Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants

David Mischoulon, Lindsay Hylek, Albert S. Yeung, Alisabet J. Clain, Lee Baer, Cristina Cusin, Dawn Flosnik Ionescu, Jonathan E. Alpert, David P. Soskin, Maurizio Fava

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background Given the proposed dopaminergic mechanism of low-dose naltrexone (LDN), we examined its efficacy as augmentation for depressive breakthrough on pro-dopaminergic antidepressant regimens. Methods 12 adults (67% female, mean age = 45±12) with recurrent DSM-IV major depressive disorder (MDD) on dopaminergic antidepressant regimens (stimulants, dopamine agonists, bupropion [≥300 mg/day], aripiprazole [≤2.5 mg/day], or sertraline [≥150 mg/day]) were randomized to naltrexone 1 mg b.i.d. (n=6) or placebo (n=6) augmentation for 3 weeks. Results All subjects completed the trial. Hamilton Depression Rating Scale (HAM-D-17) scores (primary outcome measure) decreased from 21.2±2.0 to 11.7±7.7 for LDN, from 23.7±2.3 to 17.8±5.9 for placebo (Cohen's d=0.62; p=0.3 between treatment groups). HAM-D-28 scores decreased from 26.2±4.0 to 12.0±9.8 for LDN, from 26.3±2.6 to 19.8±6.6 for placebo (d=1.15; p=0.097). Montgomery-Asberg Depression Rating Scale (MADRS-10 item) scores decreased from 30.4±4.9 to 12.2±8.4 for LDN, from 30.7±4.3 to 22.8±8.5) for placebo (d=1.45; p=0.035). MADRS-15 item scores decreased from 36.6±6.2 to 13.2±8.8 for LDN, from 36.7±4.2 to 26.0±10.0 for placebo (d=1.49; p=0.035). Clinical Global Improvement Scale-Severity (CGI-S) scores decreased from 4.3±0.5 to 3.0±1.1 for LDN, from 4.3±0.5 to 4.0±0.6 for placebo (d=1.22; p=0.064). Limitations Small study; restrictions on allowed antidepressants. Conclusion LDN augmentation showed some benefit for MDD relapse on dopaminergic agents. Confirmation in larger studies is needed.

Original languageEnglish (US)
Pages (from-to)6-14
Number of pages9
JournalJournal of Affective Disorders
Volume208
DOIs
StatePublished - Jan 15 2017
Externally publishedYes

Fingerprint

Naltrexone
Major Depressive Disorder
Antidepressive Agents
Placebos
Depression
Bupropion
Sertraline
Dopamine Agents
Dopamine Agonists
Diagnostic and Statistical Manual of Mental Disorders
Outcome Assessment (Health Care)
Recurrence

Keywords

  • Breakthrough
  • Depression
  • LDN
  • Naltrexone
  • Relapse

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants. / Mischoulon, David; Hylek, Lindsay; Yeung, Albert S.; Clain, Alisabet J.; Baer, Lee; Cusin, Cristina; Ionescu, Dawn Flosnik; Alpert, Jonathan E.; Soskin, David P.; Fava, Maurizio.

In: Journal of Affective Disorders, Vol. 208, 15.01.2017, p. 6-14.

Research output: Contribution to journalArticle

Mischoulon, David ; Hylek, Lindsay ; Yeung, Albert S. ; Clain, Alisabet J. ; Baer, Lee ; Cusin, Cristina ; Ionescu, Dawn Flosnik ; Alpert, Jonathan E. ; Soskin, David P. ; Fava, Maurizio. / Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants. In: Journal of Affective Disorders. 2017 ; Vol. 208. pp. 6-14.
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AU - Mischoulon, David

AU - Hylek, Lindsay

AU - Yeung, Albert S.

AU - Clain, Alisabet J.

AU - Baer, Lee

AU - Cusin, Cristina

AU - Ionescu, Dawn Flosnik

AU - Alpert, Jonathan E.

AU - Soskin, David P.

AU - Fava, Maurizio

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N2 - Background Given the proposed dopaminergic mechanism of low-dose naltrexone (LDN), we examined its efficacy as augmentation for depressive breakthrough on pro-dopaminergic antidepressant regimens. Methods 12 adults (67% female, mean age = 45±12) with recurrent DSM-IV major depressive disorder (MDD) on dopaminergic antidepressant regimens (stimulants, dopamine agonists, bupropion [≥300 mg/day], aripiprazole [≤2.5 mg/day], or sertraline [≥150 mg/day]) were randomized to naltrexone 1 mg b.i.d. (n=6) or placebo (n=6) augmentation for 3 weeks. Results All subjects completed the trial. Hamilton Depression Rating Scale (HAM-D-17) scores (primary outcome measure) decreased from 21.2±2.0 to 11.7±7.7 for LDN, from 23.7±2.3 to 17.8±5.9 for placebo (Cohen's d=0.62; p=0.3 between treatment groups). HAM-D-28 scores decreased from 26.2±4.0 to 12.0±9.8 for LDN, from 26.3±2.6 to 19.8±6.6 for placebo (d=1.15; p=0.097). Montgomery-Asberg Depression Rating Scale (MADRS-10 item) scores decreased from 30.4±4.9 to 12.2±8.4 for LDN, from 30.7±4.3 to 22.8±8.5) for placebo (d=1.45; p=0.035). MADRS-15 item scores decreased from 36.6±6.2 to 13.2±8.8 for LDN, from 36.7±4.2 to 26.0±10.0 for placebo (d=1.49; p=0.035). Clinical Global Improvement Scale-Severity (CGI-S) scores decreased from 4.3±0.5 to 3.0±1.1 for LDN, from 4.3±0.5 to 4.0±0.6 for placebo (d=1.22; p=0.064). Limitations Small study; restrictions on allowed antidepressants. Conclusion LDN augmentation showed some benefit for MDD relapse on dopaminergic agents. Confirmation in larger studies is needed.

AB - Background Given the proposed dopaminergic mechanism of low-dose naltrexone (LDN), we examined its efficacy as augmentation for depressive breakthrough on pro-dopaminergic antidepressant regimens. Methods 12 adults (67% female, mean age = 45±12) with recurrent DSM-IV major depressive disorder (MDD) on dopaminergic antidepressant regimens (stimulants, dopamine agonists, bupropion [≥300 mg/day], aripiprazole [≤2.5 mg/day], or sertraline [≥150 mg/day]) were randomized to naltrexone 1 mg b.i.d. (n=6) or placebo (n=6) augmentation for 3 weeks. Results All subjects completed the trial. Hamilton Depression Rating Scale (HAM-D-17) scores (primary outcome measure) decreased from 21.2±2.0 to 11.7±7.7 for LDN, from 23.7±2.3 to 17.8±5.9 for placebo (Cohen's d=0.62; p=0.3 between treatment groups). HAM-D-28 scores decreased from 26.2±4.0 to 12.0±9.8 for LDN, from 26.3±2.6 to 19.8±6.6 for placebo (d=1.15; p=0.097). Montgomery-Asberg Depression Rating Scale (MADRS-10 item) scores decreased from 30.4±4.9 to 12.2±8.4 for LDN, from 30.7±4.3 to 22.8±8.5) for placebo (d=1.45; p=0.035). MADRS-15 item scores decreased from 36.6±6.2 to 13.2±8.8 for LDN, from 36.7±4.2 to 26.0±10.0 for placebo (d=1.49; p=0.035). Clinical Global Improvement Scale-Severity (CGI-S) scores decreased from 4.3±0.5 to 3.0±1.1 for LDN, from 4.3±0.5 to 4.0±0.6 for placebo (d=1.22; p=0.064). Limitations Small study; restrictions on allowed antidepressants. Conclusion LDN augmentation showed some benefit for MDD relapse on dopaminergic agents. Confirmation in larger studies is needed.

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KW - Relapse

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