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

*Kontaktforfatter for dette arbejde

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Resumé

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.

OriginalsprogEngelsk
TidsskriftJournal of Affective Disorders
Vol/bind245
Sider (fra-til)1043-1051
ISSN0165-0327
DOI
StatusUdgivet - 15. feb. 2019

Fingeraftryk

Acetylcysteine
Placebos
Outcome Assessment (Health Care)
Depression
Therapeutic Uses

Citer dette

Ellegaard, Pernille Kempel ; Licht, Rasmus Wentzer ; Nielsen, René Ernst ; Dean, Olivia May ; Berk, Michael ; Poulsen, Henrik Enghusen ; Mohebbi, Mohammadreza ; Nielsen, Connie Thuroee. / The efficacy of adjunctive N-acetylcysteine in acute bipolar depression : A randomized placebo-controlled study. I: Journal of Affective Disorders. 2019 ; Bind 245. s. 1043-1051.
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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.",
keywords = "Bipolar disorder, Depression, Glutathione, N acetylcysteine, Treatment",
author = "Ellegaard, {Pernille Kempel} and Licht, {Rasmus Wentzer} and Nielsen, {Ren{\'e} Ernst} and Dean, {Olivia May} and Michael Berk and Poulsen, {Henrik Enghusen} and Mohammadreza Mohebbi and Nielsen, {Connie Thuroee}",
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language = "English",
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The efficacy of adjunctive N-acetylcysteine in acute bipolar depression : A randomized placebo-controlled study. / Ellegaard, Pernille Kempel; Licht, Rasmus Wentzer; Nielsen, René Ernst; Dean, Olivia May; Berk, Michael; Poulsen, Henrik Enghusen; Mohebbi, Mohammadreza; Nielsen, Connie Thuroee.

I: Journal of Affective Disorders, Bind 245, 15.02.2019, s. 1043-1051.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - The efficacy of adjunctive N-acetylcysteine in acute bipolar depression

T2 - A randomized placebo-controlled study

AU - Ellegaard, Pernille Kempel

AU - Licht, Rasmus Wentzer

AU - Nielsen, René Ernst

AU - Dean, Olivia May

AU - Berk, Michael

AU - Poulsen, Henrik Enghusen

AU - Mohebbi, Mohammadreza

AU - Nielsen, Connie Thuroee

PY - 2019/2/15

Y1 - 2019/2/15

N2 - 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.

AB - 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.

KW - Bipolar disorder

KW - Depression

KW - Glutathione

KW - N acetylcysteine

KW - Treatment

U2 - 10.1016/j.jad.2018.10.083

DO - 10.1016/j.jad.2018.10.083

M3 - Journal article

VL - 245

SP - 1043

EP - 1051

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

SN - 0165-0327

ER -