Efficacy of pentoxifylline for the treatment of bipolar I/II patients with treatment-resistant depression: A proof-of-concept, randomized, double-blind, placebo-controlled trial.

Background: Immune dysregulation can play a role in depression pathophysiology, and immunological antagonists can improve depressive symptoms in treatment-resistant bipolar depression (TRD) patients according to studies.

Objective: To evaluate the anti-depressant effects of the anti-inflammatory drug, pentoxifylline (PTX) in TRD bipolar I/II adult subjects.

Methods: This 12-week, randomized, double-blind, placebo-controlled, parallel-group trial of 60 participants was conducted at Hawler Psychiatric Hospital and Private Clinic in Erbil, Iraq. Participants were confirmed as being qualified for bipolar I/II depression based on DSM-5 criteria. Data were analyzed using modified intent-to-treat analysis.

Results: There were no significant differences between the two groups in Hamilton Rating Scale for Depression-17 (HAM-D-17) scores (χ=1.9, P =.48) or a significant time × treatment interaction (χ=7.1, P=.54). Nevertheless, a significant effect of time was observed with both groups' reduction in HAM-D-17 scores from the start to the endpoint (χ= 2.11, P=.002). Besides, a significant time × treatment × CRP interaction was found (χ=3.1, P=0.016), where there was more reduction in HAM-D-17 score in PTX-treated subjects with CRP> 7.1 mg/L. The response rate difference between PTX and the placebo group did not reach a significance level (χ=0.84, p=0.43). Furthermore, serum concentrations of TNF-α, CRP, and IL-6 significantly reduced at week 12 in the PTX group (P=.007,.04, and <.001, respectively).

Conclusion: The current proof of concept study found that in terms of overall anti-depressant effectiveness in bipolar patients with TRD, PTX is not superior to placebo. However, it may improve depressive mood in a subpopulation of subjects with a higher pretreatment inflammatory profile.