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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Andre Tomlin

André Tomlin is an Information Scientist with 20 years experience working in evidence-based healthcare. He's worked in the NHS, for Oxford University and since 2002 as Managing Director of Minervation Ltd, a consultancy company who do clever digital stuff for charities, universities and the public sector. Most recently André has been the driving force behind the Mental Elf and the National Elf Service; an innovative digital platform that helps professionals keep up to date with simple, clear and engaging summaries of evidence-based research. André is a Trustee at the Centre for Mental Health and an Honorary Research Fellow at University College London Division of Psychiatry. He lives in Bristol, surrounded by dogs, elflings and lots of woodland!

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