Antipsychotic Reduction in Schizophrenia: A Cautionary Tale

Gradual antipsychotic reduction doubled relapse risk without improving social functioning in a two-year randomized trial

STUDY: Moncrieff J et al, Lancet Psychiatry 2023;10:848–59

STUDY TYPE: Randomized controlled trial

FUNDING: National Institute for Health Research

Background

Long-term trials are difficult to conduct. In schizophrenia, some studies find improvements in social functioning off antipsychotics, while others do not, but all of these have had major flaws, including one that was interrupted by COVID. This trial overcomes those flaws, bringing clarity to the risks and benefits of antipsychotic reduction.

The Study

• 253 adults with schizophrenia or recurrent non-affective psychosis
• Randomized to gradual antipsychotic dose reduction (targeting discontinuation over 12–18 months) or maintenance treatment, with 2-year follow-up

The reduction group achieved a median 67% dose cut at some point during the trial; at 24 months the median reduction was 33%. Social functioning (Social Functioning Scale) was the primary outcome.

Reduction did not improve social functioning. The two groups were virtually identical at 24 months.

What did differ was relapse. 25% of the reduction group had a severe relapse requiring hospitalization versus 13% in the maintenance group (hazard ratio 2.2). Overall, 41% of the reduction group had any relapse versus 22% on maintenance. Serious adverse events were more common in the reduction group. No differences appeared in symptoms, quality of life, weight, or cognitive function.

Practice Implications

1. Dose reduction doesn’t improve functioning, and it dose raise the risk of relapse in schizophrenia.