Sildenafil in the treatment of antipsychotic-induced erectile dysfunction: a randomized, double-blind, placebo-controlled, flexible-dose, two-way crossover trial. Improvement in hyperprolactinemia and reproductive comorbidities in patients with schizophrenia switched from conventional antipsychotics or risperidone to olanzapine. The impact upon extra-pyramidal side effects, clinical symptoms and quality of life of a switch from conventional to atypical antipsychotics (risperidone or olanzapine) in elderly patients with schizophrenia. Sildenafil for treatment of erectile dysfunction in men with diabetes: a randomized controlled trial. Sildenafil Diabetes Study Group.
Antipsychotic-induced erectile dysfunction is a significant clinical problem and is a common reason for poor medication compliance. This report studied the efficacy and tolerability of sildenafil citrate in patients with antipsychotic-induced erectile dysfunction.
                The study design was a randomized, double-blind, placebo-controlled, flexible-dose, two-way crossover trial carried out at a tertiary referral center. Thirty-two married male outpatients with schizophrenia or delusional disorder and antipsychotic-induced erectile dysfunction were recruited for the trial. Sexual function was assessed from patient logs of sexual activity.
                Thirty-two subjects and their spouses, who agreed to take part in the study, were included in the crossover trial. Thirty-one (96.9%) completed the trial. There was no significant period effect or treatment-period interaction. Patients reported significant improvement while taking sildenafil in the number of adequate erections, satisfaction with sexual intercourse, and the duration of erections over 2 weeks. The odds ratios for adequate erections and for satisfactory sexual intercourse with sildenafil were 4.07 and 3.77, respectively. The effect of sildenafil remained significant even after adjustment for period and week effects and treatment-period interaction with Poisson regression analysis. There were no major side effects or adverse drug interactions.
                Sildenafil citrate is safe and effective in the treatment of antipsychotic-induced erectile dysfunction. It is also well tolerated. This open-label, prospective, 4-month study in hyperprolactinemic patients with schizophrenia explored whether prolactin levels decrease after switching antipsychotic therapy to olanzapine. A secondary objective was to determine if reproductive morbidities and sexual dysfunction occurring with hyperprolactinemia improved with prolactin normalization. Clinically stable patients with schizophrenia, who had hyperprolactinemia defined as >18.8 ng/ml for males and >24.2 ng/ml for females, were randomized to: remain on current therapy (n=27) or switch to olanzapine, 5-20 mg/day, (n=27). Baseline prolactin levels in female patients randomized to receive olanzapine (n=14) were 66.3+/-38.7 ng/ml and were 82.0+/-37.6 (p=.32) in those remaining on their pre-study antipsychotic medication (n=14). In male patients, baseline prolactin levels were 33.7+/-12.1 and 33.5+/-13.8 ng/ml (p=.97), respectively, for those randomized to olanzapine (n=13) or remaining on pre-study treatment (n=13). At study end, patients switched to olanzapine experienced significant reductions in mean serum prolactin levels of 19.8+/-18.1 ng/ml in males (p=.02), and 32.3+/-47.5 ng/ml in females (p=.01), but prolactin continued to be elevated in patients who remained on pre-study antipsychotic treatment. After switching to olanzapine treatment, male patients experienced significantly (p=.03) increased free testosterone levels but there were no significant improvements in total testosterone levels; some female patients experienced improved menstrual cycling, as well as resolution of galactorrhea and gynecomastia, and sexual functioning was significantly improved in both genders. Patients switched to olanzapine, as well as those remaining on their pre-study medication, maintained clinical stability, their symptoms continued to improve, although there were no significant between-treatment differences in improvement. Treatment-emergent adverse events did occur in both treatment groups; however, they were not significantly different between groups. Olanzapine-treated patients experienced significantly lower eosinophil counts and higher elevations in low-density lipoproteins and standing blood pressure than non-switched patients. Olanzapine treatment may offer sustained reduction in serum prolactin and improvement in sexual and reproductive comorbid symptoms in patients with schizophrenia who have treatment-emergent hyperprolactinemia. Atypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance, but have similar efficacy to conventional antipsychotics. Trials in the elderly have been either retrospective, small, of short duration or of a single-arm design.
                To demonstrate the effects upon motor side-effects, efficacy, safety and quality of life (QOL) of switching elderly patients with schizophrenia from conventional antipsychotics to olanzapine or risperidone.
                Elderly patients with schizophrenia were randomly allocated to olanzapine or risperidone and followed through an open-label crossover period. Between and within group intention to treat analyses were conducted.
                66 patients were randomised (mean age 69.6 [SD +/- 6.2]). Four (11.8%) patients on olanzapine and 8 (26.7%) patients on risperidone failed to complete the crossover because of treatment failure [Odds Ratio (OR) = 2.73[0.73-10.2] p = 0.14]. The mean doses upon completion of switching in each arm were 9.9 mg (SD = 4.2) and 1.7 mg (SD = 1.2) for olanzapine and risperidone respectively. In both arms there was improvement in Parkinsonism, though only olanzapine was associated with a reduction in dyskinetic symptoms. The Brief Psychiatric Rating Scale, Scale for the assessment of Negative Symptoms and Montgomery and Asberg Depression Rating Scale scores all improved through the crossover period in both arms with no between group differences. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the World Health Organisation-Quality Of Life [Brief] (WHO-QOL-BREF) scale ( p = 0.02). Patients in the olanzapine arm also demonstrated improvement from baseline in the WHO-QOL-BREF physical, psychological and health satisfaction domains, but risperidone had no effect on any Quality of Life (QOL) measure.
                After switching from a conventional antipsychotic, olanzapine and risperidone were associated with improvement in core symptoms of schizophrenia and motor side effects. Subjects switched to olanzapine were more likely to complete the switching process and show an improvement in psychological QOL.
                Copyright 2003 John Wiley & Sons, Ltd. Erectile dysfunction is common in men with diabetes.
                To assess the efficacy and safety of oral sildenafil citrate in the treatment of erectile dysfunction in men with diabetes.
                A multicenter, randomized, double-blind, placebo-controlled, flexible dose-escalation study conducted May through November 1996.
                Patients' homes and 19 clinical practice centers in the United States.
                A total of 268 men (mean age, 57 years) with erectile dysfunction (mean duration, 5.6 years) and diabetes (mean duration, 12 years).
                Patients were randomized to receive sildenafil (n = 136) or placebo (n = 132) as needed, but not more than once daily, for 12 weeks. Patients took the study drug or placebo 1 hour before anticipated sexual activity. The starting dose of sildenafil citrate was 50 mg, with the option to adjust the dose to 100 mg or 25 mg based on efficacy and tolerability, to be taken as needed.
                Self-reported ability to achieve and maintain an erection for sexual intercourse according to the International Index of Erectile Function and adverse events.
                Two hundred fifty-two patients (94%) completed the study (131/136 in the sildenafil group, 121/132 in the placebo group). By intention-to-treat analysis, at 12 weeks, 74 (56%) of 131 patients in the sildenafil group reported improved erections compared with 13 (10%) of 127 patients in the placebo group (P<.001). The proportion of men with at least 1 successful attempt at sexual intercourse was 61 % (71/ 117) for the sildenafil group vs 22% (25/114) for the placebo group (P<.001). Adverse events related to treatment were reported for 22 (16%) of 136 patients taking sildenafil and 1 (1%) of 132 patients receiving placebo. The most common adverse events were headache (11% sildenafil, 2% placebo), dyspepsia (9% sildenafil, 0% placebo), and respiratory tract disorder (6% sildenafil, 2% placebo), predominantly sinus congestion or drainage. The incidence of cardiovascular adverse events was comparable for both groups (3% sildenafil, 5% placebo).
                Oral sildenafil is an effective and well-tolerated treatment for erectile dysfunction in men with diabetes.
We are not confident that cross-over studies are appropriate for this participant group as they are best for conditions that are stable and for interventions with no physiological and psychological carry-over. Sildenafil may be a useful option in the treatment of antipsychotic-induced sexual dysfunction in men with schizophrenia, but this conclusion is based only on one small short trial. Switching to olanzapine may improve sexual functioning in men and women, but the trial assessing this was a small, open label trial. Further well designed randomised control trials that are blinded and well conducted and reported, which investigate the effects of dose reduction, drug holidays, symptomatic therapy and switching antipsychotic on sexual function in people with antipsychotic-induced sexual dysfunction are urgently needed.