抗精神病药物引起的流溢带来了巨大的负担,但是基于证据的治疗指导是不完整的,保证抗精神病药物相关性流涕药物干预的网络荟萃分析(NMA)。PubMedCentral/PsycInfo/CochraneCentral数据库/Clinicaltrials.gov/WHO-ICTRP和中国电子期刊数据库(Qikan。cqvip.com)搜索了成人抗精神病药引起的流涕(任何定义)的已发表/未发表的RCT,到06/12/2023。我们评估了全球/当地的不一致,出版偏见,偏见风险(RoB2),以及对证据的信心,进行亚组/敏感性分析。共同主要疗效结果是唾液产量的变化(标准化平均差/SMD)和研究定义的反应(风险比/RR)。可接受性结果为全因停药(RR)。主要节点是分子;作用机制(MoA)是次要的。三十四个RCT进入系统审查,33NMA(n=1958)。所有干预措施均针对患有精神障碍的受试者中氯氮平诱导的流涎。关于个体代理人和回应,甲氧氯普胺(RR=3.11,95%C.I.=1.39-6.98),赛庚啶,(RR=2.76,95%C.I.=2.00-3.82),舒必利(RR=2.49,95%C.I.=1.65-3.77),Profiteline(RR=2.39,95%C.I.=1.97-2.90),苯海拉明(RR=2.32,95%C.I.=1.88-2.86),benzhexol(RR=2.32,95%C.I.=1.59-3.38),多塞平(RR=2.30,95%C.I.=1.85-2.88),氨磺必利(RR=2.23,95%C.I.=1.30-3.81),扑尔敏(RR=2.20,95%C.I.=1.67-2.89),阿米替林(RR=2.09,95%C.I.=1.34-3.26),阿托品,(RR=2.03,95%C.I.=1.22-3.38),还有阿司咪唑,(RR=1.70,95%C.I.=1.28-2.26)优于安慰剂,但不是格隆溴铵或异丙托溴铵。跨二级节点(k=28,n=1821),抗毒蕈药(RR=2.26,95%C.I.=1.91-2.68),苯甲酰胺(RR=2.23,95%C.I.=1.75-3.10),TCAs(RR=2.23,95%C.I.=1.83-2.72),抗组胺药(RR=2.18,95%C.I.=1.83-2.59)优于安慰剂。在面对面的比较中,阿司咪唑和异丙托溴铵在几种干预措施中表现优异。所有辅助节点,除了苯甲酰胺,在持续疗效结局方面优于安慰剂.对于夜间流涎,苯甲酰胺和阿托品均不优于安慰剂。在便秘或嗜睡/嗜睡方面,积极干预与安慰剂没有显着差异。低置信度的调查结果提示在解释结果时保持谨慎。考虑到主要节点共同主要疗效结果和头对头比较,以下药物对流涎的疗效最一致,从甲氧氯普胺通过赛庚啶减少,舒必利,Proftheline,苯海拉明,benzhexol,多塞平,氨磺必利,扑尔敏,阿米替林,和阿托品(后者不适用于夜间流涕)。与患者共享决策应指导有关氯氮平相关的流涎的治疗决策。
Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of pharmacological interventions for antipsychotic-related sialorrhea. PubMed Central/PsycInfo/Cochrane Central database/Clinicaltrials.gov/WHO-ICTRP and the Chinese Electronic Journal Database (Qikan.cqvip.com) were searched for published/unpublished RCTs of antipsychotic-induced sialorrhea (any definition) in adults, up to 06/12/2023. We assessed global/local inconsistencies, publication bias, risk of bias (RoB2), and confidence in the evidence, conducting subgroup/sensitivity analyses. Co-primary efficacy outcomes were changes in saliva production (standardized mean difference/SMD) and study-defined response (risk ratios/RRs). The acceptability outcome was all-cause discontinuation (RR). Primary nodes were molecules; the mechanism of action (MoA) was secondary. Thirty-four RCTs entered a systematic review, 33 NMA (n = 1958). All interventions were for clozapine-induced sialorrhea in subjects with mental disorders. Regarding individual agents and response, metoclopramide (RR = 3.11, 95% C.I. = 1.39-6.98), cyproheptadine, (RR = 2.76, 95% C.I. = 2.00-3.82), sulpiride (RR = 2.49, 95% C.I. = 1.65-3.77), propantheline (RR = 2.39, 95% C.I. = 1.97-2.90), diphenhydramine (RR = 2.32, 95% C.I. = 1.88-2.86), benzhexol (RR = 2.32, 95% C.I. = 1.59-3.38), doxepin (RR = 2.30, 95% C.I. = 1.85-2.88), amisulpride (RR = 2.23, 95% C.I. = 1.30-3.81), chlorpheniramine (RR = 2.20, 95% C.I. = 1.67-2.89), amitriptyline (RR = 2.09, 95% C.I. = 1.34-3.26), atropine, (RR = 2.03, 95% C.I. = 1.22-3.38), and astemizole, (RR = 1.70, 95% C.I. = 1.28-2.26) outperformed placebo, but not glycopyrrolate or ipratropium. Across secondary nodes (k = 28, n = 1821), antimuscarinics (RR = 2.26, 95% C.I. = 1.91-2.68), benzamides (RR = 2.23, 95% C.I. = 1.75-3.10), TCAs (RR = 2.23, 95% C.I. = 1.83-2.72), and antihistamines (RR = 2.18, 95% C.I. = 1.83-2.59) outperformed placebo. In head-to-head comparisons, astemizole and ipratropium were outperformed by several interventions. All secondary nodes, except benzamides, outperformed the placebo on the continuous efficacy outcome. For nocturnal sialorrhea, neither benzamides nor atropine outperformed the placebo. Active interventions did not differ significantly from placebo regarding constipation or sleepiness/drowsiness. Low-confidence findings prompt caution in the interpretation of the results. Considering primary nodes\' co-primary efficacy outcomes and head-to-head comparisons, efficacy for sialorrhea is most consistent for the following agents, decreasing from metoclopramide through cyproheptadine, sulpiride, propantheline, diphenhydramine, benzhexol, doxepin, amisulpride, chlorpheniramine, to amitriptyline, and atropine (the latter not for nocturnal sialorrhea). Shared decision-making with the patient should guide treatment decisions regarding clozapine-related sialorrhea.