Bipolar Depression / Treatment as Usual (TAU) / Palmitoylethanolamide (PEA) · Phase 2 Trial

A Trial of the Fatty Acid Amide Hydrolase Inhibitor Palmitoylethanolamide in Bipolar Depression

ClinicalTrials.gov · August 13, 2026

Preliminary Why this matters to you Expert discussion

Early or partial results. Treat as a signal, not a conclusion.

AI Summary

This is a completed Phase 2 trial of palmitoylethanolamide (PEA), a fatty acid amide hydrolase inhibitor, in 34 participants with bipolar depression, comparing PEA to placebo and treatment-as-usual over 6 weeks using HAM-D as the primary outcome. No results have been posted in the registry record; the strength and direction of any effect remain unreported.

What was studied

Phase 2, Interventional, Randomized, Parallel, Triple masking, Treatment purpose. Bipolar Depression; age from 18 Years; to 70 Years. Intervention: PEA plus Treatment as Usual (TAU). Compared with: Placebo plus Treatment as Usual (TAU) — Placebo Comparator. n = 34. 1 site: United States.

Key findings

Safety

No efficacy or safety results reported in this registry record.

Who this may help

Results are not yet available in this registry record. Once posted, findings will inform whether PEA merits investigation in larger Phase 3 trials for bipolar depression; current evidence is insufficient to guide clinical practice.

Plain-language summary

Phase 2 trial in bipolar depression with small sample (n=34) and surrogate endpoint (HAM-D); recruitment completed but no results posted in registry, limiting evidence strength.

Study design

As stated by the source record.

MethodsPrimary outcome measure: Change in Depression as Assessed by the Hamilton Depression Rating Scale (HAM-D) (assessed at Baseline, 6 weeks follow up)

DesignPhase 2, Interventional, Randomized, Parallel, Triple masking, Treatment purpose

PopulationBipolar Depression; age from 18 Years; to 70 Years

Sample size34

InterventionPEA plus Treatment as Usual (TAU)

ComparatorPlacebo plus Treatment as Usual (TAU) — Placebo Comparator

Setting1 site: United States

Reported figures

Quoted from the source exactly as published.

Sample size34

PhasePhase 2

Primary endpointChange in Depression as Assessed by the Hamilton Depression Rating Scale (HAM-D), Baseline, 6 weeks follow up

Study duration6 weeks

Clinical bottom line

Caveats

No efficacy or safety results reported in this registry record.
Small sample size limits statistical power and generalizability.
Registry does not describe randomization, blinding, or whether trial was double-masked.
Mechanism of action (endogenous cannabinoid and cytokine associations) outcome results not stated.

Evidence assessment

Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.

Study design

moderate

Phase 2 interventional trial with placebo and treatment-as-usual comparators.

Directness

moderate

Primary outcome is HAM-D change, a validated depression scale in bipolar disorder.

Consistency

insufficient

No results reported; consistency cannot be assessed against other evidence.

Risk of bias

insufficient

Registry record does not describe blinding, allocation concealment, or analytic methods.

Sample adequacy

limited

Planned enrollment 34 participants; typical Phase 2 size, underpowered for definitive conclusion.

What is missing. This record has no key findings. That is a gap in the analysis, not a judgement about the study.

Source abstract

Registry record from ClinicalTrials.gov (NCT06229977). This is a study registration, not published results. Lead sponsor: Rodrigo Machado-Vieira, MD, PhD, MSc. Recruitment status: COMPLETED. Phase: PHASE2. Study type: INTERVENTIONAL. Enrollment: 34 participants (ACTUAL). Conditions: Bipolar Depression. Interventions: DRUG: Palmitoylethanolamide (PEA); DRUG: Placebo; DRUG: Treatment as Usual (TAU). Primary outcome measures: Change in Depression as Assessed by the Hamilton Depression Rating Scale (HAM-D) , Baseline, 6 weeks follow up. Brief summary: The purpose of this study is to o evaluate the antidepressant efficacy of the PEA in Bipolar Depression and the association between antidepressant response with endogenous cannabinoids and cytokine levels

Follow from this

Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.

Bipolar DepressionTreatment as Usual (TAU)NCT06229977Rodrigo Machado-Vieira, MD, PhD, MScPalmitoylethanolamide (PEA)