Systemic illness moderates the impact of N-acetyl cysteine in bipolar disorder

Prog Neuropsychopharmacol Biol Psychiatry. 2012 Apr 27;37(1):132-5. doi: 10.1016/j.pnpbp.2011.11.011. Epub 2011 Dec 23.


Objectives: Bipolar disorder (BD) is intricately associated with chronic clinical conditions. Medical comorbidity is not only more prevalent in mood disorders, but is associated with increased costs, cognitive impairment and, ultimately, premature mortality. Oxidative stress and inflammation may mediate part of this association. To further investigate the association between medical comorbidity status and clinical improvement with adjuvant N acetyl cysteine (NAC) in the context of a placebo-controlled trial.

Methods: Placebo-controlled randomized clinical trial assessing the effect of NAC over 24 weeks. Symptomatic and functional outcomes were collected over the study period. Medical comorbidities were self-reported, and we took special interest in cardiovascular and endocrine conditions. We evaluated change from baseline to endpoint and the interaction between change and reported medical comorbidities.

Results: Fifty-one percent of patients reported have a cardiovascular or endocrine comorbidity. Although not found for depressive symptoms or quality of life, a significant interaction between medical comorbidity and change scores was consistently found for all functional outcomes. This indicated an advantage of NAC over placebo in those with a clinical comorbidity.

Conclusion: Systemic illness moderated only the effect of NAC on functioning, not on depression. Demonstrating an improvement in functional outcomes with an agent that modulates redox and inflammatory pathways, this study lends empirical support to the idea that medical and psychiatric comorbidity are additive in contributing to allostatic states. One intriguing possibility is that comorbid clinical illness could be a marker for more severe oxidative stress states--and thus guide antioxidant use--in BD.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / metabolism
  • Acetylcysteine / pharmacology
  • Acetylcysteine / therapeutic use*
  • Adult
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / epidemiology*
  • Bipolar Disorder / metabolism
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / metabolism
  • Double-Blind Method
  • Endocrine System Diseases / drug therapy
  • Endocrine System Diseases / epidemiology
  • Endocrine System Diseases / metabolism
  • Female
  • Free Radical Scavengers / metabolism
  • Free Radical Scavengers / pharmacology
  • Free Radical Scavengers / therapeutic use*
  • Humans
  • Inflammation / drug therapy
  • Inflammation / epidemiology
  • Inflammation / metabolism
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology


  • Free Radical Scavengers
  • Acetylcysteine