Effect of age on the relative efficacy of clozapine in schizophrenia

Abstract

Objective: Early treatment of schizophrenia improves outcomes. Clozapine appears to have unique benefit when other antipsychotic medication has failed. This systematic review and meta-analysis aims to assess clozapine's superiority over alternative antipsychotic medication and examine whether earlier use is associated with additional benefit. Method: Systematic retrieval of blinded, randomized controlled trials comparing clozapine with alternative antipsychotics in adults with schizophrenia. The effect of mean age on relative clozapine response was examined using random effects meta-regression, and multiple linear regression on available patient data. Results: A total of 276 studies were retrieved. Thirty-four studies were included in the meta-analysis. Clozapine was significantly more effective than alternative antipsychotics in reducing psychotic symptoms and increasing response. However, meta-regression failed to show a more significant effect in younger patients (age on effect size (total psychotic symptoms) 0.00, P = 0.79 CI À0.03 to 0.03). Individual patient data were available for two studies, the larger of which showed a significant interaction between younger age and superiority of clozapine. Conclusion: The results support clozapine's superiority over other antipsychotics. A convincing effect of age on this effect was not demonstrated, although this was suggested in one study. In view of the age of many of the included studies, and changes in reporting practice over time, new clozapine RCTs, which include age of illness onset as well as age at trial time, would be welcome in order to provide metaanalysable data for future use.

Duration of prior psychotic illness and clozapine response: a retrospective observational study using electronic health records

“…[8][9][10][11] Treatment-resistant schizophrenia (TRS) is typically defined as a failure to respond to two antipsychotic trials at an adequate dose for an adequate duration. 12 Clozapine has long been the gold-standard medication for TRS, 13 and its superiority has been confirmed in randomised Duration of prior psychotic illness and clozapine response: a retrospective observational study using electronic health records controlled trials (RCTs) and meta-analyses thereof 14,15 as well as in a number of large pharmacoepidemiological studies. [16][17][18][19][20][21] However, despite the clear rationale for clozapine, its use continues to be delayed, often for decades.…”

Risk factors for clozapine‐induced myocarditis and cardiomyopathy: A systematic review and meta‐analysis

“…Clozapine is a lipophilic agent, and this may partly explain why advancing age may increase the risk of clozapine‐induced cardiomyopathy. Despite this, however, the literature also demonstrates that clozapine is significantly more effective than other antipsychotics in reducing psychotic symptoms among elderly patients with treatment resistant schizophrenia 48 . Clozapine remains the drug of choice in this population, but may require lower doses and more careful monitoring 49 …”

“…Despite this, however, the literature also demonstrates that clozapine is significantly more effective than other antipsychotics in reducing psychotic symptoms among elderly patients with treatment resistant schizophrenia. 48 Clozapine remains the drug of choice in this population, but may require lower doses and more careful monitoring. 49 Though we could identify no evidence on risk factors for clozapine-induced cardiomyopathy in the current literature, it has been previously established among the general population that acute myocarditis can progress to dilated cardiomyopathy.…”

A Repeated Time-to-Positive Symptoms Improvement among Malaysian Patients with Schizophrenia Spectrum Disorders Treated with Clozapine

“…Younger patients might have lower disease severity and duration regardless of the type of treatment they are receiving [ 34 , 35 ]; thus, it was recommended not to wait too long before initiating clozapine treatment [ 34 ]. In another systematic review of randomized control trials, age did not achieve statistical significance [ 36 ]. However, the included studies in the second review were limited to adult patients with ages ranged between 21 and 65 years old.…”