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

NCT04344678 | Withdrawn DMC

• 1 other identifier: 0044/2020
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Effect on biological markers

  12 week

Study Arms (2)

Control group

PLACEBO COMPARATOR

Escitalopram 20 mg tablet plus one placebo tablet

Drug: Placebo oral tablet

Sildenafil group

EXPERIMENTAL

Escitalopram 20 mg tablet plus one Sildenafil 50 mg tablet

Drug: Sildenafil Citrate

Interventions

Sildenafil Citrate DRUG

Esitalopram 20 mg tablet plus Sildenafil Citrate 50 mg tablet once daily

Sildenafil group

Placebo oral tablet DRUG

Esitalopram 20 mg tablet plus placebo tablet once daily

Control group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sadat City University: lead

Study Sites (1)

Faculty of Medicine

Shibīn al Kawm, Egypt

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Clinical Pharmacy, PhD.

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: April 14, 2020
• Study Start: January 1, 2020
• Primary Completion: October 31, 2024
• Study Completion: December 31, 2024
• Last Updated: July 14, 2025

Record last verified: 2025-07

Locations

EG (1)