Pentoxifylline as an Adjunct to Citalopram in Adult Patients With Major Depressive Disorder

Study Overview
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Brief Summary
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The aim of this study is to test if combining the antidepressant Citalopram with Pentoxifylline (PTX), a medicine with anti-inflammatory and phosphodiesterase inhibitory properties, enhanced antidepressant efficacy in adult patients with major depressive disorder (MDD) when compared to Citalopram alone.

Detailed Description
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According to mounting evidence, inflammation and phosphodiesterase (PDE) pathways may play a role in the pathogenesis of psychiatric diseases such as MDD. PTX is a phosphodiesterase inhibitor and has anti-inflammatory and antioxidant effects. Therefore, it has been hypothesized that MDD patients taking combined administration of the Citalopram, a Selective Serotonin Reuptake Inhibitor (SSRI), and PTX would show a higher improvement in depression symptoms. The relationship between the Hamilton Depression Rating Scale-17 items (Ham-D-17) score and various biological markers and their potential role in the therapeutic outcome of MDD will be assessed.

Official Title
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Pentoxifylline as an Adjunct to Citalopram in Adult Patients With Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Citalopram (tablet) 20 mg + Pentoxifylline (tablet) 400Mg
* Drug: Citalopram (tablet) 20 mg + Placebo (tablet)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written, voluntary informed consent prior to study enrollment. Male or female between the ages of 21 to 65. Patient must be diagnosed with a moderate to a severe depressive episode, as determined by the MADRS score >21. Prior to taking part in the trial, all patients were requested to abstain from all psychotropic and anti-inflammatory medications for at least four weeks. Exclusion Criteria: Current psychotic symptoms or perceptual problems of any kind, at the discretion of the investigator The presence of a contraindication to PTX, such as a drug allergy or xanthine derivative allergy The presence of cardiovascular diseases, including high blood pressure, a recent myocardial infarction, cardiac arrhythmia, coronary artery disease, or a coagulation disorder Renal impairment, defined as creatinine clearance less than 80ml/min Patients who have previously received electroconvulsive therapy (ECT) Patients who have inflammatory disorders Patients with a concurrent active medical condition Patients with a history of seizures Patients who are pregnant or nursing females. Patients with bipolar I or bipolar II disorder Patients with personality disorders Patients with eating disorders Patients with substance dependence or abuse

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Citalopram + Pentoxifylline group<br>Citalopram (tablet): 20 mg once a day for 12 weeks + Pentoxifylline (tablet): 400 mg twice a day for 12 weeks | Drug: Citalopram (tablet) 20 mg + Pentoxifylline (tablet) 400Mg<br>* Selective serotonin reuptake inhibitor (SSRI) + phosphodiesterase inhibitor with anti-inflammatory properties<br>|
| Placebo Comparator: Control group<br>Citalopram (tablet): 20 mg once a day for 12 weeks + placebo (tablet) twice a day for 12 weeks | Drug: Citalopram (tablet) 20 mg + Placebo (tablet)<br>* Selective serotonin reuptake inhibitor (SSRI) + placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale 17 (HDRS-17) Scores (Time Frame: Baseline, week 2,4,6,8,10, and12) | The HDRS is a 17-item scale that asks participants to rate the severity of their depression symptoms. Scoring is based on the 17-item scale. The total score ranges from 0 to 52, with higher numbers demonstrating more severe symptoms. Normal scores range from 0 to 7, mild depression ranges from 8 to 16, moderate depression ranges from 17 to 23, and scores of 24 and greater indicate severe depression. Remission is defined as HDRS total score ≤ 7 (primary outcome). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on the serum level of tumor necrosis factor-alpha (TNF-α) | Peripheral blood samples will be obtained and serum levels of TNF-α ( pg/mL) will be measured at baseline and after treatment (week 12) | 12 weeks | 
| Effect on the serum level of circulating C-reactive protein (CRP) | Peripheral blood samples will be obtained and serum levels of CRP (mg/dL) will be measured at baseline and after treatment (week 12) | 12 weeks | 
| Effect on the serum level of interleukin 6 (IL-6) | Peripheral blood samples will be obtained and serum levels of IL-6 (pg/mL) will be measured at baseline and after treatment (week 12) | 12 weeks | 
| Effect on the serum level of interleukin-1-β (IL-1-β) | Peripheral blood samples will be obtained and serum levels of IL-1-β (pg/mL) will be measured at baseline and after treatment (week 12) | 12 weeks | 
| Effect on the serum level of interleukin-10 (IL-10) | Peripheral blood samples will be obtained and serum levels of IL-10 (pg/mL) will be measured at baseline and after treatment (week 12) | 12 weeks | 
| Effect on the serum level of brain derived neurotrophic factor (BDNF) | Peripheral blood samples will be obtained and serum levels of BDNF (ng/mL) will be measured at baseline and after treatment (week 12) | 12 weeks | 
| Effect on the serum level of serotonin | Peripheral blood samples will be obtained and serum levels of serotonin (ng/mL) will be measured at baseline and after treatment (week 12) | 12 weeks |