Weight gain on antipsychotic medication is associated with sustained use among veterans with schizophrenia.

OBJECTIVE: Continuous antipsychotic treatment is important in schizophrenia, and studies have shown that rates of discontinuation are high. Some studies suggest that weight gain may lead schizophrenic patients to discontinue treatment, whereas other studies show smaller effects of weight gain on medication discontinuation, and some find weight gain associated with symptom improvement. Our retrospective cohort study investigated the effect of weight change on the continued use for 1 year (persistence) of all antipsychotics, then among users of first-generation antipsychotics and second-generation antipsychotics (SGAs), and lastly subgroups of SGAs. METHODS: We identified 2130 patients with schizophrenia starting an antipsychotic that had not used 1 in the prior year. Using multivariable logistic regression adjusted for demographic and clinical variables, we determined the odds of remaining persistent on medication among patients who either gained weight or did not gain weight in the following year. RESULTS: For all antipsychotics combined, weight change was not associated with persistence. Among SGAs, weight gain was associated with a 23% increase in the adjusted odds ratio (OR) for persistence (OR, 1.23; 95% confidence interval [CI], 1.00-1.51), whereas there was a nonsignificant decrease in the adjusted odds of persistence among first-generation antipsychotic users (OR, 0.74; 95% CI, 0.43-1.28). When SGAs were divided into subgroups (clozapine/olanzapine, risperidone/quetiapine), both had increases in the likelihood of persistence, but only the association for clozapine/olanzapine was significant at a trend level (adjusted OR, 1.46; 95% CI, 0.99-2.16). CONCLUSIONS: These findings are supportive of other research that shows weight gain does not invariably lead to medication discontinuation and may be associated with clinical improvement.

Quetiapine versus trazodone in reducing rehospitalization for alcohol dependence: a large data-base study.

Clinicians commonly use nonindicated (or "off-label") medications for the treatment of alcoholism, although there is no clear evidence to support this practice. Quetiapine and trazodone are 2 medications frequently used in this manner, especially to treat sleep disturbance associated with alcohol withdrawal. Using national administrative data from the Department of Veterans Affairs, we compared the differences among these medications in time to rehospitalization after discharge from an index hospitalization for alcohol dependence. Our outcome measure was the difference in time (weeks) to rehospitalization for patients given medications in 1 of 4 groups: quetiapine alone (median, 6.1 weeks); trazodone alone (median, 10.1 weeks); quetiapine combined (median, 7.1 weeks); and trazodone combined (median, 10.3 weeks) with other frequently used psychotropic drugs. Differences between groups were examined with Cox's proportional hazards regression using trazodone in combination with other medications as the reference category. Crude hazard ratios were determined first and then adjusted for covariates. There was no difference in the risk of rehospitalization when patients using quetiapine in combination were compared with the reference category (hazard ratio [HR] = 1.08; confidence interval [CI], 0.99-1.17; P < 0.0936). In contrast, when quetiapine was used alone there was a significantly higher risk of rehospitalization (HR = 1.22; CI = 1.06-1.41; P < 0.005). When trazodone was used alone there was no difference in risk in the unadjusted analysis (HR = 1.05; CI = 0.96-1.14; P < 0.3076); however, the HR increased to a significant level after adjusting for covariates (HR, 1.14; CI = 1.05-1.24; P < 0.0029) and for those with 2+ previous discharges (HR = 1.25; CI = 1.14-1.37; P < 0.0001). These findings suggest the need for additional studies to better understand what symptoms of alcoholism benefit from the use of these medications, at what dose levels, and with what other medication combinations.

Quetiapine for treatment of alcohol dependence.

Quetiapine is an atypical antipsychotic that has sedative effects. In this retrospective study, indices of alcohol use were compared for alcohol-dependent subjects who either were (n = 30) or were not (n = 20) treated with quetiapine (25 to 200 mg nightly) for disturbed sleep. Indices examined included total days of abstinence, number of hospitalizations for detoxification, and days to first relapse over 1 year of clinic treatment. Subjects were male veterans. All subjects had a diagnosis of alcohol dependence, and 90% of subjects in each group were also diagnosed with posttraumatic stress disorder. Both treatment groups contained a large number of subjects treated with psychiatric medications other than quetiapine. Significant differences were not found between the groups with respect to mean age, detoxifications undergone during the previous year, frequency of comorbid posttraumatic stress disorder or depression, or antidepressant use. The mean number of days abstinent was significantly greater, and the number of hospitalizations was significantly lower for the quetiapine than for the control group during the period studied. The mean number of days to relapse approached significance for the quetiapine as compared to the control group. This study has the usual limitations of a retrospective review, including the lack of standardized assessments of alcohol use. The results of this study are consistent with the hypothesis that the use of quetiapine to improve disturbed sleep may help alcohol-dependent patients maintain abstinence, although decreased drinking may also be a result of improving posttraumatic stress disorder symptoms or of a direct action of quetiapine to reduce alcohol use.

Low-dose risperidone as adjunctive therapy for irritable aggression in posttraumatic stress disorder.

Increased aggressive behavior can occur in association with posttraumatic stress disorder (PTSD). This study tested the hypothesis that low-dose risperidone reduces aggression and other PTSD-related symptoms in combat veterans. Subjects were male combat veterans with PTSD who scored 20 or higher on cluster D (hyperarousal) of the Patient Checklist for PTSD-Military Version (PCL-M). Subjects were randomly assigned to either risperidone or placebo treatment groups. Drugs were administered over a 6-week treatment period in a double-blind manner. Subjects received either risperidone (0.5 mg/day; n = 7) or matched placebo (n = 8) tablets during the first 2 weeks of the treatment period. The dose of risperidone could then be increased up to 2.0 mg/day on the basis of response. Prerandomization psychotropic regimens were continued. Subjects were evaluated with the PCL-M and the Overt Aggression Scale-Modified for Outpatients (OAS-M). In comparison with placebo treatment, reductions in scores between baseline and the last week of treatment were significantly greater for OAS-M irritability and PCL-M cluster B (intrusive thoughts) subscales and on the PCL-M total scale. These results suggest that low-dose risperidone administration reduces irritability and intrusive thoughts in combat-related PTSD.