Effects of the anti-inflammatory pentoxifylline on psychiatric and neuropsychiatric conditions: exploring various off-label utilities with meta-analyses.

Background: Chronic inflammation has been linked to many psychiatric disorders, and therefore, pertinent anti-inflammatory therapies have been empirically evaluated for management. An enduring example of long-term safety, attainability, and versatility has been pentoxifylline (PTX). PTX is a phosphodiesterase inhibitor that modulates inflammatory mediators and affects most blood components and the blood vessels.

Methods: Major databases were systematically searched to identify randomized controlled trials (RCTs) on PTX in psychiatric and neuropsychiatric disorders until September 25, 2024.

Results: 21 RCTs were included. Five studies evaluated clinical depression: four on major depressive disorder (MDD) and one on bipolar patients experiencing treatment-resistant depression. PTX significantly reduced depressive symptoms in MDD in the four double-blind, randomized, placebo-controlled trials, with the three studies combining PTX and SSRIs showing statistically significant improvements in response rates. Ten RCTs on cognitive impairment reported beneficial effects, particularly in vascular dementia. Meta-analyses support its efficacy in reducing depressive symptoms, cognitive decline, asthenia, and inflammatory markers.

Conclusion: Exploring the effects of PTX on psychiatric and neuropsychiatric conditions has provided considerable support for its utility across various disorders, most notably in moderate to severe major depressive disorder (as adjunctive therapy with SSRIs) and cognitive impairment in vascular dementia (as monotherapy). Relevantly, the potential of PTX across a wide range of conditions might prove beneficial in cases of co-occurrence.