Bipolar Disorder Therapy Response Possibly Impeded by Proinflammatory State

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An M1-like proinflammatory state is associated with a poor response to antidepressant treatment in bipolar depression with evidence suggesting increased production of cytokines in patients with mood disorders.

According to a recent study published in the Journal of Clinical Psychiatry, an M1-like proinflammatory state is associated with a poor response to antidepressant treatment in bipolar depression.1

Previous studies suggest that increased production of proinflammatory cytokines occurs in patients with mood disorders, and differing inflammatory response profiles are associated with resistance to different therapies.2 Francesco Benedetti, MD, and colleagues sought to evaluate the clinical relevance of raised levels of cytokines in bipolar disorder, specifically, to understand whether the immune system can be used as a determinant of treatment outcome.

The study evaluated 15 immune-regulating compounds at baseline in 37 consecutively admitted inpatients experiencing a major depressive episode with an underlying diagnosis of bipolar disorder, and in 24 controls. In total, 84% of patients had a lifetime history of drug resistance. Participants underwent 3 cycles of total sleep deprivation and light therapy because this combination can prompt a rapid response from antidepressants.

Twenty-three patients (62%) responded to treatment. Higher levels of 5 cytokines — interleukin-8, monocyte chemoattractant protein-1, interferon-γ, interleukin-6, and tumor necrosis factor-α — associated with a M1-like proinflammatory state were noted in nonresponders than in responders and significantly predicted therapy response to antidepressant chronotherapy for bipolar depression. Additionally, body mass index demonstrated a positive correlation with cytokines, which also hampered response.

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“This study suggests that stratification of patients with bipolar depression on the basis of immune signature could help to select a specific treatment-resistant subgroup that could benefit from the therapeutic targeting of the activated immune response system in everyday clinical practice,” concluded the researchers.


  1. Benedetti F, Poletti S, Hoogenboezem TA, et al. Higher baseline proinflammatory cytokines mark poor antidepressant response in bipolar disorder [published online September 12, 2017]. J Clin Psychiatry. doi: 10.4088/JCP.16m11310
  2. Anderson G, Maes M. Bipolar disorder: role of immune-inflammatory cytokines, oxidative and nitrosative stress and tryptophan catabolites. Curr Psychiatry Rep. 2015;17:8.