First psychotic mania: mood-stabiliser strategies linked to fewer readmissions

Design

Target trial emulation using linked observational cohorts (BD-CAUSAL)

Population

371 people aged ≥16 with a first manic episode with psychotic features, median age 22

Primary outcome

Psychiatric hospitalisation or emergency visit over 2 years

Effect

42.3% mood stabiliser, 42.2% combination, 49.5% antipsychotic alone; RR 0.82 (95% CI 0.63–0.97) vs antipsychotic

Using linked outpatient and hospital data from the BD-CAUSAL Collaboration in North America, Chile and Spain, this study emulated a pragmatic randomised trial in 371 people aged 16 or over treated at first-episode psychosis clinics for a first manic episode with psychotic features. It compared starting a mood stabiliser alone, a second-generation antipsychotic alone, or both, for continuation and maintenance over two years. Median age was 22.

Psychiatric hospitalisation or emergency visit within two years occurred in 42.3% with a mood stabiliser alone, 42.2% with combination therapy and 49.5% with an antipsychotic alone. Against antipsychotic monotherapy, both mood-stabiliser strategies carried a risk ratio of 0.82 — a risk difference of about 7 percentage points. Mood stabiliser alone and combination therapy did not differ.

Comparative evidence is scarce for the decision clinicians make after a first manic episode, where antipsychotic monotherapy is often continued because it was what controlled the acute illness. It supports discussing a mood stabiliser for maintenance rather than relying on the antipsychotic alone. It is observational, with wide intervals, and the authors themselves ask for randomised confirmation; it does not tell you which mood stabiliser.

• Discuss a mood stabiliser for maintenance after a first manic episode with psychotic features, not only the antipsychotic that settled it.
• Consider combination therapy where the antipsychotic is still needed; relapse risk matched mood stabiliser alone.
• Plan lithium or valproate monitoring and, for women who may become pregnant, avoid valproate where possible.
• Set out a two-year maintenance plan at discharge, as four in ten were readmitted in that period.
• Explain to patients that this comes from observational data and randomised trials are still needed.

Why it matters

It challenges the habit of continuing antipsychotic monotherapy because it was what worked in the acute phase.

Don't overread it

This emulates a trial with observational data; it cannot exclude confounding and does not identify which mood stabiliser.

The statistics, in plain English

A risk ratio of 0.82 means about 18% fewer readmissions or emergency visits in relative terms, or about 7 fewer per 100 people over two years. The intervals are wide — the risk difference could be as small as about 1 point or as large as 16. Target trial emulation reduces some biases of ordinary observational studies, but cannot remove confounding by who gets which drug.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.