Role of Pentoxifylline as an Adjuvant Therapy for Adult Patients With Major Depressive Disorder

Pentoxifylline as a New Adjuvant in Adult Patients With Major Depressive Disorder: Randomized, Double Blind, Placebo Controlled Trial.

This study aimed to evaluate the therapeutic benefits of pentoxifylline (PTX) in treatment of adult patients with MDD as it has anti-inflammatory and phosphodiastrase inhibition activities.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Escitalopram 20 mg tablet plus Pentoxifylline 400Mg Tablet; Drug: Escitalopram 20 mg tablet + Placebo

Detailed Description

In this study, the investigators evaluated the potential antidepressant effect of PTX in adult patients with MDD. the investigators hypothesized that MDD patients taking add-on PTX would present greater amelioration of their depressive symptoms than patients taking add-on placebo. Furthermore, the investigators assessed the relationship between HAM-D score and several peripheral biomarkers as well as their role in diagnosis and therapeutic targets of MDD.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eighty adult outpatients with the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of MDD based on a MINI Neuropsychiatric Interview (MINI) (American Psychiatric Association., 2000; Sheehan et al., 1998), without psychotic features and a total 17 item HAM-D score of at least 18 with item 1 (depressed mood) scored 2 or greater were eligible (Hamilton, 1960).
• Patients were requested to be free of all the psychotropic and anti-inflammatory medications for at least 4 weeks before participating in the study.

Exclusion Criteria:

• Patients with bipolar I or bipolar II disorder
• Patients with personality disorders
• Patients with eating disorders
• Patients with substance dependence or abuse
• Patients with concurrent active medical condition
• Patients with history of seizures
• Patients with history of receiving Electroconvulsive therapy (ECT)
• Patients with inflammatory disorders
• Patients with allergy or contraindications to the used medications
• Patients with finally pregnant or lactating females

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: Pentoxifylline group; Escitalopram 20 mg tablet once daily for 12 week plus Pentoxifylline 400 mg tablet twice daily for 12 weeks	Drug: Escitalopram 20 mg tablet plus Pentoxifylline 400Mg Tablet; Selective serotonin reuptake inhibitor plus phosphodiesterase inhibitor with anti-inflammatory properties
Placebo Comparator: Control group; Escitalopram 20 mg tablet once daily for 12 week plus placebo tablet twice daily for 12 weeks	Drug: Escitalopram 20 mg tablet + Placebo; Selective serotonin reuptake inhibitor plus placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on Hamilton Depression rating scale score (HAM-D score)	The principal measure of the outcome was the 17-items HAM-D. Scoring is based on the 17-item scale and scores of 0-7 are considered as being normal, 8-13 suggest mild depression, 14-17 moderate depression and scores over 17 are indicative of severe depression. Remission is defined as HAM-D total score ≤ 7 (primary outcome). Treatment response is defined as ≥ 50% drop in the HAM-D total score.	12 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on biological markers	Serum level of tumor necrosis factor alpha (TNF-α), Interleukin-6 (IL-6), Interleukin-10 (IL-10), brain derived neurotrophic factor (BDNF), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and serotonin were measured at the baseline and after the treatment to evaluate the biological effects of the used medications.	12 week

Collaborators and Investigators

• Sponsor: Mahmoud Samy Abdallah
• Investigators: Study Director: Sahar El-Haggar, Ph.D, Faculty of Pharmacy, Tanta University

Publications and helpful links

Helpful Links

• The Phosphodiesterase Inhibitor Pentoxifylline as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: May 31, 2018
• First Submitted That Met QC Criteria: May 31, 2018
• First Posted (Actual): June 13, 2018

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 13, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: MDD; Anti-inflammatory; Pentoxifylline; phosphodiastrase inhibitors
• 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: 0074/2015

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No