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Efficacy and safety of palmitoylethanolamide as an adjunctive treatment for acute mania: A randomized, double-blind, placebo-controlled trial

Abedini T, Hosseyni R, Ghannadi F, Sanjari Moghaddam H, Khodaei Ardakani MR, Talaei A, Akhondzadeh S. Psychiatry and Clinical Neurosciences, 2022; 76(10):505-511.

Randomised controlled trialHumans

Design
Randomised controlled trial
Subjects
70 inpatients with acute mania randomised at two hospitals in Tehran. 63 completed (32 on palmitoylethanolamide, 31 on placebo). Seven left early because of COVID-19 infection.
Dose used in the study
600 mg twice a day, added to lithium and 3 mg of risperidone. The comparison group took placebo with the same drugs.
Duration
6 weeks
What was measured
The Young Mania Rating Scale as the main outcome. The Hamilton depression scale, a movement side effect scale and a side effect checklist.

What the authors reported

The authors reported a larger fall in mania scores in the palmitoylethanolamide group from baseline to week 4 (P = 0.018) and week 6 (P = 0.002). At week 6 the mean score was 2.28 against 6.74 on placebo. Both groups improved a great deal. Movement side effects and adverse events did not differ between groups, and no serious adverse event occurred. Depression scores at week 6 were slightly lower in the placebo group.

Limits of this study

All patients also took lithium and risperidone, so the trial tested palmitoylethanolamide as an add-on. The authors name the small sample, the lack of laboratory tests and the absence of any monotherapy data. Placebo patients also improved sharply, as expected in treated acute mania. The study was funded by a grant from Tehran University of Medical Sciences, and the authors declared no conflicts.

Source

doi:10.1111/pcn.13441

Entry checked against the full text, supplied by Devlin from the publisher's page (Wiley) on 2026-09-21. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.