ABSTRACT
BACKGROUND: Selective serotonin reuptake inhibitor (SSRI)-induced ejaculatory delay is a common problem that has no treatment with established efficacy. Sildenafil citrate is effective for erectile dysfunction and appears to be safe at doses up to 200 mg. METHOD: We enrolled men who were in remission from depression according to DSM-IV criteria and who reported that they had developed new-onset ejaculatory delay in the setting of SSRI treatment. Enrolled patients were instructed to use 25 mg of sildenafil 1 hour prior to sexual activity on at least 2 occasions. If this was not effective for the ejaculatory delay, they were instructed to increase the dose progressively up to a maximum of 200 mg. We compared baseline sexual functioning to 2 phases of open treatment: low-dose phase (sildenafil 25-100 mg) and high-dose phase (sildenafil 150-200 mg). The primary outcome measure was a modified, self-report Clinical Global Impressions (CGI) scale that was specific for erectile (CGI-EF) and ejaculatory (CGI-EJF) aspects of sexual function. RESULTS: Twenty-one men (mean age = 56 years) with major depressive disorder (MDD) in remission and SSRI-associated ejaculatory delay enrolled in the study and received sildenafil. At baseline, 14 of 21(67%) had comorbid erectile dysfunction. At the low-dose phase follow-up assessment, 12 of 14 achieved full erectile dysfunction remission, and 4 of 21 achieved ejaculatory delay remission. Sixteen patients with persistent ejaculatory delay were eligible for the high-dose phase: 5 withdrew from the study, 4 increased to a maximum dose of 150 mg, and 6 increased to a maximum dose of 200 mg. The 1 patient who had clinically significant erectile dysfunction and ejaculatory delay reported improvement of both conditions after the high-dose phase. Of the 10 patients who had ejaculatory delay without significant erectile dysfunction and who chose to take high-dose sildenafil, 9 reported a significant clinical improvement in ejaculatory delay (CGI-EJF improvement score of 1 or 2) and 7 achieved full remission (CGI-EJF severity score of 1 or 2 and CGI-EJF improvement score of 1 or 2). CONCLUSION: In this open clinical trial with men who had SSRI-induced ejaculatory delay, high-dose sildenafil appeared to be effective in reducing ejaculatory latency.
Subject(s)
Depressive Disorder/drug therapy , Ejaculation/drug effects , Phosphodiesterase Inhibitors/therapeutic use , Piperazines/therapeutic use , Selective Serotonin Reuptake Inhibitors/adverse effects , Sexual Dysfunctions, Psychological/chemically induced , Sexual Dysfunctions, Psychological/drug therapy , Adult , Aged , Depressive Disorder/psychology , Dose-Response Relationship, Drug , Drug Administration Schedule , Erectile Dysfunction/chemically induced , Erectile Dysfunction/drug therapy , Erectile Dysfunction/psychology , Humans , Male , Middle Aged , Phosphodiesterase Inhibitors/administration & dosage , Piperazines/administration & dosage , Psychiatric Status Rating Scales , Purines , Selective Serotonin Reuptake Inhibitors/therapeutic use , Sildenafil Citrate , Sulfones , Treatment OutcomeABSTRACT
Depression is associated with increased cardiovascular mortality in patients with preexisting cardiac illness. A decrease in cardiac vagal function as suggested by a decrease in heart rate variability (HRV) or heart period variability has been linked to sudden death in patients with cardiac disease as well as in normal controls. Recent studies have shown decreased vagal function in cardiac patients with depression as well as in depressed patients without cardiac illness. In this study, we compared 20 h awake and sleep heart period nonlinear measures using quantification of nonlinearity and chaos in two groups of patients with major depression and ischemic heart disease (mean age 59-60 years) before and after 6 weeks of treatment with paroxetine or nortriptyline. Patients received paroxetine, 20-30 mg/day or nortriptyline targeted to 190-570 nmol/l for 6 weeks. For HRV analysis, 24 patients were included in the paroxetine treatment study and 20 patients in the nortriptyline study who had at least 20000 s of awake data. The ages of these groups were 60.4 +/- 10.5 years for paroxetine and 60.8 +/- 13.4 years for nortriptyline. There was a significant decrease in the largest Lyapunov exponent (LLE) after treatment with nortriptyline but not paroxetine. There were also significant decreases in nonlinearity scores on S(netPR) and S(netGS) after nortriptyline, which may be due to a decrease in cardiac vagal modulation of HRV. S(netGS) and awake LLE were the most significant variables that contributed to the discrimination of postparoxetine and postnortriptyline groups even with the inclusion of time and frequency domain measures. These findings suggest that nortriptyline decreases the measures of chaos probably through its stronger vagolytic effects on cardiac autonomic function compared with paroxetine, which is in agreement with previous clinical and preclinical reports. Nortriptyline was also associated with a significant decrease in nonlinearity scores, which may be due to anticholinergic and/or sympatholytic effects. As depression is associated with a strong risk factor for cardiovascular mortality, one should be careful about using any drug that adversely affects cardiac vagal function.
Subject(s)
Antidepressive Agents/therapeutic use , Depressive Disorder, Major/drug therapy , Heart Rate/drug effects , Myocardial Ischemia/drug therapy , Nortriptyline/therapeutic use , Paroxetine/therapeutic use , Aged , Analysis of Variance , Antidepressive Agents/adverse effects , Depressive Disorder, Major/complications , Depressive Disorder, Major/physiopathology , Discriminant Analysis , Humans , Middle Aged , Models, Cardiovascular , Myocardial Ischemia/complications , Myocardial Ischemia/physiopathology , Nonlinear Dynamics , Nortriptyline/adverse effects , Paroxetine/adverse effects , Psychiatric Status Rating Scales , Time FactorsABSTRACT
BACKGROUND: Studies have linked depression to sudden death and serious cardiovascular events in patients with preexisting cardiac illness. Recent studies have shown decreased vagal function in cardiac patients with depression and depressed patients without cardiac illness. METHODS: We compared 20-hour, sleeping, and awake heart period variability measures using spectral analysis, fractal dimension, and symbolic dynamics in two patient groups with major depression and ischemic heart disease (mean age 59-60 years) before and after 6 weeks of paroxetine or nortriptyline treatment. RESULTS: Spectral measures showed decreases in awake and sleeping total power (TP: 0.0-0.5 Hz), ultra low frequency power (ULF: 0-0.0033 Hz), very low frequency power (VLF: 0.0033-0.04 Hz), and low-frequency power (LF: 0.04-0.15 Hz) for nortriptyline condition and a decrease in high-frequency power (HF: 0.15-0.5 Hz) for the awake condition in patients who received nortriptyline. A measure of nonlinear complexity, WC-100, significantly increased after paroxetine during the awake condition. CONCLUSIONS: These findings suggest that nortriptyline has stronger vagolytic effects on cardiac autonomic function compared with paroxetine, which is in agreement with previous clinical and preclinical reports. Paroxetine may have some cardio-protective effects, especially in cardiac patients.
