Article type
Abstract
Background Clozapine is highly effective in treating schizophrenia, especially in treatment-resistant cases, yet its use is limited by the risk of serious blood disorders. Other atypical antipsychotics like olanzapine, risperidone and quetiapine aim for effectiveness with better tolerability.
Objective to assess the efficacy and safety of clozapine compared to olanzapine, risperidone, and quetiapine in schizophrenia and related disorders.
Methodology A systematic search was conducted in the Cochrane Schizophrenia Group's Study-Based Register of Trials to identify all double-blind, randomized controlled trials (RCT) comparing clozapine with the aforementioned antipsychotics. Risk of bias (ROB2) was assessed, and outcomes were analyzed using risk ratios and mean differences, with evidence quality evaluated by GRADE approach.
Results Twenty-one double-blind, RCT (n=1765 participants) were included: 10 trials comparing clozapine with olanzapine (N=761), 10 with risperidone (N=941), and 1 with quetiapine (N=63). Overall, ROB2 were categorized as unclear due to the missing reports. Clozapine showed no difference in global state improvement compared to olanzapine and risperidone, though it scored lower on CGI-severity than risperidone.
PANSS revealed no differences in mental state among the three. Olanzapine was superior to clozapine in reducing negative symptoms.
Regarding adverse effects (AEs), clozapine exhibited significant metabolic effects, including weight gain and elevated triglyceride levels, compared to risperidone and olanzapine, respectively. Clozapine also showed fewer extrapyramidal side-effects than risperidone but was associated with higher rates of hypersalivation than the three comparators, more sedation than quetiapine and risperidone, more constipation than quetiapine and olanzapine, and more seizures than risperidone. Prolactin levels were lower with clozapine than olanzapine.
Attrition was high (overall approx. 30%) in the studies compared with olanzapine and risperidone, leaving the interpretation of results problematic. Other differences in AEs were less documented and should be replicated. Overall, the evidence certainty was rated as low to moderate.
Conclusion While clozapine is widely regarded as the most effective antipsychotic, our review finds no significant differences in efficacy compared to other treatments. However, it notably diverges in its adverse event profile. This underscores the importance of considering not only efficacy but also the unique adverse effect profiles of antipsychotic medications in clinical decision-making and patient care.
Objective to assess the efficacy and safety of clozapine compared to olanzapine, risperidone, and quetiapine in schizophrenia and related disorders.
Methodology A systematic search was conducted in the Cochrane Schizophrenia Group's Study-Based Register of Trials to identify all double-blind, randomized controlled trials (RCT) comparing clozapine with the aforementioned antipsychotics. Risk of bias (ROB2) was assessed, and outcomes were analyzed using risk ratios and mean differences, with evidence quality evaluated by GRADE approach.
Results Twenty-one double-blind, RCT (n=1765 participants) were included: 10 trials comparing clozapine with olanzapine (N=761), 10 with risperidone (N=941), and 1 with quetiapine (N=63). Overall, ROB2 were categorized as unclear due to the missing reports. Clozapine showed no difference in global state improvement compared to olanzapine and risperidone, though it scored lower on CGI-severity than risperidone.
PANSS revealed no differences in mental state among the three. Olanzapine was superior to clozapine in reducing negative symptoms.
Regarding adverse effects (AEs), clozapine exhibited significant metabolic effects, including weight gain and elevated triglyceride levels, compared to risperidone and olanzapine, respectively. Clozapine also showed fewer extrapyramidal side-effects than risperidone but was associated with higher rates of hypersalivation than the three comparators, more sedation than quetiapine and risperidone, more constipation than quetiapine and olanzapine, and more seizures than risperidone. Prolactin levels were lower with clozapine than olanzapine.
Attrition was high (overall approx. 30%) in the studies compared with olanzapine and risperidone, leaving the interpretation of results problematic. Other differences in AEs were less documented and should be replicated. Overall, the evidence certainty was rated as low to moderate.
Conclusion While clozapine is widely regarded as the most effective antipsychotic, our review finds no significant differences in efficacy compared to other treatments. However, it notably diverges in its adverse event profile. This underscores the importance of considering not only efficacy but also the unique adverse effect profiles of antipsychotic medications in clinical decision-making and patient care.