Results from a long-term open-label extension study of adjunctive buprenorphine/samidorphan combination in patients with major depressive disorder

Michael E. Thase, Arielle D. Stanford, Asli Memisoglu, William Martin, Amy Claxton, J. Alexander Bodkin, Madhukar H. Trivedi, Maurizio Fava, Miao Yu, Sanjeev Pathak

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Buprenorphine/samidorphan (BUP/SAM; ALKS 5461) is an investigational opioid system modulator for the adjunctive treatment of patients with major depressive disorder (MDD), who did not respond adequately to prior antidepressant therapy (ADT). FORWARD-2, an open-label extension study, assessed long-term safety and tolerability of adjunctive BUP/SAM treatment in these patients. Patients from four short-term trials and de novo patients were enrolled; all had confirmed MDD and a current major depressive episode lasting 2–24 months. Patients were treated with an established ADT for ≥8 weeks before receiving sublingual, adjunctive BUP/SAM 2 mg/2 mg for up to 52 weeks. Safety (primary objective) was assessed via adverse events (AEs), the Columbia-Suicide Severity Rating Scale, and the Clinical Opiate Withdrawal Scale (COWS). Exploratory evaluation of efficacy was done using the Montgomery–Åsberg Depression Rating Scale (MADRS). Of 1485 patients, 50% completed the study and 11% discontinued due to AEs. AEs of nausea, headache, constipation, dizziness, and somnolence, each occurred in ≥10% of patients. There was no evidence of increased suicidal ideation or behavior. Euphoria-related AEs were uncommon (1.2%). Following abrupt BUP/SAM discontinuation, “drug withdrawal” AEs were infrequent (0.4%), and the incidence of COWS categorical worsening after abrupt drug discontinuation was low (6.5%). Improvements in mean MADRS scores were maintained until study end, suggesting durability of antidepressant effect in patients continuing treatment. BUP/SAM was generally well tolerated, with a low risk of abuse and an AE profile consistent with those seen in placebo-controlled studies. Withdrawal reports were uncommon and of limited clinical impact.

Original languageEnglish (US)
Pages (from-to)2268-2276
Number of pages9
JournalNeuropsychopharmacology
Volume44
Issue number13
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Fingerprint Dive into the research topics of 'Results from a long-term open-label extension study of adjunctive buprenorphine/samidorphan combination in patients with major depressive disorder'. Together they form a unique fingerprint.

  • Cite this