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.

Clonazepam for treatment of sleep disturbances associated with combat-related posttraumatic stress disorder.

BACKGROUND: Clonazepam is widely used for the treatment of posttraumatic stress disorder (PTSD)-related sleep disturbances despite very limited published data supporting its use for this indication. OBJECTIVE: We conducted a pilot-controlled trial to provide more data on this clinical practice and lay the foundation for more definitive studies. METHODS: The study was designed as a randomized, single-blind (ie, patient only), placebo-controlled, crossover clinical trial involving administration of clonazepam 1 mg at bedtime for one week followed by 2 mg at bedtime for one week. The following week served as a washout period before the alternate treatment was begun. Patients completed sleep diaries each morning upon awakening throughout the study. Parameters included quantity of sleep, quality of sleep, frequency and intensity of difficulty falling or staying asleep, and frequency and intensity of recurrent distressing dreams. RESULTS: Six patients with combat-related PTSD participated in the study. There were no statistically significant differences between clonazepam and placebo for any measure, although clonazepam therapy resulted in mild to moderate numeric improvements in difficulty falling or staying asleep. Adverse effects of clonazepam were generally mild and essentially indiscernible from those attributed to placebo. Only one patient elected to receive further treatment with clonazepam at the conclusion of the trial. CONCLUSIONS: Clonazepam therapy was largely ineffective in improving sleep disturbances, particularly nightmares, associated with combat-related PTSD. The small sample size was a significant limitation of this study, but the prospective design and single-blind, placebo-control parameters were strengths. Further studies are needed to further define the role of this widespread clinical practice.

Baclofen treatment for chronic posttraumatic stress disorder.

OBJECTIVE: Previous studies have shown the efficacy of gamma-aminobutyric acid B (GABA(B)) receptor agonists in treating anxiety in patients with panic disorder and in treating depression and anxiety in alcoholic patients. We hypothesized that baclofen, a GABA(B) agonist, would be an effective treatment in the symptomatic management of veterans with chronic posttraumatic stress disorder (PTSD). METHODS: Fourteen male veterans with chronic, combat-related PTSD were enrolled in an open-label, 8-week, monotherapy trial of baclofen titrated to a maximum of 80 mg/d in 3 divided doses. The primary outcome measure was the Clinician-Administered PTSD Scale (CAPS), and secondary outcome measures included the Hamilton Rating Scale for Anxiety, the Hamilton Rating Scale for Depression, the Global Assessment of Functioning Scale, and the Clinical Global Impressions. RESULTS: In the 11 patients who completed the 8-week trial, the mean total CAPS score decreased significantly from baseline (from 82.9 +/- 16.1 to 63.5 +/- 21.2). The avoidance and hyperarousal subscales showed significant decreases (from 36.2 +/- 6.2 to 26.5 +/- 9.6 and from 31.9 +/- 6.5 to 22.1 +/- 7.1, respectively), whereas the re-experiencing subscale remained unchanged. Significant improvements were also noted on all secondary outcome measures. Treatment response was noted within the first 4 weeks of treatment and was maintained throughout the trial. Baclofen therapy was well tolerated, as only 1 patient dropped out due to adverse effects. CONCLUSIONS: Baclofen therapy was effective in treating both the PTSD symptoms and accompanying depression and anxiety in patients with chronic PTSD due to combat. Larger, double-blind, placebo-controlled studies are needed to confirm the efficacy of baclofen in the treatment of PTSD.