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

Not Applicable

Recruiting

• Conditions: Major Depressive Disorder
• Interventions: Drug: Sildenafil Citrate; Drug: Placebo oral tablet

• Registration Number: NCT04344678
• Lead Sponsor: Sadat City University

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-01-01
• Study First Submitted: 2020-04-09
• Study First Submitted QC: 2020-04-09
• Study First Posted: 2020-04-14
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-16
• Last Update Posted: 2023-01-18
• Primary Completion: 2024-10-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sildenafil group	Sildenafil Citrate	Escitalopram 20 mg tablet plus one Sildenafil 50 mg tablet
Control group	Placebo oral tablet	Escitalopram 20 mg tablet plus one placebo tablet

Primary Outcome Measures

Name	Time	Method
Effect on Hamilton Depression rating scale score (HAM-D score)	12 week	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.

Secondary Outcome Measures

Name	Time	Method
Effect on biological markers	12 week	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.

Trial Locations

Locations (1)

Faculty of Medicine; 🇪🇬 Shibīn Al Kawm, Egypt