First psychotic mania: a mood stabiliser, alone or combined, was linked to fewer readmissions than an antipsychotic alone

Design

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

Population

371 people aged 16 or over after a first manic episode with psychotic features, median age 22

Primary outcome

Psychiatric hospitalisation or emergency visit over 2 years

Effect

49.5% antipsychotic alone vs 42.3% mood stabiliser alone (RR 0.82, 95% CI 0.63 to 0.97) and 42.2% combination (RR 0.82, 0.63 to 0.91)

Researchers in the BD-CAUSAL Collaboration used linked outpatient and hospital records from first-episode psychosis services in North America, Chile and Spain to emulate a pragmatic trial. They identified 371 people (median age 22) starting continuation treatment after a first manic episode with psychotic features, between 2006 and 2021, and compared three strategies: a mood stabiliser alone, a second-generation antipsychotic alone, or both. The outcome was a psychiatric hospitalisation or emergency visit within two years. It appeared in The Lancet Psychiatry on 1 October 2026.

Two-year risk was 49.5% with antipsychotic monotherapy, 42.3% with a mood stabiliser alone and 42.2% with the combination. Against antipsychotic monotherapy, both mood-stabiliser strategies carried a risk ratio of 0.82, an absolute difference of about 7 percentage points. The mood stabiliser and combination strategies did not differ from each other.

This matters because antipsychotic monotherapy is a common way to continue after the acute episode settles, especially when a first-episode psychosis team is the one treating. A target trial emulation is still observational: the confidence intervals are wide, and prescribers may have chosen mood stabilisers for patients who looked more clearly bipolar or more likely to adhere. The authors themselves call for randomised trials.

In practice, this supports making sure a mood stabiliser is part of the plan after a first psychotic mania, rather than leaving the patient on the antipsychotic that settled the acute phase.

• After a first manic episode with psychosis, review whether a mood stabiliser is in the continuation plan.
• Consider lithium or valproate, alone or with the antipsychotic, rather than an antipsychotic alone; avoid valproate in women who could become pregnant.
• Set up lithium monitoring (levels, renal and thyroid function) before discharge from first-episode services.
• Expect about four in ten young adults to be readmitted or seen in emergency within two years whatever the regimen, and plan relapse signatures with the patient.

Why it matters

It questions the habit of carrying the antipsychotic that treated the acute phase forward as the whole maintenance plan.

Don't overread it

This was an emulated trial on routine records, not a randomised trial, and cannot rule out that sicker or less adherent patients were given antipsychotics alone.

The statistics, in plain English

A risk ratio of 0.82 means about 18% fewer events in relative terms, or 7 fewer per 100 people over two years. The confidence intervals around the absolute difference run from about 2 to 16 percentage points, so the true benefit could be small. Target trial emulation borrows the structure of a trial to reduce some biases in observational data, but it cannot remove confounding by factors that were not recorded.

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