AimsWe compared the efficacy and safety of lamotrigine versus placebo for the treatment of acute alcohol hallucinosis comorbid depersonalization disorders.Methods10 days, randomized, double-blind, parallel study. A total of 40 patients with an ICD-10 diagnosis of acute alcohol hallucinosis comorbid depersonalization disorders were randomized to lamotrigine 300 mg/d (n = 40), or placebo (n = 40). The primary efficacy measure was the PANSS subscale for hallucinosis and Cambridge Depersonalization Scale (CDS).ResultsIamotrigine treated patients demonstrated a statistically significant greater improvement in PANSS subscale for hallucinosis and CDS than placebo-treated patients.ConclusionLamotrigine demonstrated greater efficacy than placebo in treatment of acute hallucinosis comorbid depersonalization disorders and was generally well tolerated.