Aspirin, N-Acetylcysteine Effective Adjunctive Treatments in Bipolar Depression

Aspirin tablets spilling out of bottle.
Aspirin tablets spilling out of bottle.
Investigators examine the therapeutic effects of NSAIDs and NAC in patients with bipolar disorder.

The co-administration of N-acetylcysteine (NAC) and aspirin in patients with bipolar disorder may reduce depressive symptoms, according to study data published in The Journal of Clinical Psychiatry.

The study cohort comprised 24 medicated patients with bipolar disorder recruited from the outpatient clinic of the University of Texas Health Science Center at Houston. Patients were between age 18 and 65 and had a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥20. Patients were randomly assigned to one of four study treatment regimens: (1) aspirin (1000 mg/d), (2) NAC (1000 mg/d), (3) combined aspirin and NAC (1000 mg/d each), or (4) placebo. Treatment response was characterized as a ≥50% reduction in MADRS score. At baseline and at 8- and 16-week follow-up visits, patients completed mood and global functioning questionnaires. Participants also underwent blood tests prior to and following 8 and 16 weeks of treatment. Investigators calculated the probability of treatment response for each study condition via a Bayesian analytic model.

Following 8 weeks of treatment, similar probability for successful treatment response was observed in individuals receiving NAC and aspirin (67%) and individuals receiving placebo (70%). Following 16 weeks of treatment, however, the co-administration of NAC and aspirin was associated with a higher probability of treatment response (67%) compared with placebo (55%), NAC (57%), and aspirin (33%). No treatment effect on interleukin-6 and C-reactive protein levels was observed at any time point. Further, correlations between baseline MADRS scores and inflammatory markers were not statistically significant. Adverse effects were minimal in all treatment groups.

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These data support the use of anti-inflammatory and antioxidant agents in the treatment of bipolar depression. Further research is necessary to elucidate the precise mechanism by which these medications may alleviate depressive symptoms.


Bauer IE, Green C, Colpo GD, et al. A double-blind, randomized, placebo-controlled study of aspirin and N-acetylcystein as adjunctive treatments for bipolar depression. J Clin Psychiatry. 2019;80(1):18m12200.