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

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Citalopram (tablet) 20 mg + Pentoxifylline (tablet) 400Mg; Drug: Citalopram (tablet) 20 mg + Placebo (tablet)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Iraq
  • Erbil, Iraq, 44001
    • Hawler Psychiatric Hospital and Private Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Citalopram + Pentoxifylline group; 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; Selective serotonin reuptake inhibitor (SSRI) + phosphodiesterase inhibitor with anti-inflammatory properties
Placebo Comparator: Control group; 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); Selective serotonin reuptake inhibitor (SSRI) + placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hawler Medical University
• Investigators: Principal Investigator: Talar A Merzamohammad, Pharm. D, Hawler Medical University, College of Pharmacy, Department of Pharmacology and Toxicology

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2021
• Primary Completion (Actual): February 25, 2022
• Study Completion (Actual): June 8, 2022

Study Registration Dates

• First Submitted: February 23, 2022
• First Submitted That Met QC Criteria: March 5, 2022
• First Posted (Actual): March 8, 2022

Study Record Updates

• Last Update Posted (Actual): September 7, 2022
• Last Update Submitted That Met QC Criteria: September 5, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Citalopram; Dexetimide; Pentoxifylline
• Other Study ID Numbers: HMU PE-EC 16112021/382

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No