A Double-Blind, Randomized, Placebo-Controlled Study of Aspirin and N-Acetylcysteine as Adjunctive Treatments for Bipolar Depression.

OBJECTIVE: Neuroinflammation has been implicated in the pathophysiology of bipolar disorder. Some evidence shows that nonsteroidal anti-inflammatory drugs (NSAIDs) have promising antidepressant effects. The antioxidant N-acetylcysteine (NAC) may enhance the effects of NSAIDs. No study has, however, tested the adjunctive therapeutic benefits of an NSAID and NAC in bipolar disorder. METHODS: The sample included 24 medicated patients diagnosed with DSM-IV-TR bipolar disorder who were aged 18-65 years and had a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 20. Participants were randomly assigned to receive either aspirin (1,000 mg), NAC (1,000 mg), combined aspirin and NAC (1,000 mg each), or placebo. Data were collected between 2013 and 2017. The primary outcome was a ≥ 50% reduction in MADRS scores. Participants completed mood and global functioning questionnaires. They also underwent blood tests prior to and following 8 and 16 weeks of treatment. A Bayesian analytic method was adopted, and posterior probability distributions were calculated to determine the probability of treatment response. RESULTS: Following the first 8-week treatment phase, individuals on treatment with placebo and NAC + aspirin had a similar probability for successful treatment response (about 70%). Following a 16-week treatment period, NAC + aspirin was associated with higher probability of treatment response (67%) compared to placebo (55%), NAC (57%), and aspirin (33%). There was no treatment effect on interleukin-6 and C-reactive protein levels at either 8 or 16 weeks. CONCLUSIONS: The coadministration of NAC and aspirin during a period of 16 weeks was associated with a reduction in depressive symptoms. The adverse effects were minimal. These preliminary findings may serve as a starting point for future studies assessing the efficacy, tolerability, and safety of anti-inflammatory and antioxidant agents in the treatment of bipolar depression. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01797575.

A systematic review of randomised control trials on the effects of yoga on stress measures and mood.

Stress related disorders such as depression and anxiety are leading sources of disability worldwide, and current treatment methods such as conventional antidepressant medications are not beneficial for all individuals. There is evidence that yoga has mood-enhancing properties possibly related to its inhibitory effects on physiological stress and inflammation, which are frequently associated with affective disorders. However the biological mechanisms via which yoga exerts its therapeutic mood-modulating effects are largely unknown. This systematic review investigates the effects of yoga on sympathetic nervous system and hypothalamic pituitary adrenal axis regulation measures. It focuses on studies collecting physiological parameters such as blood pressure, heart rate, cortisol, peripheral cytokine expression and/or structural and functional brain measures in regions involved in stress and mood regulation. Overall the 25 randomised control studies discussed provide preliminary evidence to suggest that yoga practice leads to better regulation of the sympathetic nervous system and hypothalamic-pituitary-adrenal system, as well as a decrease in depressive and anxious symptoms in a range of populations. Further research is warranted to confirm these preliminary findings and facilitate implementation in clinical settings.