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Biomedical subjects

Prakash S Masand

Publications and source records attributed to Prakash S Masand.

At least 19 recordsLinked to original sources

Differential pharmacology of atypical antipsychotics: clinical implications.

PURPOSE: Pharmacology of atypical antipsychotics and the clinical implications are reviewed. SUMMARY: Psychiatric disorders, such as schizophrenia and bipolar disorder, are often associated with poor outcomes. Atypical antipsychotics have become the standard of care for these disorders, and multiple agents have demonstrated efficacy for both acute and maintenance therapy. As a result of their differential pharmacologic properties, atypical antipsychotics have diverse clinical profiles, resulting in different liabilities for specific adverse events. These effects can, in turn, have an adverse impact on patient functionality, adherence to therapy, and overall health. CONCLUSION: Atypical antipsychotics have distinct pharmacological profiles which result in clinically meaningful differences in adverse effects. Clinicians should have a wide choice of agents available with which to optimize outcomes in the majority of patients with psychiatric disorders.

Antipsychotic Agents↗

Aripiprazole augmentation for treatment of patients with inadequate antidepressants response.

This study evaluated whether or not augmentation with aripiprzazole is beneficial and tolerable to patients with an inadequate response to antidepressants (ADs). Thirteen patients with nonpsychotic major depression, who had failed to respond to an adequate trial of at least one AD, were prescribed aripiprazole (dose, 5-30 mg) for 8 weeks. The dose of their preexisting ADs was not changed. The treatment response was defined as the mean changes in the scores of the Hamilton Depression Rating Scale (HAM-D) from the baseline to the end of treatment. Eleven (84.6%) patients returned for at least one follow-up visit, and 7 (53.8%) patients completed the study. The HAM-D and Clinical Global Impression-Severity (CGI-S) scores decreased significantly from the baseline to the end of treatment by 53.8% and 56.0%, respectively (Z = -2.937, P =.003; Z = -2.961, P =.003). Seven (63.6%) patients showed a > or = 50% reduction in the HAM-D score at the end of treatment. Three (27.3%) patients met the remission criteria at the end of treatment. There were no serious side effects. Despite the high dropout rate in this open study, aripiprazole appears to be reasonably effective and tolerated as an augmentation strategy in conjunction with conventional ADs treatment in patients with an inadequate AD response. These results highlight the potential benefits of aripiprazole for these patients. However, adequately powered, randomized, controlled trials are needed to confirm these results.

Adult↗

Transdermal selegiline: the new generation of monoamine oxidase inhibitors.

The clinical use of monoamine oxidase inhibitors (MAOIs) has declined due to concerns about food and drug interactions and waning physician experience. Evidence indicates that MAOIs are effective in depressive disorders, in particular depression with atypical features. Efforts to address safety issues have led to the development of more selective and reversible MAOIs, such as moclobemide. Selegiline, a selective monoamine oxidase B inhibitor, has been approved for the adjunctive treatment of Parkinson's disease at low doses. At higher doses, oral selegiline is also effective in major depressive disorder (MDD) but loses its selectivity and has the potential for tyramine interactions. To overcome these problems, a transdermal formulation of selegiline, the selegiline transdermal system (STS), was developed with novel pharmacokinetic and pharmacodynamic properties. Compared with oral administration, transdermal selegiline leads to sustained plasma concentrations of the parent compound, increasing the amount of drug delivered to the brain and decreasing metabolite production. In addition, STS allows targeted inhibition of central nervous system monoamine A (MAO-A) and monoamine B isoenzymes with minimal effects on MAO-A in the gastrointestinal and hepatic systems, thereby reducing the risk of interactions with tyramine-rich foods (the "cheese-reaction"). Clinical trials have found 6 mg/24 hours of STS to be effective in MDD without the need for dietary restrictions. The efficacy and safety profile of STS supports its use in MDD. It is possible that STS may demonstrate benefit in MDD with atypical features or MDD resistant to other antidepressants. However, more research is needed. Clinicians should familiarize themselves with the properties and indications for the new generation of MAOIs.

Administration, Cutaneous↗

Prevalence of irritable bowel syndrome in obsessive-compulsive disorder.

INTRODUCTION: Irritable bowel syndrome (IBS) occurs more frequently in psychiatric patients, especially those with anxiety and mood disorders. METHODS: We sought to determine the prevalence and phenomenology of IBS in patients diagnosed with obsessive-compulsive disorder (OCD). A semi-structured diagnostic interview was administered to patients seeking treatment for OCD in outpatient settings. Structured questions regarding gastrointestinal functioning and IBS symptoms were administered. IBS was diagnosed by a gastroenterologist using Rome I criteria. RESULTS: Thirty-seven patients (35.1%) with OCD met criteria for IBS. Of these, 53.8% had IBS with both diarrhea and constipation, 30.8% had diarrhea-predominant IBS, and 15.4% had constipation-predominant IBS. The prevalence rate of IBS in an age- and sex-matched control group (n=40) of medical patients in a family practice was 2.5%. IBS prevalence rates were significantly higher for OCD patients than control subjects (P=.0002). CONCLUSION: IBS and psychiatric illness have high rates of bi-directional comorbidity. This study shows that 35.1% of patients with OCD satisfied criteria for IBS in contrast to 2.5% of the controlled subjects. In most patients the IBS was characterized by both diarrhea and constipation. While taking the initial history clinicians should inquire about bowel symptoms in patients presenting with psychiatric illnesses, including OCD. SSRIs could potentially worsen such symptoms and lead to non-adherence.

Adult↗

A randomized, double-blind, placebo-controlled trial of augmentation with an extended release formulation of methylphenidate in outpatients with treatment-resistant depression.

We examined the efficacy and tolerability of augmentation with an extended release formulation of methylphenidate (OROS MPH, Concerta) in patients with major depression who were nonresponders or partial responders to antidepressants. Sixty subjects with treatment-resistant depression (TRD) participated in a 4-week, randomized, double-blind, placebo-controlled study of augmentation with methylphenidate (18-54 mg/d). The preexisting antidepressant dose was unchanged. The primary efficacy measure was change in the 21-item Hamilton Depression Rating Scale from randomization to end of treatment. Data were analyzed with intent-to-treat with last observation carried forward approach. There were no statistically significant differences between the methylphenidate (n = 30) and placebo (n = 30) groups in reduction in 21-item Hamilton Depression Rating Scale scores (drug, -6.9; placebo, -4.7) from baseline to end of treatment (F1,47 = 1.24, P = 0.22), although responders were numerically higher in the extended-release methylphenidate group (40.0%) than in the placebo group (23.3%). On the secondary efficacy measures of changes in Clinical Global Impression-Improvement and Severity scores and Beck Depression Inventory-Second Edition, the drug failed to separate from placebo, although the proportion of responders in the drug group were numerically higher than placebo. There were no significant differences in weight, heart rate, and blood pressure changes between the 2 groups. The common adverse events were loss of appetite, nausea, headache, and anxiety. The mean dose of drug was 34.2 mg/d. The study did not demonstrate a statistically significant benefit for augmentation with methylphenidate in TRD. Combination of methylphenidate with antidepressants was well tolerated. Adequately powered, randomized, controlled trials are necessary to fully evaluate the efficacy of extended-release methylphenidate in TRD.

Adolescent↗

An open-label, rater-blinded, augmentation study of aripiprazole in treatment-resistant depression.

BACKGROUND: About 30% to 46% of patients with major depressive disorder (MDD) fail to fully respond to initial antidepressants. While treatment-resistant depression commonly refers to nonresponse or partial response to at least 2 adequate trials with antidepressants from different classes, due to variability in terminology, a staging system based on prior treatment response has been suggested. Aripiprazole is a novel atypical antipsychotic with partial agonism at dopamine D(2) and serotonin 5-HT(1A) receptors and antagonism at the 5-HT(2) receptors. The present study evaluated whether augmentation with aripiprazole would be beneficial and tolerable in patients with treatment-resistant MDD who had failed 1 or more trials of antidepressants. METHOD: In an open-label, rater-blinded study conducted from March 2003 through December 2003, 10 patients with DSM-IV MDD without psychotic features who had failed to respond to an adequate trial of at least 1 antidepressant were prescribed aripiprazole (10-30 mg/day) for 6 weeks. The dose of preexisting antidepressants remained unchanged. Treatment response was defined as a 50% or greater reduction in score on the Hamilton Rating Scale for Depression (HAM-D) from baseline to end of treatment. Secondary efficacy measures included scores on the Clinical Global Impressions-Improvement (CGI-I) and -Severity (CGI-S) scales. RESULTS: Eight of 10 patients had failed 2 or more antidepressant trials. The mean daily dose of aripiprazole was 13.21 mg. Intent-to-treat analysis showed that mean ± SD HAM-D scores reduced significantly from baseline (23.0 ± 8.1) to end of treatment (8.1 ± 6.0) (p < .001). There was a significant reduction in CGI-I (p < .05) and a trend toward decrease in CGI-S (p = .06) score. Seventy percent of the subjects were responders and 30% achieved remission. Common adverse effects were akathisia (20%), nausea (20%), and restlessness (20%). CONCLUSIONS: The study indicates the potential utility of aripiprazole as an augmenting agent in treatment-resistant depression, particularly in those who had failed 2 or more antidepressant trials. Adequately powered, randomized controlled trials are necessary to evaluate the role of aripiprazole in treatment-resistant depression.

Journal Article↗

Paroxetine for somatic pain associated with physical illness: a review.

OBJECTIVE: The purpose of this article is to review the prevalence of somatic pain with and without depression or anxiety and the pharmacologic effects of the selective serotonin reuptake inhibitor paroxetine on pain in physical conditions with and without comorbid depression or anxiety. DATA SOURCES: MEDLINE and PsychLIT/PsycINFO database. Keywords included depression, anxiety, pain, somatic, antidepressants, and paroxetine. Only English-language publications and abstracts were considered. STUDY SELECTION: More than 100 articles that reflected the prevalence of somatic pain in patients with physical illness with and without comorbid depression or anxiety and that evaluated the efficacy of antidepressants in this population were identified and reviewed. DATA SYNTHESIS: Nearly two thirds of patients with major depressive disorder suffer from a physical illness, and about one fifth of patients with chronic physical illness are depressed. Both of these comorbidities pose diagnostic and therapeutic challenges. Therapeutic effects of antidepressants on pain improvement in patients with chronic physical illnesses and comorbid depression/anxiety have been attributed to the antidepressant or anxiolytic properties of these drugs. However, tricyclic antidepressants have demonstrated analgesic properties in patients with physical illness both with and without depression. The review looks at evidence for the efficacy of the selective serotonin reuptake inhibitor paroxetine on pain in physical illness with and without depression and the mechanisms for the relief of pain and depression. CONCLUSIONS: The efficacy of paroxetine for depression and anxiety comorbid with physical illness looks promising. Studies also allude to evidence linking the analgesic properties of paroxetine with its serotonergic and noradrenergic activity. Large randomized controlled trials within specific antidepressant classes and also comparing dualaction antidepressants are warranted that could shed some light on the unique advantage of paroxetine over other antidepressants.

Journal Article↗

Clinical variables associated with early administration of antipsychotics in bipolar mania.

This study evaluated the clinical variables associated with the early administration of antipsychotics for the treatment of bipolar mania. 63 out of 97 inpatients with bipolar I disorder according to the DSM-IV criteria and who were consecutively admitted to the Kangnam St. Mary's Hospital, between September 2002 and March 2004, were included in the study. Regression analysis was run on the clinical variables in order to identify the factors affecting the early administration of antipsychotics. The route of admission and exposure to antipsychotics at the last follow-up were found to be associated with the early administration of antipsychotics (odds ratios=33.0 and 13.1, respectively). This study suggests that some clinical factors in bipolar mania might be linked to the earlier antipsychotic treatment. However, more studies will be needed to confirm this finding.

Adult↗

A review of pharmacologic strategies for switching to atypical antipsychotics.

BACKGROUND: In daily clinical practice, frequent switching of antipsychotic medications is widespread. There are various reasons for switching, including a partial or complete lack of efficacy, adverse side effects, and partial or noncompliance with medication. Patients switched from conventional drugs to oral atypical antipsychotic drugs have been shown to benefit from significant improvements in clinical response and tolerability. This review examines the strategies for switching patients from conventional antipsychotic drugs to both oral and long-acting formulations of atypical antipsychotic drugs that are the recommended treatment in the majority of patients with schizophrenia. DATA SOURCES AND STUDY SELECTION: An electronic literature search of relevant studies using MEDLINE (January 1994-June 2004) was performed using the search terms antipsychotic, atypical, conventional, schizophrenia, and switching. English-language articles, references from bibliographies of reviews, original research articles, and other articles of interest were reviewed. DATA EXTRACTION AND SYNTHESIS: Data quality was determined by publication in the peer-reviewed literature and the most important information identified. Data from clinical trials suggest that switching to an atypical antipsychotic drug is beneficial for the patient with schizophrenia. CONCLUSIONS: If initiated appropriately, switching to atypical antipsychotic medications should not compromise patient functioning; indeed, individualized strategies have been shown to provide continuous treatment efficacy. Switching to atypical antipsychotic therapy should, therefore, be employed as a pharmacologic strategy to maximize patient outcomes.

Journal Article↗

Open-label treatment with citalopram in patients with irritable bowel syndrome: a pilot study.

BACKGROUND: This open-label pilot study investigated whether the selective serotonin reuptake inhibitor (SSRI) citalopram improves symptoms of irritable bowel syndrome (IBS), a functional gastrointestinal disorder with frequent psychiatric comorbidity. METHOD: Fifteen patients meeting Rome I criteria for IBS were administered open-label citalopram (20-40 mg/day) for 12 weeks. The study was conducted from October 2000 to August 2001. RESULTS: Twelve (80%) of the 15 subjects reported a > or = 50% decrease in the presence of abdominal pain, 10 (67%) reported a > or = 50% reduction in the severity of the symptom, and 12 (80%) reported a > or = 50% reduction in the frequency of the symptom. Approximately one half of the patients met criteria for remission (> or = 70% improvement) of abdominal pain. CONCLUSION: Results of this pilot study suggest that large controlled trials are needed to further evaluate the efficacy of SSRIs such as citalopram for the treatment of IBS.

Journal Article↗

Metabolic and endocrine disturbances in psychiatric disorders: a multidisciplinary approach to appropriate atypical antipsychotic utilization.

Patients with psychiatric disorders have an increased rate of cardiovascular morbidity and mortality compared with the general population. Metabolic issues such as weight gain, dyslipidemia, diabetes mellitus, diabetic ketoacidosis,and pancreatitis have been reported with the use of antipsychotic agents. Although atypical antipsychotics have not been linked directly to the development of metabolic syndrome, these medications have been shown to increase risk factors that can lead to metabolic and endocrine disturbances. Therefore, clinicians should provide ongoing monitoring for patients who are being treated for psychiatric disorders with these agents. According to the 2004 Consensus Report on Antipsychotics, screening measures should include baseline and follow-up monitoring of personal/family histories, weight (body mass index), waist circumference, blood pressure, fasting plasma glucose, and fasting lipid profile.

Antipsychotic Agents↗

Weight decline in patients switching from olanzapine to quetiapine.

This open-label study investigated the strategy of switching patients who had gained excessive weight on olanzapine to quetiapine, with assessments of safety and continued efficacy as well as weight change. Patients who were psychiatrically stable on olanzapine but had gained >20% in weight and had body mass index >25 mg/kg(2) were switched to quetiapine over a 4-week period and followed for 6 weeks, the total study duration being 10 weeks. Assessments included weight change, antipsychotic efficacy using the Positive and Negative Symptom Syndrome Scale (PANSS), extrapyramidal adverse events using the Simpson-Angus Scale (SAS), and laboratory studies for metabolic measures. Of 16 enrolled patients, 12 completed the study. Mean weight loss was 2.25 kg (Cohen's d = 0.12; P = 0.03). There were no significant changes in PANSS total scores, SAS scores, or metabolic parameters. Switching patients to quetiapine, appears to be a viable strategy for managing olanzapine-induced weight gain as indicated by this 10-week open-label study. Prospective controlled trials of longer duration and larger number of subjects are needed.

Basal Ganglia Diseases↗

Psychotic symptoms in patients with medical disorders.

Psychotic symptoms frequently occur in patients with comorbid medical disorders and present a diagnostic and treatment challenge. They may be a part of an independent psychiatric illness associated with the underlying medical condition or induced by substance use or medications. The presence of psychotic symptoms can contribute to misdiagnosis or complicate the management of the comorbid medical illness. Psychiatrists must be familiar with the assessment and management of psychotic disorders in patients with comorbid medical disorders. Medications that may be used to treat psychosis include antipsychotic agents, benzodiazepines, or possibly certain anticonvulsants. Selecting the appropriate medication requires knowledge of the pharmacokinetics of different agents and their side effect profile. Understanding the neuropsychiatric effects of medications and drug-drug interactions may help in preventing psychotic symptoms.

Antipsychotic Agents↗

Safety considerations in pharmacotherapy of bipolar disorder.

Bipolar disorder is a chronic, frequently relapsing illness with a prevalence of 1.2% to 3.4% in the general population. It is associated with high disability, higher comorbidity due to medical illnesses, and significant social and economical consequences for patients, their families, and society. The episodic nature of this disease warrants rational use of medications and proper monitoring for adverse events. Various drug classes, such as mood stabilizers, antipsychotics, benzodiazepines, and antidepressants, are used for the acute and maintenance treatment of bipolar disorder. Each group of drugs is associated with wide array of adverse events and drug interactions, which are the main hurdles in treatment outcome and compliance. Common side effects seen with several agents, particularly antipsychotics, are somnolence, weight gain, extrapyramidal symptoms, dyslipidemia, type-2 diabetes, and hyperprolactinemia. Major drug interactions are seen with drugs such as carbamazepine, due to hepatic enzyme induction. Adverse effects such as somnolence are tolerability concerns and can be managed easily; others, such as diabetes mellitus, are safety concerns. It is prudent to have precise knowledge of the individual drug's side-effect profile, pharmacokinetics, and pharmacodynamics, to plan a treatment regimen. More research is needed to understand potential risks of various drugs and to devise and incorporate monitoring protocols in the treatment regimen.

Bipolar Disorder↗

Management of fibromyalgia.

Fibromyalgia is characterized by widespread pain, persistent fatigue, nonrestorative sleep, and generalized morning stiffness. The diagnosis is based on patients' reports of pain and fatigue, clinical findings of multiple tender points, and exclusion of a range of connective tissue and other medical disorders. Treatment of fibromyalgia is multidisciplinary with an emphasis on active patient participation, medications, cognitive behavioral therapy, and physical modalities. No single medication has been found to effectively control all the symptoms, and a rational combination of different medications is often necessary. Currently available medication classes include the selective serotonin uptake inhibitors, the serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, analgesics, hypnotic agents, and anticonvulsants. Treatment modalities should be individualized for patients based on target symptoms and impairment in functioning. As is the case with several chronic disorders, the treatment is often prolonged and improvement may occur slowly. Patience and positive attitude on part of the physician and active involvement of patients and their families in treatment are likely to enhance improvement.

Combined Modality Therapy↗