The Efficacy of Tadalafil on Depression in Patients With ED

In This Article

Abstract and Introduction

Abstract

Background: Many studies have reported not only that depression and antidepressant medications can cause erectile dysfunction (ED), but also that having ED may increase the risk of depression. We investigated the effect of a daily low dose of a phosphodiesterase (PDE) type 5 inhibitor (tadalafil, 5 mg) on depression and levels of brain-derived neurotrophic factor (BDNF) in patients with ED.

Methods: Ten male patients with at least a 3-month history of ED [International Index of Erectile Function (IIEF)-5 score ≤21] and depression [the Korean version of the Patient Health Questionnaire (PHQ)-9 score ≥5] were analyzed in this study. The subjects were prescribed a low dose of a PDE5 inhibitor (tadalafil 5 mg) once daily for 8 weeks. The survey questionnaires were performed using the PHQ-15 and the PHQ-9 before and after administration of 8 weeks of tadalafil. Blood samples used for measuring serum BDNF levels were taken and measured at baseline and after 8 weeks of treatment.

Results: The mean changes in the PHQ-9 and PHQ-15 scores were 3.60±3.27 and 2.00±2.98, respectively. Analyses of the mean changes in the PHQ-9 scores revealed that the depressive symptoms of the subjects were significantly improved after administration of eight weeks of tadalafil (P<0.05). And, there was also a statistically significant increase in the PHQ-15 scores (P<0.05). Serum levels of BDNF were higher after tadalafil treatment compared to before treatment; however, this difference was not statistically significant.

Conclusions: The results of this prospective, clinical study suggest that daily low dose tadalafil may have a potential role in the treatment of depression in patients with ED.

Introduction

Erectile dysfunction (ED) can have a negative effect on the quality of life in males. In addition to the physical effects, ED can cause psychological issues, like lower emotional satisfaction and general happiness.^[1,2] Especially, previous studies have reported the association between ED and depressive symptoms.^[3] Many studies have reported not only that depression and antidepressant medications can cause ED, but also that having ED may increase the risk of depression.^[4–6] Therefore, the simultaneous treatment of depression and ED is needed.

Phosphodiesterase (PDE) 5 inhibitors, which regulate certain signaling pathways by elevating cyclic guanosine monophosphate (cGMP) levels, have been widely used to treat ED. PDE5 inhibitors such as tadalafil increase cGMP by blocking its breakdown at its catalytic site.^[7,8] Increased cGMP facilitates postsynaptic action in the brain, and activates downstream effectors resulting in changes in neuronal activities.^[9] Though many clinical studies have suggested a role of other PDE5 inhibitors, like sildenafil and vardenafil, as possible antidepressant medications,^[10–13] there have been only few animal studies exploring tadalafil,^[14] but no clinical studies to our knowledge.

Furthermore, accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) is associated with the pathophysiology of depressive disorders.^[15] And, the cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) was found among the transcription factors regulating BDNF expression.^[16] So, we also investigated whether tadalafil would increase BDNF levels in men with depression through nitric oxide (NO)/cGMP/protein kinase G (PKG)/CREB/BDNF signaling.

Therefore, the aim of this study was to investigate the efficacy of daily low dose tadalafil on depression and BDNF levels in patients with ED.

Table 1. Demographic and baseline parameters
Parameters	Patients (n=10)
Age, years	62.20±5.69
BMI, kg/m²	25.61±2.79
Cause of ED
Psychogenic	3
Organic	7
Duration of ED, months	30.00±16.11
Past medical history
BPH	9
Diabetes	10
Hypertension	10
Hyperlipidemia	8
Other disease	10
IIEF-5 score	5.10±5.13
PHQ-9 score	7.30±6.62
PHQ-15 score	6.20±2.94

Data are presented as means ± standard deviations or n. BMI, body mass index; ED, erectile dysfunction; BPH, benign prostate hyperplasia; IIEF, International Index of Erectile Function; PHQ, Patient Health Questionnaire.

Table 2. Mean changes in PHQ-9, PHQ-15 scores and serum BDNF levels at 8 weeks
Parameters	Mean score	P value*
PHQ-9 score		0.011
Baseline	7.30±6.62
Week 8	3.70±5.74
Mean change	3.60±3.27
PHQ-15 score		0.049
Baseline	6.20±2.94
Week 8	4.20±2.78
Mean change	2.00±2.98
BDNF (pg/mL)		0.208
Baseline	1,223.12±520.09
Week 8	1,506.36±1,112.83
Mean change	283.23±1,235.80

Data are presented as means ± standard deviations. *P values comparing baseline and 8 weeks as assessed by Wilcoxon signed-rank tests. PHQ, Patient Health Questionnaire; BDNF, brain-derived neurotrophic factor.