Efficacy and Tolerability of Clozapine versus Quetiapine in Treatment-resistant Schizophrenia

OBJECTIVES: To compare the efficacy and tolerability of clozapine and quetiapine in patients with treatment-resistant schizophrenia (TRS). PATIENTS AND METHODS: In this prospective, randomized, open label study of 14 weeks, 53 patients with schizophrenia diagnosed as per ICD-10 and fulfilling the modified version of Conley and Kelly's criteria of TRS were randomly assigned to receive clozapine or quetiapine as per a computer-generated random table. After 2-weeks of dose-titration phase, doses were fixed at minimum therapeutic dose and subsequently adjusted according to the clinical improvement. All patients received dosage of respective drug in therapeutic range. 13 patients were lost to follow up. Treatment efficacy and side effects were evaluated with standardized rating scales. RESULTS: Clozapine group (reduction in total score: mean=14.45, SD=10.39) had significantly greater reductions (P=0.004; CI=3.541-17.059) in the Positive and Negative Syndrome Scale (PANSS) total score, PANSS positive subscale and PANSS general psychopathology subscale at 14 weeks in comparison to the quetiapine group (reduction in total score: mean=4.15, SD=10.71). Significant reduction in PANSS negative subscale was seen with both drugs but no significant difference was present between the two drugs. At 14 weeks, 30% patients in clozapine group and 15% patients in quetiapine group showed response. Clozapine led to significantly greater side effects (P< 0.001, CI=2.241-6.059) on Glassgow Antipsychotic Side-effect Scale (GASS) than quetiapine. CONCLUSIONS: Clozapine was found to be more efficacious than quetiapine in patients with TRS but was associated with greater side effects. Both the drugs were found to be equally effective in reducing the negative symptoms.