sildenafil-citrate and Schizophrenia

Sexual dysfunction is an important public health problem in men and is associated with reduced quality of life. It is more common in patients with schizophrenia. It is well-established that antipsychotic drugs cause sexual dysfunction with consequences on the quality of life of patients, adherence to treatment, and public health costs. Phosphodiesterase type 5 inhibitors (PDE5 inhibitors) are indicated for the management of erectile dysfunction. However, there is little information on such treatment in schizophrenic patients. This literature review aimed to summarize the current data on the efficacy and tolerability of PDE-5 inhibitors in the erectile dysfunction in schizophrenic patients.. PubMed, PsycInfo and Cochrane databases were searched for studies published until August 2014.. Only 6 studies met the inclusion criteria. Three were randomized, double-blind, cross-over, placebo-controlled trials and three were open studies. Various scales were used to measure erectile and orgasmic function, desire, satisfaction during intercourse, overall satisfaction, quality of life and intensity of schizophrenic symptoms. In the 3 randomized studies (one with sildenafil 25-50 mg, one with lodenafil carbonate 80 mg/j and the last one with tadalafil 10 mg), the rate of participants who completed the trial was high (around 95 %). All three included patients with schizophrenia or schizophrenia spectrum disorders. Patients reported significant improvement on sexual dysfunction. However, no statistical difference was reported between lodenafil and placebo, on different scales, suggesting a very important placebo effect in patients with schizophrenia. All three found a good tolerance of PDE-5 inhibitors. Side effects were rare and were mainly nasal congestion, headaches, nausea and dizziness. There were no major side effects or drug interactions. Considering the 3 open studies, 2 involved sildenafil and one tadalafil. All concluded in improved erectile and orgasmic function, desire, satisfaction during intercourse, overall satisfaction, and even the quality of life when it was studied. However, very few patients were included.. Little data are available on the use of PDE5 inhibitors in schizophrenic patients. The 6 studies included few patients which reduces the power and the scope of their conclusions. There is also an important bias due to the use of self-questionnaires. The methodologies of the studies differ in many aspects which limits the comparability. Inclusion and exclusion criteria, drugs used and scales varied among the studies. However, the management of erectile disorder seems to be a consistent target in an integrative approach for the overall well-being of schizophrenic patients. PDE-5 inhibitors appear to be safe and could improve erectile function in schizophrenic patients.. In total, the current data suggest efficiency and good tolerance of the use of PDE-5 inhibitors in schizophrenic patients with erectile dysfunction. However, further studies focusing on PDE-5 inhibitors are needed to more deeply assess their efficacy and safety in patients with schizophrenia.

Topics: Antipsychotic Agents; Carbonates; Erectile Dysfunction; Humans; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Pyrimidines; Schizophrenia; Sildenafil Citrate; Treatment Outcome

Recent findings suggest that dopaminergic abnormalities found in psychotic disorders may be secondary to nitric oxide dysfunctions. Nitric oxide seems to influence glutamatergic and dopaminergic neurotransmission, both of which have been associated with psychosis.. To search and review published works which examined the influence of nitric oxide in psychotic disorders subjects.. The research was executed in the on-line collections of Pubmed and ISI Web of Science. The key aspects utilized were "Psychotic Disorders AND Nitric Oxide", "Psychosis AND Nitric Oxide","Schizotypal Personality Disorder AND Nitric Oxide", "Delusional Disorder AND Nitric Oxide", "Brief Psychotic Disorder AND Nitric Oxide", "Schizophreniform Disorder AND Nitric Oxide", "Schizoaffective Disorder AND Nitric Oxide", and "Schizophrenia AND Nitric Oxide". Empirical works utilizing human subjects, published in the last 10 years, in English language were included.. Initially, the search yielded a total of 95 studies. Then, 39 were elected according to the inclusion requirements. The selected articles were divided into five groups: biochemical studies (n=15; 38.5%), genetic studies (n=11; 28.2%), postmortem studies (n=6; 15.4%), clinical trials (n=6; 15.4%), and case reports (n=1; 2.5%). The studies evaluated only schizophrenic or schizoaffective disorder subjects. The great majority of them found evidence of nitric oxide dysfunctions in psychosis.. The results of the review strengthen the idea that nitric oxide has a key participation in psychotic disorders and deserves deeper investigation as a target for future pharmacological intervention.

Topics: Antipsychotic Agents; Arginine; Brain; Clinical Trials as Topic; Humans; Nitric Oxide; Nitric Oxide Synthase; Phosphodiesterase 5 Inhibitors; Psychotic Disorders; Schizophrenia; Sildenafil Citrate

There is limited evidence for the management of sexual dysfunction and/or hyperprolactinemia resulting from use of antipsychotics in patients with schizophrenia and spectrum. The aim of this study was to review and describe the strategies for the treatment of antipsychotic-induced sexual dysfunctions and/or hyperprolactinemia. The research was carried out through Medline/PubMed, Cochrane, Lilacs, Embase, and PsycINFO, and it included open labels or randomized clinical trials. The authors found 31 studies: 25 open-label noncontrolled studies and 6 randomized controlled clinical trials. The randomized, double-blind controlled studies that were conducted with adjunctive treatment that showed improvement of sexual dysfunction and/or decrease of prolactin levels were sildenafil and aripiprazole. The medication selegiline and cyproheptadine did not improve sexual function. The switch to quetiapine was demonstrated in 2 randomized controlled studies: 1 showed improvement in the primary outcome and the other did not. This reviewed data have suggested that further well-designed randomized controlled trials are needed to provide evidence for the effects of different strategies to manage sexual dysfunction and/or hyperprolactinaemia resulting from antipsychotics. These trials are necessary in order to have a better compliance and reduce the distress among patients with schizophrenia.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Drug Substitution; Drug Therapy, Combination; Erectile Dysfunction; Female; Humans; Hyperprolactinemia; Male; Piperazines; Psychotic Disorders; Purines; Quinolones; Schizophrenia; Schizophrenic Psychology; Sexual Dysfunction, Physiological; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Antipsychotic Agents; Erectile Dysfunction; Female; Humans; Male; Monoamine Oxidase Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Research; Research Design; Schizophrenia; Selegiline; Sexual Dysfunctions, Psychological; Sildenafil Citrate; Sulfones; Treatment Outcome

It has been suggested that phosphodiesterase 5 inhibitors such as sildenafil may be effective in the treatment of negative symptoms of schizophrenia.. This study was designed to investigate the effect of sildenafil added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in a double-blind and randomized clinical trial.. Eligible participants in the study were 40 patients with chronic schizophrenia with ages ranging from 18 to 45 years. All patients were inpatients and were in the active phase of the illness and met DSM-IV-TR criteria for schizophrenia. Patients were allocated in a random fashion: 20 to risperidone (6 mg/day) plus sildenafil (75 mg/day) and 20 to risperidone (6 mg/day) plus placebo. The principal measure of outcome was Positive and Negative Syndrome Scale (PANSS).. Although both protocols significantly decreased the score of the positive, negative, and general psychopathological symptoms over the trial period, the combination of risperidone and sildenafil showed a significant superiority over risperidone alone in decreasing negative symptoms and PANSS total scores over the 8-week trial (between-subjects factor; F = 4.77, df = 1; P = 0.03; F = 5.91, df = 1, P = 0.02 respectively).. Therapy with 75 mg/day of sildenafil was well tolerated, and no clinically important side effects were observed. The present study indicates sildenafil as a potential adjunctive treatment strategy for treatment of negative symptoms of schizophrenia. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N11).

Topics: Adolescent; Adult; Antipsychotic Agents; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Prospective Studies; Psychiatric Status Rating Scales; Purines; Risperidone; Schizophrenia; Schizophrenic Psychology; Sildenafil Citrate; Sulfones; Young Adult

Phosphodiesterase 5 (PDE5) inhibitors increase cyclic guanosine monophosphate (cGMP) concentrations in the intracellular pathway activated by N-methyl-D-aspartic acid receptors which is believed to mediate long-term potentiation and memory consolidation. The PDE5 inhibitor sildenafil has been shown to enhance memory in animal models. In addition, neuronal nitric oxide synthase, another component of the NMDA/nitric oxide/cGMP intracellular pathway, has been reported to be dysregulated in schizophrenia patients.. Seventeen adult schizophrenia outpatients treated with a stable dose of antipsychotic received a single oral dose of placebo, sildenafil 50 mg, and sildenafil 100 mg in random order with a 48-h interval between administrations. Psychiatric symptom ratings and a cognitive battery were performed at baseline and 1 hour following each administration of the study drug. In addition, memory consolidation was examined by testing recall 48 h later, prior to the next administration of the study drug.. Fifteen subjects completed all three treatment conditions. One subject developed irritability and required hospitalization 2 days after receiving sildenafil 100 mg. Neither dose of sildenafil significantly affected cognitive performance or symptom ratings compared to the placebo.. Despite evidence for cognitive-enhancing effects of sildenafil in animal models, the strategy for treating putative NMDA receptor-mediated memory deficits in schizophrenia with sildenafil 50 and 100 mg was not successful. It is possible that the doses used in this study were not optimal or that repeated dosing may be necessary to achieve therapeutic effects. Agents under development that inhibit other subtypes of PDE remain promising for schizophrenia and dementia.

Topics: Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Memory; Middle Aged; Neuropsychological Tests; Phosphodiesterase Inhibitors; Piperazines; Psychiatric Status Rating Scales; Psychomotor Performance; Purines; Schizophrenia; Schizophrenic Psychology; Sildenafil Citrate; Sulfones

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.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Antipsychotic Agents; Comorbidity; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Erectile Dysfunction; Follow-Up Studies; Humans; Male; Middle Aged; Piperazines; Placebos; Prolactin; Purines; Regression Analysis; Schizophrenia; Schizophrenia, Paranoid; Sexual Behavior; Sildenafil Citrate; Sulfones; Treatment Outcome

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.. 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.. 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.. Sildenafil is a useful agent for the treatment of erectile dysfunction in risperidone-treated male schizophrenia patients.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Drug Therapy, Combination; Erectile Dysfunction; Humans; Male; Patient Compliance; Patient Satisfaction; Piperazines; Purines; Risperidone; Schizophrenia; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents

Topics: Antipsychotic Agents; Humans; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Risperidone; Schizophrenia; Sildenafil Citrate; Sulfones