An open-label pilot study to evaluate the efficacy of sildenafil citrate in middle-aged men with late-onset dysthymia

Late onset dysthymic disorder (DD) in middle-aged and elderly men responds poorly to established antidepressants. Previous studies noted an improvement in mood accompanying sildenafil citrate treatment for erectile dysfunction. We sought to evaluate whether sildenafil's mood effects were independent of the effect on erectile function. A 6-week open label study was conducted with 20 male participants, aged 41-60 who were diagnosed with DD and who had normal erectile function. Participants were treated with sildenafil citrate 25 mg per day for 6 weeks. The primary outcome measure was the 21-item Hamilton Depression Rating Scale. Depressive and sexual symptoms were also evaluated using self-report questionnaires. Treatment with sildenafil resulted in a significant reduction in Hamilton Depression Rating Scale mean scores: from 14.61 +/- 3.5 at baseline to 6.39 +/- 5.13 at end of study (F(3,51) = 32.52, p 相似文献   

Randomized trial of sildenafil for the treatment of erectile dysfunction in spinal cord injury. Sildenafil Study Group.

Erectile dysfunction is a common complication of spinal cord injury. This double-blind, placebo-controlled, two-way crossover study assessed the efficacy and safety of oral sildenafil in men with erectile dysfunction caused by traumatic spinal cord injury. A total of 178 men (mean age, 38 years) received placebo or sildenafil 1 hour before sexual activity for 6 weeks; after a 2-week washout period, the men received the alternate treatment for 6 weeks. The 50-mg starting dose could be adjusted to 100 or 25 mg based on efficacy and tolerability. Efficacy was assessed by using global efficacy questions, the International Index of Erectile Function (IIEF), and a patient log of erectile activity. Of 143 men with residual erectile function at baseline, 111 (78%) reported improved erections and preferred sildenafil to placebo. For all men (including those who reported no residual erectile function at baseline), 127 of 168 (76%) reported improved erections and preferred sildenafil to placebo. For all men, 132 of 166 (80%) reported that sildenafil improved sexual intercourse compared with 17 of 166 men (10%) reporting improvement with placebo. IIEF questions assessing the ability to achieve and maintain erections and satisfaction with sexual intercourse demonstrated significant improvement with sildenafil. Sildenafil was well tolerated, with a low rate of discontinuation because of treatment-related adverse events (2% vs 1% for placebo). Oral sildenafil is an effective and well-tolerated treatment for erectile dysfunction caused by spinal cord injury.     

Efficacy of sildenafil citrate for the treatment of erectile dysfunction in men taking serotonin reuptake inhibitors.

OBJECTIVE: This study was an evaluation of whether sildenafil citrate is effective for the treatment of erectile dysfunction in men taking concomitant serotonin-reuptake-inhibiting antidepressants. METHOD: A retrospective subanalysis of combined data from 10 phase II/III double-blind, placebo-controlled, fixed- and flexible-dose trials (12-26 weeks) identified a group of men with erectile dysfunction receiving 5 to 200 mg/day of sildenafil (N=65) or placebo (N=33) and concomitant serotonin-reuptake-inhibiting antidepressants. Efficacy was measured by responses to questions from the International Index of Erectile Function on ability to achieve erection, ability to maintain erection, ejaculation frequency, orgasm frequency, and sexual desire. RESULTS: Patients with erectile dysfunction receiving sildenafil and concomitant serotonergic antidepressants had significantly greater improvements in ability to achieve and maintain an erection, frequency of ejaculation, and orgasm frequency than did patients receiving placebo, without increased sexual desire. CONCLUSIONS: Sildenafil significantly improved erectile dysfunction in patients taking concomitant serotonergic antidepressants.     

Clinical features of depressed patients who do and do not improve with placebo.

The substantial placebo response in depression confounds treatment decisions and the assessment of new therapies. Improvement with placebo occurs infrequently in patients with chronic depression and in those with pituitary-adrenocortical hyperfunction, but other consistent predictors of placebo response have not been detected. We divided 241 moderately to severely depressed patients who had received placebo on a double-blind basis for 3 to 6 weeks into responders (greater than or equal to 50% improvement in Hamilton depression score, final Hamilton depression score less than or equal to 10), extreme nonresponders (less than 25% improvement), and partial responders (all others). Improvement with placebo was associated with a relatively short illness, a precipitating event, depression of only moderate global severity, and a good response to previous antidepressant treatment. These observations suggest that depressed patients who do and do not recover with placebo have different conditions that have not yet been fully characterized.     

Efficacy and tolerability of vardenafil in men with mild depression and erectile dysfunction: the depression-related improvement with vardenafil for erectile response study

OBJECTIVE: Erectile dysfunction and depression are highly associated. Previous studies have shown benefits of phosphodiesterase-5 inhibitor treatment for erectile dysfunction associated with antidepressant therapy or subsyndromal depression. The present study assessed the safety and efficacy of vardenafil in men with erectile dysfunction and untreated mild depression. METHOD: In this 12-week, multicenter, randomized, flexible-dose, parallel-group, double-blind study, 280 men with erectile dysfunction for at least 6 months and untreated mild major depression received placebo or vardenafil, 10 mg/day, for 4 weeks, with the option to titrate to 5 mg/day or 20 mg/day after each of two consecutive 4-week intervals. Endpoints included International Index of Erectile Function erectile function domain and 17-item Hamilton Depression Rating Scale (HAM-D) scores. RESULTS: Vardenafil produced statistically significant and clinically meaningful improvement in all erectile function parameters. The International Index of Erectile Function erectile function domain score was 22.9 with vardenafil compared to 14.9 with placebo. The HAM-D score was lower in the vardenafil group (7.9) than in the placebo group (10.1). Treatment with vardenafil was the most important predictor for return to normal erectile function. Improvement in International Index of Erectile Function erectile function domain score was the most important predictor of remission in depressive symptoms. CONCLUSIONS: Vardenafil was well tolerated and highly efficacious in men with erectile dysfunction and untreated mild major depression. Significant improvements in erectile function and depression were observed in patients treated with vardenafil versus placebo. Erectile dysfunction treatment should be considered a component of therapy for men with depression and erectile dysfunction.     

Efficacy and safety of sildenafil in men with serotonergic antidepressant-associated erectile dysfunction: results from a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To evaluate the efficacy of short-term treatment with sildenafil citrate in men with serotonin reuptake inhibitor (SRI)-associated erectile dysfunction (ED). METHOD: Men (aged>or=18 years) with major depressive disorder (MDD; DSM-IV criteria) in remission and taking SRIs who experienced SRI-associated ED were enrolled in this multicenter, 6-week, randomized, flexible-dose, double-blind, placebo-controlled trial. The primary study measures were questions 3 (Q3: frequency of penetration) and 4 (Q4: frequency of maintained erections after penetration) of the International Index of Erectile Function (IIEF) questionnaire. Secondary study measures were all other questions and domains of the IIEF, the Erectile Dysfunction Index of Treatment Satisfaction (EDITS), a global efficacy questionnaire (GEQ), and a patient-maintained event log of sexual activity. RESULTS: Patients receiving sildenafil (N=71) versus placebo (N=71) reported significantly higher mean+/-SE scores on Q3 (3.9+/-0.2 vs. 3.1+/-0.2, p=.003) and Q4 (3.7+/-0.2 vs. 2.8+/-0.2, p<.001) of the IIEF and significantly higher scores on all domains of the IIEF. Patients receiving sildenafil also reported significantly improved scores on all questions of the EDITS questionnaire (p<.02) and the GEQ (p<.0001) and an increased number of successful sexual intercourse attempts per week (p<.0001) compared with patients receiving placebo. All patients remained in MDD remission (score相似文献   

A double blind, randomised study of sildenafil citrate for erectile dysfunction in men with multiple sclerosis

OBJECTIVE: Identifying and effectively treating erectile dysfunction (ED) can result in an improvement of the quality of life (QoL) in men with multiple sclerosis (MS). METHODS: This randomised, double blind (DB), placebo controlled, flexible dose study with an open label extension (OLE) assessed efficacy, QoL, and safety of sildenafil citrate in men with MS and ED. Overall, 217 men received sildenafil (25-100 mg; n = 104) or placebo (n = 113) for 12 weeks. Efficacy was assessed by the International Index of Erectile Function (IIEF) questionnaire that includes questions on achieving (Q3) and maintaining (Q4) an erection as well as a global efficacy question (GEQ). QoL was also assessed. RESULTS: After 12 weeks, patients receiving sildenafil had higher mean scores for IIEF Q3 and Q4 compared with those receiving placebo (p<0.0001), and 89% (92/103) reported improved erections compared with 24% (27/112) of patients receiving placebo (p<0.0001). At the end of the OLE phase, 95% of men reported improved erections. Patients receiving placebo during the DB phase showed a nearly fourfold increase in improved erections (97% v 26%). Men receiving sildenafil also showed improvements in five of the eight general QoL questions compared with men receiving placebo (p<0.05). The total mean score for the QoL questionnaire improved by 43% for the sildenafil group versus 13% for the placebo group (p<0.0001). Treatment related AEs were predominantly mild in nature, and no patient discontinued due to an AE. CONCLUSION: Sildenafil treatment for ED in men with MS was effective and well tolerated, and resulted in significant improvements in both general and disease specific QoL variables.     

A comparison of placebo responders and nonresponders in subgroups of depressive disorder.

The objective of this study was to determine if the placebo treatment response varied in subgroups of depressed patients (single episode, recurrent, and double depression). Data from placebo-treated patients from seven placebo-controlled clinical trials were pooled and analyzed retrospectively. The placebo response rate was highest for females with a single episode of depression (66.7%) and lowest for females with recurrent depressive episodes (13.3%). Among patients experiencing their first episode, placebo responders had lower Hamilton Rating Scale for Depression (HAMD) total scores at baseline and lower ratings of pschomotor retardation than nonresponders. For patients having a recurrence of an episode, placebo responders had lower baseline ratings of somatic anxiety. The major finding was that patients suffering from their first depressive episode differed from patients with recurrent depressive episodes in the rate of placebo response, effect of gender, and the clinical symptoms that were associated with a positive placebo response.     

High-dose sildenafil citrate for selective serotonin reuptake inhibitor-associated ejaculatory delay: open clinical trial

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.     

Placebo response in depression: a search for predictors

Although 30-40% of depressed patients respond to placebo treatment, few predictors of placebo response have been identified. We evaluated patients with moderate to severe depression who had received placebo for 3-6 weeks in multicenter clinical trials (Study 1, n = 125; Study 2, n = 88). Placebo response rates (greater than 50% improvement in Hamilton total depression score) were 38.4% and 30.7%, respectively. Despite differences in treatment outcome, baseline clinical and demographic characteristics were similar for responders and nonresponders. The studies confirmed the substantial placebo response in moderately to severely depressed patients and suggested chronicity may be a predictor.     

Correlates of therapeutic response in panic disorder presenting with palpitations: heart rate variability, sleep, and placebo effect.

OBJECTIVE: To examine the correlates of therapeutic response of patients with panic disorder presenting with palpitations, we hypothesized that therapeutic response would correlate with heart rate variability (HRV) and sleep measures. METHODS: After a 1-week placebo washout, 27 patients free of structural heart disease and not on cardioactive drugs were randomized in a double-blinded fashion to 4 weeks of treatment with clonazepam (a known antipanic agent) or placebo. We performed standard sleep measures and recorded HRV from 24-hour Holter acquisitions at baseline and end of study. We defined response to therapy as a 50% improvement in the Hamilton Anxiety Rating Scale (HARS) score, confirmed by questionnaires and reaction to sodium lactate infusion. RESULTS: There were 12 responders and 15 nonresponders. Normalization of sleep pattern (including less stage 1 and rapid eye movement [REM] sleep) was observed in both drug and placebo responders (P = 0.011 and P = 0.05, respectively) and in placebo responders alone, compared with nonresponders (P = 0.006 and P = 0.013, respectively). Placebo responders were more likely to show less depression, but even after we controlled for depression, main sleep effects remained. None of the HRV measures correlated with response, but compared with placebo, clonazepam led to a decrease in all the time and frequency domain measures of HRV (all P < 0.05). CONCLUSIONS: Central mechanisms are related to the therapeutic response of patients with panic disorder presenting with palpitations, but this does not directly correlate with HRV. Larger and longer studies may allow objective explanations of placebo response in panic disorder.     

Sildenafil citrate (Viagra) for the treatment of erectile dysfunction in men with Parkinson's disease.

Sildenafil citrate (Viagra) is a phosphodiesterase type V inhibitor used to treat erectile dysfunction. Ten men with idiopathic Parkinson's disease (PD) and erectile dysfunction were prescribed 50-100 mg sildenafil citrate to use in eight sexual encounters over a 2-month period. Patients underwent Unified Parkinson's Disease Rating Scale (UPDRS) evaluations and completed a Beck's Depression Inventory (BDI) and a Sexual Health Inventory-M version (SHI-M) at baseline and after 8 weeks. There was statistically significant improvement in total SHI-M scores (23.8 +/- 2.0 vs 16.6 +/- 2.8; p = 0.01), overall sexual satisfaction (p = 0.03), satisfaction with sexual desire (p = 0.04), ability to achieve erection (p = 0.02), ability to maintain erection (p = 0.03), and ability to reach orgasm (p = 0.04) with use of sildenafil citrate. UPDRS and BDI scores were not significantly changed. Side effects included headache in one patient during three sexual encounters. In this open-label study, sildenafil citrate significantly improved sexual function in men with PD and erectile dysfunction.     

Sleep EEG and amitryptiline treatment in depressed inpatients

We studied the baseline sleep electroencephalogram (EEG) variables and treatment-related sleep changes after 35-46 days of amitryptiline treatment (AMI) in a group of 18 depressed inpatients, mostly suffering from a major depressive disorder endogenous subtype (according to the Research Diagnostic Criteria, RDC), with a short rapid eye movement (REM) latency. The aim of the study was to identify potential sleep "predictors" of clinical response to AMI as well as short-term sleep changes associated with alleviation of depression. Clinical response to the drug was defined as a reduction of more than 50% of the Hamilton Rating Score for Depression (HRSD). Eleven men and 7 women, 25-68 years old, were included in the study. Their sleep was recorded at baseline and after an average of 39 +/- 4 days of AMI treatment, at a mean daily dose of 165 +/- 35 mg. The comparison of responders (n = 9) and nonresponders (n = 9) with Wilcoxon's test showed that responders (1) were more severely depressed at baseline, and (2) had less stage 4 sleep. A discriminant function using baseline HRSD, stage 4 and the number of stage shifts allowed for discrimination between responders and nonresponders with a 100% hit rate. Antidepressant treatment had, however, no differential effect on sleep parameters in the two response groups.     

An open-label trial of sildenafil addition in risperidone-treated male schizophrenia patients with erectile dysfunction

BACKGROUND: Sexual dysfunction frequently occurs in treated and untreated patients with schizophrenia. Sildenafil is used for treatment of erectile dysfunction caused by diverse factors. The aim of our study was to evaluate its potential value, safety, and effect on compliance with anti-psychotic medications in risperidone-treated male schizophrenia patients suffering from erectile dysfunction. METHOD: In a 6-week open-label trial, sildenafil was administered to 12 male schizophrenia (DSM-IV) patients, treated with risperidone and reporting erectile dysfunction. The starting dose was 25 mg with the possibility to increase the dose to 75 mg. Three patients who did not respond stopped sildenafil treatment after 3 weeks. The effect on sexual function was assessed by the International Index of Erectile Function and the Valevski-Weizman Male Sexual Function scale. RESULTS: Nine (75%) of the 12 patients completed the 6-week trial, and 3 patients (25%) stopped taking sildenafil after 3 weeks due to lack of response. We observed statistically significant improvements in all sexual function domains (desire, erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction) in the 9 patients who completed the trial and in most of the domains for all 12 study participants. More than half (8/12; 67%) of the patients exhibited partial or much improvement. CONCLUSION: Sildenafil is a useful agent for the treatment of erectile dysfunction in risperidone-treated male schizophrenia patients.     

Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension

OBJECTIVES: To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy. METHODS: Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital. RESULTS: Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with multiple system atrophy reported a good erectile response and were reluctant to discontinue the medication. CONCLUSIONS: Sidenafil citrate (50 mg) is efficacious in the treatment of erectile dysfunction in parkinsonism due to Parkinson's disease or multiple system atrophy; however, it may unmask or exacerbate hypotension in multiple system atrophy. As Parkinson's disease may be diagnostically difficult to distinguish from multiple system atrophy, especially in the early stages, we recommend measurement of lying and standing blood pressure before prescribing sildenafil to men with parkinsonism. Furthermore, such patients should be made aware of seeking medical advice if they develop symptoms on treatment suggestive of orthostatic hypotension.     

Sildenafil for iatrogenic serotonergic antidepressant medication-induced sexual dysfunction in 4 patients

OBJECTIVE: To evaluate the effect of sildenafil on iatrogenic serotonergic antidepressant-induced sexual dysfunction. METHOD: Four outpatients (2 men, 2 women) who developed sexual dysfunction (erectile impotence, anorgasmia) during treatment with a serotonin reuptake inhibitor antidepressant for psychiatric disorder were selected. Each subject was initially prescribed sildenafil 50 mg to be taken approximately 1 hour before sexual activity. The dose was increased to 100 mg for a partial or failed response. RESULTS: Four cases are detailed in case report fashion. All 4 had rapid reversal of their sexual dysfunction, usually with the first dose. Reversal equates to 1 successful use of sildenafil in each of 2 patients and 3 uses in 2 patients. CONCLUSION: Sildenafil may be an effective treatment for serotonergic antidepressant-induced sexual dysfunction and deserves further evaluation in randomized placebo-controlled studies.     

Day-clinic treatment of late-life depression

BACKGROUND: There are few studies evaluating treatment in gerontopsychiatric day-clinics. In this paper, data are presented on the outcome of day-clinic treatment in late-life depression. METHOD: Forty-four depressed elderly patients (mean Hamilton Depression Score: 17.6) were examined at admission and discharge for psychopathology, functioning in daily living, social situation, burden with medical disease and quality of life. RESULTS: At discharge, the patients showed a significant reduction in depressive symptoms, improvements in cognitive performance, social activities and contacts. However, a more detailed analysis revealed that only patients responding to treatment (n=20) improved in the respective parameters. Patients, who did not recover fully from depression (n=24), did not improve in any of these parameters. At admission, responders and nonresponders did not differ concerning quality of life. At discharge, responders were significantly more satisfied in 11 of 20 domains of life quality. A shorter life time duration of depressive disease and male sex were predictive for a remission of depression. Thus, it could be shown that a considerable number of patients suffering from late-life depression may be successfully treated in a gerontopsychiatric day-clinic and 45.5% fully recover from depression. CONCLUSIONS: The day-clinic setting meets the specific needs of patients suffering from late-life depression by maintaining them in the community, supporting their abilities for self-care and promoting social contacts. Treatment in a day-clinic may be recommended for many elderly depressed patients.     

Efficacy of open-label venlafaxine in subjects with major depressive disorder: associations with neuroendocrine response to serotonergic and noradrenergic probes

An open-label pilot study explored the relationship between severity of depressive symptoms and venlafaxine dose required for clinical efficacy in outpatients with major depressive disorder (MDD). The utility of the neuroendocrine response to serotonergic (ipsapirone) and noradrenergic (clonidine) probes as predictors of venlafaxine dosage required for effective treatment was also explored. Nineteen medically healthy medication-free outpatients over 18 years of age who met criteria for MDD were studied. Participants received either a 20-mg dose of ipsapirone orally, a 0.002-mg/kg intravenous dose of clonidine, or placebo. Following a 1-week single-blind placebo lead-in, all subjects were treated with immediate release venlafaxine. Low-dose responders were defined as those subjects experiencing a >50% decrease in depression score on 37.5 mg, b.i.d., and high-dose responders were defined as those subjects experiencing similar improvement on venlafaxine doses of 75 mg, b.i.d., or higher. Subjects responding to low-dose treatment had a lower mean baseline Hamilton depression score than subjects requiring high-dose treatment. Neuroendocrine and temperature responses to clonidine or ipsapirone challenges were not significantly different in the high- vs. low-dose responders. Evaluation of models of "serotonergic-responsive" and norepinephrine-responsive" depression requires larger numbers of patients.     

The impact of medical comorbidity on acute treatment in major depressive disorder

OBJECTIVE: The authors investigated the impact of medical comorbidity on the acute phase of antidepressant treatment in subjects with major depressive disorder. METHOD: A total of 384 outpatients meeting DSM-III-R criteria for major depressive disorder enrolled in 8-week open treatment with fluoxetine, 20 mg/day. The authors used the Cumulative Illness Rating Scale to measure the burden of medical comorbidity and the 17-item Hamilton Rating Scale for Depression to assess changes in depressive symptoms. The outcome measures were response to treatment (>/=50% reduction in score) and clinical remission (score 相似文献