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Novel therapeutic targets in mood disorders: Pentoxifylline (PTX) as a candidate treatment.

Abstract：

:Numerous pharmacological treatments for mood disorders are currently available; however, rates of treatment resistance, relapse and recurrence remain high. Therefore, novel treatments acting outside of the conventionally targeted monoamine system are urgently needed to improve patient outcomes. Emerging and converging evidence suggests that immune dysfunction, oxidative stress, impaired cerebral blood flow (CBF) and decreased neurotrophic factors all contribute to mood disorder pathophysiology and are therefore treatment targets of interest. Pentoxifylline (PTX) is a phosphodiesterase inhibitor with potent anti-inflammatory and antioxidant effects, with additional pleiotropic effects that lead to improved CBF and increases in brain derived neurotrophic factor (BDNF) levels. The direct effect of non-specific phosphodiesterase inhibition may also improve alertness and cognitive function through enhancing second messenger systems. Replicated preclinical studies have demonstrated antidepressant-like effects in animal models. Small preliminary clinical trials have demonstrated promising results for antidepressant and procognitive effects, however, have yet to be replicated in larger mood disorder samples. Only one randomized clinical trial (RCT) specifically assessed the effects of adjunctive PTX in major depressive disorder (MDD), showing clinically and statistically significant antidepressant effects compared to placebo. No studies have assessed PTX in bipolar disorder (BD), where inflammation and altered CBF have also been strongly implicated. Taken together, PTX presents as a promising pleiotropic agent with several potential novel mechanisms of action meriting further evaluation in clinical trials to evaluate target engagement, antidepressant, procognitive and mood stabilizing effects.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Siegel AN,Rodrigues N,Nasri F,Wilkialis L,Lipsitz O,Lee Y,Gill H,Subramaniapillai M,Phan L,Majeed A,Lui LMW,Rashidian H,Ho R,Toma S,Goldstein BI,Mansur RB,McIntyre RS,Rosenblat JD

doi

10.1016/j.pnpbp.2020.110032

subject

Has Abstract

pub_date

2021-01-10 00:00:00

pages

110032

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(20)30348-1

journal_volume

104

pub_type

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Novel therapeutic targets in mood disorders: Pentoxifylline (PTX) as a candidate treatment.