奥昔布宁速释制剂治疗氯氮平所致流涎。

Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Ann Pharmacother. 2011 Sep;45(9):e45. doi: 10.1345/aph.1Q270. Epub 2011 Aug 18.

OBJECTIVE

To describe a case of clozapine-induced sialorrhea alleviated by immediate-release oxybutynin.

CASE SUMMARY

A 53-year-old female with schizoaffective disorder-bipolar type was admitted to a psychiatric unit and initiated on clozapine. During titration to a dose of 300 mg daily and despite taking concomitant oral benztropine 1 mg twice daily, the patient began to experience mild sialorrhea. The sialorrhea became profuse when the clozapine dose reached 400 mg daily, and the patient was routinely seen with a saliva-soaked shirt. Additionally, she had become self-conscious and wanted to stop clozapine therapy. Immediate-release oxybutynin 5 mg daily was started, resulting in significant reduction of the sialorrhea within 24 hours. The patient was discharged on clozapine 300 mg daily, risperidone 6 mg at bedtime, immediate-release oxybutynin 5 mg twice daily, and oral benztropine 1.5 mg daily, with only mild sialorrhea.

DISCUSSION

It is unknown why clozapine induces sialorrhea. One speculation is that clozapine interrupts muscarinic receptor homeostasis. Immediate-release oxybutynin is an anticholinergic agent with high affinity for salivary gland M₃ receptors that may have restored muscarinic receptor imbalance in our patient. N-Desethyl-oxybutynin, an active metabolite of oxybutynin, is largely responsible for oxybutynin's anticholinergic activity. The activity of oxybutynin and its metabolite may result in dry mouth in over 80% of patients taking the immediate-release formulation, while producing dry mouth in only 40% and 7.5% of patients taking the extended-release and topical formulations, respectively.

CONCLUSIONS

To our knowledge, this is the first report of immediate-release oxybutynin successfully reducing clozapine-induced sialorrhea. If oxybutynin is considered for this indication, use of the immediate-release formulation seems prudent. Additional data, including randomized controlled trials, are needed to confirm whether immediate-release oxybutynin has a significant role in the management of this stigmatizing adverse effect.

目的

描述一例氯氮平引起的涎溢，经即释型羟丁宁缓解。

病例总结

一位 53 岁的女性，患有分裂情感障碍-双相型，被收入精神科病房，开始服用氯氮平。在滴定至每日 300mg 剂量时，尽管同时服用口服苯扎托品 1mg，每日两次，患者开始出现轻度涎溢。当氯氮平剂量达到每日 400mg 时，涎溢变得明显，患者经常穿着一件唾液浸湿的衬衫。此外，她变得很自觉，想停止氯氮平治疗。开始给予即释型羟丁宁 5mg，每日一次，24 小时内涎溢显著减少。患者出院时，氯氮平剂量为每日 300mg，瑞哌啶醇 6mg 睡前服用，即释型羟丁宁 5mg，每日两次，口服苯扎托品 1.5mg，每日一次，仅轻度涎溢。

讨论

氯氮平引起涎溢的原因尚不清楚。一种推测是氯氮平中断了毒蕈碱受体的内稳态。即释型羟丁宁是一种抗胆碱能药物，对唾液腺 M₃ 受体具有高亲和力，可能使我们的患者恢复了毒蕈碱受体失衡。羟丁宁的活性代谢物 N-去乙基羟丁宁，主要负责羟丁宁的抗胆碱能活性。即释型羟丁宁及其代谢物的活性可能导致 80%以上服用即释型制剂的患者出现口干，而服用缓释和局部制剂的患者分别只有 40%和 7.5%出现口干。