liver transplantation has led to virtual normalization of the plasma lipoprotein concentrations in 3 children homozygous for familial hypercholesterolemia, and there is evidence for regression of vascular lesions in the coronary arteries in one of these children. However, considering the expense, the difficulty in posttransplantation management, and the irreversible nature of the therapy, liver

  19. Prevention and treatment of traveler's diarrhea: a clinical pharmacological approach.

    PubMed

    Scarpignato, C; Rampal, P

    1995-01-01

    Diarrhea represents a major health problem for travelers to developing countries. Although the syndrome is usually self-limited and recovery occurs in the majority of cases without any specific form of therapy, there is a need for safe and effective ways of preventing and treating it. Since the syndrome is most often caused by an infection acquired by ingesting fecally contaminated food or beverages, precautions regarding dietary habits remain the cornerstone of prophylaxis, but dietary self-restrictions do not always translate to reduced rates of diarrheal illness. Administration of probiotics (e.g. lactobacilli or Saccharomyces boulardii) and immunoprophylaxis with the newer oral cholera vaccines have been tried with promising results. Antimicrobials remain, however, the most successful form of prophylaxis, being effective in up to 90% of travelers. For those with impaired health who will take prophylaxis, systemic agents with proved efficacy should be recommended. For other otherwise healthy persons, poorly absorbed agents are preferable in order to avoid the serious, albeit rare, toxicity of systemic drugs. The key factor in the management of acute watery traveler's diarrhea, particularly in infants and young children, is the restoration of water and electrolyte balance. This does not reduce the duration of the illness but will limit dehydration and prevent acidosis. Many patients will require no additional therapy, whereas some will need pharmacologic treatment to shorten the duration of diarrhea or to relieve the accompanying symptoms, like abdominal discomfort, nausea and vomiting. A typical 3- to 5-day illness can be reduced to approximately 1 day by trimethoprim-sulfamethoxazole (TMP-SMX) combination. Some other systemic antimicrobials have been successfully used but, during the last few years, the 4-fluoroquinolone drugs have received considerable attention and have been shown to be highly effective in reducing the duration of traveler's diarrhea. These

  20. Behavioral, Cognitive, and Pharmacological Treatments of Panic Disorder with Agoraphobia: Critique and Synthesis.

    ERIC Educational Resources Information Center

    Michelson, Larry K.; Marchione, Karen

    1991-01-01

    Examines theoretical, methodologic, and research issues as well as strengths, limitations, and possible interactions pertaining to behavioral, cognitive, and pharmacological treatments of panic disorder with agoraphobia. Compares attrition, outcome, and maintenance effects and presents composite indices of significant improvement, endstate…

  1. Soft tissue infection caused by Legionella bozemanii in a patient with ongoing immunosuppressive treatment

    PubMed Central

    Neiderud, Carl-Johan; Vidh, Angela Lagerqvist; Salaneck, Erik

    2013-01-01

    The Legionellaceae family consists of approximately 50 species, of which the most commonly identified species is L. pneumophila, the causative agent of Legionnaires’ disease. Other Legionella ssp. most often cause clinical infections in the immune-compromised patients, in which L. bozemanii has been known to cause both pneumonia and lung abscesses. In the presented case, a soft tissue infection in a patient with ongoing immunosuppression was determined to be due to L. bozemanii. Hence, in immune-deficient patients, L. bozemanii could be considered a possible agent in soft tissue infections when other common pathogens have been ruled out. PMID:24023988

  2. The effect of childhood trauma on pharmacological treatment response in depressed inpatients.

    PubMed

    Douglas, Katie M; Porter, Richard J

    2012-12-30

    Childhood trauma and its association with pharmacological treatment response were examined in depressed inpatients. Treatment non-responders (n=31) reported significantly more severe trauma than treatment responders (n=25) and healthy controls (n=49), suggesting that the experience of childhood trauma in those hospitalised with depression can be detrimental to treatment success. PMID:22770764

  3. More ubiquitous effects from non-pharmacologic than from pharmacologic treatments for fibromyalgia syndrome: a meta-analysis examining six core symptoms.

    PubMed

    Perrot, S; Russell, I J

    2014-09-01

    This study aimed to characterize and compare the efficacy profile on six fibromyalgia syndrome (FM) core symptoms associated with pharmacologic and non-pharmacologic treatments. We screened PubMed, Embase and the Cochrane Library for FM articles from 1990 to September 2012 to analyse randomized controlled trials comparing pharmacologic or non-pharmacologic treatments to placebo or sham. Papers including assessments of at least 2 of the 6 main FM symptom domains - pain, sleep disturbance, fatigue, affective symptoms (depression/anxiety), functional deficit and cognitive impairment - were selected for analysis. Studies exploring pharmacologic approaches (n = 21) were mainly dedicated to treating a small number of dimensions, mostly pain. They were of good quality but were not prospectively designed to simultaneously document efficacy for the management of multiple core FM symptom domains. Only amitriptyline demonstrated a significant effect on as many as three core FM symptoms, but it exhibited many adverse effects and was subject to early tachyphylaxis. Studies involving non-pharmacologic approaches (n = 64) were typically of poorer quality but were more often dedicated to multidimensional targets. Pool therapy demonstrated significant effects on five symptom domains, repetitive transcranial magnetic stimulation on four domains, balneotherapy on three domains and exercise, cognitive behaviour therapy and massage on two domains each. Differences between pharmacologic and non-pharmacologic approaches may be related to different modes of action, tolerability profiles and study designs. Very few drugs in well-designed clinical trials have demonstrated significant relief for multiple FM symptom domains, whereas non-pharmacologic treatments with weaker study designs have demonstrated multidimensional effects. Future therapeutic trials for FM should prospectively examine each of the core domains and should attempt to combine pharmacologic and non-pharmacologic

  4. Pharmacologic options for the treatment and management of food allergy.

    PubMed

    Kobernick, Aaron K; Chambliss, Jeffrey; Burks, A Wesley

    2015-01-01

    Food allergy affects approximately 5% of adults and 8% of children in developed countries, and there is currently no cure. Current pharmacologic management is limited to using intramuscular epinephrine or oral antihistamines in response to food allergen exposure. Recent trials have examined the efficacy and safety of subcutaneous, oral, sublingual, and epicutaneous immunotherapy, with varying levels of efficacy and safety demonstrated. Bacterial adjuvants, use of anti-IgE monoclonal antibodies, and Chinese herbal formulations represent exciting potential for development of future pharmacotherapeutic agents. Ultimately, immunotherapy may be a viable option for patients with food allergy, although efficacy and safety are likely to be less than ideal. PMID:26289224

  5. Treatment of ongoing autoimmune encephalomyelitis with activated B-cell progenitors maturing into regulatory B cells.

    PubMed

    Korniotis, Sarantis; Gras, Christophe; Letscher, Hélène; Montandon, Ruddy; Mégret, Jérôme; Siegert, Stefanie; Ezine, Sophie; Fallon, Padraic G; Luther, Sanjiv A; Fillatreau, Simon; Zavala, Flora

    2016-01-01

    The influence of signals perceived by immature B cells during their development in bone marrow on their subsequent functions as mature cells are poorly defined. Here, we show that bone marrow cells transiently stimulated in vivo or in vitro through the Toll-like receptor 9 generate proB cells (CpG-proBs) that interrupt experimental autoimmune encephalomyelitis (EAE) when transferred at the onset of clinical symptoms. Protection requires differentiation of CpG-proBs into mature B cells that home to reactive lymph nodes, where they trap T cells by releasing the CCR7 ligand, CCL19, and to inflamed central nervous system, where they locally limit immunopathogenesis through interleukin-10 production, thereby cooperatively inhibiting ongoing EAE. These data demonstrate that a transient inflammation at the environment, where proB cells develop, is sufficient to confer regulatory functions onto their mature B-cell progeny. In addition, these properties of CpG-proBs open interesting perspectives for cell therapy of autoimmune diseases. PMID:27396388

  6. Pharmacological Treatment of Attention Deficit Hyperactivity Disorder in Children and Adolescents: Clinical Strategies

    PubMed Central

    Shier, Anna C.; Reichenbacher, Thomas; Ghuman, Harinder S.; Ghuman, Jaswinder K.

    2013-01-01

    Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder of childhood that can result in significant functional impairment, and if not adequately treated can lead to impaired quality of life. Pharmacotherapy is considered the first-line treatment for ADHD in children and adolescents. We review both recent literature and seminal studies regarding the pharmacological treatment of ADHD in children and adolescents. There is ample evidence for the efficacy and safety of both stimulants and non-stimulants in the treatment of ADHD. We review important aspects of evaluation and assessment and discuss first-line pharmacological treatments and as well as when to consider using alternative pharmacological agents. Treatment approaches to manage frequently seen comorbid disorders with ADHD are also covered. PMID:23650474

  7. Ongoing Inquiry

    ERIC Educational Resources Information Center

    Ashbrook, Peggy

    2011-01-01

    An in-depth science inquiry is an ongoing investigation in which children are introduced to materials through hands-on experiences and, with teacher guidance, begin to investigate a question that they can answer through their own actions, observations, and with teacher-assisted research. Qualities that make an experience appropriate to include in…

  8. Pharmacological Approaches in the Treatment and Maintenance of Weight Loss.

    PubMed

    Van Gaal, Luc; Dirinck, Eveline

    2016-08-01

    Obesity is a growing global health concern, associated with a number of important comorbid conditions. It increases the risk of diabetes and contributes to development of cardiovascular disease. While the benefits of weight loss are well established, weight reduction remains a difficult-to-reach goal in overweight and obese individuals due to several metabolic and psychological factors. For many patients, lifestyle intervention is insufficient to achieve long-term weight loss, and additional options, such as pharmacotherapy, need to be considered. Besides the challenging enterprise of weight reduction, weight maintenance remains an even more crucial and outcome-determining aspect of weight management. This article focuses on the potential of currently available pharmacological strategies to support weight loss and maintenance goals in individuals at risk. Two pharmacotherapy types are considered: those developed primarily to induce weight loss and those developed primarily for blood glucose control that have a favorable effect on body weight. Finally, the potential of very low- and low-calorie diets combined with pharmacotherapy and pharmacological combination therapies are discussed, as well as emerging approaches in development. PMID:27440841

  9. Treatment of hemophilia: a review of current advances and ongoing issues

    PubMed Central

    Coppola, Antonio; Di Capua, Mirko; Di Minno, Matteo Nicola Dario; Di Palo, Mariagiovanna; Marrone, Emiliana; Ieranò, Paola; Arturo, Claudia; Tufano, Antonella; Cerbone, Anna Maria

    2010-01-01

    Replacement of the congenitally deficient factor VIII or IX through plasma-derived or recombinant concentrates is the mainstay of treatment for hemophilia. Concentrate infusions when hemorrhages occur typically in joint and muscles (on-demand treatment) is able to resolve bleeding, but does not prevent the progressive joint deterioration leading to crippling hemophilic arthropathy. Therefore, primary prophylaxis, ie, regular infusion of concentrates started after the first joint bleed and/or before the age of two years, is now recognized as first-line treatment in children with severe hemophilia. Secondary prophylaxis, whenever started, aims to avoid (or delay) the progression of arthropathy and improve patient quality of life. Interestingly, recent data suggest a role for early prophylaxis also in preventing development of inhibitors, the most serious complication of treatment in hemophilia, in which multiple genetic and environmental factors may be involved. Treatment of bleeds in patients with inhibitors requires bypassing agents (activated prothrombin complex concentrates, recombinant factor VIIa). However, eradication of inhibitors by induction of immune tolerance should be the first choice for patients with recent onset inhibitors. The wide availability of safe factor concentrates and programs for comprehensive care has now resulted in highly satisfactory treatment of hemophilia patients in developed countries. Unfortunately, this is not true for more than two-thirds of persons with hemophilia, who live in developing countries. PMID:22282697

  10. Current and emerging pharmacological treatments for sarcoidosis: a review

    PubMed Central

    Beegle, Scott H; Barba, Kerry; Gobunsuy, Romel; Judson, Marc A

    2013-01-01

    The treatment of sarcoidosis is not standardized. Because sarcoidosis may never cause significant symptoms or organ dysfunction, treatment is not mandatory. When treatment is indicated, oral corticosteroids are usually recommended because they are highly likely to be effective in a relative short period of time. However, because sarcoidosis is often a chronic condition, long-term treatment with corticosteroids may cause significant toxicity. Therefore, corticosteroid sparing agents are often indicated in patients requiring chronic therapy. This review outlines the indications for treatment, corticosteroid treatment, and corticosteroid sparing treatments for sarcoidosis. PMID:23596348

  11. [Pharmacological treatment of substance dependence from a neuroscientific perspective (I): opiates and cocaine].

    PubMed

    Haro, G; Cervera, G; Martínez-Raga, J; Pérez-Gálvez, B; Fernández-Garcés, M; Sanjuan, J

    2003-01-01

    In this review paper it is intended to analyze the most recent publications on pharmacological treatment of drug dependences from a neuroscientific perspective. It has been divided into two parts, the first one focuses on the treatment of illegal substance dependence, specifically opiates and cocaine; and the second part deals with the pharmacological treatments of three substances, two legal drugs such as alcohol and tobacco, and a group of medications with abuse potential, benzodiazepines. In this first part the neuroscientific aspects (genetic, neurochemistry, circuits involved, neuroimaging and neuropsychological deficits) relevant to understanding the pharmacological treatment of the main drug addictions are summarized. The pharmacotherapies of opiate dependence, both for detoxification and for dehabituation, are then discussed. Finally, the main medications that have been proposed to treat cocaine dependence are also reviewed. PMID:12838444

  12. Hemisphere Asymmetry of Response to Pharmacologic Treatment in an Alzheimer's Disease Mouse Model.

    PubMed

    Manousopoulou, Antigoni; Saito, Satoshi; Yamamoto, Yumi; Al-Daghri, Nasser M; Ihara, Masafumi; Carare, Roxana O; Garbis, Spiros D

    2016-01-01

    The aim of this study was to examine hemisphere asymmetry of response to pharmacologic treatment in an Alzheimer's disease mouse model using cilostazol as a chemical stimulus. Eight-month-old mice were assigned to vehicle or cilostazol treatment for three months and hemispheres were analyzed using quantitative proteomics. Bioinformatics interpretation showed that following treatment, aggregation of blood platelets significantly decreased in the right hemisphere whereas neurodegeneration significantly decreased and synaptic transmission increased in the left hemisphere only. Our study provides novel evidence on cerebral laterality of pharmacologic activity, with important implications in deciphering regional pharmacodynamic effects of existing drugs thus uncovering novel hemisphere-specific therapeutic targets. PMID:26836196

  13. Dental ethics case 6. Stalled payment for ongoing orthodontic treatment--balancing responsibilities.

    PubMed

    Doyal, L; Naidoo, S

    2010-10-01

    It is not always easy for an orthodontist to strike the right balance between a caring, supportive and patient-centered approach, and the need to make a living and to run a profitable business in order to achieve this. Striving to act ethically and professionally at all times will help find this elusive balance and ultimately it will be more rewarding and professionally satisfying. Especially when dealing with children whose lives may be dramatically affected by the interruption or cessation of treatment, orthodontists have a duty to reassure themselves about the financial stability of their contractual relationships with patients or parents. Having consistent financial policies and flexible payment options may assist in this regard. Even in the face of non-payment of fees, treatments that have begun must in some form continue if their cessation would compromise the best interests of patients. PMID:21180294

  14. Partners' Ongoing Treatment for Chronic Disease and the Risk of Psychological Distress after the Great East Japan Earthquake.

    PubMed

    Nakaya, Naoki; Narita, Akira; Tsuchiya, Naho; Nakamura, Tomohiro; Tsuji, Ichiro; Hozawa, Atsushi; Tomita, Hiroaki

    2016-01-01

    Several studies have reported that not only patients with chronic diseases but also their partners are likely to face major psychosocial problems. This study examined the association between a partner's ongoing treatment for chronic disease and the risk of psychological distress after the Great East Japan Earthquake (GEJE). In 2012, a questionnaire was distributed as part of a cross-sectional study of participants aged 20 years or older living in a municipality that had been severely inundated by the tsunami following the GEJE. We identified couples using the household numbers of the municipality and collected self-reported information on ongoing chronic disease treatment for stroke, cancer, myocardial infarction, and angina. Psychological distress was evaluated using the Kessler 6 scale (K6) and was defined as a score ≥ 5/24 points. Among 1,246 couples (2,492 participants) thus identified, 2,369 completed the K6. The number of participants whose partners were under treatment for chronic diseases was 209 (9%). Overall, participants with partners who were receiving treatment for chronic diseases (odds ratio [OR] = 1.3, 95% confidence interval [CI] = 0.95-1.8, P = 0.09) did not show a significantly higher risk of psychological distress using logistic regression analysis. Women, but not men, whose partners were receiving treatment for chronic diseases, had a higher risk of psychological distress (women: OR = 1.6, P = 0.02; men: OR = 1.0, P = 0.92). After the GEJE, only in women the presence of partners under treatment for chronic diseases appears to be a risk factor for psychological distress. PMID:27506650

  15. Non-Pharmacological Treatments for ADHD in Youth

    PubMed Central

    Sharma, Anup; Gerbarg, Patricia L.; Brown, Richard P.

    2016-01-01

    Background Complementary and alternative medicine (CAM) in psychiatry or integrative psychiatry covers a wide range of biological, psychological and mind-body treatments that enhance standard medical practices and patient outcomes. While CAM approaches are popular amongst patients in their practice as well as in self-report because of their ease of use, health professionals have received limited education in these interventions and often are unaware of their patients’ use of CAM treatments. Method This overview highlights evidence-based CAM treatments for attention deficit hyperactivity disorder (ADHD) including dietary interventions, phytomedicines, mind-body practices and neurofeedback. Results While conventional treatments are the mainstays for ADHD, there are a large number of available treatments that can be used to enhance treatment response. Conclusion With improved education and further scientific and clinical research, validated integrative treatments will provide more effective, lower risk and lower cost care for patients with ADHD. PMID:27489754

  16. Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review

    PubMed Central

    de Kleine, Rianne A.; Rothbaum, Barbara O.; van Minnen, Agnes

    2013-01-01

    There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD). Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: d-cycloserine, MDMA, hydrocortisone, and propranolol. PMID:24147208

  17. Behavioral and emerging pharmacologic treatment options for cognitive impairment in schizophrenia.

    PubMed

    Vinogradov, Sophia; Schulz, S Charles

    2016-02-01

    In recent years, the goal of treatment for individuals with schizophrenia has shifted from symptom control to functional recovery. For recovery to occur, the substantial cognitive impairments associated with this disorder must be addressed. Advances in neuroscience have paved the way for the development of more effective behavioral and pharmacologic treatments. Behavioral interventions such as cognitive training are tapping into the innate plasticity and adaptive qualities of the brain. Emerging pharmacologic treatments are targeting new neurotransmitters and systems, such as the glutamatergic system and the nicotinic-cholinergic system, which are involved in the cognitive and sensory deficits that lead to impairment. The best chances for recovery will most likely occur by combining behavioral and pharmacologic interventions. PMID:26919053

  18. Pharmacological treatment of laser eye injuries by neuroprotection

    NASA Astrophysics Data System (ADS)

    Solberg, Yoram; Rosner, Mordechai; Belkin, Michael

    1996-04-01

    Many retinal injuries result in an irreversible neuronal loss, which can not yet be reduced by pharmacological methods. To determine whether glutamate-receptor blockers can serve as neuroprotective agents in the retina, as they do in the central nervous system, we examined the effects of MK-801, an NMDA-receptor antagonist, on laser-induced retinal injury in a rat model. Immediately and 8 h after argon laser retinal photocoagulation, rats were treated with intraperitoneal injections of MK-801 (3 mg/kg) or saline. After 3, 20 or 60 days the animals were sacrificed and their retinal lesions were evaluated histologically and morphometrically. Photoreceptor cell loss, both immediately and up to 2 months after laser irradiation, was significantly smaller in MK-801-treated rats than controls. MK-801 exhibits neuroprotective property in the retina. This points to the involvement of glutamate in the laser-induced retinal neuronal damage. Glutamate-receptor blockers should be further investigated for therapy of retinal diseases characterized by neuronal cell destruction.

  19. Delayed Cytotoxic T Lymphocyte-Associated Protein 4-Immunoglobulin Treatment Reverses Ongoing Alloantibody Responses and Rescues Allografts From Acute Rejection.

    PubMed

    Young, J S; Chen, J; Miller, M L; Vu, V; Tian, C; Moon, J J; Alegre, M-L; Sciammas, R; Chong, A S

    2016-08-01

    Antibody-mediated rejection has emerged as the leading cause of late graft loss in kidney transplant recipients, and inhibition of donor-specific antibody production should lead to improved transplant outcomes. The fusion protein cytotoxic T lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) blocks T cell activation and consequently inhibits T-dependent B cell antibody production, and the current paradigm is that CTLA4-Ig is effective with naïve T cells and less so with activated or memory T cells. In this study, we used a mouse model of allosensitization to investigate the efficacy of continuous CTLA4-Ig treatment, initiated 7 or 14 days after sensitization, for inhibiting ongoing allospecific B cell responses. Delayed treatment with CTLA4-Ig collapsed the allospecific germinal center B cell response and inhibited alloantibody production. Using adoptively transferred T cell receptor transgenic T cells and a novel approach to track endogenous graft-specific T cells, we demonstrate that delayed CTLA4-Ig minimally inhibited graft-specific CD4(+) and T follicular helper responses. Remarkably, delaying CTLA4-Ig until day 6 after transplantation in a fully mismatched heart transplant model inhibited alloantibody production and prevented acute rejection, whereas transferred hyperimmune sera reversed the effects of delayed CTLA4-Ig. Collectively, our studies revealed the unexpected efficacy of CTLA4-Ig for inhibiting ongoing B cell responses even when the graft-specific T cell response was robustly established. PMID:26928966

  20. Current Concepts and Ongoing Research in the Prevention and Treatment of Open Fracture Infections

    PubMed Central

    Hannigan, Geoffrey D.; Pulos, Nicholas; Grice, Elizabeth A.; Mehta, Samir

    2015-01-01

    Significance: Open fractures are fractures in which the bone has violated the skin and soft tissue. Because of their severity, open fractures are associated with complications that can result in increased lengths of hospital stays, multiple operative interventions, and even amputation. One of the factors thought to influence the extent of these complications is exposure and contamination of the open fracture with environmental microorganisms, potentially those that are pathogenic in nature. Recent Advances: Current open fracture care aims to prevent infection by wound classification, prophylactic antibiotic administration, debridement and irrigation, and stable fracture fixation. Critical Issues: Despite these established treatment paradigms, infections and infection-related complications remain a significant clinical burden. To address this, improvements need to be made in our ability to detect bacterial infections, effectively remove wound contamination, eradicate infections, and treat and prevent biofilm formation associated with fracture fixation hardware. Future Directions: Current research is addressing these critical issues. While culture methods are of limited value, culture-independent molecular techniques are being developed to provide informative detection of bacterial contamination and infection. Other advanced contamination- and infection-detecting techniques are also being investigated. New hardware-coating methods are being developed to minimize the risk of biofilm formation in wounds, and immune stimulation techniques are being developed to prevent open fracture infections. PMID:25566415

  1. Pharmacological treatments for obsessive-compulsive disorder in children and adolescents: a qualitative review.

    PubMed

    Rosa-Alcázar, Ana I; Iniesta-Sepúlveda, Marina; Rosa-Alcázar, Angel

    2013-01-01

    We present the results of a systematic review on the effectiveness of pharmacological treatments for children and adolescents with obsessive-compulsive disorder. Sixty-four studies fulfilled the selection criteria, being the most of them focused in SSRI and Clomipramine. The trials on augmentation strategies and third line monotherapies are scarce, being the majority open-trials and case series. Similarly, studies on combined treatment (psychological and pharmacological) are few; furthermore this is a relevant future research line. It is also remarkable the lack of quasi-experimental and experimental comparison studies and the long-term follow-up measures. PMID:23803803

  2. Role of "old" pharmacological agents in the treatment of Cushing's syndrome.

    PubMed

    Ambrogio, A G; Cavagnini, F

    2016-09-01

    Despite recent advances in the management of endogenous Cushing's syndrome (CS), its treatment remains a challenge. When surgery has been unsuccessful or unfeasible as well in case of recurrence, the "old" pharmacological agents represent an important alternative for both ACTH-dependent and independent hypercortisolism. Especially in the latter, the advent of novel molecules directly targeting ACTH secretion has not outweighed the "old" drugs, which continue to be largely employed and have recently undergone a reappraisal. This review provides a survey of the "old" pharmacological agents in the treatment of CS. PMID:27086313

  3. Adherence to Pharmacological Treatment for Juvenile Bipolar Disorder

    ERIC Educational Resources Information Center

    Drotar, Dennis; Greenley, Rachel Neff; Demeter, Christine A.; McNamara, Nora K.; Stansbrey, Robert J.; Calabrese, Joseph R.; Stange, Jonathan; Vijay, Priya; Findling, Robert L.

    2007-01-01

    Objective: The objective of this study was to describe the prevalence and correlates of adherence to divalproex sodium (DVPX) and lithium carbonate (Li) combination treatment during the initial stabilization treatment phase. Method: Adherence to Li/DVPX combination therapy was measured by the presence or absence of minimum serum concentrations of…

  4. Pharmacological treatment of migraine during pregnancy and breastfeeding.

    PubMed

    Amundsen, Siri; Nordeng, Hedvig; Nezvalová-Henriksen, Kateřina; Stovner, Lars Jacob; Spigset, Olav

    2015-04-01

    Migraine affects up to 25% of women of reproductive age. In the majority of these women, migraine improves progressively during pregnancy, but symptoms generally recur shortly after delivery. As suboptimally treated migraine in pregnancy could have negative consequences for both mother and fetus, the primary aim of clinicians should be to provide optimal treatment according to stage of pregnancy, while minimising possible risks related to drug therapy. Nonpharmacological approaches are always first-line treatment, and should also be used to complement any required drug treatment. Paracetamol is the preferred drug for acute treatment throughout pregnancy. If paracetamol is not sufficiently effective, sporadic use of sumatriptan can be considered. NSAIDs such as ibuprofen can also be used under certain circumstances, though their intake in the first and third trimesters is associated with specific risks and contraindications. Preventive treatment should only be considered in the most severe cases. In women contemplating pregnancy, counselling is essential to promote a safe and healthy pregnancy and postpartum period for the mother and child, and should involve a dialogue addressing maternal concerns and expectations about drug treatment. This Review summarizes current evidence of the safety of the most common antimigraine medications during pregnancy and breastfeeding, and provides treatment recommendations for use in clinical practice. PMID:25776823

  5. Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence.

    PubMed

    Sinclair, Julia M A; Chambers, Sophia E; Shiles, Celia J; Baldwin, David S

    2016-07-01

    Alcohol use disorders (AUD) cause significant morbidity and mortality worldwide, but pharmacological treatments for them are underused, despite evidence of efficacy. Acamprosate, naltrexone, nalmefene and disulfiram are all approved in one or more region for the treatment of AUD. Baclofen currently has a temporary indication in France. Safety considerations for using psychopharmacological treatments in this patient group include the impact of concurrent alcohol consumption at high levels; multiple physical comorbidities that may interfere with pharmacological effects, distribution and metabolism; and concomitant medication for the treatment of comorbid physical and psychiatric conditions. The five drugs, including an extended-release injectable suspension of naltrexone, have different safety profiles that need to be balanced with the treatment objective (initiation or continuation of abstinence, or reduction of drinking), individual patient preferences and comorbid conditions. Appropriate treatment will be based on the unique risk-benefit profile in each case. PMID:27023898

  6. Pharmacological approaches to the challenge of treatment-resistant depression.

    PubMed

    Ionescu, Dawn F; Rosenbaum, Jerrold F; Alpert, Jonathan E

    2015-06-01

    Although monoaminergic antidepressants revolutionized the treatment of Major Depressive Disorder (MDD) over a half-century ago, approximately one third of depressed patients experience treatment-resistant depression (TRD). Such patients account for a disproportionately large burden of disease, as evidenced by increased disability, cost, human suffering, and suicide. This review addresses the definition, causes, evaluation, and treatment of unipolar TRD, as well as the major treatment strategies, including optimization, augmentation, combination, and switch therapies. Evidence for these options, as outlined in this review, is mainly focused on large-scale trials or meta-analyses. Finally, we briefly review emerging targets for antidepressant drug discovery and the novel effects of rapidly acting antidepressants, with a focus on ketamine. PMID:26246787

  7. [Pharmacological treatment of other types of secondary osteoporosis].

    PubMed

    Okazaki, Ryo

    2015-10-01

    This article reviews the treatment strategy for the secondary osteoporosis excluding those caused by diabetes, CKD, endocrine disorders, or glucocorticoid, which proceeding articles deal with. Among numerous possible causes for such secondary osteoporosis, the author has selected osteogenesis imperfecta (OI), osteoporosis associated with gastrectomy or bariatric surgery, inflammatory bowel diseases (IBD), and chronic obstructive pulmonary disease (COPD). For OI, current standard treatment is bisphosphonates (BPs), of which efficacy for fracture inhibition has recently been of issue. Other treatment modalities, e.g. PTH, have just been explored. Osteoporosis associated with gastrectomy, bariatric surgery or IBD, have been treated with vitamin D, calcium, and BPs. Despite high fracture rates, there are almost no treatment data for osteoporosis associated with COPD. PMID:26529940

  8. Pharmacological Approaches for Treatment-resistant Bipolar Disorder.

    PubMed

    Hui Poon, Shi; Sim, Kang; Baldessarini, Ross J

    2015-01-01

    Bipolar disorder is prevalent, with high risks of disability, substance abuse and premature mortality. Treatment responses typically are incomplete, especially for depressive components, so that many cases can be considered "treatment resistant." We reviewed reports on experimental treatments for such patients: there is a striking paucity of such research, mainly involving small incompletely controlled trials of add-on treatment, and findings remain preliminary. Encouraging results have been reported by adding aripiprazole, bupropion, clozapine, ketamine, memantine, pramipexole, pregabalin, and perhaps tri-iodothyronine in resistant manic or depressive phases. The urgency of incomplete responses in such a severe illness underscores the need for more systematic, simpler, and better controlled studies in more homogeneous samples of patients. PMID:26467409

  9. Pharmacological approaches to the challenge of treatment-resistant depression

    PubMed Central

    Ionescu, Dawn F.; Rosenbaum, Jerrold F.; Alpert, Jonathan E.

    2015-01-01

    Although monoaminergic antidepressants revolutionized the treatment of Major Depressive Disorder (MDD) over a half-century ago, approximately one third of depressed patients experience treatment-resistant depression (TRD). Such patients account for a disproportionately large burden of disease, as evidenced by increased disability, cost, human suffering, and suicide. This review addresses the definition, causes, evaluation, and treatment of unipolar TRD, as well as the major treatment strategies, including optimization, augmentation, combination, and switch therapies. Evidence for these options, as outlined in this review, is mainly focused on large-scale trials or meta-analyses. Finally, we briefly review emerging targets for antidepressant drug discovery and the novel effects of rapidly acting antidepressants, with a focus on ketamine. PMID:26246787

  10. Pharmacological Approaches for Treatment-resistant Bipolar Disorder

    PubMed Central

    Poon, Shi Hui; Sim, Kang; Baldessarini, Ross J.

    2015-01-01

    Bipolar disorder is prevalent, with high risks of disability, substance abuse and premature mortality. Treatment responses typically are incomplete, especially for depressive components, so that many cases can be considered “treatment resistant.” We reviewed reports on experimental treatments for such patients: there is a striking paucity of such research, mainly involving small incompletely controlled trials of add-on treatment, and findings remain preliminary. Encouraging results have been reported by adding aripiprazole, bupropion, clozapine, ketamine, memantine, pramipexole, pregabalin, and perhaps tri-iodothyronine in resistant manic or depressive phases. The urgency of incomplete responses in such a severe illness underscores the need for more systematic, simpler, and better controlled studies in more homogeneous samples of patients. PMID:26467409

  11. The pharmacological treatment of opioid addiction--a clinical perspective.

    PubMed

    Lobmaier, Philipp; Gossop, Michael; Waal, Helge; Bramness, Jorgen

    2010-06-01

    This article reviews the main pharmacotherapies that are currently being used to treat opioid addiction. Treatments include detoxification using tapered methadone, buprenorphine, adrenergic agonists such as clonidine and lofexidine, and forms of rapid detoxification. In opioid maintenance treatment (OMT), methadone is most widely used. OMT with buprenorphine, buprenorphine-naloxone combination, or other opioid agonists is also discussed. The use of the opioid antagonists naloxone (for the treatment of intoxication and overdose) and oral and sustained-release formulations of naltrexone (for relapse prevention) is also considered. Although recent advances in the neurobiology of addictions may lead to the development of new pharmacotherapies for the treatment of addictive disorders, a major challenge lies in delivering existing treatments more effectively. Pharmacotherapy of opioid addiction alone is usually insufficient, and a complete treatment should also include effective psychosocial support or other interventions. Combining pharmacotherapies with psychosocial support strategies that are tailored to meet the patients' needs represents the best way to treat opioid addiction effectively. PMID:20169438

  12. Pharmacological treatment of catarrh in Iranian traditional medicine

    PubMed Central

    Choopani, Rasool; Sadr, Saeed; Kaveh, Shahpar; Kaveh, Narges; Dehghan, Sohrab

    2015-01-01

    Catarrh is a condition that is carefully explained in Iranian traditional medicine. Medieval Iranian physicians used some medicinal plants in the treatment of the catarrh. Some of these substances are used in treatment today, although still more of these materials can be used in modern medicine. In this study we searched known sources of Iranian traditional medicine and collected the ideas of former great scholars and physicians about medicinal plants that are used for treatment of catarrh. Then we searched PubMed, Google Scholar, Scopus, and Web of Science databases and found 10 medicinal herbs that have the ability to treat catarrh. Plants discussed in this study are consistent with new research and can be used in modern treatments. According to rising bacterial resistance to antibiotics and complications of antibiotic and anti-inflammatory drugs, it seems that the various components of the medicinal herbs can be beneficial in producing new drugs. Also it is hoped that more investigations on medicinal plants will be conducted in the future treatment of catarrh and other diseases related to it. PMID:26151014

  13. Pharmacologic Therapies in Women's Health: Contraception and Menopause Treatment.

    PubMed

    Allen, Caitlin; Evans, Ginger; Sutton, Eliza L

    2016-07-01

    Female hormones play a significant role in the etiology and treatment of many women's health conditions. This article focuses on the common uses of hormonal therapy. When prescribing estrogen-containing regimens throughout the span of a woman's life, the risks are similar (ie, cardiovascular risk and venous thromboembolism), but the degree of risk varies significantly depending on a woman's particular set of risk factors and the details of the hormone regimen. In addition to estrogens and progestogens, this article also touches on the use of selective steroid receptor modulators in emergency contraception and in treatment of menopause symptoms. PMID:27235614

  14. Psychophysiological Outcome of Behavioral and Pharmacological Treatments of Agoraphobia.

    ERIC Educational Resources Information Center

    Michelson, Larry; Mavissakalian, Matig

    1985-01-01

    Examined relative and combined effectiveness of behavior therapy and pharmacotherapy in 62 severe, chronic agoraphobics. Identified differential temporal response and treatment patterns across psychophysiological domains. Synchrony/desynchrony phenomena yielded significant findings with regard to process and clinical outcome status. Exploratory…

  15. Current status of pharmacological treatment of colorectal cancer

    PubMed Central

    Akhtar, Reyhan; Chandel, Shammy; Sarotra, Pooja; Medhi, Bikash

    2014-01-01

    AIM: To review the clinical trials for the development in drugs for chemotherapeutic treatment of colorectal cancer (CRC). METHODS: A systematic review identified randomized controlled trials (RCTs) assessing drugs for the treatment of CRC or adenomatous polyps from www.clinicaltrials.gov. Various online medical databases were searched for relevant publications. RESULTS: Combination treatment regimens of standard drugs with newer agents have been shown to improve overall survival, disease-free survival, time to progression and quality of life compared to that with standard drugs alone in patients with advanced colorectal cancer. The FOLFOXIRI regimen has been associated with a significantly higher response rate, progression-free survival and overall survival compared to the FOLFIRI regimen. CONCLUSION: Oxaliplatin plus intravenous bolus fluorouracil and leucovorin has been shown to be superior for disease-free survival when compared to intravenous bolus fluorouracil and leucovorin. In addition, oxaliplatin regimens were more likely to result in successful surgical resections. First line treatment with cetuximab plus fluorouracil, leucovorin and irinotecan has been found to reduce the risk of metastatic progression in patients with epidermal growth factor receptor-positive colorectal cancer with unresectable metastases. The addition of bevacizumab has been shown to significantly increase overall and progression-free survival when given in combination with standard therapy. PMID:24936228

  16. Pharmacologically assisted treatment of opioid-dependent youth.

    PubMed

    Pecoraro, Anna; Fishman, Marc; Ma, Michelle; Piralishvili, Gvantsa; Woody, George E

    2013-12-01

    Opioid misuse, abuse, and dependence are global problems whose patterns vary across cultures. In the USA, the non-medical use of prescription opioids has become particularly serious because of its association with addiction and overdose death. Agonist and antagonist medications have been shown to be effective for opioid-dependent adults, and there is a growing body of data that they are also effective for youth. Here, we summarize evidence that detoxification alone results in high rates of treatment dropout and relapse but that the limited but growing data on the extended use of medication-assisted treatment for opioid-dependent youth have been positive. The implementation of medication-assisted treatment as a standard practice is feasible, easily integrated with counseling or psychotherapy, and has potential to greatly improve outcomes. Although concerns about safety and efficacy with youth require more research, and we do not advocate indefinite maintenance, we suggest that opioid-dependent youth should be considered as candidates for medication-assisted treatment delivered in a comprehensive, developmentally appropriate context, beginning at the first episode of care, with the strength of the recommendation to use medication increasing with each care episode. PMID:23912754

  17. Pharmacological Management of Treatment-Resistant Pediatric Depression

    ERIC Educational Resources Information Center

    Kratochvil, Christopher J.; Wagner, Karen Dineen; Emslie, Graham; March, John

    2005-01-01

    A 13-year-old boy presents with treatment-resistant symptoms of major depression. This is his first episode of depression, initially treated with 200 mg sertraline for 12 weeks with no significant benefit. The severe depression has shown a partial response to weekly cognitive-behavioral therapy (CBT) and fluoxetine, which was titrated up to 60 mg…

  18. Options for pharmacological treatment of refractory bipolar depression.

    PubMed

    Tondo, Leonardo; Vázquez, Gustavo H; Baldessarini, Ross J

    2014-02-01

    Bipolar disorders of types I and II, even when treated by currently standard options, show a marked excess of depressive morbidity. Treated, type I patients in mid-course or from the onset of illness are ill, overall, 50 % of weeks of follow-up, and 75 % of that unresolved morbidity is depressive. Currently widely held impressions are that bipolar depression typically is poorly responsive to antidepressants, that treatment-resistant depression (TRD) is characteristic of the disorder, and that risk of mania with antidepressant treatment is very high. However, none of these views is supported consistently by available research. TRD may be more prevalent in bipolar than unipolar mood disorders. Relatively intense research attention is directed toward characteristics and treatments of TRD in unipolar depression, but studies of bipolar TRD are uncommon. We found only five controlled trials, plus 10 uncontrolled trials, providing data on a total of 13 drug treatments, all of which involved one or two trials, in 87 % as add-ons to complex, uncontrolled regimens. In two controlled trials, ketamine was superior to placebo but it is short-acting and not orally active; pramipexole was weakly superior to placebo in one controlled trial; three other drugs failed to outperform controls. Other pharmacotherapies are inadequately evaluated and nonpharmacological options are virtually untested in bipolar TRD. The available research supports the view that antidepressants may be effective in bipolar depression provided that currently agitated patients are excluded, that risk of mania with antidepressants is only moderately greater than risk of spontaneous mania, and that bipolar TRD is not necessarily resistant to all treatments. PMID:24425269

  19. Recovery of function in humans: Cortical stimulation and pharmacological treatments after stroke

    PubMed Central

    Floel, Agnes; Cohen, Leonardo G.

    2016-01-01

    In this contribution, we first provide an overview of general principles of reorganisation in the human brain, and point out possible biomarkers of recovery. Subsequently, we expand on possibilities of adjuvant therapy in human rehabilitation using cortical stimulation and pharmacological treatments. Finally, we suggest future directions for research in this field. PMID:19520165

  20. Approved and Off-Label Uses of Obesity Medications, and Potential New Pharmacologic Treatment Options

    PubMed Central

    Isidro, Maria Luisa; Cordido, Fernando

    2010-01-01

    Available anti-obesity pharmacotherapy options remain very limited and development of more effective drugs has become a priority. The potential strategies to achieve weight loss are to reduce energy intake by stimulating anorexigenic signals or by blocking orexigenic signals, and to increase energy expenditure. This review will focus on approved obesity medications, as well as potential new pharmacologic treatment options.

  1. SMOKING CESSATION FOR ADOLESCENTS: A REVIEW OF PHARMACOLOGICAL AND PSYCHOSOCIAL TREATMENTS

    PubMed Central

    Schepis, TS; Rao, U

    2016-01-01

    Unlike the vast literature on smoking cessation in adults, research in adolescents has gained significant attention only within the last decade. Even with this increase in focus, research into pharmacological aids for smoking cessation in adolescents (e.g., nicotine replacement therapy, bupropion) is a more recent phenomenon and has produced only modest results. While more extensive, much of the research on behaviorally- or psychosocially-based adolescent smoking cessation interventions has been limited by a lack of control for contact time, biochemical verification of self-reported abstinence, and/or a theoretical focus for the interventions. The MEDLINE, PubMed, PSYCInfo CINHAL and Cochrane Systematic Review databases were searched for articles relevant to adolescent smoking cessation treatment. After briefly examining the adolescent smoking cessation research prior to 2000, more recent developments in pharmacological aids and psychological treatment will be reviewed. Investigations have made progress in elucidating efficacious treatments for adolescent smokers, but much work remains to be done in both pharmacological and non-pharmacological areas of treatment. With the current state of the literature as a guide, future directions for research into smoking cessation for adolescents will be proposed. PMID:19630713

  2. Commissioning Pharmacological Treatments for Drug Users: A Brief Review of the Evidence Base

    ERIC Educational Resources Information Center

    Keen, Jenny; Oliver, Philip

    2004-01-01

    Aims: To provide a brief review of relevant existing evidence regarding pharmacological treatment for drug users, in order to enable commissioners and service providers to make informed decisions that are evidence based wherever possible. Methods: The review process involved an examination of key reference texts and literature derived from…

  3. Pharmacological Treatment of Bipolar Disorder among Children and Adolescents

    PubMed Central

    Blader, Joseph C.; Kafantaris, Vivian

    2010-01-01

    Summary There is growing recognition that bipolar disorder (BD) frequently first presents in adolescence. Preadolescents with volatile behavior and severe mood swings also comprise a large group of patients whose difficulties may lie within the bipolar spectrum. However, the preponderance of scientific effort and clinical trials for this condition have focused on adults. This review summarizes the BD's complexity and diagnosis among young people. It proceeds to review the principles of pharmacotherapy, to assess current treatment options, and to highlight areas where evidence-based guidance is lacking. Recent developments have enlarged the range of potential treatments for BD. Nonetheless, differences in the phenomenology, course, and sequelae of BD among young people compel greater attention to the benefits and liabilities of therapy for those affected by this illness’ early onset. PMID:17341174

  4. Challenges in the pharmacological treatment of geriatric asthma.

    PubMed

    Agusta, Fabio; Battaglia, Salvatore; Benfante, Alida; Spatafora, Mario; Scichilone, Nicola

    2016-07-01

    Asthma in older populations is characterized by frequent comorbid conditions, which increase the risk of side effects and of detrimental interactions between respiratory and non-respiratory drugs. These observations lead to the need to manage asthma in older populations by applying a multidimensional assessment and a multidisciplinary treatment; therefore, we favor the use of the 'geriatric' term to define asthma in the elderly. Geriatric asthma is a complex disease, which may not necessarily imply that it is also complicated, although the two conditions may often coexist. On this basis, the switch from an organ-driven management to the holistic approach may be the key factor to attain optimal control of the disease in this age range. The current review discusses the age-related factors affecting asthma treatment in the oldest individuals, such as the comorbid conditions, and age-related changes of metabolism and excretion that can impair the efficacy and safety of drugs. PMID:26986042

  5. [Non-pharmacologic treatment of arterial hypertension in hemodialysis patients].

    PubMed

    Chazot, C; Charra, B

    2007-10-01

    High blood pressure in dialysis patients is related to extracellular volume excess and the related increase of systemic vascular resistances. Scribner has early described the treatment of hypertension with ultrafiltration and low salt diet, without any drugs. The dry weight method relies on the progressive reduction of the postdialysis body weight until blood pressure is normalized. Additional measures are needed such as low salt diet, neutral sodium balance during dialysis treatment, stop of antihypertensive drugs, adequate length of the dialysis session, and patient education. It may exist a lag time between the normalization of the extracellular volume and blood pressure. It is related to the correction of the hemodynamic consequences of the extracellular volume overload. Moreover, the dry weight may potentially vary in patients undergoing catabolic intercurrent events. The complications of these changes (severe hypertension, pulmonary oedema) must be anticipated by the nephrologist and the staff to avoid additional morbidity to the patient. PMID:18340684

  6. Update on the pharmacological treatment of adult myositis.

    PubMed

    Oddis, C V

    2016-07-01

    The management of patients with idiopathic inflammatory myopathy (IIM) remains a challenge given the systemic features beyond active myositis. That is, recognizing the inflammatory arthropathy, varying dermatomyositis rashes, and overt and occult features of interstitial lung disease in addition to myositis adds to the complexity of diagnosis and treatment of IIM. However, clinicians now have available many more immunosuppressive drugs as well as biologic agents for use in patients with myositis and other autoimmune diseases. Here, the use of these agents is reviewed and support based on available published literature is provided even though many studies have been small and results somewhat anecdotal. Glucocorticoids remain the initial treatment of choice in most instances and methotrexate and azathioprine are often used early in the treatment course. These agents are followed by other immunosuppressive drugs, for example mycophenolate mofetil, tacrolimus, cyclosporine and cyclophosphamide, some of which are used alone while combinations of these agents also provide an effective option. There is more rationale for the use of biologic agents such as rituximab from a mechanistic perspective and, given the incorporation of validated core set measures in assessing myositis patients, we can look forward to better designed clinical trials in the future. PMID:27098592

  7. Pharmacological approach of the treatment of drinking problems: a critical overview.

    PubMed

    Verbanck, P; Barrias, J; Besson, J; Borg, S

    1993-01-01

    Many pharmacological agents have been proposed for the treatment of drinking problems. However, there are many pitfalls in the assessment of the clinical interest of those drugs. In this paper, we propose a new classification of drugs of interest for treating alcohol abuse and related problems. We also review the major clinical studies about those pharmacological agents and discuss, through the studies about serotonergic agents, lithium salts, disulfiram and related compounds, some peculiar aspects of those trials that we think to be important to develop better strategies for the evaluation of pharmacotherapy of alcoholism. PMID:7748291

  8. Defense style in panic disorder before and after pharmacological treatment.

    PubMed

    Marchesi, Carlo; Parenti, Paola; Aprile, Sonia; Cabrino, Chiara; De Panfilis, Chiara

    2011-05-30

    Whether or not the use of maladaptive defense style is a trait, as opposed to a state dependent phenomenon, in panic disorder (PD) is a topic still very much up for debate. The aim of the study was to verify whether PD patients, both before and after treatment, used different defense style than the control group. Sixty-one PD patients (recruited from an original sample of 90 patients) and 64 healthy controls were evaluated against the Structured Clinical Interview for DSM-IV disorders, the Symptoms Check List-90, the Hamilton Rating Scales for Anxiety and for Depression and finally the Defense Style Questionnaire-40 (DSQ). The patients were treated with paroxetine or citalopram and were evaluated monthly for one year to assess the remission. The DSQ was re-administered to the patients at the end of the study. Before treatment, PD patients used more neurotic and immature forms of defense than controls. After treatment, those in remission used the same defense styles as the control group, whereas non-remitters still used more immature defenses. However, all the aforementioned difference disappeared, after excluding the effect of symptom severity. Our data supports the hypothesis that the use of maladaptive defenses might be the consequence of PD: when subjects fall ill, their capacity to use mature adaptive defenses may diminish, but when they recover their defensive style returns to a greater maturity. The present results are however limited by the dropout rate (one third of patients did not complete the study) and the use of just one questionnaire to evaluate the complexity of defense styles. PMID:20692044

  9. Guanfacine Extended Release: A New Pharmacological Treatment Option in Europe.

    PubMed

    Huss, Michael; Chen, Wai; Ludolph, Andrea G

    2016-01-01

    Children/adolescents with attention-deficit/hyperactivity disorder (ADHD) may have a poor or inadequate response to psychostimulants or be unable to tolerate their side-effects; furthermore, stimulants may be inappropriate because of co-existing conditions. Only one non-stimulant ADHD pharmacotherapy, the noradrenaline transporter inhibitor atomoxetine, is currently approved for use in Europe. We review recent advances in understanding of the pathophysiology of ADHD with a focus on the roles of catecholamine receptors in context of the α2A-adrenergic receptor agonist guanfacine extended release (GXR), a new non-stimulant treatment option in Europe. Neuroimaging studies of children/adolescents with ADHD show impaired brain maturation, and structural and functional anomalies in brain regions and networks. Neurobiological studies in ADHD and medication response patterns support involvement of monoaminergic neurotransmitters (primarily dopamine and noradrenaline). Guanfacine is a selective α2A-adrenergic receptor agonist that has been shown to improve prefrontal cortical cognitive function, including working memory. The hypothesized mode of action of guanfacine centres on direct stimulation of post-synaptic α2A-adrenergic receptors to enhance noradrenaline neurotransmission. Preclinical data suggest that guanfacine also influences dendritic spine growth and maturation. Clinical trials have demonstrated the efficacy of GXR in ADHD, and it is approved as monotherapy or adjunctive therapy to stimulants in Canada and the USA (for children and adolescents). GXR was approved recently in Europe for the treatment of ADHD in children and adolescents for whom stimulants are not suitable, not tolerated or have been shown to be ineffective. GXR may provide particular benefit for children/adolescents who have specific co-morbidities such as chronic tic disorders or oppositional defiant disorder (or oppositional symptoms) that have failed to respond to first-line treatment

  10. Advances in the pharmacological treatment of Graves' orbitopathy.

    PubMed

    Ruchała, Marek; Sawicka-Gutaj, Nadia

    2016-07-01

    Graves' orbitopathy has a deteriorating effect on patients' appearance and vision, thus significantly decreases their quality of life. A multidisciplinary team of endocrinologists, ophthalmologists, head and neck surgeons, nuclear medicine physicians, radiologists, and psychologists should constitute a standard health care team for those patients. It is vital that the therapy is based on an individual approach, with patients being well informed and involved in the decision-making process. Generally, traditional therapies include immunosuppression with steroids, orbital irradiation and surgical decompression. Novel treatment modalities include: biological agents, somatostatin analogs, antioxidants, methotrexate. Better insight into pathogenesis of Graves' orbitopathy is the only chance for targeted therapy development. PMID:26966785

  11. Pharmacological options for the treatment of Tourette's disorder.

    PubMed

    Jiménez-Jiménez, F J; García-Ruiz, P J

    2001-01-01

    Tourette's disorder is a neuropsychiatric disorder characterised clinically by motor and vocal tics, which may be associated to conductual disorders such as obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD). Although the neurochemistry of Tourette's disorder is not well known, there are some effective therapies for tics, OCD and ADHD. However, these are not devoid of adverse effects. Tics only require treatment when they interfere with the functioning of the patient. If therapy is needed, monotherapy at the minimal effective dose is desirable, but some patients may require two or more drugs. The most frequently used drugs for tics are antipsychotics (mainly pimozide and haloperidol) and clonidine. The potential usefulness of atypical antipsychotic drugs (risperidone, olanzapine, clozapine, ziprasidone) and other dopaminergic drugs (fluphenazine, sulpiride, tiapride, metoclopramide, piquindone, tetrabenazine), clonazepam, calcium channel antagonists, botulinum toxin, dopamine agonists, selegiline, and other drugs is discussed. The drugs of choice for OCD in patients with Tourette's disorder are the selective serotonin reuptake inhibitors (SSRIs), although the tricyclic antidepressant clomiplamine, which inhibits both serotonin and noradrenaline uptake, has also been found to be useful. ADHD can be treated with some psychostimulants, mainly methylphenidate, although these drugs must be used with caution. Other potentially useful drugs for the treatment of ADHD in patients with Tourette's disorder are clonidine, guanfacine, selegiline, some tricyclic antidepressants, sertraline, pimozide and clonazepam. Finally, the potential value of some nonpharmacological therapies (hypnotherapy, biofeedback, conductual therapies, electroconvulsive therapy, acupuncture and surgery) is briefly reviewed. PMID:11772131

  12. The Pharmacological Options in the Treatment of Eating Disorders

    PubMed Central

    Milano, W.; De Rosa, M.; Milano, L.; Riccio, A.; Sanseverino, B.; Capasso, A.

    2013-01-01

    The eating disorders (DCA) are complex systemic diseases with high social impact, which tend to become chronic with significant medical and psychiatric comorbidities. The literature data showed that there is good evidence to suggest the use of SSRIs, particularly at high doses of fluoxetine, in the treatment of BN reducing both the crisis of binge that the phenomena compensates and reducing the episodes of binge in patients with BED in the short term. Also, the topiramate (an AED) showed a good effectiveness in reducing the frequency and magnitude of episodes of binge with body weight reduction, both in the BN that is in the therapy of BED. To date, modest data support the use of low doses of second-generation antipsychotics in an attempt to reduce the creation of polarized weight and body shapes, the obsessive component, and anxiety in patients with AN. Data in the literature on long-term drug treatment of eating disorders are still very modest. It is essential to remember that the pharmacotherapy has, however, a remarkable efficacy in treating psychiatric disorders that occur in comorbidity with eating disorders, such as mood disorders, anxiety, insomnia, and obsessive-compulsive personality disorders and behavior. PMID:23956871

  13. Pharmacological treatment options for mast cell activation disease.

    PubMed

    Molderings, Gerhard J; Haenisch, Britta; Brettner, Stefan; Homann, Jürgen; Menzen, Markus; Dumoulin, Franz Ludwig; Panse, Jens; Butterfield, Joseph; Afrin, Lawrence B

    2016-07-01

    Mast cell activation disease (MCAD) is a term referring to a heterogeneous group of disorders characterized by aberrant release of variable subsets of mast cell (MC) mediators together with accumulation of either morphologically altered and immunohistochemically identifiable mutated MCs due to MC proliferation (systemic mastocytosis [SM] and MC leukemia [MCL]) or morphologically ordinary MCs due to decreased apoptosis (MC activation syndrome [MCAS] and well-differentiated SM). Clinical signs and symptoms in MCAD vary depending on disease subtype and result from excessive mediator release by MCs and, in aggressive forms, from organ failure related to MC infiltration. In most cases, treatment of MCAD is directed primarily at controlling the symptoms associated with MC mediator release. In advanced forms, such as aggressive SM and MCL, agents targeting MC proliferation such as kinase inhibitors may be provided. Targeted therapies aimed at blocking mutant protein variants and/or downstream signaling pathways are currently being developed. Other targets, such as specific surface antigens expressed on neoplastic MCs, might be considered for the development of future therapies. Since clinicians are often underprepared to evaluate, diagnose, and effectively treat this clinically heterogeneous disease, we seek to familiarize clinicians with MCAD and review current and future treatment approaches. PMID:27132234

  14. Suicidal Behavior in Mood Disorders: Response to Pharmacological Treatment.

    PubMed

    Tondo, Leonardo; Baldessarini, Ross J

    2016-09-01

    Suicidal behavior is strongly associated with depression, especially if accompanied by behavioral activation, dysphoria, or agitation. It may respond to some treatments, but the design of scientifically sound, ethical trials to test for therapeutic effects on suicidal behavior is highly challenging. In bipolar disorder, and possibly also unipolar major depression, an underprescribed medical intervention with substantial evidence of preventive effects on suicidal behavior is long-term treatment with lithium. It is unclear whether this effect is specifically antisuicidal or reflects beneficial effects of lithium on depression, mood instability, and perhaps aggression and impulsivity. Antisuicidal effects of anticonvulsant mood stabilizers (carbamazepine, lamotrigine, valproate) appear to be less than with lithium. Further evaluation is needed for potential antisuicidal effects of atypical antipsychotics with growing evidence of efficacy in depression, particularly acute bipolar depression, while generally lacking risk of inducing agitation, mania, or mood instability. Short-term and long-term value and safety of antidepressants are relatively secure for unipolar depression but uncertain and poorly tested for bipolar depression; their effects on suicidal risk in unipolar depression may be age-dependent. Sedative anxiolytics are virtually unstudied as regards suicidal risks. Adequate management of suicidal risks in mood disorder patients requires comprehensive, clinically skillful monitoring and timely interventions. PMID:27542851

  15. The Management and Outcomes of Pharmacological Treatments for Tinnitus

    PubMed Central

    Palumbo, Devon Beebe; Joos, Kathleen; Ridder, Dirk De; Vanneste, Sven

    2015-01-01

    Tinnitus, a phantom sensation experienced by people around the world, currently is endured without a known cure. Some find the condition tolerable, while others are tortured on a daily basis from the incessant phantom noises. For those who seek treatment, oftentimes, they have a comorbid condition (e.g., depression, anxiety, insomnia), which is treated pharmaceutically. These products aim to reduce the comorbities associated with tinnitus thereby minimizing the overall burden present. Because of the phantom nature of tinnitus, it is often compared to neurologic pain. Since pain can be managed with pharmaceutical options, it is reasonable to assume that similar agents might work to alleviate tinnitus. The effects of antidepressants, benzodiazepines, anticonvulsants, and glutamate antagonists are reviewed in this paper. Table 1 summarizes the pharmaceutical products discussed. Due to the variety of comorbid factors and potential causes of tinnitus, there may not be one pharmaceutical treatment that will combat every type of tinnitus. Nevertheless, a product that finally addresses the true cause of tinnitus, and not just its comorbidities, will benefit millions of people worldwide. PMID:26467416

  16. Pharmacological treatment of cognitive deficits in Alzheimer's disease.

    PubMed

    Brodaty, H; Ames, D; Boundy, K L; Hecker, J; Snowdon, J; Storey, E; Yates, M W

    2001-09-17

    Clinical trials and independent reviews support the use of cholinesterase inhibitors for treating the symptoms of patients with mild to moderate Alzheimer's disease (AD). Before initiating cholinesterase inhibitor therapy, patients should be thoroughly assessed, and the diagnosis confirmed, preferably by a specialist. Compliance with cholinesterase inhibitor therapy should be monitored and the response (in global, cognitive, functional and behavioural domains) reassessed after 2-3 months of treatment. Vitamin E may be protective against AD, and therapy with 1000 IU twice daily may be considered. There is insufficient evidence to support the use of other antioxidant agents, anti-inflammatory agents, monoamine oxidase B inhibitors, folate/homocysteine or antihypertensive drugs in patients with AD, or hormone replacement therapy in affected women. PMID:11665948

  17. Update on the Pharmacological Treatment of Pathological Gambling

    PubMed Central

    Bullock, Scott A.; Potenza, Marc N.

    2014-01-01

    This is an update to a previously published article discussing the neuropsychopharmacology of pathological gambling (PG) (1). In the prior manuscript, we described how cortico-limbic circuitry and neurotransmitter systems (norepinephrine, serotonin, dopamine, opioids, glutamate, and gamma-aminobutyric acid (GABA)) have been implicated in PG. These systems represent potential targets for psychopharmacological treatments for PG, with opioid antagonists arguably showing the most consistent benefit in RCTs. In the past year and half since this publication was prepared, there has been one additional randomized clinical trial (RCT) published along with a single case study. Our original manuscript did not describe in detail findings from case studies or open-label studies so in addition to the new RCT data and a new case report involving naltrexone, here we describe case and open-label findings. A PubMed search was conducted using terms such as “pathological gambling treatment”, “clinical trials and gambling”, and “gambling psychopharmacology.” Using these search terms, numerous results were obtained, necessitating further search modifiers. For example, using just “pathological gambling treatment” results in over 1600 hits. In order to focus in on the search modalities, we searched within the initial results for specific phrases such as “psychopharmacology, clinical trial, medication, serotonergic, dopaminergic, etc.” in addition to searching for specific medications. Results not directly related to the treatment of pathological gambling were not included. The study of pathological gambling is relatively new. As such, our search did not exclude any studies due to age of material, but with a few exceptions, the majority of the studies discussed were published later than 2000. This resulted in 24 case studies and/or RCTs not previously included in our original review article. These findings in conjunction with our prior publication provide a

  18. Long term outcomes of pharmacological treatments for opioid dependence: does methadone still lead the pack?

    PubMed Central

    Garcia-Portilla, Maria Paz; Bobes-Bascaran, Maria Teresa; Bascaran, Maria Teresa; Saiz, Pilar Alejandra; Bobes, Julio

    2014-01-01

    The aim of this review was to update and summarize the scientific knowledge on the long term outcomes of the different pharmacological treatment options for opioid dependence currently available and to provide a critical discussion on the different treatment options based on these results. We performed a literature search using the PubMed databases and the reference lists of the identified articles. Data from research show that the three pharmacological options reviewed are effective treatments for opioid dependence with positive long term outcomes. However, each one has its specific target population and setting. While methadone and buprenorphine are first line options, heroin-assisted treatment is a second line option for those patients refractory to treatment with methadone with concomitant severe physical, mental, social and/or functional problems. Buprenorphine seems to be the best option for use in primary care offices. The field of opioid dependence treatment is poised to undergo a process of reinforcement and transformation. Further efforts from researchers, clinicians and authorities should be made to turn new pharmacological options into clinical reality and to overcome the structural and functional obstacles that maintenance programmes face in combatting opioid dependence. PMID:23145768

  19. PTSD and comorbid AUD: a review of pharmacological and alternative treatment options

    PubMed Central

    Ralevski, Elizabeth; Olivera-Figueroa, Lening A; Petrakis, Ismene

    2014-01-01

    Background Although posttraumatic stress disorder (PTSD) and alcohol use disorders (AUD) frequently co-occur there are no specific treatments for individuals diagnosed with these comorbid conditions. The main objectives of this paper are to review the literature on pharmacological options for PTSD and comorbid AUD, and to summarize promising behavioral and alternative interventions for those with these dual diagnoses. Methods We conducted a comprehensive search on PsycINFO and MEDLINE/PubMed databases using Medical Subject Headings terms in various combinations to identify articles that used pharmacotherapy for individuals with dual diagnoses of PTSD and AUD. Similar strategies were used to identify articles on behavioral and alternative treatments for AUD and PTSD. We identified and reviewed six studies that tested pharmacological treatments for patients with PTSD and comorbid AUD. Results The literature on treatment with US Food and Drug Administration approved medications for patients with dual diagnosis of PTSD and AUD is very limited and inconclusive. Promising evidence indicates that topiramate and prazosin may be effective in reducing PTSD and AUD symptoms in individuals with comorbidity. Seeking safety has had mixed efficacy in clinical trials. The efficacy of other behavioral and alternative treatments (mindfulness-based, yoga, and acupuncture) is more difficult to evaluate since the evidence comes from small, single studies without comparison groups. Conclusion There is a clear need for more systematic and rigorous study of pharmacological, behavioral, and alternative treatments for patients with dual diagnoses of PTSD and AUD. PMID:24648794

  20. Current Controversies in the Pharmacological Treatment of Chronic Obstructive Pulmonary Disease.

    PubMed

    Singh, Dave; Roche, Nicolas; Halpin, David; Agusti, Alvar; Wedzicha, Jadwiga A; Martinez, Fernando J

    2016-09-01

    Clinical phenotyping is currently used to guide pharmacological treatment decisions in chronic obstructive pulmonary disease (COPD), a personalized approach to care. Precision medicine integrates biological (endotype) and clinical (phenotype) information for a more individualized approach to pharmacotherapy, to maximize the benefit versus risk ratio. Biomarkers can be used to identify endotypes. To evolve toward precision medicine in COPD, the most appropriate biomarkers and clinical characteristics that reliably predict treatment responses need to be identified. FEV1 is a marker of COPD severity and has historically been used to guide pharmacotherapy choices. However, we now understand that the trajectory of FEV1 change, as an indicator of disease activity, is more important than a single FEV1 measurement. There is a need to develop biomarkers of disease activity to enable a more targeted and individualized approach to pharmacotherapy. Recent clinical trials testing commonly used COPD treatments have provided new information that is likely to influence pharmacological treatment decisions both at initial presentation and at follow up. In this Perspective, we consider the impact of recent clinical trials on current COPD treatment recommendations. We also focus on the movement toward precision medicine and propose how this field needs to evolve in terms of using clinical characteristics and biomarkers to identify the most appropriate patients for a given pharmacological treatment. PMID:27585383

  1. Are we taking full advantage of the growing number of pharmacological treatment options for osteoporosis?

    PubMed Central

    Jepsen, Karl J.; Schlecht, Stephen H.; Kozloff, Kenneth M.

    2014-01-01

    We are becoming increasingly aware that the manner in which our skeleton ages is not uniform within and between populations. Pharmacological treatment options with the potential to combat age-related reductions in skeletal strength continue to become available on the market, notwithstanding our current inability to fully utilize these treatments by accounting for an individual’s unique biomechanical needs. Revealing new molecular mechanisms that improve the targeted delivery of pharmaceuticals is important; however, this only addresses one part of the solution for differential age-related bone loss. To improve current treatment regimes, we must also consider specific biomechanical mechanisms that define how these molecular pathways ultimately impact whole bone fracture resistance. By improving our understanding of the relationship between molecular and biomechanical mechanisms, clinicians will be better equipped to take full advantage of the mounting pharmacological treatments available. Ultimately this will enable us to reduce fracture risk among the elderly more strategically, more effectively, and more economically. In this interest, the following review summarizes the biomechanical basis of current treatment strategies while defining how different biomechanical mechanisms lead to reduced fracture resistance. It is hoped that this may serve as a template for the identification of new targets for pharmacological treatments that will enable clinicians to personalize care so that fracture incidence may be globally reduced. PMID:24747363

  2. PHARMACOLOGIC TREATMENT OF HYPERALGESIA EXPERIMENTALLY INDUCED BY NUCLEUS PULPOSUS

    PubMed Central

    de Souza Grava, André Luiz; Ferrari, Luiz Fernando; Parada, Carlos Amílcar; Defino, Helton Luiz Aparecido

    2015-01-01

    Objective: To evaluate the effect of anti-inflammatory drugs (dexamethasone, indomethacin, atenolol and indomethacin plus atenolol) and analgesic drugs (morphine) on hyperalgesia experimentally induced by the nucleus pulposus (NP) in contact with the L5 dorsal root ganglion (DRG). Methods: Thirty male Wistar rats of weights ranging from 220 to 250 g were used in the study. Hyperalgesia was induced by means of a fragment of NP removed from the sacrococcygeal region that was placed in contact with the L5 dorsal root ganglion. The 30 animals were divided into experimental groups according to the drug used. The drugs were administered for two weeks after the surgical procedure to induce hyperalgesia. Mechanical and thermal hyperalgesia was evaluated using the paw pressure test, von Frey electronic test and Hargreaves test, over a seven-week period. Results: The greatest reduction of hyperalgesia was observed in the group of animals treated with morphine, followed by dexamethasone, indomethacin and atenolol. Reductions in hyperalgesia were observed after drug administration ceased, except for the group of animals treated with morphine, in which there was an increase in hyperalgesia after discontinuation of the treatment. Conclusion: Hyperalgesia induced by NP contact with the DRG can be reduced through administration of anti-inflammatory and analgesic drugs, but a greater reduction was observed with the administration of dexamethasone. PMID:27026966

  3. The meaning of pharmacological treatment for schizophrenic patients1

    PubMed Central

    Vedana, Kelly Graziani Giacchero; Miasso, Adriana Inocenti

    2014-01-01

    OBJECTIVE: to understand the meaning of medication therapy for schizophrenic patients and formulate a theoretical model about the study phenomenon. METHOD: a qualitative approach was employed, using Symbolic Interactionism as the theoretical and Grounded Theory as the methodological framework. The research was developed between 2008 and 2010 at three community mental health services in the interior of the State of São Paulo - Brazil. Thirty-six patients and thirty-six family members were selected through theoretical sampling. The data were mainly collected through open interviews and observation and simultaneously analyzed through open, axial and selective coding. RESULTS: the meaning of the pharmacotherapy is centered on the phenomenon "Living with a help that bothers", which expresses the patients' ambivalence towards the medication and determines their decision making. The insight, access, limitations for self-administration of the drugs and interactions with family members and the health team influenced the patient's medication-related behavior. CONCLUSION: the theory presented in this study provides a comprehensive, contextualized, motivational and dynamic understanding of the relation the patient experiences and indicates potentials and barriers to follow the medication treatment. PMID:25296152

  4. Physical Training as Non-Pharmacological Treatment of Neurocardiogenic Syncope

    PubMed Central

    Takahagi, Vanessa Cristina Miranda; Costa, Daniela Caetano; Crescêncio, Júlio César; Gallo, Lourenço

    2014-01-01

    Background Characterized as a sudden and temporary loss of consciousness and postural tone, with quick and spontaneous recovery, syncope is caused by an acute reduction of systemic arterial pressure and, therefore, of cerebral blood flow. Unsatisfactory results with the use of drugs allowed the nonpharmacological treatment of neurocardiogenic syncope was contemplated as the first therapeutic option. Objectives To compare, in patients with neurocardiogenic syncope, the impact of a moderate intensity aerobic physical training (AFT) and a control intervention on the positivity of head-up tilting test (HUT) and orthostatic tolerance time. Methods Were studied 21 patients with a history of recurrent neurocardiogenic syncope and HUT. The patients were randomized into: trained group (TG), n = 11, and control group (CG), n = 10. The TG was submitted to 12 weeks of AFT supervised, in cycle ergometer, and the CG to a control procedure that consisted in 15 minutes of stretching and 15 minutes of light walk. Results The TG had a positive effect to physical training, with a significant increase in peak oxygen consumption. The CG did not show any statistically significant change before and after the intervention. After the intervention period, 72.7% of the TG sample had negative results to the HUT, not having syncope in the revaluation. Conclusion The program of supervised aerobic physical training for 12 weeks was able to reduce the number of positive HUT, as it was able to increase tolerance time in orthostatic position during the HUT after the intervention period. PMID:24714795

  5. Pharmacological treatment of antipsychotic-induced dyslipidemia and hypertension.

    PubMed

    Tse, Lurdes; Procyshyn, Ric M; Fredrikson, Diane H; Boyda, Heidi N; Honer, William G; Barr, Alasdair M

    2014-05-01

    Second-generation antipsychotics (SGAs) are associated with significant comorbid metabolic abnormalities. Adjunct medications may be prescribed to treat these metabolic side effects, but the evidence supporting this practice (especially for the management of antipsychotic-associated dyslipidemia and hypertension) is limited. The purpose of this review was to evaluate the effects of adjunct medications on triglyceride, total cholesterol, low-density lipoprotein, high-density lipoprotein, and blood pressure levels in participants taking SGAs for psychosis. Studies were systematically searched and evaluated. Studies were included for review if participants were taking SGAs and if lipid and/or blood pressure levels were included as outcome measures. Statins, conventional lipid-lowering agents, fluvoxamine, ramelteon, topiramate, valsartan, telmisartan, omega-3 fatty acids, metformin (including both immediate-release and extended-release formulations), and a combination of metformin-sibutramine seemed to have beneficial effects on lipid levels. Valsartan, telmisartan, and topiramate appeared to be effective for controlling increases in blood pressure. The literature on adjunct medications for the treatment of antipsychotic-associated dyslipidemia and hypertension is not exhaustive, and long-term randomized-controlled trials would offer valuable results. PMID:24169026

  6. Pharmacological interventions in the treatment of the acute effects of cannabis: a systematic review of literature

    PubMed Central

    2012-01-01

    Background Cannabis intoxication is related to a number of physical and mental health risks with ensuing social costs. However, little attention has been given to the investigation of possible pharmacological interactions in this condition. Objective To review the available scientific literature concerning pharmacological interventions for the treatment of the acute effects of cannabis. Methods A search was performed on the Pubmed, Lilacs, and Scielo online databases by combining the terms cannabis, intoxication, psychosis, anxiety, and treatment. The articles selected from this search had their reference lists checked for additional publications related to the topic of the review. Results The reviewed articles consisted of case reports and controlled clinical trials and are presented according to interventions targeting the physiological, psychiatric, and cognitive symptoms provoked by cannabis. The pharmacological interventions reported in these studies include: beta-blockers, antiarrhythmic agents, antagonists of CB-1 and GABA-benzodiazepine receptors, antipsychotics, and cannabidiol. Conclusion Although scarce, the evidence on pharmacological interventions for the management of cannabis intoxication suggests that propanolol and rimonabant are the most effective compounds currently available to treat the physiological and subjective effects of the drug. Further studies are necessary to establish the real effectiveness of these two medications, as well as the effectiveness of other candidate compounds to counteract the effects of cannabis intoxication, such as cannabidiol and flumazenil. PMID:22273390

  7. Patient Preference for Psychological vs. Pharmacological Treatment of Psychiatric Disorders: A Meta-Analytic Review

    PubMed Central

    McHugh, R. Kathryn; Whitton, Sarah W.; Peckham, Andrew D.; Welge, Jeffrey A.; Otto, Michael W.

    2014-01-01

    Objective Models of evidence-based practice emphasize the consideration of treatment efficacy/effectiveness, clinical expertise, and patient preference in treatment selection and implementation. However, patient preference for psychiatric treatment has been understudied. The aim of this meta-analytic review was to provide an estimate of the proportion of patients preferring psychological treatment relative to medication for psychiatric disorders. Data Sources A literature search was conducted using PubMed, PsycINFO, and the Cochrane Collaboration Library through August, 2011 for studies written in English that assessed patient preferences for the treatment of psychiatric disorders. Study Selection Studies assessing the preferred type of treatment including at least one psychological treatment and one pharmacological treatment were included. Of the 641 articles initially identified, 34 met criteria for inclusion. Data Extraction Authors extracted relevant data including the proportion of participants reporting preference for psychological and pharmacological treatment. Results Across studies, the proportion preferring psychological treatment was 0.75 (95% CI: 0.69 to 0.80), which was significantly higher than equivalent preference (i.e., higher than 0.50, p < .001). Sensitivity analyses suggested that younger patients (p < .05) and women (p < .01) were significantly more like to choose psychological treatment. A preference for psychological treatment was consistently evident in both treatment-seeking and unselected samples (ps < .05), but was somewhat stronger for the unselected samples. Conclusions Aggregation of patient preferences across diverse settings yielded a significant three-fold preference for psychological treatment relative to medication. Given the similar efficacy of these treatments for depression and anxiety, improving access to evidence-based psychological treatment is needed to connect more patients to their preferred treatment. PMID:23842011

  8. Addressing the unmet needs of patients with persistent negative symptoms of schizophrenia: emerging pharmacological treatment options

    PubMed Central

    Chue, Pierre; Lalonde, Justine K

    2014-01-01

    The negative symptoms of schizophrenia represent an impairment of normal emotional responses, thought processes and behaviors, and include blunting or flattening of affect, alogia/aprosody, avolition/apathy, anhedonia, and asociality. Negative symptoms contribute to a reduced quality of life, increased functional disability, increased burden of illness, and poorer long-term outcomes, to a greater degree than positive symptoms. Primary negative symptoms are prominent and persistent in up to 26% of patients with schizophrenia, and they are estimated to occur in up to 58% of outpatients at any given time. Negative symptoms respond less well to medications than positive symptoms, and to date treatment options for negative symptoms have been limited, with no accepted standard treatment. Modest benefits have been reported with a variety of different agents, including second-generation antipsychotics and add-on therapy with antidepressants and other pharmacological classes. Recent clinical research focusing on negative symptoms target novel biological systems, such as glutamatergic neurotransmission. Different approaches include: enhancing N-methyl-D-aspartate receptor function with agents that bind directly to the glycine ligand site or with glycine reuptake inhibitors; influencing the metabotropic glutamate receptor (mGluR2/3) with positive allosteric modulators; and stimulating nicotinic acetylcholine receptors. In conclusion, the lack of clearly efficacious pharmacological treatments for the management of negative symptoms represents a significant unmet need, especially considering the importance of these symptoms on patient outcomes. Hence, further research to identify and characterize novel pharmacological treatments for negative symptoms is greatly needed. PMID:24855363

  9. Systematic Review of Pharmacological and Behavioral Treatments for Skin Picking Disorder.

    PubMed

    Schumer, Maya C; Bartley, Christine A; Bloch, Michael H

    2016-04-01

    Skin picking disorder (SPD) is a newly recognized psychiatric disorder in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. A systematic review was conducted to assess the efficacy of pharmacological and behavioral interventions for SPD. Electronic databases were searched for randomized controlled trials (RCTs) or uncontrolled trials involving at least 10 subjects that examined the efficacy of pharmacological and behavioral interventions for SPD. We examined the improvement associated with interventions compared with inactive control conditions in RCTs and improvement over time in uncontrolled trials and within the treatment arms of RCTs. We stratified studies on the basis of intervention type. Meta-analysis included 11 studies. All interventions (including inactive control conditions) demonstrated significant improvement over the course of short-term clinical trials in SPD. Only behavioral treatments demonstrated significant benefits compared with inactive control conditions. There was no evidence from RCTs that pharmacotherapy with selective serotonin reuptake inhibitors or lamotrigine were more effective at treating SPD than placebo. Our meta-analysis suggests that subjects with SPD show significant improvement during short-term trials, regardless of the efficacy of the underlying intervention. This finding suggests that uncontrolled trials are of particularly limited utility for assessing efficacy of treatments in SPD. Future research should concentrate on developing larger placebo-controlled RCTs to examine efficacy of novel pharmacological agents. In addition, research should focus on improving accessibility of behavioral treatments with demonstrated efficacy for SPD. PMID:26872117

  10. Pharmacological treatments for fatigue associated with palliative care: executive summary of a Cochrane Collaboration systematic review

    PubMed Central

    Mochamat; Cuhls, Henning; Peuckmann‐Post, Vera; Minton, Ollie; Stone, Patrick; Radbruch, Lukas

    2016-01-01

    Abstract Background In palliative care patients, fatigue can be severely debilitating and is often not counteracted with rest, thereby impacting daily activity and quality of life. Further complicating issues are the multidimensionality, subjective nature and lack of a consensus definition of fatigue. The review aimed to evaluate the efficacy of pharmacological treatments for fatigue in palliative care, with a focus on patients at an advanced stage of disease, including patients with cancer and other chronic diseases. Methods We considered randomized controlled trials concerning adult palliative care with a focus on pharmacological treatment of fatigue compared with placebo, application of two drugs, usual care or a non‐pharmacological intervention. The primary outcome had to be non‐specific fatigue (or related terms such as asthenia). We searched the CENTRAL, MEDLINE, PsycINFO and EMBASE, and a selection of cancer journals up to 28 April 2014. Two review authors independently assessed trial quality and extracted the data. Results We screened 1645 publications of which 45 met the inclusion criteria. In total, we analysed data from 18 drugs and 4696 participants. There was a very high degree of statistical and clinical heterogeneity in the trials. Meta‐analysis of data was possible for modafinil, pemoline, and methylphenidate. Conclusions Due to the limited evidence, we cannot recommend a specific drug for the treatment of fatigue in palliative care patients. Some drugs, which may be beneficial for the treatment of fatigue associated with palliative care such as amantadine, methylphenidate, and modafinil, should be further researched. PMID:27066315

  11. Pharmacological treatment and demographic characteristics of pediatric patients with Attention Deficit Hyperactivity Disorder, Sweden.

    PubMed

    Bahmanyar, Shahram; Sundström, Anders; Kaijser, Magnus; von Knorring, Anne-Liis; Kieler, Helle

    2013-12-01

    The aim of this study was to describe the pediatric population with ADHD and their pharmacological treatment. Using the Swedish National Patient Register and the Prescribed Drug Register we identified individuals below 19 years of age who were diagnosed or medically treated for ADHD for the first time 2006-2007. The unique patient identifiers were used to link information from the two registers to describe demographic characteristics, hospital care and drug treatments. Logistic regression model estimated the association between age, sex, frequency of hospitalization, diagnosis or treatment for other mental disorders and risk of gap in the treatment. Totally the study included 7931 patients of whom 74% were males. The mean age at first diagnosis was 12 years. Some 84% were medically treated for ADHD and approximately 90% received methylphenidate as the first substance. Combination therapy was rare and the most common combination was methylphenidate and atomoxetine. More than 55% of the patients, which could be followed up for two years after start of treatment, had at least one treatment gap of six months. Older age at diagnosis, lower number of hospitalizations and comorbidity with other mental disorders increased risks of gaps in medication. Approximately one fifth of the patients recorded in the National Patient Register as diagnosed with ADHD did not receive pharmacological treatment. Medication adherence seems to be low, when measured as gaps in treatment. PMID:23953271

  12. Investigation of original multivalent iminosugars as pharmacological chaperones for the treatment of Gaucher disease.

    PubMed

    Laigre, Eugénie; Hazelard, Damien; Casas, Josefina; Serra-Vinardell, Jenny; Michelakakis, Helen; Mavridou, Irene; Aerts, Johannes M F G; Delgado, Antonio; Compain, Philippe

    2016-06-24

    Multivalent iminosugars conjugated with a morpholine moiety and/or designed as prodrugs have been prepared and evaluated as new classes of pharmacological chaperones for the treatment of Gaucher disease. This study further confirms the interest of the prodrug concept and shows that the addition of a lysosome-targeting morpholine unit into iminosugar cluster structures has no significant impact on the chaperone activity on Gaucher cells. PMID:27063390

  13. [Major depression in the child: validation of the syndrome and pharmacologic treatment].

    PubMed

    Goulet, J

    1989-02-01

    The concept of childhood depression has been the object of controversies over many years. Recent developments have permitted rapid progress in many areas of research. The author offers an update on the validity of the diagnosis of major depression in childhood and on pharmacological treatment. He then attempts to delineate the uses and limitations of this therapeutic approach. In the latter part, practical advice on the use of drugs in childhood depression is given. PMID:2647269

  14. Treating the insomniac patient - General measures and psychological and pharmacological treatment

    NASA Technical Reports Server (NTRS)

    Kales, A.; Bixler, E. O.; Kales, J. D.

    1975-01-01

    The general preliminary measures for treating insomnia include moderate physical exercise several hours before bedtime, and the relaxation of complex mental activity before bedtime. A case history concerning a woman with marital troubles is offered as evidence that insomnia may be caused by deeply rooted psychological and situational problems. Another case history illustrates how prior pharmacological treatment may complicate the process of clinically evaluating an insomniac.

  15. Long-Term Pharmacological Treatments of Anxiety Disorders: An Updated Systematic Review.

    PubMed

    Perna, Giampaolo; Alciati, Alessandra; Riva, Alice; Micieli, Wilma; Caldirola, Daniela

    2016-03-01

    Many aspects of long-term pharmacological treatments for anxiety disorders (AnxDs) are still debated. We undertook an updated systematic review of long-term pharmacological studies on panic disorder (PD), generalized anxiety disorder (GAD), and social anxiety disorder (SAD). Relevant studies dating from January 1, 2012 to August 31, 2015 were identified using the PubMed database and a review of bibliographies. Of 372 records identified in the search, five studies on PD and 15 on GAD were included in the review. No studies on SAD were found. Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy. Paroxetine, escitalopram, and clonazepam can be effective for long-term treatment of PD. However, further studies are needed to draw conclusions about the long-term benzodiazepine use in PD, particularly for the possible cognitive side-effects over time. Pregabalin and quetiapine can be effective for long-term treatment of GAD, while preliminary suggestions emerged for agomelatine and vortioxetine. We did not find any evidence for determining the optimal length and/or dosage of medications to minimize the relapse risk. Few investigations have attempted to identify potential predictors of long-term treatment response. Personalized treatments for AnxDs can be implemented using predictive tools to explore those factors affecting treatment response/tolerability heterogeneity, including neurobiological functions/clinical profiles, comorbidity, biomarkers, and genetic features, and to tailor medications according to each patient's unique features. PMID:26830881

  16. Pharmacological treatment of Alzheimer's dementia: state of the art and current dilemmas.

    PubMed

    Omerovic, Muamer; Hampel, Harald; Teipel, Stefan J; Buerger, Katharina

    2008-01-01

    Alzheimer's disease (AD) is one of the most frequent disorders of the central nervous system characterised by a progressive cognitive decline. The demographic changes of our aging population lead to increased numbers of patients and a need of early diagnosis and treatment of cognitive and behavioural symptoms of AD. Drugs are available for symptomatic treatment of AD. The pharmacological treatment of behavioural disturbances experienced dynamic changes in the last years. In this paper, we present the current state and future perspectives in the treatment of AD. Furthermore, we discuss current difficulties regarding AD treatment by looking for explanations for a still unsatisfying rate of state-of-the-art treatment of AD-patients. PMID:17886162

  17. Pharmacological induction of mitochondrial biogenesis as a therapeutic strategy for the treatment of type 2 diabetes.

    PubMed

    Zamora, Mònica; Pardo, Rosario; Villena, Josep A

    2015-11-01

    Defects in mitochondrial oxidative function have been associated with the onset of type 2 diabetes. Although the causal relationship between mitochondrial dysfunction and diabetes has not been fully established, numerous studies indicate that improved glucose homeostasis achieved via lifestyle interventions, such as exercise or calorie restriction, is tightly associated with increased mitochondrial biogenesis and oxidative function. Therefore, it is conceivable that potentiating mitochondrial biogenesis by pharmacological means could constitute an efficacious therapeutic strategy that would particularly benefit those diabetic patients who cannot adhere to comprehensive programs based on changes in lifestyle or that require a relatively rapid improvement in their diabetic status. In this review, we discuss several pharmacological targets and drugs that modulate mitochondrial biogenesis as well as their potential use as treatments for insulin resistance and diabetes. PMID:26212547

  18. Managing insomnia: an overview of insomnia and pharmacologic treatment strategies in use and on the horizon.

    PubMed

    Schwartz, Thomas L; Goradia, Viral

    2013-10-01

    This review explores basic sleep physiology, the mechanism of action for each class of hypnotic agents, their clinical application based on pharmacodynamic and pharmacokinetic factors, and potential pharmacologic sleep-inducing mechanisms of future hypnotics. The paper challenges the reader to understand the neuroscientific basis of insomnia and use this knowledge to guide prescription of hypnotic agents. Currently indicated hypnotic agents are discussed with regard to their mechanism of drug action and clinical application. A broader discussion is developed throughout this paper regarding other non-indicated agents that may improve sleep and describing newer pharmacological treatments that may become available in the future for use in sleep disorders and their comorbid conditions. PMID:24432044

  19. Managing insomnia: an overview of insomnia and pharmacologic treatment strategies in use and on the horizon

    PubMed Central

    Schwartz, Thomas L; Goradia, Viral

    2013-01-01

    This review explores basic sleep physiology, the mechanism of action for each class of hypnotic agents, their clinical application based on pharmacodynamic and pharmacokinetic factors, and potential pharmacologic sleep-inducing mechanisms of future hypnotics. The paper challenges the reader to understand the neuroscientific basis of insomnia and use this knowledge to guide prescription of hypnotic agents. Currently indicated hypnotic agents are discussed with regard to their mechanism of drug action and clinical application. A broader discussion is developed throughout this paper regarding other non-indicated agents that may improve sleep and describing newer pharmacological treatments that may become available in the future for use in sleep disorders and their comorbid conditions. PMID:24432044

  20. Pharmacologic Considerations in the Treatment of Hepatitis C Virus in Persons With HIV.

    PubMed

    MacBrayne, Christine E; Kiser, Jennifer J

    2016-07-15

    Roughly one-third of individuals living with the human immunodeficiency virus (HIV) are coinfected with the hepatitis C virus (HCV) due to shared routes of transmission. HIV accelerates the progression of HCV disease; thus, coinfected individuals are at high priority for HCV treatment. Several new HCV therapies, called direct-acting antiviral agents (DAAs), are available that achieve cure rates of >90% in many patient populations including individuals with HIV. The primary consideration in treating HCV in HIV-infected persons is the potential for drug interactions. We describe the clinical pharmacology and drug interaction potential of the DAAs, review the interaction data with DAAs and antiretroviral agents, and identify the knowledge gaps in the pharmacologic aspects of treating HCV in individuals with HIV coinfection. This review will focus on DAAs that have received regulatory approval in the United States and Europe and agents in late stages of clinical development. PMID:27363437

  1. Pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders across the lifespan

    PubMed Central

    Doyle, Carolyn A.; McDougle, Christopher J.

    2012-01-01

    This review outlines pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders (ASDs) in children, adolescents, and adults. Symptom domains include repetitive and stereotyped behaviors, irritability and aggression, hyperactivity and inattention, and social impairment. Medications covered include serotonin reuptake inhibitors (SRIs), mirtazapine, antipsychotics, psychostimulants, atomoxetine, α-2 agonists, D-cycloserine, and memantine. Overall, SRIs are less efficacious and more poorly tolerated in children with ASDs than in adults. Antipsychotics are the most efficacious drugs for the treatment of irritability in ASDs, and may be useful in the treatment of other symptoms. Psychostimulants demonstrate some benefit for the treatment of hyperactivity and inattention in individuals with ASDs, but are less efficacious and associated with more adverse effects compared with individuals with ADHD. D-cycloserine and memantine appear helpful in the treatment of social impairment, although further research is needed. PMID:23226952

  2. Clinical practices in the pharmacological treatment of comorbid psychopathology in adolescents with alcohol use disorders.

    PubMed

    Clark, Duncan B; Wood, D Scott; Cornelius, Jack R; Bukstein, Oscar G; Martin, Christopher S

    2003-12-01

    This study examined the use of psychiatric medications in 277 adolescents in treatment for alcohol use disorders. Subjects were recruited from addictions treatment sites, psychiatric programs, and juvenile justice settings. Characteristics studied included the use of and indications for specific medications, changes in clinical practices from 1991 through 2000, and continuation of psychopharmacological treatment over a 1-year followup period. Among adolescents taking psychiatric medications at baseline (n = 51), indicated DSM-IV mental disorders were typically present, use of antidepressants was most common (n = 41), benzodiazepine prescription was rare, and about one third reported continuing pharmacological treatment at one-year followup. In those with comorbid major depressive disorder and alcohol use disorders (n = 110), antidepressant medication use increased significantly from 18% to 55% over the decade studied. The treatment setting did not significantly influence antidepressant prescribing practices. The common and increasing use of psychiatric medications in this population emphasizes the urgent need for empirically based clinical guidelines. PMID:14693259

  3. Recurrent Vascular Headache: Home-Based Behavioral Treatment versus Abortive Pharmacological Treatment.

    ERIC Educational Resources Information Center

    Holroyd, Kenneth A.; And Others

    1988-01-01

    Compared the effectiveness of a home-based behavioral intervention (relaxation and thermal biofeedback training) with an abortive pharmacological intervention (with compliance training) for treating recurrent migraine and migraine/tension headaches. Both interventions yielded reductions in headache activity, psychosomatic symptoms, and daily life…

  4. Combining Pharmacological and Psychological Treatments for Binge Eating Disorder: Current Status, Limitations, and Future Directions.

    PubMed

    Grilo, Carlos M; Reas, Deborah L; Mitchell, James E

    2016-06-01

    Binge eating disorder (BED) is characterized by recurrent binge eating and marked distress about binge eating without the extreme compensatory behaviors for weight control that characterize other eating disorders. BED is prevalent, associated strongly with obesity, and is associated with heightened levels of psychological, psychiatric, and medical concerns. This article provides an overview of randomized controlled treatments for combined psychological and pharmacological treatment of BED to inform current clinical practice and future treatment research. In contrast to the prevalence and significance of BED, to date, limited research has been performed on combining psychological and pharmacological treatments for BED to enhance outcomes. Our review here found that combining certain medications with cognitive behavioral therapy (CBT) or behavioral weight loss (BWL) interventions produces superior outcomes to pharmacotherapy only but does not substantially improve outcomes achieved with CBT/BWL only. One medication (orlistat) has improved weight losses with CBT/BWL albeit minimally, and only one medication (topiramate) has enhanced reductions achieved with CBT in both binge eating and weight. Implications for future research are discussed. PMID:27086316

  5. Identification of validated questionnaires to measure adherence to pharmacological antihypertensive treatments

    PubMed Central

    Pérez-Escamilla, Beatriz; Franco-Trigo, Lucía; Moullin, Joanna C; Martínez-Martínez, Fernando; García-Corpas, José P

    2015-01-01

    Background Low adherence to pharmacological treatments is one of the factors associated with poor blood pressure control. Questionnaires are an indirect measurement method that is both economic and easy to use. However, questionnaires should meet specific criteria, to minimize error and ensure reproducibility of results. Numerous studies have been conducted to design questionnaires that quantify adherence to pharmacological antihypertensive treatments. Nevertheless, it is unknown whether questionnaires fulfil the minimum requirements of validity and reliability. The aim of this study was to compile validated questionnaires measuring adherence to pharmacological antihypertensive treatments that had at least one measure of validity and one measure of reliability. Methods A literature search was undertaken in PubMed, the Excerpta Medica Database (EMBASE), and the Latin American and Caribbean Health Sciences Literature database (Literatura Latino-Americana e do Caribe em Ciências da Saúde [LILACS]). References from included articles were hand-searched. The included papers were all that were published in English, French, Portuguese, and Spanish from the beginning of the database’s indexing until July 8, 2013, where a validation of a questionnaire (at least one demonstration of the validity and at least one of reliability) was performed to measure adherence to antihypertensive pharmacological treatments. Results A total of 234 potential papers were identified in the electronic database search; of these, 12 met the eligibility criteria. Within these 12 papers, six questionnaires were validated: the Morisky–Green–Levine; Brief Medication Questionnaire; Hill-Bone Compliance to High Blood Pressure Therapy Scale; Morisky Medication Adherence Scale; Treatment Adherence Questionnaire for Patients with Hypertension (TAQPH); and Martín–Bayarre–Grau. Questionnaire length ranged from four to 28 items. Internal consistency, assessed by Cronbach’s α, varied from 0

  6. Development of a self-treatment approach for patients with COPD and comorbidities: an ongoing learning process

    PubMed Central

    Lenferink, Anke; Buckman, Julie; Spicer, Deborah; Cafarella, Paul A.; Burt, Morton G.; Bassett, Katherine L.; van Ommeren, Clara; Anesbury, Sally; van der Valk, Paul D L P M; Frith, Peter A.; van der Palen, Job

    2014-01-01

    Background Patient-initiated action plans are an important component of COPD self-management (SM) interventions. When integrated into SM interventions, these action plans have proven to be effective in reducing exacerbation severity, hospitalisations, and costs and in improving health status in patients with COPD without severe comorbidities. Because of overlap in symptoms, a self-treatment (ST) approach that focuses solely on traditional symptoms of COPD is inadequate for patients with COPD and comorbidities. The COPE-III SM intervention combines (I) patient-initiated action plans that are tailored to the individual’s co-morbid disease(s), and (II) ongoing nurse support. In this paper we provide information regarding the integration of information from two previous COPD SM studies (COPE I and II) in the development of the current COPE-III ST approach. Materials and methods COPE-III ST materials include daily symptom diaries and action plans that take patient’s common comorbidities [chronic heart failure (CHF), anxiety, depression, ischaemic heart disease (IHD), and diabetes] into account. The comorbid diary and action plans components were developed in collaboration with multiple disease-experts. Results Previous SM studies have highlighted some essential topics that need to be considered when developing a SM or ST approach: ‘when to initiate ST’, ‘how to optimize materials and safety’, and ‘how to achieve behavioural change’. In the COPE-III study, ST is initiated after a significant change in symptoms. This is consistent with the COPE-II approach and was implemented because disease symptoms are often present even when patients are stable. We have tried to ensure patient safety by providing an easily accessible case-manager to patients throughout their involvement in the study. Furthermore, a psychologist has ensured the use of behavioural change techniques throughout the intervention. Conclusions We should continue to learn from our experiences

  7. Pharmacological telomerase inhibition can sensitize drug-resistant and drug-sensitive cells to chemotherapeutic treatment.

    PubMed

    Ward, Ryan J; Autexier, Chantal

    2005-09-01

    Effective strategies to reverse or prevent chemotherapeutic resistance are required before cancer therapies can be curative. Telomerase is the ribonucleoprotein responsible for de novo synthesis and maintenance of telomeres, and its activity is predominantly observed in cancer cells. The telomerase enzyme has been successfully inhibited or inactivated to sensitize cells to cellular stresses; however, no studies have determined yet the effect of combining a pharmacological inhibitor of telomerase catalysis and traditional chemotherapeutics for the treatment of drug-sensitive or drug-resistant cancers. Here, we describe the effect of 2-[(E)-3-naphtalen-2-yl-but-2-enoylamino]-benzoic acid (BIBR1532), a small-molecule inhibitor of telomerase catalytic activity, on drug-resistant leukemia and breast cancer cells and their parental counterparts when treated in combination with chemotherapeutics. We observed that BIBR1532-treated cells show progressive telomere shortening, decreased proliferative capacity, and sensitization to chemotherapeutic treatment. These effects are telomere length-dependent, because cells insensitive to BIBR1532 or cells released from telomerase inhibition did not demonstrate changes in growth ability or drug sensitivity. Our novel observations suggest that pharmacological telomerase inhibition in combination therapy may be a valid strategy for the treatment of both drug-sensitive and drug-resistant cancers. PMID:15939802

  8. Longitudinal clinical course following pharmacological treatment of methamphetamine psychosis which persists after long-term abstinence.

    PubMed

    Akiyama, Kazufumi

    2006-08-01

    The present article investigated clinical symptoms and their longitudinal clinical course following pharmacological treatment in 32 female incarcerated patients suffering from methamphetamine (METH) psychosis who were referred to psychiatric consultation. The length of METH-abuse periods of the patients ranged from 2 to 31 years. A total of 31 patients suffered from psychosis at abstinence after 5-31 months from the self-injection of METH. Nine of these 31 patients experienced episodes of psychotic relapse. The following symptoms were observed: auditory hallucination (29 cases), delusion of persecution (29 cases), thought broadcasting (24 cases), visual hallucination (22 cases), depressive mood (29 cases), and suicidal idea (22 cases). Patients exhibited symptoms of psychosis and depression, which persisted for more than several months despite commencement of administration of antipsychotics and antidepressants. There were significant correlations among length of periods required for improvement in total Brief Psychiatric Rating Scale (BPRS) scores, and BPRS subscale scores representing positive symptoms and depression/anxiety dimensions. Three groups of patients, according to severity of positive and depressive/anxiety symptoms, showed apparent differences in prognoses during pharmacological treatment. Average degree of extrapyramidal symptoms significantly correlated with average daily dose of antipsychotics and length-of-treatment period required for improvement in BPRS subscale scores representing positive symptom dimension. These results suggest that both psychotic and affective symptoms are involved in therapeutic response and prognosis of METH psychosis. PMID:17105910

  9. Pharmacological and psychosomatic treatments for an elderly patient with severe nausea and vomiting in reaction to postoperative stress.

    PubMed

    Otera, Masako; Machida, Takatsugu; Machida, Tomomi; Abe, Mai; Ichie, Masayoshi; Fukudo, Shin

    2015-10-01

    Here we present a case of successful treatment employing a mixed approach including pharmacological and psychosomatic treatments for a 72-year-old woman who experienced severe nausea and vomiting in reaction to postoperative stress from gastric cancer surgery. This case demonstrates that appropriate provision of psychosomatic treatments, including a psychotherapeutic session and autogenic training, enhances the efficacy of pharmacotherapy. PMID:26259848

  10. Novel pharmacologic treatment in acute binge eating disorder - role of lisdexamfetamine.

    PubMed

    Guerdjikova, Anna I; Mori, Nicole; Casuto, Leah S; McElroy, Susan L

    2016-01-01

    Binge eating disorder (BED) is the most common eating disorder and an important public health problem. It is characterized by recurrent episodes of excessive food consumption accompanied by a sense of loss of control over the binge eating behavior without the inappropriate compensatory weight loss behaviors of bulimia nervosa. BED affects both sexes and all age groups and is associated with medical and psychiatric comorbidities. Until recently, self-help and psychotherapy were the primary treatment options for patients with BED. In early 2015, lisdexamfetamine dimesylate, a prodrug stimulant marketed for attention deficit hyperactive disorder, was the first pharmacologic agent to be approved by the US Food and Drug Administration for the treatment of moderate or severe BED in adults. This article summarizes BED clinical presentation, and discusses the pharmacokinetic profile, efficacy, and safety of lisdexamfetamine dimesylate in the treatment of BED in adults. PMID:27143885

  11. Pharmacological Treatment of Obesity in Children and Adolescents: Present and Future

    PubMed Central

    Iughetti, Lorenzo; China, Mariachiara; Berri, Rossella; Predieri, Barbara

    2011-01-01

    The prevalence of overweight and obesity is increasing in children and adolescents worldwide raising the question on the approach to this condition because of the potential morbidity, mortality, and economic tolls. Dietetic and behavioral treatments alone have only limited success; consequently, discussion on strategies for treating childhood and adolescent obesity has been promoted. Considering that our knowledge on the physiological systems regulating food intake and body weight is considerably increased, many studies have underlined the scientific and clinical relevance of potential treatments based on management of peripheral or central neuropeptides signals by drugs. In this paper, we analyze the data on the currently approved obesity pharmacological treatment suggesting the new potential drugs. PMID:21197151

  12. Novel pharmacologic treatment in acute binge eating disorder – role of lisdexamfetamine

    PubMed Central

    Guerdjikova, Anna I; Mori, Nicole; Casuto, Leah S; McElroy, Susan L

    2016-01-01

    Binge eating disorder (BED) is the most common eating disorder and an important public health problem. It is characterized by recurrent episodes of excessive food consumption accompanied by a sense of loss of control over the binge eating behavior without the inappropriate compensatory weight loss behaviors of bulimia nervosa. BED affects both sexes and all age groups and is associated with medical and psychiatric comorbidities. Until recently, self-help and psychotherapy were the primary treatment options for patients with BED. In early 2015, lisdexamfetamine dimesylate, a prodrug stimulant marketed for attention deficit hyperactive disorder, was the first pharmacologic agent to be approved by the US Food and Drug Administration for the treatment of moderate or severe BED in adults. This article summarizes BED clinical presentation, and discusses the pharmacokinetic profile, efficacy, and safety of lisdexamfetamine dimesylate in the treatment of BED in adults. PMID:27143885

  13. Relaxin for the Treatment of Acute Decompensated Heart Failure: Pharmacology, Mechanisms of Action, and Clinical Evidence.

    PubMed

    Ng, Tien M H; Goland, Sorel; Elkayam, Uri

    2016-01-01

    Acute heart failure remains a major cause of morbidity, and its treatment requires an increasing investment of the health care system. Whereas success in treating chronic heart failure has been achieved over the last decades, several pharmacological approaches for acute heart failure have been introduced but have failed to demonstrate any clinical benefit. Serelaxin is a recombinant human relaxin-2 vasoactive peptide that causes systemic and renal vasodilation. Data suggest that the clinical benefits may be attributable to a potential combination of multiple actions of serelaxin, including improving systemic, cardiac, and renal hemodynamics, and protecting cells and organs from damage via neurohormonal, anti-inflammatory, antiremodeling, antifibrotic, anti-ischemic, and proangiogenic effects. Recently, a number of clinical trials have demonstrated that serelaxin infusion over 48 hours improved dyspnea with more rapid relief of congestion during the first days after admission for heart failure. In addition, administration of serelaxin diminished cardiac, renal, and hepatic damage, which were associated with improved long-term mortality. Available data support substantial clinical benefits and significant promise for serelaxin as a treatment option for patients with acute heart failure. This review focuses on the pharmacology and mechanisms of action of serelaxin and provides a detailed discussion of the clinical evidence for this novel therapy in acute heart failure. PMID:26331289

  14. Diagnosis of dementia and treatment of Alzheimer's disease. Pharmacologic management of disease progression and cognitive impairment.

    PubMed Central

    van Reekum, R.; Simard, M.; Farcnik, K.

    1999-01-01

    OBJECTIVE: To highlight the importance of family physicians in the management of Alzheimer's disease (AD) and related dementias. To provide an update on the diagnostic workup of people with suspected dementia and on the pharmacologic management of cognitive impairment and disease progression in AD. QUALITY OF EVIDENCE: MEDLINE and Psychological Abstracts were searched using the terms "cognitive enhancers" or a specific drug name and "dementia (exp)." Evidence is generally limited but promising. Methodologic flaws in existing research likely to affect clinicians are briefly reviewed. MAIN MESSAGE: Increasing evidence suggests that early intervention can delay the progression of AD and improve the symptoms and function of those affected. Available treatments have modest but important effects on the outcome of patients with AD; some patients respond dramatically. Most currently available treatments are relatively safe in carefully selected cases. CONCLUSIONS: The diagnostic workup of most cases of dementia can at least be initiated in family physicians' offices. Beginning the workup is important because, for treating AD, the earlier you start, the better. Donepezil, vitamin E, and, in the near future, propentofylline are the main pharmacologic choices for improving cognition and slowing disease progression. PMID:10216793

  15. Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment.

    PubMed

    Gao, Li; Hao, Jian; Niu, Yang-Yang; Tian, Miao; Yang, Xue; Zhu, Cui-Hong; Ding, Xiu-Li; Liu, Xiao-Hui; Zhang, Hao-Ran; Liu, Chang; Qin, Xue-Mei; Wu, Xiong-Zhi

    2016-08-01

    Increasing evidence has shown that Chinese Herbal Medicine (CHM) has efficient therapeutic effects for advanced gastric adenocarcinoma, while the therapeutic mechanisms underlying this treatment remain unclear.In this study, the Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of CHM treatment, and correlation analysis was applied to identify the most effective components in the formulas. A network pharmacological approach was developed to decipher the potential therapeutic mechanisms of CHM.CHM treatment was an independent protective factor. The hazard ratio was 0.364 (95% CI 0.245-0.540; P < 0.001). The median survival time was 18 months for patients who received CHM treatment, while for patients without CHM treatment was decreased to 9 months (P < 0.001). Thirteen out of the total 204 herbs were significantly correlated with favorable survival outcomes (P < 0.05), likely representing the most effective components in these formulas. Bioinformatics analyses suggested that the simultaneous manipulation of multiple targets in proliferation pathways (such as epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor 2, proliferating cell nuclear antigen, and insulin like growth factor 2) and the process of cancer metastasis (collagen families, fibronectin 1 and matrix metalloproteinases families) might largely account for the mechanisms of the 13 herbs against gastric adenocarcinoma.A network pharmacology method was introduced to decipher the underlying mechanisms of CHM, which provides a good foundation for herbal research based on clinical data. PMID:27583849

  16. Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment

    PubMed Central

    Gao, Li; Hao, Jian; Niu, Yang-Yang; Tian, Miao; Yang, Xue; Zhu, Cui-Hong; Ding, Xiu-Li; Liu, Xiao-Hui; Zhang, Hao-Ran; Liu, Chang; Qin, Xue-Mei; Wu, Xiong-Zhi

    2016-01-01

    Abstract Increasing evidence has shown that Chinese Herbal Medicine (CHM) has efficient therapeutic effects for advanced gastric adenocarcinoma, while the therapeutic mechanisms underlying this treatment remain unclear. In this study, the Kaplan–Meier method and Cox regression analysis were used to evaluate the survival benefit of CHM treatment, and correlation analysis was applied to identify the most effective components in the formulas. A network pharmacological approach was developed to decipher the potential therapeutic mechanisms of CHM. CHM treatment was an independent protective factor. The hazard ratio was 0.364 (95% CI 0.245–0.540; P < 0.001). The median survival time was 18 months for patients who received CHM treatment, while for patients without CHM treatment was decreased to 9 months (P < 0.001). Thirteen out of the total 204 herbs were significantly correlated with favorable survival outcomes (P < 0.05), likely representing the most effective components in these formulas. Bioinformatics analyses suggested that the simultaneous manipulation of multiple targets in proliferation pathways (such as epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor 2, proliferating cell nuclear antigen, and insulin like growth factor 2) and the process of cancer metastasis (collagen families, fibronectin 1 and matrix metalloproteinases families) might largely account for the mechanisms of the 13 herbs against gastric adenocarcinoma. A network pharmacology method was introduced to decipher the underlying mechanisms of CHM, which provides a good foundation for herbal research based on clinical data. PMID:27583849

  17. ITI-007 in the treatment of schizophrenia: from novel pharmacology to clinical outcomes.

    PubMed

    Davis, Robert E; Correll, Christoph U

    2016-06-01

    ITI-007 is an investigational drug being developed for schizophrenia and other neuropsychiatric/neurodegenerative diseases. ITI-007 has a unique pharmacological profile, combining potent 5-HT2a receptor antagonism with cell-type-specific dopamine and glutamate receptor modulation, plus serotonin reuptake inhibition. At dopamine-D2 receptors, ITI-007 acts as a post-synaptic antagonist and pre-synaptic partial agonist. Additionally, ITI-007 stimulates phosphorylation of glutamatergic NMDA-NR2B receptors, downstream of dopamine-D1 receptor intracellular signaling. Based on a large, placebo and risperidone controlled, Phase-II trial, ITI-007 60 mg was shown to be effective in reducing symptoms in patients with acutely exacerbated schizophrenia. The antipsychotic efficacy of ITI-007 60 mg in this patient population was confirmed in a recently completed Phase III study. ITI-007 was associated with minimal safety risk compared to risperidone (Phase II study) or placebo (both studies) for neuromotor disturbances, prolactin changes, weight gain and metabolic abnormalities. A second 6-week, placebo and risperidone-controlled Phase-III trial in acutely exacerbated schizophrenia is ongoing. PMID:27042868

  18. Pharmacological treatment of comorbid PTSD and substance use disorder: recent progress.

    PubMed

    Sofuoglu, Mehmet; Rosenheck, Robert; Petrakis, Ismene

    2014-02-01

    Previous research has identified a strong association between posttraumatic stress disorder (PTSD) and substance use disorder (SUD), necessitating the development of treatments that address both conditions. Some pharmacotherapies are effective for the treatment of PTSD and SUD alone, however; no medications have been proven to be effective for the combination of these conditions. We review the recent advances in pharmacological treatment of comorbid PTSD and SUD. A randomized clinical trial of sertraline, a serotonin reuptake inhibitor (SSRI), did not show overall efficacy for comorbid PTSD and alcohol dependence (AD), although it may have efficacy among light drinkers. Another clinical trial demonstrated the efficacy of both disulfiram and naltrexone for the treatment of AD in individuals with PTSD. A more recent clinical trial suggested that norepinephrine uptake inhibitors may also have efficacy for the treatment of comorbid PTSD and AD. In animal and preliminary human studies, brain norepinephrine and glutamate/GABA have emerged as potential treatment targets for comorbid PTSD and SUD. Noradrenergic medications that are promising for comorbid PTSD and SUD include prazosin, guanfacine, and atomoxetine. Promising glutamate/GABA medications include topiramate, memantine, acamprosate, N-acetylcysteine (NAC), and ketamine. The safety and efficacy of these medications for the treatment of PTSD and SUD need to be tested in controlled clinical trials. PMID:24035645

  19. Pharmacological and psychosocial treatments for adolescents with ADHD: an updated systematic review of the literature.

    PubMed

    Sibley, Margaret H; Kuriyan, Aparajita B; Evans, Steven W; Waxmonsky, James G; Smith, Bradley H

    2014-04-01

    Smith, Waschbusch, Willoughby, and Evans (2000) reviewed a small treatment literature on ADHD in adolescents and concluded that methylphenidate stimulant medication was a well-established treatment and behavior therapy (BT) demonstrated preliminary efficacy. This review extends and updates the findings of the prior one based on the previous 15years of research. Studies published since 1999 were identified and coded using standard criteria and effect sizes were calculated where appropriate. Highlights of the last 15years of research include an expansion of pharmacological treatment options and developmentally appropriate psychosocial treatment packages for adolescents with ADHD. Additionally, nonstimulant medications (e.g., atomoxetine) are now approved for the treatment of ADHD in adolescence. The review concludes that medication and BT produce a similar range of therapeutic effects on the symptoms of adolescents with ADHD. However, results suggest that BT may produce greater overall benefits on measures of impairment. There was no evidence that cognitive enhancement trainings, such as working memory training or neurofeedback improved the functioning of adolescents with ADHD. Whether to use medication, BT, or their combination to treat an adolescent with ADHD is complicated and we provide evidence-informed guidelines for treatment selection. The reviewed evidence does not support current American Academy of Pediatrics and American Academy of Child and Adolescent Psychiatry professional guidelines, which state that stimulant medication is the preferred treatment for adolescents with ADHD. Recommendations for assessment, practice guidelines, and future research are discussed. PMID:24632046

  20. The pathophysiological and pharmacological basis of current drug treatment of migraine headache.

    PubMed

    Reddy, Doodipala Samba

    2013-05-01

    Migraine is a common neurological syndrome that affects approximately 10-20% of the population. The pathophysiology of migraine is unclear. 5-hydroxytriptamine is a key mediator in the pathogenesis of migraine and thus 5-HT1-receptor agonists are the principal drugs for acute migraine therapy. There are three classes of drugs for migraine: over-the-counter analgesics and nonsteroidal anti-inflammatory drugs for acute mild migraine, specific prescription drugs (triptans and ergot alkaloids) for acute severe migraine and pharmacological agents for prophylaxis of migraine. Sumatriptan, naratriptan and others, referred to as 'triptans', are the mainstay for acute treatment of migraine. Ergot alkaloids (ergotamine, dihydroergotamine) are used in patients with frequent, moderate migraine, but are less effective than triptans. There are several agents for prevention of migraine occurrence in patients with frequent or severe disabling migraine attacks. New drugs with improved efficacy and reduced side effects are needed for effective treatment and prevention of migraine. PMID:23656340

  1. Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes

    PubMed Central

    Wang, Hansen; Pati, Sandipan; Pozzo-Miller, Lucas; Doering, Laurie C.

    2015-01-01

    Autism spectrum disorders (ASDs) are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases. PMID:25767435

  2. Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes.

    PubMed

    Wang, Hansen; Pati, Sandipan; Pozzo-Miller, Lucas; Doering, Laurie C

    2015-01-01

    Autism spectrum disorders (ASDs) are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases. PMID:25767435

  3. Incorporating Stage-Specific Drug Action into Pharmacological Modeling of Antimalarial Drug Treatment

    PubMed Central

    2016-01-01

    Pharmacological modeling of antiparasitic treatment based on a drug's pharmacokinetic and pharmacodynamic properties plays an increasingly important role in identifying optimal drug dosing regimens and predicting their potential impact on control and elimination programs. Conventional modeling of treatment relies on methods that do not distinguish between parasites at different developmental stages. This is problematic for malaria parasites, as their sensitivity to drugs varies substantially during their 48-h developmental cycle. We investigated four drug types (short or long half-lives with or without stage-specific killing) to quantify the accuracy of the standard methodology. The treatment dynamics of three drug types were well characterized with standard modeling. The exception were short-half-life drugs with stage-specific killing (i.e., artemisinins) because, depending on time of treatment, parasites might be in highly drug-sensitive stages or in much less sensitive stages. We describe how to bring such drugs into pharmacological modeling by including additional variation into the drug's maximal killing rate. Finally, we show that artemisinin kill rates may have been substantially overestimated in previous modeling studies because (i) the parasite reduction ratio (PRR) (generally estimated to be 104) is based on observed changes in circulating parasite numbers, which generally overestimate the “true” PRR, which should include both circulating and sequestered parasites, and (ii) the third dose of artemisinin at 48 h targets exactly those stages initially hit at time zero, so it is incorrect to extrapolate the PRR measured over 48 h to predict the impact of doses at 48 h and later. PMID:26902760

  4. Incorporating Stage-Specific Drug Action into Pharmacological Modeling of Antimalarial Drug Treatment.

    PubMed

    Hodel, Eva Maria; Kay, Katherine; Hastings, Ian M

    2016-05-01

    Pharmacological modeling of antiparasitic treatment based on a drug's pharmacokinetic and pharmacodynamic properties plays an increasingly important role in identifying optimal drug dosing regimens and predicting their potential impact on control and elimination programs. Conventional modeling of treatment relies on methods that do not distinguish between parasites at different developmental stages. This is problematic for malaria parasites, as their sensitivity to drugs varies substantially during their 48-h developmental cycle. We investigated four drug types (short or long half-lives with or without stage-specific killing) to quantify the accuracy of the standard methodology. The treatment dynamics of three drug types were well characterized with standard modeling. The exception were short-half-life drugs with stage-specific killing (i.e., artemisinins) because, depending on time of treatment, parasites might be in highly drug-sensitive stages or in much less sensitive stages. We describe how to bring such drugs into pharmacological modeling by including additional variation into the drug's maximal killing rate. Finally, we show that artemisinin kill rates may have been substantially overestimated in previous modeling studies because (i) the parasite reduction ratio (PRR) (generally estimated to be 10(4)) is based on observed changes in circulating parasite numbers, which generally overestimate the "true" PRR, which should include both circulating and sequestered parasites, and (ii) the third dose of artemisinin at 48 h targets exactly those stages initially hit at time zero, so it is incorrect to extrapolate the PRR measured over 48 h to predict the impact of doses at 48 h and later. PMID:26902760

  5. Pharmacologic vitreolysis.

    PubMed

    Rhéaume, Marc-André; Vavvas, Demetrios

    2010-01-01

    It is now well recognized that vitreous plays an important role in the pathogenesis of various retinal disorders. In many instances it can be addressed with pars plana vitrectomy, although this approach, like any surgery, has its limitations. The search for alternatives or adjunct to surgery has led to the development of pharmacologic vitreolysis. The use of intravitreal agents to alter the vitreous in order to reduce or eliminate its role in disease seems promising. The purpose of this article is to summarize the present knowledge on pharmacologic vitreolysis. A review of the different agents used and of ongoing trials will be presented. Also, current understanding of vitreous structure and its interaction with the retina will be discussed. PMID:21091015

  6. Systems Pharmacology Dissection of the Integrated Treatment for Cardiovascular and Gastrointestinal Disorders by Traditional Chinese Medicine

    PubMed Central

    Zhang, Wenjuan; Tao, Qin; Guo, Zihu; Fu, Yingxue; Chen, Xuetong; Shar, Piar Ali; Shahen, Mohamed; Zhu, Jinglin; Xue, Jun; Bai, Yaofei; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Wang, Yonghua

    2016-01-01

    Though cardiovascular diseases (CVDs) and gastrointestinal disorders (GIDs) are different diseases associated with different organs, they are highly correlated clinically. Importantly, in Traditional Chinese Medicine (TCM), similar treatment strategies have been applied in both diseases. However, the etiological mechanisms underlying them remain unclear. Here, an integrated systems pharmacology approach is presented for illustrating the molecular correlations between CVDs and GIDs. Firstly, we identified pairs of genes that are associated with CVDs and GIDs and found that these genes are functionally related. Then, the association between 115 heart meridian (HM) herbs and 163 stomach meridian (SM) herbs and their combination application in Chinese patent medicine was investigated, implying that both CVDs and GIDs can be treated by the same strategy. Exemplified by a classical formula Sanhe Decoration (SHD) treating chronic gastritis, we applied systems-based analysis to introduce a drug-target-pathway-organ network that clarifies mechanisms of different diseases being treated by the same strategy. The results indicate that SHD regulated several pathological processes involved in both CVDs and GIDs. We experimentally confirmed the predictions implied by the effect of SHD for myocardial ischemia. The systems pharmacology suggests a novel integrated strategy for rational drug development for complex associated diseases. PMID:27597117

  7. Systems Pharmacology Dissection of the Integrated Treatment for Cardiovascular and Gastrointestinal Disorders by Traditional Chinese Medicine.

    PubMed

    Zhang, Wenjuan; Tao, Qin; Guo, Zihu; Fu, Yingxue; Chen, Xuetong; Shar, Piar Ali; Shahen, Mohamed; Zhu, Jinglin; Xue, Jun; Bai, Yaofei; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Wang, Yonghua

    2016-01-01

    Though cardiovascular diseases (CVDs) and gastrointestinal disorders (GIDs) are different diseases associated with different organs, they are highly correlated clinically. Importantly, in Traditional Chinese Medicine (TCM), similar treatment strategies have been applied in both diseases. However, the etiological mechanisms underlying them remain unclear. Here, an integrated systems pharmacology approach is presented for illustrating the molecular correlations between CVDs and GIDs. Firstly, we identified pairs of genes that are associated with CVDs and GIDs and found that these genes are functionally related. Then, the association between 115 heart meridian (HM) herbs and 163 stomach meridian (SM) herbs and their combination application in Chinese patent medicine was investigated, implying that both CVDs and GIDs can be treated by the same strategy. Exemplified by a classical formula Sanhe Decoration (SHD) treating chronic gastritis, we applied systems-based analysis to introduce a drug-target-pathway-organ network that clarifies mechanisms of different diseases being treated by the same strategy. The results indicate that SHD regulated several pathological processes involved in both CVDs and GIDs. We experimentally confirmed the predictions implied by the effect of SHD for myocardial ischemia. The systems pharmacology suggests a novel integrated strategy for rational drug development for complex associated diseases. PMID:27597117

  8. Methamphetamine: An Update on Epidemiology, Pharmacology, Clinical Phenomenology, and Treatment Literature

    PubMed Central

    Courtney, Kelly E.; Ray, Lara A.

    2014-01-01

    Background Despite initial reports of a decline in use in the early 2000s, methamphetamine remains a significant public health concern with known neurotoxic and neurocognitive effects to the user. The goal of this review is to update the literature on methamphetamine use and addiction since its assent to peak popularity in 1990s. Methods Specifically, we first review recent epidemiological reports with a focus on methamphetamine accessibility, changes in use and disorder prevalence rates over time, and accurate estimates of the associated burden of care to the individual and society. Second, we review methamphetamine pharmacology literature with emphasis on the structural and functional neurotoxic effects associated with repeated use of the drug. Third, we briefly outline the findings on methamphetamine-related neurocognitive deficits as assessed via behavioral and neuroimaging paradigms. Lastly, we review the clinical presentation of methamphetamine addiction and the evidence supporting the available psychosocial and pharmacological treatments within the context of an addiction biology framework. Conclusion Taken together, this review provides a broad-based update of the available literature covering methamphetamine research over the past two decades and concludes with recommendations for future research. PMID:25176528

  9. Pain in the cancer patient: different pain characteristics CHANGE pharmacological treatment requirements.

    PubMed

    Müller-Schwefe, Gerhard; Ahlbeck, Karsten; Aldington, Dominic; Alon, Eli; Coaccioli, Stefano; Coluzzi, Flaminia; Huygen, Frank; Jaksch, Wolfgang; Kalso, Eija; Kocot-Kępska, Magdalena; Kress, Hans-Georg; Mangas, Ana Cristina; Ferri, Cesar Margarit; Morlion, Bart; Nicolaou, Andrew; Hernández, Concepción Pérez; Pergolizzi, Joseph; Schäfer, Michael; Sichère, Patrick

    2014-09-01

    Twenty years ago, the main barriers to successful cancer pain management were poor assessment by physicians, and patients' reluctance to report pain and take opioids. Those barriers are almost exactly the same today. Cancer pain remains under-treated; in Europe, almost three-quarters of cancer patients experience pain, and almost a quarter of those with moderate to severe pain do not receive any analgesic medication. Yet it has been suggested that pain management could be improved simply by ensuring that every consultation includes the patient's rating of pain, that the physician pays attention to this rating, and a plan is agreed to increase analgesia when it is inadequate. After outlining current concepts of carcinogenesis in some detail, this paper describes different methods of classifying and diagnosing cancer pain and the extent of current under-treatment. Key points are made regarding cancer pain management. Firstly, the pain may be caused by multiple different mechanisms and therapy should reflect those underlying mechanisms - rather than being simply based on pain intensity as recommended by the WHO three-step ladder. Secondly, a multidisciplinary approach is required which combines both pharmacological and non-pharmacological treatment, such as psychotherapy, exercise therapy and electrostimulation. The choice of analgesic agent and its route of administration are considered, along with various interventional procedures and the requirements of palliative care. Special attention is paid to the treatment of breakthrough pain (particularly with fast-acting fentanyl formulations, which have pharmacokinetic profiles that closely match those of breakthrough pain episodes) and chemotherapy-induced neuropathic pain, which affects around one third of patients who receive chemotherapy. Finally, the point is made that medical education should place a greater emphasis on pain therapy, both at undergraduate and postgraduate level. PMID:24841174

  10. Review of Clinical Pharmacology of Aloe vera L. in the Treatment of Psoriasis.

    PubMed

    Miroddi, Marco; Navarra, Michele; Calapai, Fabrizio; Mancari, Ferdinando; Giofrè, Salvatore Vincenzo; Gangemi, Sebastiano; Calapai, Gioacchino

    2015-05-01

    Aloe vera L., is a plant used worldwide as folk remedy for the treatment of various ailments, including skin disorders. Its gel is present in cosmetics, medicinal products and food supplements. Psoriasis, an immune-mediated chronic inflammatory disease, involving mainly the skin, affects about the 2-3% of general population. Conventional pharmacological treatments for psoriasis can have limited effectiveness and can cause adverse reactions. For this reason often psoriatic patients look for alternative treatments based on natural products containing Aloe vera. We conducted a systematic review of clinical trials assessing effectiveness and safety of aloe for the treatment of psoriasis. Clinical studies published in English were considered; a total of four clinical trials met inclusion criteria. Studies were also evaluated by using the Jadad scale and Consort Statement in Reporting Clinical trials of Herbal Medicine Intervention. Quality and methodological accuracy of considered studies varied considerably, and some crucial information to reproduce clinical results was missing. We conclude that administration of aloe as cutaneous treatment is generally well tolerated, as no serious side effects were reported. Results on the effectiveness of Aloe vera are contradictory; our analysis reveals the presence of methodological gaps preventing to reach final conclusions. PMID:25756474

  11. Predictors of adherence to pharmacological and behavioral treatment in a cessation trial among smokers in Aleppo, Syria

    PubMed Central

    Ben Taleb, Ziyad; Ward, Kenneth D; Asfar, Taghrid; Bahelah, Raed; Maziak, Wasim

    2015-01-01

    Introduction The development of evidence-based smoking cessation programs is in its infancy in developing countries, which continue to bear the main brunt of the tobacco epidemic. Adherence to treatment recommendations is an important determinant of the success of smoking cessation programs, but little is known about factors influencing adherence to either pharmacological or behavioral treatment in developing countries settings. Our study represents the first attempt to examine the predictors of adherence to cessation treatment in a low-income developing country. Methods Predictors of adherence to pharmacological and behavioral treatment were identified by analyzing data from a multi-site, two-group, parallel-arm, double-blind, randomized, placebo-controlled smoking cessation trial in primary care clinics in Aleppo, Syria. Participants received 3 in-person behavioral counseling sessions plus 5 brief follow-up phone counseling sessions, and were randomized to either 6 weeks of nicotine or placebo patch. Results Of the 269 participants, 68% adhered to pharmacological treatment, while 70% adhered to behavioral counseling. In logistic regression modeling, lower adherence to pharmacological and behavioral treatment was associated with higher daily smoking at baseline, greater withdrawal symptoms, and perception of receiving placebo instead of active nicotine patch. Women showed lower adherence than men to behavioral treatment, while being assigned to placebo condition and baseline waterpipe use were associated with lower adherence to pharmacological treatment. Conclusion Adherence to cessation treatment for cigarette smokers in low-income countries such as Syria may benefit from integrated cessation components that provide intensive treatment for subjects with higher nicotine dependence, and address concurrent waterpipe use at all stages. PMID:26077603

  12. Comparative Cost Analysis of Sequential, Adaptive, Behavioral, Pharmacological, and Combined Treatments for Childhood ADHD.

    PubMed

    Page, Timothy F; Pelham, William E; Fabiano, Gregory A; Greiner, Andrew R; Gnagy, Elizabeth M; Hart, Katie C; Coxe, Stefany; Waxmonsky, James G; Foster, E Michael; Pelham, William E

    2016-01-01

    We conducted a cost analysis of the behavioral, pharmacological, and combined interventions employed in a sequential, multiple assignment, randomized, and adaptive trial investigating the sequencing and enhancement of treatment for children with attention deficit hyperactivity disorder (ADHD; Pelham et al., 201X; N = 146, 76% male, 80% Caucasian). The quantity of resources expended on each child's treatment was determined from records that listed the type, date, location, persons present, and duration of all services provided. The inputs considered were the amount of physician time, clinician time, paraprofessional time, teacher time, parent time, medication, and gasoline. Quantities of these inputs were converted into costs in 2013 USD using national wage estimates from the Bureau of Labor Statistics, the prices of 30-day supplies of prescription drugs from the national Express Scripts service, and mean fuel prices from the Energy Information Administration. Beginning treatment with a low-dose/intensity regimen of behavior modification (large-group parent training) was less costly for a school year of treatment ($961) than beginning treatment with a low dose of stimulant medication ($1,669), regardless of whether the initial treatment was intensified with a higher "dose" or if the other modality was added. Outcome data from the parent study (Pelham et al., 201X) found equivalent or superior outcomes for treatments beginning with low-intensity behavior modification compared to intervention beginning with medication. Combined with the present analyses, these findings suggest that initiating treatment with behavior modification rather than medication is the more cost-effective option for children with ADHD. PMID:26808137

  13. Report of the Canadian Hypertension Society Consensus Conference: 3. Pharmacologic treatment of hypertensive disorders in pregnancy

    PubMed Central

    Rey, E; LeLorier, J; Burgess, E; Lange, I R; Leduc, L

    1997-01-01

    OBJECTIVE: To provide Canadian physicians with evidence-based guidelines for the pharmacologic treatment of hypertensive disorders in pregnancy. OPTIONS: No medication, or treatment with antihypertensive or anticonvulsant drugs. OUTCOMES: Prevention of maternal complications, and prevention of perinatal complications and death. EVIDENCE: Pertinent articles published from 1962 to September 1996 retrieved from the Pregnancy and Childbirth Module of the Cochrane Database of Systematic Reviews and from MEDLINE; additional articles retrieved through a manual search of bibliographies; and expert opinion. Recommendations were graded according to levels of evidence. VALUES: Maternal and fetal well-being were equally valued, with the belief that treatment side effects should be minimized. BENEFITS, HARMS AND COSTS: Reduction in the rate of adverse perinatal outcomes, including death. Potential side effects of antihypertensive drugs include placental hypoperfusion, intrauterine growth retardation and long-term effects on the infant. RECOMMENDATIONS: A systolic blood pressure greater than 169 mm Hg or a diastolic pressure greater than 109 mm Hg in a pregnant woman should be considered an emergency and pharmacologic treatment with hydralazine, labetalol or nifedipine started. Otherwise, the thresholds at which to start antihypertensive treatment are a systolic pressure of 140 mm Hg or a diastolic pressure of 90 mm Hg in women with gestational hypertension without proteinuria or pre-existing hypertension before 28 weeks' gestation, those with gestational hypertension and proteinuria or symptoms at any time during the pregnancy, those with pre-existing hypertension and underlying conditions or target-organ damage, and those with pre-existing hypertension and superimposed gestational hypertension. The thresholds in other circumstances are a systolic pressure of 150 mm Hg or a diastolic pressure of 95 mm Hg. For nonsevere hypertension, methyldopa is the first-line drug; labetalol

  14. Physical exercise as non-pharmacological treatment of chronic pain: Why and when

    PubMed Central

    Ambrose, Kirsten R.; Golightly, Yvonne M.

    2015-01-01

    Chronic pain broadly encompasses both objectively defined conditions and idiopathic conditions that lack physical findings. Despite variance in origin or pathogenesis, these conditions are similarly characterized by chronic pain, poor physical function, mobility limitations, depression, anxiety and sleep disturbance and are treated alone or in combination by pharmacologic and nonpharmacologic approaches, such as physical activity (aerobic conditioning, muscle strengthening, flexibility training and movement therapies). Physical activity improves general health, disease risk and progression of chronic illnesses such as cardiovascular disease, type-2 diabetes and obesity. When applied to chronic pain conditions within appropriate parameters (frequency, duration, intensity), physical activity significantly improves pain and related symptoms. For chronic pain, strict guidelines for physical activity are lacking, but frequent movement is preferable to sedentary behavior. This gives considerable freedom in prescribing physical activity treatments, which are most successful when tailored individually, progressed slowly and account for physical limitations, psychosocial needs and available resources. PMID:26267006

  15. Pharmacological targeting of the serotonergic system for the treatment of obesity

    PubMed Central

    Garfield, Alastair S; Heisler, Lora K

    2009-01-01

    The attenuation of food intake as induced by an increase in serotonergic (5-hydroxytryptamine, 5-HT) efficacy has been a target of antiobesity pharmacotherapies. However, the induction of tolerance and/or side-effects limited the clinical utility of the earliest serotonin-related medications. With the global prevalence of obesity rising, there has been renewed interest in the manipulation of the serotonergic system as a point of pharmacological intervention. The serotonin2C receptor (5-HT2CR), serotonin1B (rodent)/serotonin1Dβ (human) receptor (5-HT1B/1DβR) and serotonin6 receptor (5-HT6R) represent the most promising serotonin receptor therapeutic targets. Canonical serotonin receptor compounds have given way to a myriad of novel receptor-selective ligands, many of which have observable anorectic effects. Here we review serotonergic compounds reducing ingestive behaviour and discuss their clinical potential for the treatment of obesity. PMID:19029184

  16. [Clinical aspects of pharmacological treatment of diabetic neuropathy - cooperation with neurologists and diabetologists].

    PubMed

    Janíčková Žďárská, Denisa; Kvapil, Milan

    2016-03-01

    The development and progression of symptomatic diabetic neuropathy (SDN) is linked to hyperglycemia. The effort to improve compensation of diabetes mellitus during therapy is therefore very important. This is where the cooperation between the diabetologist and neurologist within therapy plays an important role. The pharmaco-logical therapy of symptomatic sensitive peripheral diabetic neuropathy is difficult and with a less than satisfactory effect. A variety of active substances is used in symptomatic therapy, primarily designed for intervention in other pathological conditions. The recommended guidelines include antidepressants, anticonvulsants, opiates and their derivatives. However this therapy brings with it a relatively high incidence of adverse effects which detract from patients adherence to treatment. Very good results are reached by the therapy with thioctacid. PMID:27180665

  17. The influence of clinical and pharmacological factors on enuresis treatment with imipramine.

    PubMed Central

    Fernández de Gatta, M M; Galindo, P; Rey, F; Gutierrez, J; Tamayo, M; García, M J; Domínguez-Gil, A

    1990-01-01

    1. The aim of this study has been to evaluate the response to imipramine treatment in enuretic children through the use of a series of clinical and pharmacological variables and by applying a multivariate (principal components) analysis technique. 2. The study was carried out on 146 children whose ages ranged from 5 to 14 years, and who received variable doses of imipramine (12.5 to 100 mg day-1). 3. The quantitative variables analyzed were: drug dosage, serum levels of imipramine and its metabolite desipramine, the relationship between them both, the duration of treatment, age and weight. 4. The qualitative variables were: compliance, presence of side-effects, enuretic and/or psychiatric antecedents, intelligence quotient (I.Q.), the existence (or absence) of related pathologies, sex, and the type of enuresis. 5. The response to treatment was quantified by means of the percentage of decrease in frequency of enuresis as compared with the initial frequency. 6. The results obtained show that the variables which are most associated with the reduction of enuresis are, in decreasing order: the dosage of imipramine administered, the duration of treatment, compliance and the level/dose ratio for the sum of the drug and metabolite levels. PMID:2271368

  18. The influence of clinical and pharmacological factors on enuresis treatment with imipramine.

    PubMed

    Fernández de Gatta, M M; Galindo, P; Rey, F; Gutierrez, J; Tamayo, M; García, M J; Domínguez-Gil, A

    1990-11-01

    1. The aim of this study has been to evaluate the response to imipramine treatment in enuretic children through the use of a series of clinical and pharmacological variables and by applying a multivariate (principal components) analysis technique. 2. The study was carried out on 146 children whose ages ranged from 5 to 14 years, and who received variable doses of imipramine (12.5 to 100 mg day-1). 3. The quantitative variables analyzed were: drug dosage, serum levels of imipramine and its metabolite desipramine, the relationship between them both, the duration of treatment, age and weight. 4. The qualitative variables were: compliance, presence of side-effects, enuretic and/or psychiatric antecedents, intelligence quotient (I.Q.), the existence (or absence) of related pathologies, sex, and the type of enuresis. 5. The response to treatment was quantified by means of the percentage of decrease in frequency of enuresis as compared with the initial frequency. 6. The results obtained show that the variables which are most associated with the reduction of enuresis are, in decreasing order: the dosage of imipramine administered, the duration of treatment, compliance and the level/dose ratio for the sum of the drug and metabolite levels. PMID:2271368

  19. Ulipristal acetate: a novel pharmacological approach for the treatment of uterine fibroids

    PubMed Central

    Biglia, Nicoletta; Carinelli, Silvestro; Maiorana, Antonio; D’Alonzo, Marta; Lo Monte, Giuseppe; Marci, Roberto

    2014-01-01

    Uterine fibroids are the most common benign tumors of the female genital tract. The management of symptomatic fibroids has traditionally been surgical; however, alternative pharmacological approaches have been proposed to control symptoms. To date, gonadotropin-releasing hormone analogs are the only available drugs for the preoperative treatment of fibroids. However, the US Food and Drug Administration recently authorized ulipristal acetate (UPA), an oral selective progesterone-receptor modulator, for the same indication. UPA is a new, effective, and well-tolerated option for the preoperative treatment of moderate and severe symptoms of uterine fibroids in women of reproductive age. According to clinical data, UPA shows several advantages: it is faster than leuprolide in reducing the fibroid-associated bleeding, it significantly improves hemoglobin and hematocrit levels in anemic patients, and it grants a significant reduction in the size of fibroids, which lasts for at least 6 months after the end of the treatment. Furthermore, UPA displays a better tolerability profile when compared to leuprolide; in fact, it keeps estradiol levels at mid follicular phase range, thereby reducing the incidence of hot flushes and exerting no impact on bone turnover. On the grounds of this evidence, the administration of 5 mg/day ulipristal acetate for 3 months is suggested for different patient categories and allows for planning a treatment strategy tailored to meet an individual patient’s needs. PMID:24591818

  20. Patient-reported outcomes in post-traumatic stress disorder Part II: Focus on pharmacological treatment

    PubMed Central

    Kapfhammer, Hans-Peter

    2014-01-01

    Post-traumatic stress disorder (PTSD) may be associated with long-lasting psychological suffering, distressing psychosocial disability, markedly reduced health-related quality of life, and increased morbidity and mortality in a subgroup of individuals in the aftermath of serious traumatic events. Both etiopathogenesis and treatment modalities of PTSD are best conceptualized within a biopsychosotial model. Pharmacotherapy may lay claim to a major role in the multimodal treatment approaches. Here we outline two different pharmacotherapeutic trends that aim to modify the encoding, consolidation, and rehearsal of traumatic memory in order to reduce the risk of PTSD immediately after trauma exposure on the one hand, and that endeavor to treat the clinical state of PTSD on the other. The theoretical rationales of both pharmacological strategies are the complex neurobiological underpinnings that characterize traumatic memory organization and clinical PTSD. Meanwhile, promising data from randomized controlled trials have been obtained for both approaches. Empirical evidence may inform clinicians in their clinical efforts for this special group of patients. The efficacy of several classes of drugs that have been investigated within a context of research should be evaluated critically and still have to stand the test of effectiveness in daily clinical practice. From a patient perspective, empirical results may serve as a psychoeducative guideline to what pharmacotherapeutic approaches may realistically achieve, what their risks and benefits are, and what their limits are in contributing to reducing the often major chronic suffering caused by serious traumatic events. Ethical issues have to be considered, particularly in the context of pharmacological strategies projected to prevent PTSD in the aftermath of traumatic exposure. PMID:25152660

  1. Overview of experimental and conventional pharmacological approaches in the treatment of sleep and wake disorders.

    PubMed

    Renger, John J

    2008-01-01

    The fundamental purpose of sleep remains one of the most compelling questions yet to be answered in the area of neuroscience, if not all of biology. A pervasive behavior among members of the animal kingdom, the functional necessity of engaging regularly in sleep is best demonstrated by showing that failing to do so leads to a broad repertoire of pathological outcomes including cognitive, immunological, hormonal, and metabolic outcomes, among others. Indeed, an absolute requirement for sleep has been shown in studies that have demonstrated that continuous total deprivation of sleep for as short a period as 15 days is generally lethal in some species. The most common clinical sleep disorder, insomnia, is both a principal disease (primary insomnia) as well as a co-morbidity of a large number of other ostensibly unrelated diseases including chronic pain, attention deficit hyperactivity disorder, and depression. From a treatment perspective, restoring normal healthy sleep delivers subsequent benefits in waking cognitive function and mood with the potential for beneficial therapeutic impact on daily functioning across multiple diseases for which restorative healthy sleep is compromised. Our remarkable escalation in understanding the anatomy and physiology of sleep/wake control mechanisms provides new opportunities to modify the neurobiology of sleep and wake-related behaviors in novel and exciting ways. In parallel, expansion of sleep research into novel interfaces between sleep-wake biology and disease states is revealing additional extensive implications of lost sleep. Current investigational and conventional pharmacological approaches for the treatment of sleep and wake disorders are discussed based on their mechanism of action within the CNS and their effect on sleep and wake. This review of recent sleep biology and sleep pharmacology peers into the future of sleep therapeutics to highlight both mechanistic safety and functional outcomes as key for differentiating

  2. Preclinical studies identify novel targeted pharmacological strategies for treatment of human malignant pleural mesothelioma

    PubMed Central

    Favoni, Roberto E; Daga, Antonio; Malatesta, Paolo; Florio, Tullio

    2012-01-01

    The incidence of human malignant pleural mesothelioma (hMPM) is still increasing worldwide. hMPM prognosis is poor even if the median survival time has been slightly improved after the introduction of the up-to-date chemotherapy. Nevertheless, large phase II/III trials support the combination of platinum derivatives and pemetrexed or raltitrexed, as preferred first-line schedule. Better understanding of the molecular machinery of hMPM will lead to the design and synthesis of novel compounds targeted against pathways identified as crucial for hMPM cell proliferation and spreading. Among them, several receptors tyrosine kinase show altered activity in subsets of hMPM. This observation suggests that these kinases might represent novel therapeutic targets in this chemotherapy-resistant disease. Over these foundations, several promising studies are ongoing at preclinical level and novel molecules are currently under evaluation as well. Yet, established tumour cell lines, used for decades to investigate the efficacy of anticancer agents, although still the main source of drug efficacy studies, after long-term cultures tend to biologically diverge from the original tumour, limiting the predictive potential of in vivo efficacy. Cancer stem cells (CSCs), a subpopulation of malignant cells capable of self-renewal and multilineage differentiation, are believed to play an essential role in cancer initiation, growth, metastasization and relapse, being responsible of chemo- and radiotherapy refractoriness. According to the current carcinogenesis theory, CSCs represent the tumour-initiating cell (TIC) fraction, the only clonogenic subpopulation able to originate a tumour mass. Consequently, the recently described isolation of TICs from hMPM, the proposed main pharmacological target for novel antitumoural drugs, may contribute to better dissect the biology and multidrug resistance pathways controlling hMPM growth. PMID:22289125

  3. [Pharmacological treatment strategy and mirror visual feedback treatment for neuropathic pain].

    PubMed

    Sumitani, Masahiko; Miyauchi, Satoru; Yamada, Yoshitsugu

    2012-11-01

    Neuropathic pain is a debilitating condition, and pharmacotherapy is the most established treatment strategy. A variety of pharmacotherapies is used for neuropathic pain management: however, pharmacotherapies with evidence for analgesic potency are less common. Several pharmacotherapeutic treatment guidelines for neuropathic pain treatment recommend the first- to third-line drugs on the basis of evidence-based medicine; however, neuropathic pain is often resistant to pharmacotherapies. We have treated pharmacotherapy-resistant neuropathic pain with neurorehabilitation techniques such as mirror visual feedback (MVF) treatment. Further to our clinical experience using MVF, we discuss the cerebral mechanism associated with neuropathic pain in this study. PMID:23131739

  4. Postpartum and nonpostpartum depression: differences in presentation and response to pharmacologic treatment.

    PubMed

    Hendrick, V; Altshuler, L; Strouse, T; Grosser, S

    2000-01-01

    Following childbirth, major depression (postpartum depression) affects approximately 8-12% of new mothers. However, little is known about the pharmacological management of postpartum depression, and no studies to date have assessed differences in treatment response between women with postpartum and nonpostpartum major depression. The authors reviewed the records of 26 women with postpartum major depression and 25 women with major depression unrelated to childbearing (nonpostpartum depression) who presented to them for treatment over a 4-year period. Compared with the nonpostpartum depressed patients, the postpartum depressed women were significantly more likely to present with anxious features. Also, cases of postpartum depression were more severe than cases of nonpostpartum depression. While the postpartum patients were equally as likely to recover (as defined by a Clinical Global Impression score of 1 or 2) compared to the nonpostpartum-depressed patients, their time to response was significantly longer. By 3 weeks of pharmacotherapy, 75% of the nonpostpartum cases had recovered, in contrast to only 36% of the postpartum cases. Further, postpartum patients were significantly more likely to be receiving more than one antidepressant agent at the time of response to treatment. Length of depression prior to treatment did not explain the difference in treatment response. Presence of depressive symptoms during pregnancy and timing of onset of the depression (before vs. after 4 weeks of delivery) did not affect likelihood of treatment response in this sample. Women with postpartum depression appear to be significantly more likely than the nonpostpartum women to present with anxious features, take longer to respond to pharmacotherapy for depression, and require more antidepressant agents at the time of response to treatment. PMID:10812531

  5. Opioid antagonists for pharmacological treatment of alcohol dependence - a critical review.

    PubMed

    Soyka, Michael; Rösner, Susanne

    2008-11-01

    Alcohol dependence is a widespread psychiatric disorder. While relapse prevention therapy in alcoholism was exclusively dominated by social and psychological treatments for many years, in the last decades the benefits of pharmacological agents for the rehabilitation treatment in alcoholism have become increasingly evident. Naltrexone, an opiate receptor antagonist, blocks the pleasant and reinforcing effects of alcohol by preventing the stimulation of opioid receptors and the reduction of dopamine release in the ventral tegmental area (VTA). Clinical evidence about the effectiveness of the substance is not always consistent, but meta-analyses confirm naltrexone's effect on the risk of heavy drinking. Evidence about the abstinence-maintaining effects of the substance comes from a relatively small database and needs further investigation. The evaluation of differential effects of naltrexone depending on biological or psychological profiles, which could further enhance the effectiveness of treatments for alcohol dependence, remains a challenge. Nalmefene, another opioid antagonist, as well as naltrexone depot, a sustained release formulation of naltrexone, are further promising strategies for the treatment of alcohol dependence. The review at hand gives on overview of the current evidence on opioid antagonists for the treatment of alcohol dependence regarding the possible mechanism of action, the substances' safety profiles and their effectiveness. The corresponding evidence is critically reviewed taking into consideration the influence of the study design on the magnitude and consistency of effect sizes as well the impact of patient characteristics on the response to the treatment with opioid antagonists. Future studies on the role of different subtypes of alcoholics according to their genetic or psychological profile to explain or even predict the effects of opioid antagonists in the treatment of alcohol dependence are needed. PMID:19630726

  6. A novel method for imaging the pharmacological effects of antibiotic treatment on Clostridium difficile.

    PubMed

    Endres, Bradley T; Bassères, Eugénie; Memariani, Ali; Chang, Long; Alam, M Jahangir; Vickers, Richard J; Kakadiaris, Ioannis A; Garey, Kevin W

    2016-08-01

    Clostridium difficile is a significant cause of nosocomial-acquired infection that results in severe diarrhea and can lead to mortality. Treatment options for C. difficile infection (CDI) are limited, however, new antibiotics are being developed. Current methods for determining efficacy of experimental antibiotics on C. difficile involve antibiotic killing rates and do not give insight into the drug's pharmacologic effects. Considering this, we hypothesized that by using scanning electron microscopy (SEM) in tandem to drug killing curves, we would be able to determine efficacy and visualize the phenotypic response to drug treatment. To test this hypothesis, supraMIC kill curves were conducted using vancomycin, metronidazole, fidaxomicin, and ridinilazole. Following collection, cells were either plated or imaged using a scanning electron microscope (SEM). Consistent with previous reports, we found that the tested antibiotics had significant bactericidal activity at supraMIC concentrations. By SEM imaging and using a semi-automatic pipeline for image analysis, we were able to determine that vancomycin and to a lesser extent fidaxomicin and ridinilazole significantly affected the cell wall, whereas metronidazole, fidaxomicin, and ridinilazole had significant effects on cell length suggesting a metabolic effect. While the phenotypic response to drug treatment has not been documented previously in this manner, the results observed are consistent with the drug's mechanism of action. These techniques demonstrate the versatility and reliability of imaging and measurements that could be applied to other experimental compounds. We believe the strategies laid out here are vital for characterizing new antibiotics in development for treating CDI. PMID:27108094

  7. A Systematic Review of Pharmacological Treatments of Pain Following Spinal Cord Injury

    PubMed Central

    Teasell, Robert W.; Mehta, Swati; Aubut, Jo-Anne L.; Foulon, Brianne; Wolfe, Dalton L.; Hsieh, Jane T.C.; Townson, Andrea F.; Short, Christine

    2011-01-01

    Objective To conduct a systematic review of published research on the pharmacological treatment of pain after spinal cord injury (SCI). Data Sources Medline, CINAHL, EMBASE and PsycINFO databases were searched for articles published 1980 to June 2009 addressing the treatment of pain post SCI. Randomized controlled trials (RCTs) were assessed for methodological quality using the PEDro assessment scale, while non-RCTs were assessed using the Downs and Black evaluation tool. A level of evidence was assigned to each intervention using a modified Sackett scale. Study Selection The review included randomized controlled trials and non-randomized controlled trials which included prospective controlled trials, cohort, case series, case-control, pre-post and post studies. Case studies were included only when there were no other studies found. Data Extraction Data extracted included the PEDro or Downs and Black score, the type of study, a brief summary of intervention outcomes, type of pain, type of pain scale and the study findings.. Data Synthesis Articles selected for this particular review evaluated different interventions in the pharmacological management of pain post SCI. 28 studies met inclusion criteria: there were 21 randomized controlled trials of these 19 had Level 1 evidence. Treatments were divided into five categories: anticonvulsants, antidepressants, analgesics, cannabinoids and antispasticity medications. Conclusions Most studies did not specify participants’ types of pain; hence making it difficult to identify the type of pain being targeted by the treatment. Anticonvulsant and analgesic drugs had the highest levels of evidence and were the drugs most often studied. Gabapentin and pregabalin had strong evidence (five Level 1 RCTs) for effectiveness in treating post-SCI neuropathic pain, as did intravenous analgesics (lidocaine, ketamine and morphine) but the latter only had short term benefits. Tricyclic antidepressants only showed benefit for neuropathic

  8. Pharmacological agents in the treatment of venous disease: an update of the available evidence.

    PubMed

    Gohel, Manjit S; Davies, Alun H

    2009-07-01

    Varicose veins and the complications of venous disease are thought to affect over a quarter of the adult population and the management of these conditions are a major cause of health service expense. Advances in the understanding of venous pathophysiology have highlighted numerous potential targets for pharmacotherapy. This review considers the evidence for pharmacological agents used for the treatment of chronic venous disease. A literature search using Pubmed, Embase and Cinahl databases was performed. The initial search terms 'varicose vein', 'venous ulcer' and 'venous disease' were used with appropriate search limits to identify prospective studies of pharmacotherapy in venous disease. A wide range of venoactive and non-venoactive drugs have been studied in patients with venous disease. The use of micronized purified flavonoid fraction (Daflon) can reduce symptoms of pain, heaviness and oedema in patients with venous reflux and a recent meta-analysis concluded that Daflon improves healing in patients with venous ulceration treated with compression. Pentoxifylline may be a useful adjunct to compression therapy for patients with venous ulceration. Oxerutins and calcium dobesilate may be of benefit in reducing oedema and rutosides may help to relieve the symptoms of varicose veins in pregnancy. The clinical benefits of other medications remain unproven. Although numerous pharmacological agents have been proposed and studied, Daflon has demonstrated the greatest clinical benefits in patients with venous disease. Further research is needed to define the role of venoactive drugs in clinical care and improve our understanding of the pathophysiology of venous disease to help identify new therapeutic avenues. PMID:19601855

  9. Pharmacologic Treatment of First-Episode Schizophrenia: A Review of the Literature

    PubMed Central

    Nandhra, Harpal Sing; Singh, Swaran P.

    2012-01-01

    Objective: To review the evidence base for the efficacy and tolerability of antipsychotic medication for the treatment of the first episode of schizophrenia. Data Source: MEDLINE databases were searched for published articles in English over the last 25 years, from January 1986 to January 2011, on choice of antipsychotic treatment for the first episode of schizophrenia, with an emphasis on efficacy and tolerability of antipsychotic drugs in the acute phase of psychotic illness. Study Selection: The keywords antipsychotic drugs and schizophrenia were used in combination with drug treatment, pharmacologic treatment, efficacy, and tolerability in addition to atypical antipsychotics, first-generation antipsychotics, second-generation antipsychotics, first-episode psychosis, and acute psychotic episode. Data Synthesis: At present, there is no convincing evidence to guide clinicians in choosing a single first-line antipsychotic that is effective in treating the positive and negative symptoms of the first episode of schizophrenia. Even though second-generation antipsychotic drugs offer potential benefits in terms of less extrapyramidal side effects and some benefits in treating negative, affective, and cognitive symptoms, these drugs are not without their own side effects. Conclusions: With the introduction of a number of second-generation antipsychotic drugs there have been significant advances in antipsychotic drug treatment over the last decade. Despite these advances, there are still a number of limitations in continued use of some antipsychotic medications due to their efficacy and tolerability issues in the acute and early maintenance phases of psychosis. Active research in this area would provide more promising results of improved efficacy and tolerability of antipsychotic medication. PMID:22690369

  10. Validation of the AQT Color-Form Additive Model for Screening and Monitoring Pharmacological Treatment of ADHD

    ERIC Educational Resources Information Center

    Nielsen, Niels Peter; Wiig, Elisabeth Hemmersam

    2013-01-01

    Objective:This retrospective study used A Quick Test of Cognitive Speed (AQT) processing-speed and efficiency measures for evaluating sensitivity and monitoring effects during pharmacological treatment of adults with ADHD. Method: Color (C), form (F), and color-form (CF) combination naming were administered to 69 adults during outpatient…

  11. Do pharmacological and behavioral interventions differentially affect treatment outcome for children with social phobia?

    PubMed

    Scharfstein, Lindsay A; Beidel, Deborah C; Finnell, Laura Rendon; Distler, Aaron; Carter, Nathan T

    2011-09-01

    In a randomized trial for children with social phobia (SP), Social Effectiveness Therapy for Children (SET-C; a treatment consisting of exposure and social skills training) and fluoxetine were more effective than pill placebo in reducing social distress and behavioral avoidance, but only SET-C demonstrated significantly improved overall social skill and social competence. In the current study, the authors examined the specific social skills enhanced by SET-C using a recently developed coding schema. At posttreatment, children treated with SET-C displayed a more effective ability to manage the conversational topic (pragmatic social behaviors) and more appropriate motor movement, facial orientation, and posture (paralinguistic social behaviors) than children treated with fluoxetine or placebo. In contrast, children treated with fluoxetine displayed no more pragmatic or paralinguistic skill than children given a pill placebo. There were no group differences on ratings of voice volume and vocal inflection (speech and prosodic social behaviors). Furthermore, only children treated with SET-C improved from pre- to posttreatment on all three skill variables. Findings suggest that pharmacological interventions that only target reduction in anxious arousal may not have an impact on social skill deficits and may not be adequate to optimally treat SP. The relationship of social skill to social avoidance and the importance of social skills training to enhance social competence in the treatment of childhood SP are discussed. PMID:21586501

  12. Pharmacological approach to the treatment of long and short QT syndromes.

    PubMed

    Patel, Chinmay; Antzelevitch, Charles

    2008-04-01

    Inherited channelopathies have received increasing attention in recent years. The past decade has witnessed impressive progress in our understanding of the molecular and cellular basis of arrhythmogenesis associated with inherited channelopathies. An imbalance in ionic forces induced by these channelopathies affects the duration of ventricular repolarization and amplifies the intrinsic electrical heterogeneity of the myocardium, creating an arrhythmogenic milieu. Today, many of the channelopathies have been linked to mutations in specific genes encoding either components of ion channels or membrane or regulatory proteins. Many of the channelopathies are genetically heterogeneous with a variable degree of expression of the disease. Defining the molecular basis of channelopathies can have a profound impact on patient management, particularly in cases in which genotype-specific pharmacotherapy is available. The long QT syndrome (LQTS) is one of the first identified and most studied channelopathies where abnormal prolongation of ventricular repolarization predisposes an individual to life threatening ventricular arrhythmia called Torsade de Pointes. On the other hand of the spectrum, molecular defects favoring premature repolarization lead to Short QT syndrome (SQTS), a recently described inherited channelopathy. Both of these channelopathies are associated with a high risk of sudden cardiac death due to malignant ventricular arrhythmia. Whereas pharmacological therapy is first line treatment for LQTS, defibrillators are considered as primary treatment for SQTS. This review provides a comprehensive review of the molecular genetics, clinical features, genotype-phenotype correlations and genotype-specific approach to pharmacotherapy of these two mirror-image channelopathies, SQTS and LQTS. PMID:18378319

  13. Pharmacological approach to the treatment of long and short QT syndromes☆

    PubMed Central

    Patel, Chinmay; Antzelevitch, Charles

    2008-01-01

    Inherited channelopathies have received increasing attention in recent years. The past decade has witnessed impressive progress in our understanding of the molecular and cellular basis of arrhythmogenesis associated with inherited channelopathies. An imbalance in ionic forces induced by these channelopathies affects the duration of ventricular repolarization and amplifies the intrinsic electrical heterogeneity of the myocardium, creating an arrhythmogenic milieu. Today, many of the channelopathies have been linked to mutations in specific genes encoding either components of ion channels or membrane or regulatory proteins. Many of the channelopathies are genetically heterogeneous with a variable degree of expression of the disease. Defining the molecular basis of channelopathies can have a profound impact on patient management, particularly in cases in which genotype-specific pharmacotherapy is available. The long QT syndrome (LQTS) is one of the first identified and most studied channelopathies where abnormal prolongation of ventricular repolarization predisposes an individual to life threatening ventricular arrhythmia called Torsade de Pointes. On the other hand of the spectrum, molecular defects favoring premature repolarization lead to Short QT syndrome (SQTS), a recently described inherited channelopathy. Both of these channelopathies are associated with a high risk of sudden cardiac death due to malignant ventricular arrhythmia. Whereas pharmacological therapy is first line treatment for LQTS, defibrillators are considered as primary treatment for SQTS. This review provides a comprehensive review of the molecular genetics, clinical features, genotype–phenotype correlations and genotype-specific approach to pharmacotherapy of these two mirror-image channelopathies, SQTS and LQTS. PMID:18378319

  14. The clinical pharmacology and pharmacokinetics of ulipristal acetate for the treatment of uterine fibroids.

    PubMed

    Pohl, Oliver; Zobrist, R Howard; Gotteland, Jean-Pierre

    2015-04-01

    Uterine fibroids are benign hormone-sensitive tumors of uterine smooth muscle cells leading to heavy menstrual bleeding and pelvic pain. Ulipristal acetate (UPA) is an emerging medical treatment of fibroids with the potential to be used for long-term treatment. In this context, the present article summarizes UPA's main clinical pharmacology and pharmacokinetic (PK) properties. Ulipristal acetate has good oral bioavailability and a half-life allowing one single oral administration per day for the management of fibroids. As a steroid, UPA is a substrate for cytochrome P450 (CYP) 3A4 but does not act as an inducer or inhibitor of the CYP system or transporter proteins. With the exception of drugs modulating CYP3A4 activity, risks of drug-drug interactions with UPA are unlikely. In conclusion, besides its pharmacodynamic characteristics, UPA shows favorable PK properties that contribute to a good efficacy-safety ratio for the long-term management of uterine fibroids in clinical practice. PMID:25228633

  15. Sodium Oxybate: A Potential New Pharmacological Option for the Treatment of Fibromyalgia Syndrome

    PubMed Central

    Swick, Todd J.

    2011-01-01

    Fibromyalgia syndrome (FMS) is a common disorder, characterized by diffuse pain and tenderness, stiffness, fatigue, affective disorders and significant sleep pathology. A new set of diagnostic criteria have been developed which should make it easier for a busy clinician to diagnose the condition. US Food and Drug Administration (FDA) approved medications for the treatment of FMS have, for the most part, been geared to modulate the pain pathways to give the patient some degree of relief. A different kind of pharmacological agent, sodium oxybate (SXB), is described that is currently approved for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. SXB, an endogenous metabolite of the inhibitory neurotransmitter gamma-hydroxybutyrate, is thought to act independently as a neurotransmitter with a presumed ability to modulate numerous other central nervous system neurotransmitters. In addition SXB has been shown to robustly increase slow wave sleep and decrease sleep fragmentation. Several large clinical trials have demonstrated SXB's ability to statistically improve pain, fatigue and a wide array of quality of life measurements of patients with fibromyalgia. SXB is not FDA approved to treat fibromyalgia. PMID:22870476

  16.  NASH: A glance at the landscape of pharmacological treatment.

    PubMed

    Brodosi, Lucia; Marchignoli, Francesca; Petroni, Maria Letizia; Marchesini, Giulio

    2016-01-01

     The role of nonalcoholic fatty liver disease, namely nonalcoholic steatohepatitis (NASH), as risk factor for liver- and non-liver-related morbidity and mortality has been extensively reported. In addition to lifestyle changes, capable of removing the metabolic factors driving disease progression, there is an urgent need for drugs able to reduce hepatic necroinflammation without worsening of fibrosis. This goal is considered by regulatory agencies as surrogate marker to define the effectiveness in pharmacological compounds in NASH, and fast-track approval was granted by the Food and Drug Administration in consideration of disease severity and unmet medical needs. Several compounds are in the pipeline of pharmaceutical industries and are being studied in phase II trials, but only a few (obeticholic acid, elafibranor) have started phase III trials. This concise review is intended to offer a systematic analysis of the most promising therapeutic intervention in NASH. In conclusion, there is reasonable expectation that drug may help curb the burden of NASH, and we look forward to obtaining solid data on their long-term safety and effectiveness. However, we should not forget that behavioral interventions remain a mandatory background treatment, able to stop disease progression in compliant overweight/ obese patients, with results that compare favorably with - and add to - the beneficial effects of drug treatment. PMID:27493105

  17. The Clinical Pharmacology and Pharmacokinetics of Ulipristal Acetate for the Treatment of Uterine Fibroids

    PubMed Central

    Pohl, Oliver; Zobrist, R. Howard

    2014-01-01

    Uterine fibroids are benign hormone-sensitive tumors of uterine smooth muscle cells leading to heavy menstrual bleeding and pelvic pain. Ulipristal acetate (UPA) is an emerging medical treatment of fibroids with the potential to be used for long-term treatment. In this context, the present article summarizes UPA’s main clinical pharmacology and pharmacokinetic (PK) properties. Ulipristal acetate has good oral bioavailability and a half-life allowing one single oral administration per day for the management of fibroids. As a steroid, UPA is a substrate for cytochrome P450 (CYP) 3A4 but does not act as an inducer or inhibitor of the CYP system or transporter proteins. With the exception of drugs modulating CYP3A4 activity, risks of drug–drug interactions with UPA are unlikely. In conclusion, besides its pharmacodynamic characteristics, UPA shows favorable PK properties that contribute to a good efficacy–safety ratio for the long-term management of uterine fibroids in clinical practice. PMID:25228633

  18. Pharmacological cognitive enhancement: treatment of neuropsychiatric disorders and lifestyle use by healthy people.

    PubMed

    Sahakian, Barbara J; Morein-Zamir, Sharon

    2015-04-01

    Neuropsychiatric disorders typically manifest as problems with attentional biases, aberrant learning, dysfunctional reward systems, and an absence of top-down cognitive control by the prefrontal cortex. In view of the cost of common mental health disorders, in terms of distress to the individual and family in addition to the financial cost to society and governments, new developments for treatments that address cognitive dysfunction should be a priority so that all members of society can flourish. Cognitive enhancing drugs, such as cholinesterase inhibitors and methylphenidate, are used as treatments for the cognitive symptoms of Alzheimer's disease and attention deficit hyperactivity disorder. However, these drugs and others, including modafinil, are being increasingly used by healthy people for enhancement purposes. Importantly for ethical and safety reasons, the drivers for this increasing lifestyle use of so-called smart drugs by healthy people should be considered and discussions must occur about how to ensure present and future pharmacological cognitive enhancers are used for the benefit of society. PMID:26360089

  19. Medical treatment overview: traditional and novel psycho-pharmacological and complementary and alternative medications

    PubMed Central

    Anagnostou, Evdokia; Hansen, Robin

    2016-01-01

    Purpose of review Up to 35% of children and youth with autism spectrum disorder (ASD) receive at least one psychotropic medication. 50–70% of this population also receives biologically based complementary and alternative medicine (CAM). The data evaluating such practices are being reviewed. Recent findings There are accumulating data to suggest that atypical antipsychotics and stimulants may be useful for the treatment of irritability and hyperactivity in children and youth with ASD. The data for the use of selective serotonin reuptake inhibitors are less promising. New avenues of pharmacologic research targeting molecular targets identified by genomics, animal models and neuropathology are being evaluated. Areas of interest include glutamate/gamma-aminobutyric acid systems, neuropeptides such as oxytocin, and immune dysfunction, among others. In the case of biologically based CAM, a few compounds have been shown to be well tolerated, although efficacy is still being evaluated, such as melatonin, certain vitamins, and omega 3 fatty acids. Others have safety concerns without demonstrated efficacy, such as chelation therapies. Summary Accumulating data suggest a series of existing medications may be useful in ASD and large randomized clinical trials are necessary to evaluate safety and efficacy of both pharmaceuticals and alternative treatments. PMID:22001766

  20. Aspects of the non-pharmacological treatment of irritable bowel syndrome.

    PubMed

    Eriksson, Elsa Maria; Andrén, Kristina Ingrid; Kurlberg, Göran Karl; Eriksson, Henry Ture

    2015-10-28

    Irritable bowel syndrome (IBS) is one of the most commonly diagnosed gastrointestinal conditions. It represents a significant healthcare burden and remains a clinical challenge. Over the years IBS has been described from a variety of different perspectives; from a strict illness of the gastrointestinal tract (medical model) to a more complex multi-symptomatic disorder of the brain-gut axis (biopsychosocial/psychosomatic model). In this article we present aspects of the pathophysiology and the non-pharmacological treatment of IBS based on current knowledge. Effects of conditioned stress and/or traumatic influences on the emotional system (top-down) as well as effects on the intestine through stressors, infection, inflammation, food and dysbiosis (bottom-up) can affect brain-gut communication and result in dysregulation of the autonomic nervous system (ANS), playing an important role in the pathophysiology of IBS. Conditioned stress together with dysregulation of the autonomic nervous system and the emotional system may involve reactions in which the distress inside the body is not recognized due to low body awareness. This may explain why patients have difficulty identifying their symptoms despite dysfunction in muscle tension, movement patterns, and posture and biochemical functions in addition to gastrointestinal symptoms. IBS shares many features with other idiopathic conditions, such as fibromyalgia, chronic fatigue syndrome and somatoform disorders. The key to effective treatment is a thorough examination, including a gastroenterological examination to exclude other diseases along with an assessment of body awareness by a body-mind therapist. The literature suggests that early interdisciplinary diagnostic co-operation between gastroenterologists and body-mind therapists is necessary. Re-establishing balance in the ANS is an important component of IBS treatment. This article discusses the current knowledge of body-mind treatment, addressing the topic from a

  1. Aspects of the non-pharmacological treatment of irritable bowel syndrome

    PubMed Central

    Eriksson, Elsa Maria; Andrén, Kristina Ingrid; Kurlberg, Göran Karl; Eriksson, Henry Ture

    2015-01-01

    Irritable bowel syndrome (IBS) is one of the most commonly diagnosed gastrointestinal conditions. It represents a significant healthcare burden and remains a clinical challenge. Over the years IBS has been described from a variety of different perspectives; from a strict illness of the gastrointestinal tract (medical model) to a more complex multi-symptomatic disorder of the brain-gut axis (biopsychosocial/psychosomatic model). In this article we present aspects of the pathophysiology and the non-pharmacological treatment of IBS based on current knowledge. Effects of conditioned stress and/or traumatic influences on the emotional system (top-down) as well as effects on the intestine through stressors, infection, inflammation, food and dysbiosis (bottom-up) can affect brain-gut communication and result in dysregulation of the autonomic nervous system (ANS), playing an important role in the pathophysiology of IBS. Conditioned stress together with dysregulation of the autonomic nervous system and the emotional system may involve reactions in which the distress inside the body is not recognized due to low body awareness. This may explain why patients have difficulty identifying their symptoms despite dysfunction in muscle tension, movement patterns, and posture and biochemical functions in addition to gastrointestinal symptoms. IBS shares many features with other idiopathic conditions, such as fibromyalgia, chronic fatigue syndrome and somatoform disorders. The key to effective treatment is a thorough examination, including a gastroenterological examination to exclude other diseases along with an assessment of body awareness by a body-mind therapist. The literature suggests that early interdisciplinary diagnostic co-operation between gastroenterologists and body-mind therapists is necessary. Re-establishing balance in the ANS is an important component of IBS treatment. This article discusses the current knowledge of body-mind treatment, addressing the topic from a

  2. Pharmacological Treatment of Sleep Disturbance in Developmental Disabilities: A Review of the Literature

    ERIC Educational Resources Information Center

    Hollway, Jill A.; Aman, Michael G.

    2011-01-01

    Sleep disturbance is a common problem in children with developmental disabilities. Effective pharmacologic interventions are needed to ameliorate sleep problems that persist when behavior therapy alone is insufficient. The aim of the present study was to provide an overview of the quantity and quality of pharmacologic research targeting sleep in…

  3. The role of dental therapists in pharmacological and non-pharmacological treatment of anxious and phobic patients.

    PubMed

    MacLeavey, Christine

    2013-01-01

    Dental Therapists are in a prime position to be involved with the management of anxious and phobic patients. They earn less than dentists and are therefore a more cost-effective way of providing specialised care for anxious patients. Dental Therapists can spend more time educating and acclimatising these patients, do most if not all of the patient's treatment, only referring back to the dentist for RCT, crown/bridgework/dentures and permanent extractions. Ultimately this means that the patient receives high quality continuity of care. Treating anxious and phobic patients is time-consuming but ultimately very rewarding. If handled correctly and sensitively the anxious and phobic patient will not always be anxious or phobic, in the same way that children won't always be children. Dental Therapists can now extend their duties to include Relative Analgesia. This should enhance their employability and role within the dental team especially in the management of anxious and phobic patients. Employing a therapist with a toolbox of techniques at their disposal can be seen as part of a long-term practice plan to ensure that anxious and phobic patients become rehabilitated, happy, compliant and loyal to the practice! In fact .... the sort of patients every dentist really wants to see. PMID:23544223

  4. Regulated recycling of mutant CFTR is partially restored by pharmacological treatment.

    PubMed

    Holleran, John P; Zeng, Jianxin; Frizzell, Raymond A; Watkins, Simon C

    2013-06-15

    Efficient trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) to and from the cell surface is essential for maintaining channel density at the plasma membrane (PM) and ensuring proper physiological activity. The most common mutation, F508del, exhibits reduced surface expression and impaired function despite treatment with currently available pharmacological small molecules, called correctors. To gain more detailed insight into whether CFTR enters compartments that allow corrector stabilization in the cell periphery, we investigated the peripheral trafficking itineraries and kinetics of wild type (WT) and F508del in living cells using high-speed fluorescence microscopy together with fluorogen activating protein detection. We directly visualized internalization and accumulation of CFTR WT from the PM to a perinuclear compartment that colocalized with the endosomal recycling compartment (ERC) markers Rab11 and EHD1, reaching steady-state distribution by 25 minutes. Stimulation by protein kinase A (PKA) depleted this intracellular pool and redistributed CFTR channels to the cell surface, elicited by reduced endocytosis and active translocation to the PM. Corrector or temperature rescue of F508del also resulted in targeting to the ERC and exhibited subsequent PKA-stimulated trafficking to the PM. Corrector treatment (24 hours) led to persistent residence of F508del in the ERC, while thermally destabilized F508del was targeted to lysosomal compartments by 3 hours. Acute addition of individual correctors, C4 or C18, acted on peripheral trafficking steps to partially block lysosomal targeting of thermally destabilized F508del. Taken together, corrector treatment redirects F508del trafficking from a degradative pathway to a regulated recycling route, and proteins that mediate this process become potential targets for improving the efficacy of current and future correctors. PMID:23572510

  5. [Non-pharmacological treatment of ventricular tachycardia (anti-arrhythmic surgery excluded)].

    PubMed

    Touboul, P

    1993-05-01

    There has been real change in the treatment of VT in recent years including the promotion of non-medical methods. In the large group of non-responders to medical therapy, only a minority offers possibilities of radical surgical treatment of VT. In the others, two options remain: ablative methods and implantable automatic cardioverter defibrillators. The destruction of foci of tachycardia by catheterisation necessitates prior investigation of the ventricular endocardium with recordings of endocardial electrograms during VT. Criteria defining the zone for ablation are two-fold: either the zone of earliest endocardial depolarisation or the exit zone (generally preceding the tachycardia QRS complexes by 20 to 30 ms). The second is the zone of slow conduction which corresponds to the cardiac substrate in which the tachycardia arises. In the absence of satisfactory mapping, localisation of the ablation target may be performed by stimulating the endocardium at different points with the aim of reproducing the tachycardia QRS complexes. Two types of physical agents have been used for ablation: high energy electric shocks and, at present, radiofrequency currents. Complications of the procedure are rare: thromboembolism, cardiac rupture, cardiogenic shock in patients with initially poor hemodynamic conditions. Prevention of VT is obtained in over half the cases providing complementary antiarrhythmic therapy is prescribed. The other alternative is the implantable automatic defibrillator which is tending to take over the leading role in non-pharmacological treatment of VT. At first, these devices were exclusively defibrillators but nowadays they have anti-tachycardia functions which widen the indications to include subjects with sustained VT even in the absence of cardiac arrest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8267510

  6. Clinical pharmacology study of cariprazine (MP-214) in patients with schizophrenia (12-week treatment)

    PubMed Central

    Nakamura, Tadakatsu; Kubota, Tomoko; Iwakaji, Atsushi; Imada, Masayoshi; Kapás, Margit; Morio, Yasunori

    2016-01-01

    Purpose Cariprazine is a potent dopamine D3-preferring D3/D2 receptor partial agonist in development for the treatment of schizophrenia, bipolar mania, and depression. Pharmacokinetics of cariprazine and the two clinically relevant metabolites (desmethyl- and didesmethyl-cariprazine) was evaluated in a clinical pharmacology study. Methods This was a multicenter, randomized, open-label, parallel-group, fixed-dose (3, 6, or 9 mg/day) study of 28-week duration (≤4-week observation, 12-week open-label treatment, and 12-week follow-up). Once-daily cariprazine was administered to 38 adult patients with schizophrenia. The pharmacokinetics of cariprazine, metabolites, and total active moieties (sum of cariprazine and two metabolites) was evaluated; efficacy and safety were also assessed. Results Steady state was reached within 1–2 weeks for cariprazine and desmethyl-cariprazine, 4 weeks for didesmethyl-cariprazine, and 3 weeks for total active moieties. Cariprazine and desmethyl-cariprazine levels decreased >90% within 1 week after the last dose, didesmethyl-cariprazine decreased ~50% at 1 week, and total active moieties decreased ~90% within 4 weeks. Terminal half-lives of cariprazine, desmethyl-cariprazine, and didesmethyl-cariprazine ranged from 31.6 to 68.4, 29.7 to 37.5, and 314 to 446 hours, respectively. Effective half-life (calculated from time to steady state) of total active moieties was ~1 week. Incidence of treatment-emergent adverse events was 97.4%; 15.8% of patients discontinued due to adverse events. No abnormal laboratory values or major differences from baseline in extrapyramidal symptoms were observed. Conclusion Cariprazine and its active metabolites reached steady state within 4 weeks, and exposure was dose proportional over the range of 3–9 mg/day. Once-daily cariprazine was generally well tolerated in adult patients with schizophrenia. PMID:26834462

  7. Raynaud's phenomenon and digital ischaemia--pharmacologic approach and alternative treatment options.

    PubMed

    Linnemann, Birgit; Erbe, Matthias

    2016-01-01

    The primary goal of therapy is to reduce the frequency and intensity of Raynaud's attacks and to minimize the related morbidity rather than to cure the underlying condition. Treatment strategies depend on whether Raynaud's phenomenon (RP) is primary or secondary. All patients should be instructed about general measures to maintain body warmth and to avoid triggers of RP attacks. Pharmacologic intervention can be useful for patients with severe and frequent RP episodes that impair the patient's quality of life. Calcium channel blockers are currently the most prescribed and studied medications for this purpose. There has been limited evidence for the efficacy of alpha-1-adrenergic receptor antagonists, angiotensin receptor blockers, topical nitrates or fluoxetine to treat RP. The intravenously administered prostacyclin analogue iloprost can reduce the frequency and severity of RP attacks and is considered a second-line therapy in patients with markedly impaired quality of life, critical digital ischaemia and skin ulcers who are at risk for substantial tissue loss and amputation. Phosphodiesterase inhibitors (e.g., sildenafil) can also improve RP symptoms and ulcer healing whereas endothelin-1 receptor antagonists (e.g., bosentan) are mainly considered treatment options in secondary prevention for patients with digital skin ulcers related to systemic sclerosis. However, their use in clinical practice has been limited by their high cost. Antiplatelet therapy with low-dose aspirin is recommended for all patients who suffer from secondary RP due to ischaemia caused by structural vessel damage. Anticoagulant therapy can be considered during the acute phase of digital ischaemia in patients with suspected vascular occlusive disease attributed to the occurrence of new thromboses. In patients with critical digital ischaemia, consideration should be given to hospitalisation, optimisation of medical treatment in accordance with the underlying disease and evaluation for a

  8. Pharmacologic treatment approaches for children and adolescents with posttraumatic stress disorder.

    PubMed

    Donnelly, Craig L

    2003-04-01

    should target anxiety, mood, and reexperiencing symptoms. Adrenergic agents, such as clonidine, used either alone or in combination with an SSRI may be useful when symptoms of hyperarousal and impulsivity are problematic. Supplementing with a mood stabilizer may be necessary in severe affective dyscontrol. Similarly, introduction of an atypical neuroleptic agent may be necessary in cases of severe self-injurious behavior, dissociation, psychosis, or aggression. Comorbid conditions such as ADHD should be targeted with pharmacotherapy known to be effective, such as psychostimulants or newer agents such as atomoxetine. Pharmacologic treatment of PTSD in childhood is one approach to alleviating the acute and chronic symptoms of the disorder. Despite the lack of well-designed, randomized, controlled trials that support efficacy, medication can be used in a rational and safe manner. Reduction in even one disabling symptom, such as insomnia or hyperarousal, may have a positive ripple effect on a child's overall functioning. Pharmacotherapy is typically used as one component of a more comprehensive multiple modality treatment package, including psychoeducation of the parent and child, focused exposure-based psychotherapy with adjunctive family therapy when indicated, and long-term booster interventions that use an admixture of psychodynamic, cognitive-behavioral, and pharmacologic interventions. PMID:12725011

  9. Pharmacological Chaperone Therapy: Preclinical Development, Clinical Translation, and Prospects for the Treatment of Lysosomal Storage Disorders

    PubMed Central

    Parenti, Giancarlo; Andria, Generoso; Valenzano, Kenneth J

    2015-01-01

    Lysosomal storage disorders (LSDs) are a group of inborn metabolic diseases caused by mutations in genes that encode proteins involved in different lysosomal functions, in most instances acidic hydrolases. Different therapeutic approaches have been developed to treat these disorders. Pharmacological chaperone therapy (PCT) is an emerging approach based on small-molecule ligands that selectively bind and stabilize mutant enzymes, increase their cellular levels, and improve lysosomal trafficking and activity. Compared to other approaches, PCT shows advantages, particularly in terms of oral administration, broad biodistribution, and positive impact on patients' quality of life. After preclinical in vitro and in vivo studies, PCT is now being translated in the first clinical trials, either as monotherapy or in combination with enzyme replacement therapy, for some of the most prevalent LSDs. For some LSDs, the results of the first clinical trials are encouraging and warrant further development. Future research in the field of PCT will be directed toward the identification of novel chaperones, including new allosteric drugs, and the exploitation of synergies between chaperone treatment and other therapeutic approaches. PMID:25881001

  10. Multitarget Multiscale Simulation for Pharmacological Treatment of Dystonia in Motor Cortex

    PubMed Central

    Neymotin, Samuel A.; Dura-Bernal, Salvador; Lakatos, Peter; Sanger, Terence D.; Lytton, William W.

    2016-01-01

    A large number of physiomic pathologies can produce hyperexcitability in cortex. Depending on severity, cortical hyperexcitability may manifest clinically as a hyperkinetic movement disorder or as epilpesy. We focus here on dystonia, a movement disorder that produces involuntary muscle contractions and involves pathology in multiple brain areas including basal ganglia, thalamus, cerebellum, and sensory and motor cortices. Most research in dystonia has focused on basal ganglia, while much pharmacological treatment is provided directly at muscles to prevent contraction. Motor cortex is another potential target for therapy that exhibits pathological dynamics in dystonia, including heightened activity and altered beta oscillations. We developed a multiscale model of primary motor cortex, ranging from molecular, up to cellular, and network levels, containing 1715 compartmental model neurons with multiple ion channels and intracellular molecular dynamics. We wired the model based on electrophysiological data obtained from mouse motor cortex circuit mapping experiments. We used the model to reproduce patterns of heightened activity seen in dystonia by applying independent random variations in parameters to identify pathological parameter sets. These models demonstrated degeneracy, meaning that there were many ways of obtaining the pathological syndrome. There was no single parameter alteration which would consistently distinguish pathological from physiological dynamics. At higher dimensions in parameter space, we were able to use support vector machines to distinguish the two patterns in different regions of space and thereby trace multitarget routes from dystonic to physiological dynamics. These results suggest the use of in silico models for discovery of multitarget drug cocktails. PMID:27378922