Pentoxifylline for Treatment of Resistant Major Depression
Condition: Resistant Major Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      A growing body of evidence has highlighted the role of inflammation and phosphodiesterases
      (PDE)-related pathways in the pathogenesis of neuropsychiatric illnesses such as
      depression/mood disorders. Herein, we aimed to evaluate the therapeutic benefits of
      pentoxifylline (PTX) in the treatment of therapy-resistant depression (TRD) in adult patients
      with bipolar depression.
    

Detailed description: 
      Depression, which affects an estimated 300 million people worldwide, is the main cause of
      mental health-related illness burden. Depression keeps people from attaining their full
      potential, depletes human capital, and is linked to suicide and other forms of mortality.
      Despite the fact that depressive disorders have a better prognosis than primary psychotic
      illnesses like schizophrenia, 20%-40% of patients treated with antidepressants do not respond
      to their initial treatment regimens, and up to 15% do not respond to multiple antidepressant
      regimens and modalities, such as electroconvulsive shock (ECT) therapy. Since the treatment
      resistance has been shown to increase the likelihood of full symptomatic recurrence, worsen
      the treatment course and quality of life; therefore, there is a critical need for innovative
      treatment techniques for patients who have failed to respond to traditional treatments.
      Inflammation is one factor that has gotten a lot of attention lately as an etiologic
      mechanism of treatment-resistant depression (TRD). Increased levels of (pro) inflammatory
      markers such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, and IL-6 are
      reported in a considerable percentage of patients with major depressive disorders with or
      without other comorbidities, including bipolar depression and TRD patients. Also, clinical
      factors connected to antidepressant response are linked to the reduction of inflammatory
      cytokines.

      Moreover, cytokine antagonists, such as the chimeric anti-TNF-alpha antibody infliximab, has
      shown antidepressant efficacy. Hence, given the elevated levels of inflammatory activity in
      TRD patients, new treatments with anti-inflammatory effect might be an effective approach to
      treat these patients. Pentoxifylline (PTX) is a methylated xanthine derivative that has been
      used to treat peripheral vascular disease for more than two decades. PTX has
      anti-inflammatory and phosphodiesterase (PDE) inhibitory effects that enables it to inhibit
      PDEs competitively. Subsequently, it can increase cAMP levels, activate protein kinase A
      (PKA), inhibit ILs and TNF-α production, and reduce inflammation. Therefore, PTX-decreased
      inflammatory activity, may give rapid symptomatic alleviation for medically healthy
      individuals with TRD depression.
    

Intervention name(s): Pentoxifylline; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): All participants will receive pentoxifylline 400 mg (orally ingested) twice a day for 12 weeks.; All participants will receive placebo (orally ingested) twice a day for 12 weeks.
Other intervention name(s): Trental; Sugar Pills
Intervention MeSH terms: Pentoxifylline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Bipolar Depression; Pentoxifylline; Resistant Major Depression