RESUMO
BACKGROUND: This study aimed to conduct a systematic review and meta-analysis on cognitive performances of patients with treatment-resistant schizophrenia (TRS) after clozapine treatment and to examine the potential effect of follow-up duration and clozapine dosage. METHODS: Five electronic databases were searched and studies were included if treatment-resistant schizophrenia patients were treated with clozapine and with baseline and follow-up cognitive functions assessments. Cognitive measures were categorised into six domains based on DSM-5-TR. Random-effect model analysis was used to pool the effect estimates. Moderator effects of clozapine dosage, follow up duration, duration of illness, age, years of education and change in positive symptoms severity were examined with meta-regression. FINDINGS: Nineteen articles were included with 50 cognitive measures reported. Systematic review found inconsistent results. Twelve cognitive measures were included for meta-analysis and found overall improvement of cognitive performances after clozapine treatment SMD = 0.11 [95 % CI 0.02, 0.20] (p = 0.021). Patients with younger age, more years of education and improvements in positive symptoms are more likely to improve in cognitive performances. Subgroup analysis found significant improvement in studies with follow-up periods of 6-months or longer but not for studies with shorter follow-up periods. CONCLUSION: Clozapine may improve some domains of cognitive function, particularly over a longer period. However, the overall inconsistent results suggest that more studies with larger sample size and standard cognitive function assessments would be needed to enhance our understanding of the impact of clozapine on the cognitive functions in the TRS patients.
RESUMO
RATIONALE: Though clozapine is recommended for treatment of tardive dyskinesia (TD) relating to the use of antipsychotic medications, studies comprehensively investigating the treatment effect of clozapine on TD are still limited. OBJECTIVES: This review examines the effectiveness of clozapine as an intervention for tardive dyskinesia and dystonia in patients with all psychiatric conditions. Effectiveness of clozapine, duration to exert the effect and dosage used were also analysed. METHODS: A search in the PubMed, PsycINFO and clinicaltrials databases was performed, using the search terms "Clozapine" AND "dyskinesia" OR "dystonia". Full-text articles that reported the use of clozapine to treat abnormal involuntary movements and were written in English were included. RESULTS: A total of 48 studies were identified, of which 13 were clinical trials and 35 were case reports. Significant improvement was seen in 86.7% of patients with schizophrenia spectrum disorders (average dose of clozapine = 355 mg/day) and 93% of patients with other psychiatric disorders (average dose of clozapine = 152.5 mg/day). Patients with other psychiatric diagnoses had faster improvement than the patients with schizophrenia spectrum disorders. Variation in improvements and dosage were also seen in the clinical trials. CONCLUSION: Results suggested an overall effectiveness of clozapine in the treatment of TD for patients with a range of psychiatric conditions. Different response time and clozapine dosage were seen in patients with different psychiatric conditions, suggesting different treatment protocols are required for different conditions. Most of the studies identified are of inadequate qualities, highlighting the need for high quality studies to provide clearer evidence.
