TY - JOUR
T1 - A double-blind, randomized, placebo-controlled study of aspirin and N-acetylcysteine as adjunctive treatments for bipolar depression
AU - Bauer, Isabelle E.
AU - Green, Charles
AU - Colpo, Gabriela D.
AU - Teixeira, Antonio L.
AU - Selvaraj, Sudhakar
AU - Durkin, Katherine
AU - Zunta-Soares, Giovana B.
AU - Soares, Jair C.
N1 - Funding Information:
Submitted: February 20, 2018; accepted June 8, 2018. Published online: December 4, 2018. Author contributions: The corresponding author had full access to all data in the study and had final responsibility for the decision to submit for publication. Potential conflicts of interest: Dr Soares has received grants/research support from Forrest, Bristol-Myers Squibb, Merck, Stanley Medical Research Institute (SMRI), and the National Institutes of Health and has been a speaker for Pfizer and Abbott. Drs Bauer, Green, Colpo, Teixeira, Selvaraj, and Zunta-Soares and Ms Durkin have no conflicts of interest to declare. Funding/support: This research was supported by a grant from the Stanley Brain Foundation (SMRI Grant 11T-009). Role of the sponsor: The supporting source had no involvement in the study design, collection, analysis, and interpretation of the data; in the writing of the report; or in the decision to submit the report for publication. Acknowledgments: The authors thank Stanley I. Rapoport, MD, Brain Physiology Section, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, for his scientific advice and contribution to the design of this study and drafting of the grant submission to the Stanley Foundation. Dr. Rapaport has no conflicts of interest regarding this work.
Publisher Copyright:
© Copyright 2018 Physicians Postgraduate Press, Inc.
PY - 2019/1
Y1 - 2019/1
N2 - Objective: Neuroinflammation has been implicated in the pathophysiology of bipolar disorder. Some evidence shows that nonsteroidal anti-inflammatory drugs (NSAIDs) have promising antidepressant effects. The antioxidant N-acetylcysteine (NAC) may enhance the effects of NSAIDs. No study has, however, tested the adjunctive therapeutic benefits of an NSAID and NAC in bipolar disorder. Methods: The sample included 24 medicated patients diagnosed with DSM-IV-TR bipolar disorder who were aged 18-65 years and had a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 20. Participants were randomly assigned to receive either aspirin (1,000 mg), NAC (1,000 mg), combined aspirin and NAC (1,000 mg each), or placebo. Data were collected between 2013 and 2017. The primary outcome was a ≥ 50% reduction in MADRS scores. Participants completed mood and global functioning questionnaires. They also underwent blood tests prior to and following 8 and 16 weeks of treatment. A Bayesian analytic method was adopted, and posterior probability distributions were calculated to determine the probability of treatment response. Results: Following the first 8-week treatment phase, individuals on treatment with placebo and NAC + aspirin had a similar probability for successful treatment response (about 70%). Following a 16-week treatment period, NAC + aspirin was associated with higher probability of treatment response (67%) compared to placebo (55%), NAC (57%), and aspirin (33%). There was no treatment effect on interleukin-6 and C-reactive protein levels at either 8 or 16 weeks. Conclusions: The coadministration of NAC and aspirin during a period of 16 weeks was associated with a reduction in depressive symptoms. The adverse effects were minimal. These preliminary findings may serve as a starting point for future studies assessing the efficacy, tolerability, and safety of anti-inflammatory and antioxidant agents in the treatment of bipolar depression.
AB - Objective: Neuroinflammation has been implicated in the pathophysiology of bipolar disorder. Some evidence shows that nonsteroidal anti-inflammatory drugs (NSAIDs) have promising antidepressant effects. The antioxidant N-acetylcysteine (NAC) may enhance the effects of NSAIDs. No study has, however, tested the adjunctive therapeutic benefits of an NSAID and NAC in bipolar disorder. Methods: The sample included 24 medicated patients diagnosed with DSM-IV-TR bipolar disorder who were aged 18-65 years and had a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 20. Participants were randomly assigned to receive either aspirin (1,000 mg), NAC (1,000 mg), combined aspirin and NAC (1,000 mg each), or placebo. Data were collected between 2013 and 2017. The primary outcome was a ≥ 50% reduction in MADRS scores. Participants completed mood and global functioning questionnaires. They also underwent blood tests prior to and following 8 and 16 weeks of treatment. A Bayesian analytic method was adopted, and posterior probability distributions were calculated to determine the probability of treatment response. Results: Following the first 8-week treatment phase, individuals on treatment with placebo and NAC + aspirin had a similar probability for successful treatment response (about 70%). Following a 16-week treatment period, NAC + aspirin was associated with higher probability of treatment response (67%) compared to placebo (55%), NAC (57%), and aspirin (33%). There was no treatment effect on interleukin-6 and C-reactive protein levels at either 8 or 16 weeks. Conclusions: The coadministration of NAC and aspirin during a period of 16 weeks was associated with a reduction in depressive symptoms. The adverse effects were minimal. These preliminary findings may serve as a starting point for future studies assessing the efficacy, tolerability, and safety of anti-inflammatory and antioxidant agents in the treatment of bipolar depression.
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U2 - 10.4088/JCP.18m12200
DO - 10.4088/JCP.18m12200
M3 - Article
C2 - 30549489
AN - SCOPUS:85058730093
SN - 0160-6689
VL - 80
JO - Journal of Clinical Psychiatry
JF - Journal of Clinical Psychiatry
IS - 1
ER -