N-acetylcysteine for major depressive episodes in bipolar disorder

Magalhães, Pedro Vieira da Silva; Dean, Olivia; Bush, Ashley I.; Copolov, David L.; Malhi, Gin S; Kohlmann, Kristy; Jeavons, Sue; Schapkaitz, Ian; Anderson-Hunt, Murray; Berk, Michael

doi:10.1590/s1516-44462011000400011

Cited by 100 publications

(56 citation statements)

References 35 publications

(41 reference statements)

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“…Interestingly, 17 participants in that study met criteria for MDD, and of the 10 participants on N-acetylcysteine, 8 were responders at end point, contrasting with 1 responder of 7 participants allocated to placebo. 9 Further, in the 2-month, open-label phase of a randomized, placebo-controlled, maintenance clinical trial of bipolar disorder, with an index polarity of depression, the mean BDRS score at baseline was 19.7 (standard error [SE] = 0.8), declining to 11.1 (SE = 0.8) after the 8-week open-label treatment phase (P < .001). Again, significant improvements in functioning and quality of life were seen.…”

Section: Figure 2 Mean ± Se Estimates From Mixed-effects Model Repeamentioning

confidence: 99%

“…[6][7][8][9][10] We therefore aimed to test its efficacy in the acute treatment of major depressive disorder (MDD) by conducting a randomized, placebo-controlled trial of N-acetylcysteine as adjunctive treatment. Specifically, we hypothesized that addition of N-acetylcysteine would reduce MontgomeryAsberg Depression Rating Scale (MADRS) 11 scores (primary outcome) in comparison to placebo.…”

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confidence: 99%

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The Efficacy of AdjunctiveN-Acetylcysteine in Major Depressive Disorder

Berk

Dean²,

Cotton³

et al. 2014

J. Clin. Psychiatry

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144

135

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Objective: Major depressive disorder (MDD) is one of the most common psychiatric disorders, conferring considerable individual, family, and community burden. To date, treatments for MDD have been derived from the monoamine hypothesis, and there is a paucity of emerging antidepressants, especially with novel mechanisms of action and treatment targets. N-acetylcysteine (NAC) is a redox-active glutathione precursor that decreases inflammatory cytokines, modulates glutamate, promotes neurogenesis, and decreases apoptosis, all of which contribute to the neurobiology of depression.Method: Participants with a current episode of MDD diagnosed according to DSM-IV-TR criteria (N = 252) were treated with NAC or placebo in addition to treatment as usual for 12 weeks and were followed to 16 weeks. Data were collected between 2007 and 2011. Results:The omnibus interaction between group and visit for the Montgomery-Asberg Depression Rating Scale (MADRS), the primary outcome measure, was not significant (F 1,520.9 = 1.98, P = .067), and the groups did not separate at week 12 (t 360.3 = −1.12, P = .265). However, at week 12, the scores on the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT) differed from placebo (P = .03). Among participants with a MADRS score ≥ 25, NAC separated from placebo at weeks 6, 8, 12, and 16 (P < .05). Additionally, the rate of change between baseline and week 16 was significant (t 221.03 = −2.11, P = .036). NAC treatment was superior to placebo at week 16 for secondary readouts of function and clinical impression. Remission and response were greater in the NAC group at week 16, but not at week 12. The NAC group had a greater rate of gastrointestinal and musculoskeletal adverse events. Conclusions:Being negative at the week 12 end point, and with some positive secondary signals, the study provides only limited support for the role of NAC as a novel adjunctive therapy for MDD. These data implicate the pathways influenced by NAC in depression pathogenesis, principally oxidative and inflammatory stress and glutamate, although definitive confirmation remains necessary.Trial Registration: www.anzctr.org.au Identifier: ACTRN12607000134426 Clin Psychiatry 2014;75(6):628-636 J

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Section: Figure 2 Mean ± Se Estimates From Mixed-effects Model Repeamentioning

confidence: 99%

mentioning

confidence: 99%

The Efficacy of AdjunctiveN-Acetylcysteine in Major Depressive Disorder

Berk

Dean²,

Cotton³

et al. 2014

J. Clin. Psychiatry

Self Cite

144

135

View full text Add to dashboard Cite

show abstract

“…Depression is also associated with increased plasma levels of peroxides and xanthine oxidase (Herken et al, 2007, Maes et al, 2010. The efficacy of antioxidant therapies for depression is unknown, although N-acetylcysteine, a powerful antioxidant, was found to be useful for depressive episodes in bipolar disorder (Berk et al, 2008, Magalhaes et al, 2011 and zinc, which serves as a strong antioxidant, also has antidepressant activity (Szewczyk et al, 2011).…”

Section: Oxidative and Nitrosative Stressmentioning

confidence: 99%

A review of lifestyle factors that contribute to important pathways associated with major depression: Diet, sleep and exercise

Lopresti

Hood

Drummond

2013

Journal of Affective Disorders

479

384

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Research on major depression has confirmed that it is caused by an array of biopsychosocial and lifestyle factors. Diet, exercise and sleep are three such influences that play a significant mediating role in the development, progression and treatment of this condition. This review summarises animal and human-based studies on the relationship between these three lifestyle factors and major depressive disorder, and their influence on dysregulated pathways associated with depression, namely neurotransmitter processes, immuno-inflammatory pathways, hypothalamic-pituitary-adrenal (HPA) axis disturbances, oxidative stress and antioxidant defence systems, neuroprogression, and mitochondrial disturbances. Increased attention in future clinical studies on the influence of diet, sleep and exercise on major depressive disorder and investigations of their effect on physiological processes will help to expand our understanding and treatment of major depressive disorder. Mental health interventions, taking into account the bidirectional relationship between these lifestyle factors and major depression are also likely to enhance the efficacy of interventions associated with this disorder.

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“…For the past years, attention has been given to N-acetylcysteine (NAC), a chemical with antioxidant properties primarily used as a mucolytic agent and in the treatment of paracetamol overdose. A study by Magalhães et al 1 published in this issue of RBP shows that add-on NAC therapy improved depressive symptoms and functional outcomes in bipolar disorder patients, which increases the interest in studying the mechanisms by which this drug may present neuroprotective effects.…”

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confidence: 98%