PMID- 31254971
OWN - NLM
STAT- MEDLINE
DCOM- 20200708
LR  - 20220417
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 44
IP  - 13
DP  - 2019 Dec
TI  - Results from a long-term open-label extension study of adjunctive 
      buprenorphine/samidorphan combination in patients with major depressive disorder.
PG  - 2268-2276
LID - 10.1038/s41386-019-0451-3 [doi]
AB  - 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-Asberg 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.
FAU - Thase, Michael E
AU  - Thase ME
AD  - Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania 
      School of Medicine, 3535 Market Street, Suite 670, Philadelphia, PA, 19104-3309, 
      USA. thase@mail.med.upenn.edu.
FAU - Stanford, Arielle D
AU  - Stanford AD
AD  - Alkermes, Inc., Waltham, MA, USA.
FAU - Memisoglu, Asli
AU  - Memisoglu A
AD  - Alkermes, Inc., Waltham, MA, USA.
FAU - Martin, William
AU  - Martin W
AUID- ORCID: 0000-0002-8740-9014
AD  - Alkermes, Inc., Waltham, MA, USA.
FAU - Claxton, Amy
AU  - Claxton A
AD  - Alkermes, Inc., Waltham, MA, USA.
FAU - Bodkin, J Alexander
AU  - Bodkin JA
AD  - McLean Hospital, Belmont, MA, USA.
AD  - Harvard Medical School, Boston, MA, USA.
FAU - Trivedi, Madhukar H
AU  - Trivedi MH
AUID- ORCID: 0000-0002-2983-1110
AD  - University of Texas Southwestern Medical Center, Dallas, TX, USA.
FAU - Fava, Maurizio
AU  - Fava M
AD  - Harvard Medical School, Boston, MA, USA.
AD  - Massachusetts General Hospital, Boston, MA, USA.
FAU - Yu, Miao
AU  - Yu M
AD  - Alkermes, Inc., Waltham, MA, USA.
FAU - Pathak, Sanjeev
AU  - Pathak S
AD  - Alkermes, Inc., Waltham, MA, USA.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190629
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Antidepressive Agents)
RN  - 40D3SCR4GZ (Buprenorphine)
RN  - 5S6W795CQM (Naltrexone)
RN  - 7W2581Z5L8 (3-carboxamido-4-hydroxynaltrexone)
SB  - IM
MH  - Adult
MH  - Antidepressive Agents/*therapeutic use
MH  - Buprenorphine/*therapeutic use
MH  - Depressive Disorder, Major/*drug therapy
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Naltrexone/*analogs & derivatives/therapeutic use
MH  - Psychiatric Status Rating Scales
MH  - Treatment Outcome
PMC - PMC6897901
EDAT- 2019/06/30 06:00
MHDA- 2020/07/09 06:00
PMCR- 2019/06/29
CRDT- 2019/06/30 06:00
PHST- 2019/01/30 00:00 [received]
PHST- 2019/06/11 00:00 [accepted]
PHST- 2019/05/22 00:00 [revised]
PHST- 2019/06/30 06:00 [pubmed]
PHST- 2020/07/09 06:00 [medline]
PHST- 2019/06/30 06:00 [entrez]
PHST- 2019/06/29 00:00 [pmc-release]
AID - 10.1038/s41386-019-0451-3 [pii]
AID - 451 [pii]
AID - 10.1038/s41386-019-0451-3 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2019 Dec;44(13):2268-2276. doi: 
      10.1038/s41386-019-0451-3. Epub 2019 Jun 29.