Fuller M A, Borovicka M C, Jaskiw G E, Simon M R, Kwon K, Konicki P E
Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
J Clin Psychiatry. 1996 Nov;57(11):514-8. doi: 10.4088/jcp.v57n1102.
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.
非典型抗精神病药物氯氮平治疗似乎与尿失禁（UI）发生率增加有关。我们推测氯氮平强大的抗α-肾上腺素能作用与之相关，因此α-肾上腺素能激动剂会减少尿失禁。我们使用已获批准的α-肾上腺素能激动剂麻黄碱来验证这一假设。
57例符合凯恩难治性治疗标准的精神分裂症或分裂情感性障碍（DSM-IV）住院患者接受氯氮平治疗（75 - 900毫克/天）。出现尿失禁的患者随后接受麻黄碱公开治疗，剂量逐渐增加，直至尿失禁减轻或达到150毫克/天的剂量。
17例患者出现尿失禁，表现为床单/衣物有尿渍或患者直接报告。2例患者尿失禁非常严重，不得不使用成人尿布。对出现尿失禁和未出现尿失禁的患者进行比较，结果显示尿失禁与女性性别以及同时使用典型抗精神病药物有关。1例患者接受行为治疗方案，但其余16例患者接受麻黄碱治疗。麻黄碱治疗非常有效，16例患者中有15例在达到最大麻黄碱剂量后24小时内症状改善。16例患者中有12例（包括2例最严重的）最终尿失禁完全缓解。其余4例患者中，3例尿失禁频率降低，1例无反应。在随后的12个月治疗过程中，数例患者的这些益处得以维持。使用麻黄碱未出现副作用，神经精神状态也无任何变化。
麻黄碱似乎是治疗氯氮平相关尿失禁的一种安全有效的方法。由此推断，氯氮平可能通过其抗α-肾上腺素能特性导致尿失禁。
