The most effective treatments for preventing relapse in first episode psychosis: a new systematic review and meta-analysis


Patients with first episode psychosis often relapse after initial remission, so it is perhaps surprising that treatment guidelines for the condition are generally based on poor quality evidence.

Antipsychotic drugs are frequently discontinued, but clinicians don’t have ready access to information that shows how to determine which patients can be successfully tapered off of antipsychotic medications without relapse.

This is the first systematic review and meta-analysis to evaluate pharmacological and non-pharmacological interventions to prevent relapse in patients with first-episode psychosis. The reviewers from Spain and Australia conducted a systematic search and found 18 randomised controlled trials to include in their review:

  • 3 compared specialist first episode psychosis programmes versus treatment as usual
  • 2 compared family therapy versus treatment as usual
  • 3 compared first-generation antipsychotics versus placebo
  • 4 compared second-generation antipsychotics versus first-generation antipsychotics
  • 1 compared different first-generation antipsychotics
  • 1 compared treatment maintenance versus discontinuation
  • the rest compared different psychosocial programmes

Here’s what they found:

  • Specialist first episode psychosis programmes reduced relapse when compared with treatment as usual (OR 1.80, 95% CI 1.31 to 2.48, p<0.001; NNT 8 )
  • Family therapy did not reduce relapse compared with treatment as usual (OR 2.82, 95% CI 0.54 to 14.75)
  • Cognitive behavioural therapy did not reduce relapse compared with supportive counselling (OR 1.11, 95% CI 0.63 to 1.95)
  • Cognitive behavioural therapy did not reduce relapse compared with treatment as usual (OR 1.15, 95% CI 0.65 to 2.04)
  • First-generation antipsychotics did not reduce relapse compared with placebo (OR 5.17, 95% CI 0.87 to 30.63)
  • When grouped together, the 4 trials showed that second-generation antipsychotics reduced relapse compared with first-generation antipsychotics (OR 1.47, 95% CI 1.07 to 2.01, p<0.02; NNT approximately 10)

The reviewers concluded:

Specialist first episode psychosis 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 first episode psychosis programs.

Overall, the available data suggest that first-generation antipsychotics and second-generation antipsychotics 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.

Alvarez-Jiménez M, Parker AG, Hetrick SE, et al. Preventing the second episode: a systematic review and meta-analysis of psychosocial and pharmacological trials in first-episode psychosis. Schizophr Bull 2011;37:619–30.

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