Preventing the second episode: a systematic review and meta-analysis of psychosocial and pharmacological trials in first-episode psychosis

Abstract

Objective: The majority of first-episode psychosis (FEP) patients reach clinical remission; however, rates of relapse are high. This study sought to undertake a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effectiveness of pharmacological and non-pharmacological interventions to prevent relapse in FEP patients.

Methods: Systematic review and meta-analysis of RCTs.

Results: Of 66 studies retrieved, 18 were eligible for inclusion. Nine studies investigated psychosocial interventions and 9 pharmacological treatments. The analysis of 3 RCTs of psychosocial interventions comparing specialist FEP programs vs treatment as usual involving 679 patients demonstrated the former to be more effective in preventing relapse (odds ratio [OR]=1.80, 95% confidence interval [CI]=1.31-2.48; P<.001; number needed to treat [NNT]=10). While the analysis of 3 different cognitive-behavioral studies not specifically intended at preventing relapse showed no further benefits compared with specialist FEP programs (OR=1.95, 95% CI=0.76-5.00; P=.17), the combination of specific individual and family intervention targeted at relapse prevention may further improve upon these outcomes (OR=4.88, 95% CI=0.97-24.60; P=.06). Only 3 small studies compared first-generation antipsychotics (FGAs) with placebo with no significant differences regarding relapse prevention although all individual estimates favored FGAs (OR=2.82, 95% CI=0.54-14.75; P=.22). Exploratory analysis involving 1055 FEP patients revealed that relapse rates were significantly lower with second-generation antipsychotics (SGAs) compared with FGAs (OR=1.47, 95% CI=1.07-2.01; P<.02; NNT=10).

Conclusions: Specialist FEP programs are effective in preventing relapse. Cognitive-based individual and family interventions may need to specifically target relapse to obtain relapse prevention benefits that extend beyond those provided by specialist FEP programs. Overall, the available data suggest that FGAs and SGAs have the potential to reduce relapse rates. Future trials should examine the effectiveness of placebo vs antipsychotics in combination with intensive psychosocial interventions in preventing relapse in the early course of psychosis. Further studies should identify those patients who may not need antipsychotic medication to be able to recover from psychosis.

© The Author 2009. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.

Figures

Fig. 1.

Study Selection.

Fig. 2.

Differences in Risk of Relapse in FEP Patients in Studies Comparing Specialist FEP Programs With TAU, Individual CBT, and Individual and Family RPT. FEP, first-episode psychosis; CBT, cognitive-behavioral therapy; RPT, relapse prevention therapy; TAU, treatment as usual; M-H random, Mantel-Haenszel method random effects; CI, confidence interval. Note: event = number of relapses; weight = it is indicated by the size of the square on each graph line and is related to the number of participants and events in the study.

Fig. 3.

Differences in Risk of Relapse in FEP Patients in Studies Comparing Antipsychotic Medications With Placebo. FEP, first-episode psychosis; FGAs, first-generation antipsychotics; M-H random, Mantel-Haenszel method random effects; CI, confidence interval. Note: event = number of relapses; weight = it is indicated by the size of the square on each graph line and is related to the number of participants and events in the study.

Fig. 4.

Differences in Risk of Relapse in FEP Patients in Studies Comparing SGAs With FGAs. FEP, first-episode psychosis; FGAs, first-generation antipsychotics; SGAs, second-generation antipsychotics; M-H random, Mantel-Haenszel method random effects; CI, confidence interval. Note: event = number of relapses; weight = it is indicated by the size of the square on each graph line and is related to the number of participants and events in the study.