clozapine and Urinary-Incontinence

Since its introduction to the United States in 1990, the benefits of clozapine use have been repeatedly validated. Clozapine remains the only antipsychotic with proven efficacy in treatment-resistant schizophrenia. Because clozapine has been part of the psychiatric pharmacopeia for considerably less time than neuroleptics, which have dominated the field for over 4 decades, its underutilization may be partly attributed to a lack of experience in managing associated side effects. Most side effects associated with clozapine are typical of antipsychotics in general, and with clozapine, these side effects are typically benign, tolerable, and manageable. It is conceivable that there remains a concern over the risk of agranulocytosis. However, the mandatory blood monitoring carried out through the Clozaril National Registry has considerably reduced the incidence of fully developed cases of agranulocytosis from premarketing values of approximately 1% to 2% to current values of 0.38% and virtually prevented mortalities. These values are likely to decrease further with the application of cytokine augmentation therapy among patients developing blood dyscrasias. Many side effects of clozapine are observed early after treatment onset and are greatly reduced by dose adjustments. Appropriate management of side effects will facilitate a maximization of the benefits of clozapine treatment. Clearly, the benefits of clozapine therapy far outweigh its risks.

Topics: Agranulocytosis; Antipsychotic Agents; Basal Ganglia Diseases; Chemical and Drug Induced Liver Injury; Clozapine; Drug Administration Schedule; Drug Monitoring; Humans; Incidence; Risk Factors; Schizophrenia; Sleep Wake Disorders; Tachycardia; Urinary Incontinence; Weight Gain

Clozapine is an effective atypical antipsychotic that has high affinity for many neurotransmitter receptors. Among the adverse effects of clozapine, urinary incontinence is commonly found and is suggested to be caused by alpha-adrenergic blockade. We tested the hypothesis that clozapine-induced urinary incontinence is related to a genetic variant of the alpha(1a)-adrenoceptor. We also tested whether the alpha(1a)-receptor gene confers susceptibility to schizophrenic disorders. Our result indicated that the alpha(1a)-adrenoceptor gene polymorphism investigated plays no major role in the pathogenesis of schizophrenia or in clozapine-induced urinary incontinence. Considering the superior effects of clozapine and its potent adrenergic antagonistic effects, it is of interest to investigate the association between this polymorphism and the treatment response.

Topics: Adult; Alleles; Antipsychotic Agents; Clozapine; Female; Genotype; Humans; Male; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Psychiatric Status Rating Scales; Receptors, Adrenergic, alpha-1; Schizophrenia; Schizophrenic Psychology; Urinary Incontinence

Treatment with the atypical antipsychotic drug clozapine appears to be associated with an increased incidence of urinary incontinence (UI). We posited that the potent anti-alpha-adrenergic effects of clozapine were involved, and hence that an alpha-adrenergic agonist would reduce UI. We tested this hypothesis by using ephedrine, an approved alpha-adrenergic agonist.. Fifty-seven inpatients with schizophrenia or schizoaffective disorder (DSM-IV) who met the Kane criteria for being treatment refractory were treated with clozapine (75-900 mg/day). Patients who developed UI were then openly treated with ephedrine in increasing doses until UI was attenuated or a dose of 150 mg/day was attained.. Seventeen patients developed UI as evidenced by either urine-stained sheets/clothing or direct patient reports. In 2 cases, the UI was sufficiently severe that adult diapers had to be used. Comparison of patients who developed UI and those who did not showed that UI was associated with female gender and with concomitant treatment with typical antipsychotic drugs. One patient was treated with a behavioral program, but the remaining 16 patients were treated with ephedrine. Ephedrine treatment was very effective, with 15/16 patients showing improvement within 24 hours after reaching maximum ephedrine dosage. Twelve of 16 (including the 2 most severe) eventually had a complete remission of their UI. In the remaining 4 patients, 3 had a reduction in the frequency of UI and 1 showed no response. These benefits have been maintained over the course of 12 months of subsequent treatment for several patients. There were no side effects associated with the use of ephedrine nor were there any changes in neuropsychiatric status.. Ephedrine appears to be a safe and effective treatment clozapine-associated UI. By inference, it is likely that clozapine may cause UI via its anti-alpha-adrenergic properties.

Topics: Adrenergic alpha-Agonists; Adult; Aged; Antipsychotic Agents; Clozapine; Drug Therapy, Combination; Ephedrine; Female; Humans; Incidence; Male; Middle Aged; Psychotic Disorders; Schizophrenia; Treatment Outcome; Urinary Incontinence

Topics: Antipsychotic Agents; Clozapine; Enuresis; Humans; Urinary Incontinence

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Interactions; Dystonia; Female; Humans; Middle Aged; Posture; Thiazoles; Urinary Incontinence

Topics: Antipsychotic Agents; Aripiprazole; Bethanechol; Clozapine; Female; Humans; Middle Aged; Schizophrenia; Urinary Incontinence

Urinary incontinence and enuresis are well-known side effects of clozapine. However, clinical experience has shown that patients also suffer from diverse lower urinary tract symptoms (LUTS). The natural course of clozapine-related LUTS is unclear. Thus, a longitudinal follow-up study is needed. A total of 101 subjects who were taking clozapine initially participated. Their LUTS were evaluated using the International Prostate Symptom Score (IPSS), other questionnaires, and a medical records review. After 2 years, 87 of the original subjects could be contacted, and the status of their LUTS was re-evaluated. The average IPSS total was 7.4 +/- 5.9 at the initial evaluation. Although only 11 subjects (10.9%) reported actual incontinence, 42 subjects (41.6%) were found to have clinically significant LUTS (IPSS total score > or =8). No influencing factors could be found among the demographic and clinical variables. At the follow-up, the average IPSS total (7.9 +/- 6.0) and the percentage of subjects with clinically significant LUTS (43.7%) had both increased, although the change was not statistically significant. The prevalence of LUTS in clozapine-medicated patients was higher than in the general population of the same age. However, the prevalence of incontinence was only a quarter of that of LUTS. If clinicians focus only on incontinence, distress from LUTS will not receive appropriate attention. Furthermore, contrary to literature observations, clozapine-related LUTS did not remit easily but rather persisted even into the long-term maintenance phase. More concern should be directed at these troublesome and often neglected side effects.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Follow-Up Studies; Humans; Male; Medical Records; Prospective Studies; Quality of Life; Stress, Psychological; Surveys and Questionnaires; Time Factors; Urinary Incontinence; Urination Disorders; Young Adult

Topics: Adult; Antipsychotic Agents; Clozapine; Fecal Incontinence; Humans; Male; Urinary Incontinence

Topics: Antipsychotic Agents; Clozapine; Cross-Sectional Studies; Humans; Mental Disorders; Retrospective Studies; Urinary Incontinence

This study investigated the incidence of clozapine-associated urinary incontinence (UI) in schizophrenic patients, the percentage of these patients with persistent urinary incontinence (PUI), and the possible factors affecting the occurrence of UI.. A total of 61 Chinese in-patients with schizophrenia (according to DSM-IV) treated with clozapine for more than 3 months were assessed retrospectively for the occurrence of UI. Patients who still had UI at the time of assessment were classified as having PUI. Patients whose UI had resolved at the time of assessment were classified as having self-limited urinary incontinence (SUI). We compared the characteristics of UI and non-UI cases and of PUI and SUI cases.. The results showed that urinary incontinence developed at some time in 27 of 61 patients (44.3%), and that it was persistent in 15 of 61 patients (25%). There were no statistically significant differences in age, sex, clozapine dose, duration of clozapine use, duration of index admission, duration of illness, age at onset of schizophrenia, or concurrent treatment with other psychiatric medications between the UI and non-UI groups and between the PUI and SUI groups.. Clozapine-associated urinary incontinence may be persistent in some patients, and it should be cautiously monitored in every patient taking clozapine.

Topics: Adult; Antipsychotic Agents; Chronic Disease; Clozapine; Ethnicity; Female; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Schizophrenia; Taiwan; Urinary Incontinence

Topics: Administration, Intranasal; Adult; Ambulatory Care; Clozapine; Deamino Arginine Vasopressin; Female; Humans; Male; Mandelic Acids; Treatment Outcome; Urinary Incontinence

Urinary incontinence may occur in patients with severe mental illness. Psychosis and neuroleptic medication have both been implicated, but there has been a lack of systematic evaluation of the precise relationship between these phenomena. Incontinence has been recognized as a complication of clozapine treatment and we examined this in 16 consecutively treated patients. Thirteen were established on therapeutic doses, one of whom was excluded from further study due to pre-existing incontinence. Retrospective assessment revealed that nocturnal incontinence was experienced by five of the remaining 12 patients, occurring in the first 3 months of treatment and resolving spontaneously in all cases. Incontinence was documented in the case notes in only one of the five cases and there was a tendency for affected patients to be embarrassed and reluctant to report it to staff. Specific enquiry may be necessary to elicit this phenomenon and incontinence should be considered as a possible factor in poor compliance with clozapine.

Topics: Adult; Clozapine; Dose-Response Relationship, Drug; Enuresis; Female; Humans; Male; Middle Aged; Patient Compliance; Psychotic Disorders; Retrospective Studies; Urinary Incontinence