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

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

Status

Withdrawn

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05030623

Enrollment

Registered

2021-09-01

Start date

2021-08-01

Completion date

2024-12-31

Last updated

2025-07-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Major Depressive Disorder

Brief summary

Antidepressant-like effects of tadalafil to its ability to modulate transduction pathways responsible for neuroplasticity. Treatment with tadalafil 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. Low-dose tadalafil improved both depressive symptoms in patients with erectile dysfunction.

Interventions

DRUGTadalafil 5Mg Tab

Tadalafil 5Mg Tab plus Fluoxetine 20 mg capsule

DRUGPlacebo

Placebo Tab plus Fluoxetine 20 mg capsule

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 50 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Effect on Hamilton Depression rating scale score (HAM-D score)	12 weeks	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

Measure	Time frame	Description
Effect on biological markers	At baseline and after 12 weeks of intervention	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.

Countries

Egypt

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026