The efficacy of adjunctive N-acetylcysteine in acute bipolar depression: A randomized placebo-controlled study.

Pernille Kempel Ellegaard, Rasmus Wentzer Licht, René Ernst Nielsen, Olivia May Dean, Michael Berk, Henrik Enghusen Poulsen, Mohammadreza Mohebbi, Connie Thuroee Nielsen

Journal: Journal of affective disorders 2019;245():1043-1051

PMID: 30699846

Full Text on Elsevier Science View on PubMed

Abstract

OBJECTIVE

To investigate the efficacy of adjunctive N-acetylcysteine (NAC) for the treatment of acute bipolar depression.

METHOD

A randomized, double-blind, multicentre, placebo-controlled trial including adult subjects diagnosed with bipolar disorder, currently experiencing a depressive episode. Participants were treated with 3 g/day NAC or placebo as an adjunctive to standard treatment for 20 weeks, followed by a 4-week washout where the blinding was maintained. The primary outcome was the mean change in the Montgomery Asberg Depression Rating Scale (MADRS) score over the 20-week treatment phase. Linear Mixed Effects Repeated Measures (LMERM) was used for analysing the primary outcome.

RESULTS

A total of 80 subjects were included. The mean MADRS score at baseline was 30.1 and 28.8 in participants randomized to NAC and placebo, respectively. Regarding the primary outcome measure, the between-group difference (NAC vs. placebo) was 0.5, which was statistically non-significant (95% CI: -7.0-5.9;p = 0.88). All findings regarding secondary outcomes were statistically or clinically insignificant.

LIMITATIONS

The study had a placebo response rate of 55.6% - high placebo response rates are associated with failure to separate from placebo.

CONCLUSIONS

Based on our primary outcome measure, we could not confirm previous studies showing a therapeutic effect of adjunctive NAC treatment on acute bipolar depression. Further studies with larger samples are needed to elucidate if specific subgroups could benefit from adjunctive NAC treatment.

Address: Institute of Regional Health Services Research, Faculty of Health Sciences, University of Southern Denmark, Denmark; Research Unit, Mental Health Service Esbjerg, The Region of Southern Denmark, Denmark; OPEN, Odense Patient Data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Denmark. Electronic address: [email protected].; Unit for Psychiatric Research, Psychiatry, Aalborg University Hospital, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.; Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Australia; Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Australia; University of Melbourne, Department of Psychiatry, Royal Melbourne Hospital, Parkville, Australia.; Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Australia; Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Australia; University of Melbourne, Department of Psychiatry, Royal Melbourne Hospital, Parkville, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Victoria, Australia.; Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Clinical Pharmacology, Bispebjerg Frederiksberg Hospital, Denmark.; Biostatistics Unit, Faculty of Health, Deakin University, Geelong, Australia.; Institute of Regional Health Services Research, Faculty of Health Sciences, University of Southern Denmark, Denmark; Mental Health Service Vejle, The Region of Southern Denmark, Denmark.

DOI: 10.1016/j.jad.2018.10.083

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MeSH Terms: Acetylcysteine, Adult, Antidepressive Agents, Bipolar Disorder, Brief Psychiatric Rating Scale, Depressive Disorder, Double-Blind Method, Female, Humans, Male, Middle Aged, Young Adult