Treatment of Bipolar Depression With Pentoxifylline

Growing evidence has demonstrated that inflammation and alterations in cerebral blood flow (CBF) contribute to the pathophysiology of bipolar depression (BD). Pentoxifylline is a phosphodiesterase inhibitor that improves CBF and has potent anti-inflammatory and antioxidant effects. We therefore hypothesize that pentoxifylline may have antidepressant effects in BD. We will conduct an 8-week, open-label, single-armed, feasibility study assessing clinical and neurobiological effects of adjunctive pentoxifylline in the acute treatment of BD. Feasibility will be determined by evaluating recruitment/retention rates, target engagement (e.g., changes in biomarkers with pentoxifylline treatment) and preliminary efficacy testing with 6 participants. Evaluating pentoxifylline's effects may further our understanding of BD pathophysiology and help identify novel treatment targets.

Inclusion criteria

• Provide written, voluntary informed consent prior to study enrollment. Substitute decision makers will not be allowed to consent to study on a potential patients behalf.
• Male or female between the age of 18 to 65, inclusive.
• Meets DSM-5 criteria for Bipolar I or II Disorder, currently experiencing a Major Depressive Episode. Diagnosis will be confirmed using the Mini-International Neuropsychiatric Interview (MINI) conducted by a delegated physician or trained research study while assessing eligibility.
• Patient must present with a moderate to severe depressive episode, as determined by the MADRS score greater than 21.
• Patient must be receiving guideline-concordant pharmacotherapy without changes in the last month.

Exclusion criteria

• Currently exhibiting symptoms of mania, as determined by the Young Mania Rating Scale (YMRS) score greater than 11.
• Current symptoms of psychosis or perceptual disturbances of any kind per investigator discretion
• History of neurological disorders
• Presence of active suicidality, as determined by the MADRS suicidality item (Item #10) score greater than 4
• Presence of a contraindication to PTX, including a drug allergy or allergy to xanthine derivatives, low or labile blood pressure, acute myocardial infarction, cardiac arrhythmia, peptic ulcers, coronary artery disease or coagulation disorder.
• Renal impairment, assessed as creatinine clearance less than 80ml/min
• Abnormal liver function, assessed as ALT or AST ≥ 3 x ULN or bilirubin ≥ 2 x ULN
• Severe myocardial infarction
• Patients with standard contraindications to magnetic resonance imaging (MRI), such as non-MRI compatible implanted metallic devices
• Patients with a history of cerebrovascular disease or history of intercranial hemorrhage.
• Laboratory biochemical evidence of abnormal bleeding and/or coagulopathy
• Pregnant or breastfeeding women. Patients who are sexually active must agree to use a highly effective contraceptive method
• Use of prohibited concomitant medications