Jehan Marino

Paliperidone Extended-Release for the Treatment of Schizophrenia

Paliperidone, the major active metabolite of risperidone (9‐hydroxy‐risperidone), is a second‐generation antipsychotic that was recently approved by the United States Food and Drug Administration for treatment of acute schizophrenia and for maintenance treatment of schizophrenia. We performed a literature search of PreMEDLINE, MEDLINE, and International Pharmaceutical Abstracts from 1966‐October 2007 to review the available data on the pharmacology, pharmacokinetics, clinical evidence, and safety and tolerability profile of paliperidone extended‐release (ER). Articles from randomized controlled trials, abstracts, and posters presented at national scientific meetings were included in this review. Paliperidone ER has been shown to be significantly more effective in improving schizophrenic symptoms according to the Positive and Negative Symptom Scale (PANSS), Clinical Global Impressions‐Severity Scale, and Personal and Social Performance Scale compared with placebo (p<0.05). In addition, limited evidence suggests similar efficacy between paliperidone ER 6–12 mg/day and risperidone 4–6 mg/day. A 2‐week, double‐blind comparison with quetiapine demonstrated that paliperidone ER was significantly better than quetiapine in improving PANSS scores (p<0.001). Paliperidone ER appears to be well tolerated at the recommended starting dosage of 6 mg/day. The most commonly reported adverse effect was dose‐related extrapyramidal symptoms. Weight gain and metabolic disturbances were minimal. The cost of paliperidone ER appears to be slightly higher than that of other second‐generation antipsychotics. Paliperidone ER tablets may be a safe and effective treatment option for acute schizophrenia and maintenance treatment of schizophrenia compared with placebo. Because well‐designed comparative data are lacking, an additional benefit over other antipsychotics is yet to be determined.

Iloperidone for the Treatment of Schizophrenia

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety data of iloperidone for the treatment of schizophrenia. DATA SOURCES: Data were selected by searching Pre-MEDLINE, MEDLINE, and International Pharmaceutical Abstracts (1966-January 2010). Abstracts, scientific posters, and unpublished data provided by the manufacturer in the English language were also assessed. STUDY SELECTION AND DATA EXTRACTION: All published data including pharmacologic, pharmacokinetic, pharmacodynamic, and clinical studies related to iloperidone were considered for inclusion. Selected studies included randomized controlled trials, abstracts, and posters presented at national scientific meetings providing pertinent data. data synthesis: Iloperidone is a benzisoxazole phenylethanone with a higher affinity for serotonin-2a than dopamine-2 receptors. The recommended therapeutic total daily dose is 12-24 mg divided in 2 doses titrated over 1 week to avoid orthostasis. Acute, 6-week, randomized, placebo-controlled, and active-controlled studies demonstrated iloperidones efficacy in reducing psychotic symptoms according to changes in the total positive and negative symptom scale (PANSS-T) score from baseline. A long-term maintenance trial demonstrated similar efficacy with haloperidol in preventing time to relapse. Pharmacogenomic studies reported possible single nucleotide polymorphisms related to QT interval prolongation and efficacy with iloperidone. Common adverse effects included dizziness, dry mouth, and sustained orthostasis occurring more frequently with higher doses. Weight gain is possible at any dose. Additionally, studies showed that QTc interval prolongation may be dose related. The incidence of extrapyramidal symptoms appears to be low across all dosage ranges; however, akathisia may be more frequent with higher doses. CONCLUSIONS: Iloperidone demonstrated efficacy in acute exacerbations and long-term maintenance in adults with schizophrenia. Caution may be warranted in elderly patients and patients with cardiac disease, due to orthostasis. Further studies regarding pharmacogenomic testing related to the drugs efficacy and tolerability are needed to justify its routine use in practice.

Role of Omega-3 Fatty Acids for Prevention or Treatment of Perinatal Depression

Perinatal depression is a complex mental health disorder that can manifest during pregnancy or after childbirth. Women with perinatal depression may not receive proper medical treatment because of concerns over teratogenic effects related to drug therapy. Evidence suggests that low levels of omega‐3 fatty acids are correlated with depressive symptoms during pregnancy and after delivery. Omega‐3 fatty acids may produce antidepressant effects due to their role in serotonin functioning. A literature search identified seven clinical trials of omega‐3 fatty acids for the prevention or treatment of perinatal depression. Depression rating scale scores used in the studies improved, but results were statistically significant in only three trials. Four studies were randomized and placebo controlled, and three were open label. One study evaluating the prevention of postpartum depression in women with a history of depression was discontinued early due to relapse of depressive symptoms. In the trials we evaluated, the most common adverse effects were foul breath and/or unpleasant taste, and gastrointestinal complaints; no serious adverse events were reported. The seven studies were limited by small sample sizes and variable dosing and study durations. In the studies that demonstrated statistical significance, improvement in depression rating scale scores for omega‐3 fatty acids was comparable to placebo. Overall, results have been inconclusive, but further investigation of omega‐3 fatty acids is warranted because they did improve depression scores and appeared to be safe during pregnancy.

Graves’ Hyperthyroidism-Induced Psychosis Treated With Aripiprazole—A Case Report

Graves’ disease is an autoimmune syndrome with symptoms such as tachycardia, atrial fibrillation, and psychiatric symptoms. Limited evidence exists for the treatment of Graves’ hyperthyroidism-induced psychosis with atypical antipsychotics. A 47-year-old female with a psychiatric history of bipolar disorder presented for the first time to the psychiatric hospital. She was agitated and grossly psychotic with delusions. Electrocardiogram showed atrial fibrillation and tachycardia. Drug screen urinalysis was negative. Endocrine workup resulted in a diagnosis of Graves’ disease (thyroid-stimulating hormone [TSH]: 0.005 μIU/mL, triiodothyronine [T3]: 537 ng/dL, thyroxine [T4]: 24 mcg/dL, free T4: 4.5 ng/dL, positive antithyroid peroxidase antibody, and antinuclear antibody). Aripiprazole 10 mg daily was initiated and titrated to 15 mg daily on day 4. On day 16, her suspicious behavior, judgment, and insight improved. Other medications given included aspirin 325 mg daily, metoprolol 25 mg twice daily, titrated to 12.5 mg twice daily, and methimazole 30 mg daily, titrated to 20 mg twice daily, and discontinued on day 29. The patient received radioiodine I-131 treatment 1 week later. We report the first known case on the use of aripriprazole to treat Graves’ hyperthyroidism-induced psychosis. Further studies examining the long-term effects and appropriate dose and duration of aripiprazole in this patient population are needed.

The role of paliperidone extended release for the treatment of bipolar disorder

Background Bipolar disorder (BD) is a chronic, relapsing, episodic mental illness associated with other psychiatric comorbidities. There is a substantial economic burden with BD, which makes it challenging to treat. The aim of this review is to evaluate the pharmacology, clinical efficacy, and safety data related to paliperidone extended release (ER) for the treatment of BD. Methods A literature search was performed from January 1966 through January 2012 using PreMEDLINE, MEDLINE, EMBASE, IPA, and ClinicalTrials.gov to identify articles in English regarding the pharmacology, clinical efficacy, and safety of paliperidone ER in acute mania or mixed episodes or in the maintenance treatment of BD I. Results There are currently three published studies relating to the use of paliperidone ER for the treatment of BD. Two of these evaluated paliperidone ER as monotherapy for acute mania, while the other assessed its role as adjunct with a mood stabilizer. Conclusion According to the limited available evidence, paliperidone at higher doses of ER 9–12 mg/day may be a safe and efficacious treatment option for acute episodes of mania in BD. A once-daily dose formulation may improve patient adherence to treatment; however, the cost of paliperidone ER, which is higher than that of generically available second-generation antipsychotics (such as olanzapine and risperidone), and a lack of alternative dosage forms (ie, liquid, intramuscular) compared with other agents may limit its usefulness in the treatment of BD. The role of paliperidone ER as an adjunctive agent or for long-term use requires further investigation.

Difficulty and discrimination indices of multiple-choice examination items in a college of pharmacy therapeutics and pathophysiology course sequence

The purpose of this study was to identify differences in difficulty and discrimination among multiple‐choice examination items with regard to format and content in pharmacy therapeutics and pathophysiology (TP) courses.