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

Study Overview
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Brief Summary
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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.

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

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Tadalafil 5Mg Tab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tadalafil<br> | Drug: Tadalafil 5Mg Tab<br>* Tadalafil 5Mg Tab plus Fluoxetine 20 mg capsule<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo Tab plus Fluoxetine 20 mg capsule<br>|

What is the study measuring?
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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 weeks | 

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. | At baseline and after 12 weeks of intervention |