Mood stabiliser strategies were linked to fewer relapses after first psychotic mania

Design

Target trial emulation using linked observational cohorts

Population

371 people aged 16 and over after a first manic episode with psychotic features

Primary outcome

Psychiatric admission or emergency visit over 2 years

Effect

42.3% mood stabiliser, 42.2% combination, 49.5% antipsychotic alone; RR 0.82 vs antipsychotic

BD-CAUSAL emulated a pragmatic trial using linked records from first-episode psychosis services in North America, Chile and Spain, 2006–2021. It included 371 people (median age 22) starting treatment after a first manic episode with psychotic features, outside hospital and without recent mood stabiliser or second-generation antipsychotic use, and followed them for up to two years.

The two-year risk of a psychiatric admission or emergency visit was 42.3% with mood stabiliser monotherapy, 42.2% with combination therapy, and 49.5% with antipsychotic monotherapy. Against antipsychotic monotherapy, both mood stabiliser strategies were associated with about seven percentage points lower risk (risk ratio 0.82 for each; for monotherapy 0.63 to 0.97). Mood stabiliser alone and combination were similar.

This is the kind of question that rarely gets a randomised trial, and a target trial emulation adjusted for time-varying confounding is a serious attempt to answer it. It remains observational, and the authors say a trial is needed. In practice it supports including a mood stabiliser — usually lithium or valproate, with valproate avoided in women who could become pregnant — when planning maintenance after a first psychotic mania, rather than continuing an antipsychotic alone by default.

• After a first psychotic manic episode, consider a mood stabiliser as part of maintenance, not only an antipsychotic.
• Discuss lithium early, while the patient is engaged and before relapse patterns set in.
• Avoid valproate in women and girls who could become pregnant, in line with current regulatory advice.
• If you continue antipsychotic monotherapy, plan closer follow-up for relapse.
• Arrange baseline renal, thyroid and calcium tests before lithium, and level monitoring after.

Why it matters

Antipsychotic monotherapy is often continued by default after a first episode; this questions that habit.

Don't overread it

This is an emulated trial on observational data — it has not been confirmed by randomisation.

The statistics, in plain English

A risk ratio of 0.82 means about 18% fewer relapses in relative terms, or about 7 fewer per 100 patients over two years. The confidence intervals stay below 1.0, but this design can only adjust for factors that were recorded, so unmeasured differences between the patients given each strategy could explain some of it.

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