Is Lurasidone Antimanic or Promanic?

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A case report adds to the concern

STUDY: Alzain NM et al, Front Psychiatry 2026

STUDY TYPE: Case report

FUNDING: Independent

Background

Lurasidone is approved for bipolar depression, but has no major trials in bipolar mania. It did improve mixed symptoms in large trials, and manic symptoms in a small randomized trial.

On the other hand, its mechanism suggests a possible manic effect by raising dopamine release in the prefrontal cortex. Most second generation antipsychotics have been linked to mania in case reports, even those that are FDA-approved for mania. This paradoxical reaction is something to watch for.

The Case

• A 43-year-old man with bipolar I disorder presented with a severe depressive episode following the death of his grandmother.
• His serum valproate level was less than 13 µg/mL, far below the therapeutic range of 50–100 µg/mL.
• Lamotrigine, quetiapine, and lithium were each contraindicated, leaving lurasidone as the only option. It was started at 40 mg and titrated to 120 mg daily.

At 80 mg, early hypomanic signals appeared: less sleep, irritability, and increased energy. Titration continued anyway. By day 10, the patient had a full manic episode: grandiose delusions, mood described as “flying to the sky,” and only 1.5 hours of sleep per night. Lorazepam did nothing. Lurasidone was stopped, valproate was increased to 3,000 mg, and paliperidone was added. Manic symptoms resolved quickly. The patient was discharged after 64 days on valproate and a long-acting paliperidone injection.

Using the Naranjo Adverse Drug Reaction Probability Scale, the authors scored this a 9, placing it in the “definite” adverse drug reaction category.

Limitations

Single case, no rechallenge, and though he improved off lurasidone they also started raising valproate at that time.

Practice Implications

1. Second-generation antipsychotics have complex mechanisms.
2. Don’t assume they all treat mania (some, like brexpiprazole, failed there), and watch for paradoxical reactions.
3. Lurasidone has around four reports of mania, and I’ve heard about or seen a few cases myself. Here’s the breakdown of other antipsychotic induced manias: olanzapine (seven cases), quetiapine (five cases), ziprasidone (five cases), aripiprazole (four cases), amisulpride (two cases), zotepine (two cases), perospirone (two cases) and paliperidone (one case).

—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report

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