Clinical and pharmacoeconomic evaluation of switch to olanzapine in veterans with schizophrenia or schizoaffective disorder.

BACKGROUND: Second-generation atypical antipsychotics improve the outcome of patients with schizophrenia, although studies of their cost efficacy in comparison to first-generation conventional antipsychotics have yielded mixed results. OBJECTIVES: This study examines the cost effectiveness outcome of olanzapine treatment in veterans with schizophrenia (n 5 22) or schizoaffective disorder (n 5 4). METHODS: Health-care utilization and costs associated with prospective olanzapine treatment were compared with those of retrospective first-generation neuroleptic treatment in a mirror-image design. RESULTS: The analysis of variance with repeated measures for the Positive and Negative Syndrome Scale (PANSS; n 5 22) showed a significant main effect of olanzapine treatment (p , .025), and the effect was of medium-to-large size (h2 5 .13). The PANSS-positive subscale (p , .005) and the PANSS general subscale (p , .005) significantly decreased, but the PANSS negative subscale did not change. The quality of life survey (n 5 21) significantly increased (p , .025), and the effect size was large (h2 5 .14). For VA outpatient and inpatient care, study patients incurred an average cost difference of 2$1,289 (NS) and 2$6,682 (NS), respectively. Combining inpatient and outpatient VA care, patients incurred an annual difference of 2$7,971 per patient (NS). These numerically lower costs were due, in part, to a slower growth rate in outpatient encounters (p 5 .013), lower overall cost per outpatient encounter (p 5 .008), and a lower overall inpatient encounter rate (p 5 .005). CONCLUSIONS: Olanzapine treatment resulted in improvements in positive and general psychiatric symptoms, as well as quality of life. Negative symptoms did not change significantly. Though not statistically significant, the postbaseline health-care costs and utilization declined.

A pharmacokinetic and clinical evaluation of switching patients with bipolar I disorder from delayed-release to extended-release divalproex.

OBJECTIVE: To determine the optimal strategy for converting stable bipolar patients from twice-daily divalproex delayed release (DR) to once-daily divalproex extended release (ER). METHOD: This prospective, open-label, crossover study compared 4 divalproex regimens in euthymic outpatients with bipolar I disorder (DSM-IV diagnosis confirmed by Mini-International Neuropsychiatric Interview). Serum valproic acid levels were collected 12, 16, 20, and 24 hours after the last bedtime dose of the following regimens: DR twice daily (DR b.i.d.) during week 1; total daily DR dose once daily (DR q.h.s.) during week 2; once-daily ER at equal daily DR dose (ER 1:1) during week 3; and once-daily ER with the dose increased by 500 mg (ER + 500) during week 4. Patients continued on ER + 500 for 4 additional weeks after the pharmacokinetic phase. Side effects and psychiatric symptoms were assessed at weeks 1 through 4, 6, and 8. Twenty-one patients were enrolled from July 2002 to July 2004. RESULTS: Of the regimens tested, DR q.h.s. produced the widest fluctuations in valproic acid levels, with the highest 12-hour (82 mug/mL) and lowest 24-hour (44 mug/mL) levels. The ER + 500 dose was the only regimen that maintained the mean minimum valproic acid concentration above 50 mug/mL. Each regimen was well tolerated, and no significant changes in psychometric indices were observed. CONCLUSIONS: When converting stable bipolar patients from twice-daily divalproex DR to once-daily ER, we recommend increasing the total daily dose by 250 to 500 mg to ensure maintenance of therapeutic valproic acid levels.

Long-term pharmacotherapy for post-traumatic stress disorder.

This article reviews the literature on the long-term pharmacological treatment of post-traumatic stress disorder (PTSD). A PUBMED search was conducted; only studies on the effects of long-term (>14-weeks) pharmacological treatment for PTSD in adults or children were considered. Our search identified three randomised, double-blind, placebo-controlled studies (one each for sertraline, fluoxetine and risperidone), four open-label studies (one each for sertraline, paroxetine, nefazodone and valproate), one retrospective case series (clozapine) and one pooled analysis (sertraline). All studies involved adult populations, with the exception of the study of clozapine. The studies demonstrate that long-term treatment of PTSD with SSRIs effectively maintains the previous treatment response and improvement in quality of life, converts more patients to responder status and accounts for one-third of overall treatment gains. Greater PTSD severity predicts a longer time to response to these drugs. Discontinuation of SSRI treatment after 12 weeks results in a greater risk of relapse and symptom exacerbation compared with extended treatment. In addition to improved PTSD symptoms, extended treatment with paroxetine improves verbal declarative memory and increases hippocampal volume. Long-term treatment of PTSD with atypical antipsychotics (risperidone and clozapine), non-SSRI antidepressants (nefazodone) and antiepileptic drugs (AEDs; valproate) also appears to result in significant improvements in PTSD symptoms. In conclusion, long-term treatment of PTSD with SSRIs improves the psychiatric and clinical outcome of patients with the disorder and prevents relapse and symptom exacerbation. The effect of other agents (atypical antipsychotics, AEDs and other psychotropic medications) requires further controlled study.