First-generation versus second-generation antipsychotics for preventing relapse in schizophrenia


This new systematic review compares how effective first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) are at preventing relapse in patients with schizophrenia.

The authors carried out a meta-analysis of 23 randomised controlled trials that lasted for ≥6 months and compared FGAs with SGAs in schizophrenia.

The outcomes they studied were:

  • Study defined relapse
  • Relapse at 3, 6 and 12 months
  • Treatment failure
  • Hospitalisation
  • Any cause drop-out
  • Non-adherence
  • Intolerability

Here’s what they found:

  • None of the individual SGAs outperformed FGAs (mainly haloperidol) regarding study-defined relapse, except for isolated, single trial-based superiority, and except for risperidone’s superiority at 3 and 6 months when requiring ≥3 trials
  • Grouped together, however, SGAs prevented relapse more than FGAs (29.0 versus 37.5%, RR=0.80, CI: 0.70-0.91, P=0.0007, I(2)=37%; NNT=17, CI: 10-50, P=0.003)
  • SGAs were also superior regarding relapse at 3, 6 and 12 months (P=0.04, P<0.0001, P=0.0001), treatment failure (P=0.003) and hospitalisation (P=0.004)
  • SGAs showed trend-level superiority for dropout owing to intolerability (P=0.05)
  • There was no significant heterogeneity or publication bias

The authors concluded:

The relevance of the somewhat greater efficacy of SGAs over FGAs on several key outcomes depends on whether SGAs form a meaningful group and whether mid- or low-potency FGAs differ from haloperidol. Regardless, treatment selection needs to be individualised considering patient- and medication-related factors.

Kishimoto T, Agarwal V, Kishi T, Leucht S, Kane JM, Correll CU. Relapse prevention in schizophrenia: a systematic review and meta-analysis of second-generation antipsychotics versus first-generation antipsychotics. Mol Psychiatry. 2011 Nov 29. doi: 10.1038/mp.2011.143. [Epub ahead of print] [PubMed abstract]

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