Bipolar disorder can be highly debilitating, as sub-optimal recovery is often seen in individuals experiencing bipolar depression. The current series of investigations aimed to explore factors that may improve outcomes for participants with bipolar depression. Diet, body composition, physical activity and interpersonal relationships were explored in sub-analyses as potential mediators and effect modifiers of depression, functioning and quality of life outcomes from an adjunctive randomised controlled trial (MITO-NAC).
The MITO-NAC study explored the efficacy of N-acetylcysteine (NAC) alone and NAC in combination with other nutraceuticals compared to placebo in a 16-week, three-armed, randomised controlled trial for the treatment of bipolar depression. A follow-up visit was also conducted at Week 20. Generalised estimating equations were used to assess whether diet, body composition, physical activity and interpersonal relationships were mediators or moderators of outcomes in the study.
The relationship between NAC, combination treatment or placebo received in the study and depression scores (MADRS and BDRS) were not mediated by Australian Recommended Food Score, inflammatory potential of diet or BMI. Higher Australian Recommended Food Score was associated with reduced depression symptoms (MADRS: χ2(1) = 7.2, p = 0.01 and BDRS: χ2(1) = 4.7, p = 0.03) and greater CGI-I (χ2(1) = 5.7, p = 0.02) irrespective of treatment and time. A more anti-inflammatory diet pattern was associated with less impairment in functioning (SOFAS: χ2(1) = 7.3, p = 0.01; LIFE-RIFT: χ2(1) = 6.9, p = 0.01). This relationship may be attenuated by the combination treatment reducing the adverse effects of pro-inflammatory diet on LIFE-RIFT scores (χ2(1) = 4.6, p = 0.03). Participants showed greater improvement on CGI-I when they had lower BMI and received the combination treatment (χ2(1) = 5.4, p = 0.02) or N-acetylcysteine (χ2(1) = 5.4, p = 0.02), compared to placebo.
Physical activity was not associated with changes in MADRS scores. There was a greater reduction in BDRS scores for participants who received the combination treatment and had a higher continuous IPAQ-SF score (χ2(1) = 4.9, p = 0.03), or exceeded World Health Organisation recommendations (χ2 (1) = 4.8, p = 0.03). However, there was a worsening of BDRS scores for participants who received NAC and were in the High category of the IPAQ-SF scoring guide (χ2 (1) = 3.9, p = 0.047).
Participants’ interpersonal relationships did not mediate the relationship between trial outcomes and treatment arm. However, irrespective of treatment allocation, there was a significant association between changes in scores across the study for interpersonal relationships and depression (MADRS: c2(1) = 6.4, p = 0.01; BDRS c2(1) = 6.8), functioning (SOFAS: c2 (1) = 11.1, p = 0.001 and LIFE-RIFT: c2 (1) = 5.5, p = 0.02) and quality of life measures (c2 (1) = 5.5, p = 0.02).
These studies explored the potential for easily accessible and safe lifestyle-related treatments and nutraceuticals to address the shortfall in recovery for individuals with bipolar depression. Cautious interpretation of the outcomes presented is required due to the exploratory nature of the statistical analyses given they are conducted as secondary outcomes from the primary clinical trial. However, recommendations can be made for research trials to control for lifestyle factors and for clinicians to be assessing these outcomes in an aim to engage in personalised medicine.