Melatonin In Acute Mania Investigation (MIAMI‐UK). A randomized controlled trial of add‐on melatonin in bipolar disorder

Objectives Current options for treating emergent episodes of hypomania and mania in bipolar disorder are limited. Our objective was to compare the effectiveness and safety of add‐on melatonin in hypomania or mania over 3 weeks as a well‐tolerated therapy. Methods A randomized, double‐blind, parallel‐group, 3‐week comparison of modified release melatonin (n = 21) vs placebo (n = 20) in adult bipolar patients aged 18‐65 years. Permuted block randomization was used with participants and investigators masked to treatment allocation. Trial registration is ISRCTN28988273 and EUdraCT2008‐000281‐23. Approved by the South Central National Research Ethics Service (Oxford REC A) ref: 09/H0604/63. Results The trial was negative as there was no significant difference between melatonin and placebo on the primary outcome—mean Young Mania Rating Scale (YMRS) score at Day 21: (mean difference [MD] −1.77 ([95% CI: −6.39 to 2.85]; P = .447). Significantly fewer patients on melatonin scored 10 or more on the Altman Self Rating Mania Scale: (odds ratio [OR] 0.164 [95% CI: 0.0260‐1.0002]; P = .05). Quick Inventory of Depression Symptomatology Clinician Version‐16 (QIDS‐C16) scores were not significantly different. (OR 1.77 [95% CI: 0.43‐7.29]; P = .430). The proportion of patients scoring less than or equal to 5 on the self‐report QIDS‐SR16 at end‐point was greater for the melatonin group (OR 8.35 [95% CI: 1.04‐67.23]; P = .046). Conclusions In this small trial, melatonin did not effectively treat emerging hypomania or mania as there was no significant difference on the primary outcome. The sample size limitation and secondary outcomes suggest further investigation of melatonin treatment in mood episodes is indicated.