Effectiveness and Tolerability (with focus on metabolic effects) of three atypical Antipsychotics in the treatment of schizophrenia- A 48 week observational study.

Background and Objectives: The use of atypical antipsychotics in schizophrenia has increased. This prospective, observational study with was carried out with objectives of evaluation of effectiveness and tolerability with focus on metabolic side effects of atypical antipsychotics in schizophrenic outpatients over 48-weeks period. Materials and Methods: Outpatients of 18-65 years age, male or female, diagnosed with schizophrenia meeting DSM-IV diagnosis criteria of the disease, who were on risperidone or olanzapine or clozapine were included. Patients were observed at scheduled visits for subjective-wellbeing, global functioning, efficacy and illness severity/improvement, body weight and BMI, fasting biochemical parameters (blood glucose and lipid profile) and adverse effects over a period of 48 weeks. Results: Of 154 patients available post-baseline visit onwards, with respect to changes in subjective well-being, global functioning, PANSS total and CGI Improvement scores show three drug groups to have comparative improvement at endpoint over 48 weeks irrespective of baseline psychopathological scores. The clinically significant (? 7%) weight gain at endpoint (increase from baseline) was observed in 42 (27.3%) patients. However, no significant difference was found between three drug groups in this respect (p > 0.05). With respect to biochemical parameters, in case of fasting blood glucose, although borderline changes (100 to 125 mg/dL) were observed, no clinically significant changes (? 126 mg/dL) were observed. With respect to fasting lipid changes (total cholesterol, LDL cholesterol, triglycerides), there were 42 cases at week 12 (Ris 23, Ola 17, Cloz 2) of which 8 patients showed clinically significant lipid changes with overall female preponderance. Remaining 34 cases were with borderline lipid changes. Of 41 cases with lipid changes observed at endpoint, all had borderline changes. Tolerability profile of three drugs in safety group (N=168) found weight gain 53(31.5%) as most common adverse effect (AE) followed by extrapyramidal side effects in 26(15.5 %). Discontinuation due to all-cause (or any cause) was, Cloz: 0, Ola 12(19.3%), and Ris 18(20.6%) patients over a period of 48 weeks. The mean survival time (time-to-medication discontinuation till 48 weeks) was found 48.00 ± 00.00 weeks in clozapine group followed by risperidone 41.79±13.34 weeks and olanzapine 40.71±15.30 weeks. No significant difference was found between three groups (p > 0.05) with respect to discontinuation rate and time-to-all-cause discontinuation. Conclusion: Results of this prospective, observational study point out similarities and differences in the response to three atypical antipsychotics examined for various domains regarding effectiveness and tolerability. The study showed the effect of atypical antipsychotics on clinically significant lipid changes within initial 12 weeks of treatment. It upholds the role of periodic metabolic monitoring based on recommended guidelines such as ADA/APA guideline along with education, diet control and simple behavioral measures in averting metabolic abnormalities in schizophrenic patients on long-term treatment with atypical antipsychotics.