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

Siegel, Ashley; Rodrigues, Nelson B.; Nasri, Flora; Wilkialis, Linas; Lipsitz, Orly; Lee, Yena; Gill, Hartej; Subramaniapillai, Mehala; Phan, Lee; Majeed, Amna; Lui, Leanna M.W.; Rashidian, Houman; Ho, Roger; Toma, Simina; Goldstein, Benjamin I.; Mansur, Rodrigo B.; McIntyre, Roger S.; Rosenblat, Joshua D.

doi:10.1016/j.pnpbp.2020.110032

Cited by 7 publications

(2 citation statements)

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“…A significant negative correlation between BDNF and depression scores in MDD patients was observed, which is well documented, and it is thought that it plays an important role in controlling depressive symptoms (i. e., suicidal thoughts) 28 48 . Mechanistically, BDNF can exert its action by protecting against stress-induced neuronal damage and improving neurogenesis in the hippocampus, which provides a potential explanation for the observed antidepressant effect of PTX 49 . PTX inhibits PDEs, which in turn increases the cAMP level, which may raise the BDNF level as a downstream element 50 .…”

Section: Discussionmentioning

confidence: 99%

Pentoxifylline as a Novel Add-on Therapy for Major Depressive Disorder in Adult Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

Merza Mohammad,

Salman

et al. 2024

Pharmacopsychiatry

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Background Evidence indicates an association between immune dysregulation and major depressive disorder (MDD). Pentoxifylline (PTX), a phosphodiesterase inhibitor, has been shown to reduce pro-inflammatory activities. The aim of this study was to evaluate changes in depressive symptoms and pro-inflammatory markers after administration of PTX as an adjunctive agent to citalopram in patients with MDD. Methods One hundred patients were randomly assigned to either citalopram (20 mg/day) plus placebo (twice daily) (n=50) or citalopram (20 mg/day) plus PTX (400 mg) (twice daily) (n=50). The Hamilton Depression Rating Scale-17 (HAM-D-17) scores at baseline, weeks 2, 4, 6, 8, 10, and 12 and serum levels of interleukin1-β (IL-1-β), tumor necrosis factor-α, C-reactive protein, IL-6, serotonin, IL-10, and brain-derived neurotrophic factor (BDNF) at baseline and week 12 were evaluated. Results HAM-D-17 score in the PTX group significantly reduced in comparison to the control group after weeks 4, 6, 8,10, and 12 ((LSMD): − 2.193, p=0.021; − 2.597, p=0.036; − 2.916, p=0.019; − 4.336, p=0.005; and − 4.087, p=0.008, respectively). Patients who received PTX had a better response (83%) and remission rate (79%) compared to the placebo group (49% and 40%, p=0.006 and p=0.01, respectively). Moreover, the reduction in serum concentrations of pro-inflammatory factors and increase in serotonin and BDNF in the PTX group was significantly greater than in the placebo group (p<0.001). Conclusion These findings support the safety and efficacy of PTX as an adjunctive antidepressant agent with anti-inflammatory effects in patients with MDD.

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Section: Discussionmentioning

confidence: 99%

Pentoxifylline as a Novel Add-on Therapy for Major Depressive Disorder in Adult Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

Merza Mohammad,

Salman

et al. 2024

Pharmacopsychiatry

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“…In a study, Siegel et al (2021) reviewed the effects of Pentoxifylline on mood disorders. They found that it has antioxidant, anti-inflammatory, neuron growth stimulating, and anti-depressant effects (Siegel et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Pentoxifylline as adjunctive therapy in cognitive deficits and symptoms of schizophrenia: A randomized double-blind placebo-controlled clinical trial

Sinichi,

Farid Hosseini,

Fayyazi-Bordbar

et al. 2023

J Psychopharmacol

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Background: Due to the inflammatory factors in the pathophysiology of schizophrenia, Pentoxifylline, as anti-inflammatory medication, seems to improve the symptoms of schizophrenia. This study aims to evaluate the efficacy of Pentoxifylline as an adjunctive therapy on cognitive deficits and symptoms of schizophrenia. Methods: This randomized double-blind placebo-controlled clinical trial was conducted on 52 patients diagnosed with chronic schizophrenia. All patients were divided into two, treatment and control groups. They received a 400 mg dose of Pentoxifylline and the placebo in the treatment and control groups, respectively, twice a day for 8 weeks. Then, they were tested with the Positive and Negative Syndrome Scale (PANSS), Wisconsin Card Sorting Test (WCST), digit span, Stroop test, and Rey Auditory and Verbal Learning Test at baseline and the end of the weeks 4 and 8. Data analysis was done by Kolmogorov–Smirnov test, t-test, Mann–Whitney test, chi-square test, and generalized estimating equation model. Results: After analyzing the data, it was revealed that the positive symptoms of PANSS, the number of errors in the incongruent Stroop test, and reaction time in the congruent Stroop test were significantly lower in the treatment group ( p < 0.05). Moreover, the number of categories of WCST was significantly higher in the treatment group ( p < 0.05). There was no statistically significant difference in other parameters between the control and treatment groups ( p > 0.05). Conclusions: As evidenced by the results of this study, Pentoxifylline can help alleviate schizophrenia cognitive deficits and can reduce psychotic symptoms. Therefore, it can potentially be useful for schizophrenia treatment.

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Novel Antidepressant Approaches for Refractory Depression

Postorivo

Tye

2021

Curr Treat Options Psych

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

Cited by 7 publications

References 100 publications

Pentoxifylline as a Novel Add-on Therapy for Major Depressive Disorder in Adult Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

Pentoxifylline as a Novel Add-on Therapy for Major Depressive Disorder in Adult Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

Pentoxifylline as adjunctive therapy in cognitive deficits and symptoms of schizophrenia: A randomized double-blind placebo-controlled clinical trial

Novel Antidepressant Approaches for Refractory Depression

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