Scopolamine Ointment for Clozapine-Associated Sialorrhea: A Case Report.
Scopolamine Ointment for Clozapine-Associated Sialorrhea: A Case Report.
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东莨菪碱软膏治疗氯氮平相关流涎：病例报告。
DOI：
10.1097/jcp.0000000000000613
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Wada Y.
中科院分区：
文献类型：
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作者：
Goto T;Kato M;Matsumura Y;Omata N;Yoshida M;Watanabe K;Takahashi T;Higashima M;Wada Y.
根据先前的研究，所有的毒蕈碱受体都影响唾液分泌。[11]尽管由于氯氮平的M4毒蕈碱激动和抗胆碱能（M1、M2、M3和M5）活性，CAS的确切病理生理学尚不清楚，但已假设毒蕈碱受体在CAS中起作用。尽管已经报道了CAS的各种药物治疗，但没有发现药物明显上级其他药物。4早期关于CAS药物治疗的报告主要集中在抗胆碱能药物12;然而，口服抗胆碱能药物与氯氮平联合使用可增强全身抗胆碱能作用。它可能导致严重的并发症，如结肠穿孔。东莨菪碱贴剂通过微血管皮肤（人体最具渗透性的部位）吸收，并显示出全身作用，如预防运动病和减少唾液分泌。6经皮给药允许高度控制和最小剂量，9经皮东莨菪碱的不良反应发生率低于口服东莨菪碱，因为对照药物血浆浓度较高。6两份病例报告描述了使用东莨菪碱贴剂治疗CAS。McKane等人8描述了4例重度CAS患者的相应临床病程，这些患者对东莨菪碱贴剂（1 mg/72小时）反应良好。Gaftanyuk和Trestman 9报告了东莨菪碱贴剂（1.5 mg/72小时）对CAS患者的有效性，该患者对其他药物（即托特罗定、可乐定贴剂或苯扎托品）无反应。东莨菪碱贴剂的效果在数小时内出现，并持续数月。日本报道了使用东莨菪碱软膏治疗与各种疾病相关的流口水，13，14，那里没有东莨菪碱贴剂。在我们的病例中，软膏显著改善了CAS，而没有东莨菪碱透皮给药的常见不良反应（例如，口干、皮肤反应、嗜睡和眼调节受损）6，7以及其他严重的抗胆碱能不良反应。因此，我们能够将氯氮平的剂量增加到最佳水平。我们推测，软膏的透皮吸收导致降低不良反应，以及东莨菪碱贴剂。
DISCUSSIONAccording to previous studies, all muscarinic receptors impact on salivation. 11 It has been hypothesized that muscarinic receptors play a role in CAS, although the exact pathophysiology of CAS remains unclear because of clozapine's M4 muscarinic agonism and anticholinergic (M1, M2, M3, and M5) activities. Although various pharmacological treatments of CAS have been reported, no drug has been found to be markedly superior to others. 4 Earlier reports about medications for CAS have mainly focused on anticholinergic medications12; however, combining oral anticholinergic drugs with clozapine potentiates systemic anticholinergic effects. It can result in severe complications such as colon perforation. 11, 12 Scopolamine patches are absorbed through postauricular skin (the most permeable site in the human body) and show systemic effects such as preventing motion sickness and reducing salivation. 6 The transdermal delivery allows for a highly controlled and minimal dose, 9 and transdermal scopolamine has been associated with a lower incidence of adverse effects than oral scopolamine because of greater control drug plasma concentrations. 6 Two case reports have described the treatment of CAS with scopolamine patches. McKane et al8 described the respective clinical courses of 4 patients with severe CAS who responded well to scopolamine patches (1 mg per 72 hours). Gaftanyuk and Trestman9 reported the usefulness of scopolamine patches (1.5 mg per 72 hours) for a patient with CAS who responded to no additional medications (ie, tolterodine, clonidine patch, or benztropine). The effect of scopolamine patches emerged within hours and persisted for several months.Treatment of drooling associated with various diseases using scopolamine ointment has been reported in Japan, 13, 14 where scopolamine patches are unavailable. In our case, the ointment improved CAS considerably without frequent adverse effects of transdermal scopolamine (eg, dry mouth, skin reaction, drowsiness, and impaired ocular accommodation) 6, 7 as well as other severe anticholinergic adverse effects. Consequently, we were able to increase the dose of clozapine to the optimal level. We speculate that transdermal absorption of the ointment led to lowering adverse effects as well as scopolamine patches.