Patrizia Cavazzoni

A retrospective cohort study of diabetes mellitus and antipsychotic treatment in the United States.

Treatment-emergent diabetes mellitus (DM) has been described for conventional and atypical antipsychotics. In our study, antipsychotic prescription claims from AdvancePCSs database were used to identify patients starting antipsychotic monotherapy. The relative risk of developing DM was determined using prescription claims for antidiabetic agents in the following cohorts: AdvancePCS general patient population, combined conventional antipsychotics, and combined atypical antipsychotics. Cox proportional hazards regression was used to adjust for differences in age, gender, and duration of antipsychotic exposure between cohorts in the estimation of risk of developing diabetes. Hazard ratios for developing DM in the combined conventional, combined atypical, and individual conventional and atypical antipsychotic treatment cohorts were greater than the AdvancePCS general patient population cohort. An increased risk of developing diabetes compared with the AdvancePCS general patient population was observed during treatment with conventional or atypical antipsychotics.

Nizatidine for prevention of weight gain with olanzapine: a double-blind placebo-controlled trial.

Weight gain is associated with treatment with olanzapine and other psychotropic agents. Nizatidine, a histamine H-2 receptor antagonist, has been proposed to have weight-reducing effects. This double-blind trial evaluated the efficacy of nizatidine in limiting weight gain in patients with schizophrenia and related disorders who were treated with olanzapine for up to 16 weeks. After an initial screening period, 175 patients were randomized to receive olanzapine (5-20 mg) with either placebo or nizatidine (150 mg b.i.d. or 300 mg b.i.d.). Significantly less weight gain was observed on average at weeks 3 and 4 with olanzapine+nizatidine 300 mg b.i.d. (P<0.05) compared to olanzapine+placebo, but the difference was not statistically significant at 16 weeks. Nizatidine was well-tolerated and did not adversely affect clinical outcomes. Nizatidine 300 mg b.i.d. may have an early transient effect in limiting the weight gain, but this potential early effect appeared to be diminished or eliminated by 16 weeks.

Amantadine for weight gain associated with olanzapine treatment

Patients with schizophrenia (Sch), schizoaffective, schizophreniform, or bipolar (BP) I disorders [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)]; not manic or acutely psychotic [Brief Psychiatric Rating Scale (BPRS) total score < or =45]; treated with olanzapine for 1-24 months; and who had gained > or =5% of their initial body weight were examined to determine whether amantadine could attenuate weight gain or promote weight loss. Olanzapine (Olz; 5-20 mg/day) was co-administered with double-blind treatment of 100-300 mg/day amantadine (Olz+Amt, n=60) or placebo (Olz+Plc, n=65). Visit-wise analysis of weight showed that weight change from baseline [last-observation-carried-forward (LOCF)] in the Olz+Amt group was significantly different from the Olz+Plc group at weeks 8 (P=0.042), 12 (P=0.029), and 16 (primary endpoint, mean+/-S.D.: -0.19+/-4.58 versus 1.28+/-4.26 kg, P=0.045). Mean BPRS total score, positive subscale, and anxiety-depression scores improved comparably in both groups, and Montgomery-Asberg Depression Rating Scale (MADRS) total score improved in the Olz+Amt group. Overall, amantadine was safe, was well tolerated, and attenuated weight gain or promoted weight loss in some patients who had gained weight during olanzapine therapy.

Case Reports of Postmarketing Adverse Event Experiences With Olanzapine Intramuscular Treatment in Patients With Agitation

OBJECTIVE Agitation is a medical emergency with increased risk for poor outcome. Successful treatment often requires intramuscular (IM) psychotropics. Safety data from the first 21 months of olanzapine IM, approved in the United States for the treatment of agitation associated with schizophrenia and bipolar disorder, are presented. METHOD A Lilly-maintained safety database was searched for all spontaneous adverse events (AEs) reported in temporal association with olanzapine IM treatment. RESULTS The estimated worldwide patient exposure to olanzapine IM from January 1, 2004, through September 30, 2005, was 539,000; 160 cases containing AEs were reported from patients with schizophrenia (30%), bipolar disorder (21%), unspecified psychosis (10%), dementia (8%), and depression (5%). Many reported concomitant treatment with benzodiazepines (39%) or other antipsychotics (54%). The most frequently reported events involved the following organ systems: central nervous (21%), cardiac (12%), respiratory (6%), vascular (6%), and psychiatric (5%). Eighty-three cases were considered serious, including 29 fatalities. In these fatalities, concomitant benzodiazepines or other antipsychotics were reported in 66% and 76% of cases, respectively. The most frequently reported events in the fatal cases involved the following organ systems: cardiovascular (41%), respiratory (21%), general (17%), and central nervous (10%). The majority of fatal cases (76%) included comorbid conditions and potentially clinically significant risk factors for AEs. CONCLUSIONS Clinicians should use care when treating agitated patients, especially when they present with concurrent medical conditions and are treated with multiple medications, which may increase the risk of poor or even fatal outcomes. Clinicians should use caution when using olanzapine IM and parenteral benzodiazepines simultaneously.

P.2.132 A retrospective cohort study of diabetes mellitus and antipsychotic treatment in the United Kingdom

OBJECTIVE Treatment-emergent diabetes has been reported during exposure to conventional and atypical antipsychotics. This retrospective cohort study explored the UK General Practice Research Database (GPRD) to determine hazard ratios of diabetes for patients prescribed antipsychotics. METHODS A Cox proportional hazard regression model using age, gender, and obesity (BMI > 30 kg/m2) was used to determine the hazard ratio (HR) of diabetes development in conventional antipsychotic (N = 59,089), atypical antipsychotic (N = 9053), individual antipsychotic, and general patient population cohorts (N = 1,491,548). RESULTS Compared with the general GPRD patient population, patients exposed to conventional or atypical antipsychotics had a higher risk of developing diabetes (atypical antipsychotic cohort: HR = 2.9, CI = 2.0-4.4; and conventional antipsychotic cohort: HR = 1.9, CI = 1.6-2.3). The risk of developing diabetes during thioridazine, risperidone, or olanzapine treatment was significantly higher compared with the general GPRD patient population. CONCLUSION Consistent with other epidemiology studies, this study supports an increased risk of developing diabetes during treatment with antipsychotics.