The Phosphodiesterase 5 Inhibitor Sildenafil as an Adjunct to Antidepressants in Major Depressive Disorder Patients

The Phosphodiesterase 5 Inhibitor Sildenafil as an Adjunct to Antidepressants in Major Depressive Disorder Patients: Randomized, Double-Blind, Placebo-Controlled Trial

Antidepressant-like effects of sildenafil to its ability to modulate transduction pathways responsible for neuroplasticity. Treatment with sildenafil was shown to be PKG-dependent and lead to increased expression of cGMP, pCREB, BDNF and VGF in the hippocampus and prefrontal cortex (PFC), brain areas relevant to mood disorders pathophysiology. Sildenafil produces antidepressant-like effects by inhibiting oxidative stress in the hippocampus and by decreasing the levels of IL-1β in the hippocampus and striatum.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo oral tablet; Drug: Sildenafil Citrate

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mahmoud Abdallah; Phone Number: 00201063340887; Email: Mahmoud.samy@fop.usc.edu.eg

Study Locations

• Egypt
  • Shibīn Al Kawm, Egypt
    • Recruiting
    • Faculty of medicine
    • Contact: Mahmoud Abdallah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (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
• Cardiovascular disorders
• Severe renal impairment: creatinine clearance of ≤ 25 ml/min
• Moderate or severe hepatic impairment

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
Placebo Comparator: Control group; Escitalopram 20 mg tablet plus one placebo tablet	Drug: Placebo oral tablet; Esitalopram 20 mg tablet plus placebo tablet once daily
Experimental: Sildenafil group; Escitalopram 20 mg tablet plus one Sildenafil 50 mg tablet	Drug: Sildenafil Citrate; Esitalopram 20 mg tablet plus Sildenafil Citrate 50 mg tablet once daily

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), and brain derived neurotrophic factor (BDNF) were measured at the baseline and after the treatment to evaluate the biological effects of the used medications.	12 week

Collaborators and Investigators

• Sponsor: Sadat City University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): October 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: April 9, 2020
• First Submitted That Met QC Criteria: April 9, 2020
• First Posted (Actual): April 14, 2020

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 16, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: 0044/2020

Drug and device information, study documents

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