Bipolar disorder (BD) is a severe, chronic affective disorder, associated with significant disability, morbidity and premature mortality. Omega-3 polyunsaturated fatty acids (PUFAs) play several important roles in brain development and functioning. Evidence from animal models of dietary omega-3 (n-3) PUFA deficiency suggest that these fatty acids are relevant to promote brain development and to regulate behavioral and neurochemical aspects related to mood disorders, such as stress responses, depression and aggression, as well as dopaminergic content and function. Preclinical and clinical evidence suggests roles for PUFAs in BD. n-3 PUFAs seem to be an effective adjunctive treatment for unipolar and bipolar depression, but further large-scale, well-controlled trials are needed to examine its clinical utility in BD.
The literature shows that ω-3 fatty acids provide numerous health benefits and that changes in their concentration in organisms are connected to a variety of psychiatric symptoms and disorders, including stress, anxiety, cognitive impairment, mood disorders, and schizophrenia. Further studies are necessary to confirm ω-3 fatty acids’ supplementation as a potential rational treatment in psychiatric disorders.
Evidence is accumulating to support the presence of redox dysregulation in a number of psychiatric disorders, including bipolar disorder. This dysregulation may be amenable to therapeutic intervention. Glutathione is the predominant non-enzymatic intracellular free radical scavenger in the brain, and the most generic of all endogenous antioxidants in terms of action. N-acetylcysteine (NAC) is a glutathione precursor that effectively replenishes brain glutathione. Given the failure of almost all modern trials of antidepressants in bipolar disorder to demonstrate efficacy, and the limited efficacy of mood stabilisers in the depressive phase of the disorder, this is a major unmet need.
This study reports data on the treatment of 149 individuals with moderate depression during the 2month open label phase of a randomised placebo controlled clinical trial of the efficacy of 1g BID of NAC that examined the use of NAC as a maintenance treatment for bipolar disorder.
In this trial, the estimated mean baseline Bipolar Depression Rating Scale (BDRS) score was 19.7 (SE=0.8), and the mean BDRS score at the end of the 8week open label treatment phase was 11.1 (SE=0.8). This reduction was statistically significant (p<0.001). Improvements in functioning and quality of life were similarly evident. CONCLUSION: These open label data demonstrate a robust decrement in depression scores with NAC treatment. Large placebo controlled trials of acute bipolar depression are warranted.
Whereas the mechanisms of NAC are only beginning to be understood, it is likely that NAC is exerting benefits beyond being a precursor to the antioxidant, glutathione, modulating glutamatergic, neurotropic and inflammatory pathways. This review outlines the current literature regarding the use of NAC in disorders including addiction, compulsive and grooming disorders, schizophrenia and bipolar disorder. N-acetylcysteine has shown promising results in populations with these disorders, including those in whom treatment efficacy has previously been limited. The therapeutic potential of this acetylated amino acid is beginning to emerge in the field of psychiatric research.
This meta-analysis demonstrates an association between the MTHFR C677T variant and depression, schizophrenia, and bipolar disorder, raising the possibility of the use of folate in treatment and prevention.