REVIEW OF: Abedini T et al, Psychiatry Clin Neurosci 2022;76(10):505–511

STUDY TYPE: Randomized, double-blind, placebo-controlled trial

Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide found in foods like peanuts and eggs. It has anti-inflammatory, neuroprotective, and analgesic effects. PEA successfully augmented antidepressants in a small, trial (Hashemi et al, J Affect Disord 2018;232:127–133), and the current study explored its potential in bipolar mania.

Researchers conducted a six-week, randomized, double-blind, placebo-controlled study of PEA as an adjunctive treatment for mania. They enrolled 63 adult patients who were admitted for bipolar mania at two hospitals in Iran. All patients were taking combined lithium (0.8–1.1 mEq/L) with risperidone (3 mg), and half additionally received a PEA tablet (600 mg) while the other half got a placebo pill. Manic symptoms were assessed at baseline and weeks one, two, four, and six by the Young Mania Rating Scale (YMRS). The primary outcome was reduction of YMRS scores from baseline to study endpoint between the PEA and placebo groups.

Patients in the PEA and placebo groups started with statistically similar YMRS scores (31.34 and 29.96, respectively), indicating moderate mania. Those randomized to adjunctive PEA had a significant reduction in YMRS scores compared to placebo at four weeks (-22.46 vs -18.00, p=0.018) and six weeks (-29.06 vs -23.22, p=0.002). Both groups had low YMRS scores at the end of the six-week trial, though scores were significantly lower in the PEA group (2.28 vs 6.74, p=0.004). PEA was well tolerated, with no difference in adverse events between the PEA and placebo groups.

CARLAT TAKE

This study adds to a small but growing body of literature suggesting that anti-inflammatory agents like PEA may be effective adjunctive treatments for acute mania, but we’ll need more than a single study before recommending PEA in practice.