Gallagher Keith E, Funaro Melissa C, Woods Scott W
From the Department of Psychiatry, Yale University School of Medicine.
Harvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, CT.
J Clin Psychopharmacol. 2022;42(3):308-314. doi: 10.1097/JCP.0000000000001552.
PURPOSE/BACKGROUND: Stimulants can cause psychotic symptoms at high doses and with parenteral use, but it remains uncertain whether the clinical use of prescription stimulants (PS) at therapeutic doses precipitates psychosis or influences long-term psychosis risk. Although serious, psychosis is a relatively uncommon event that is difficult to detect in brief randomized controlled trials. There have been several large-scale observational studies of PS and psychosis risk, which have not been reviewed; therefore, we conducted a systematic review of observational studies of PS and psychosis risk in adults and children.
METHODS/PROCEDURE: We conducted a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered with International Prospective Register of Systematic Reviews (CRD42021243484). Eligible studies were longitudinal observational studies, either cohort or case-control, published in English that reported on PS exposure and risk of psychotic events or disorders. Risk of bias assessments were performed with the ROBINS-I instrument.
FINDINGS/RESULTS: There were 10,736 reports screened, and 8 were ultimately included (n = 232,567 patients): 4 retrospective cohort studies, 1 nested case-control study, 2 self-controlled case series, and 1 prospective cohort study. Exposure to methylphenidate (MPH) was more commonly studied than amphetamine (AMPH). In the 3 studies with lowest risk of bias, there was no effect of MPH exposure on psychosis risk, but there was evidence for increased risk with AMPH in 1 study.
IMPLICATIONS/CONCLUSIONS: We conclude that observational studies do not support a clear-cut effect of prescribed MPH on psychosis risk but that AMPH has been less well studied and may increase psychosis risk.
目的/背景：兴奋剂在高剂量使用及肠胃外给药时可引发精神症状，但治疗剂量的处方兴奋剂（PS）的临床使用是否会引发精神病或影响长期精神病风险仍不确定。尽管精神病很严重，但它是一种相对不常见的情况，在简短的随机对照试验中很难检测到。已有多项关于PS与精神病风险的大规模观察性研究，但尚未进行综述；因此，我们对成人和儿童中PS与精神病风险的观察性研究进行了系统综述。
方法/程序：我们根据系统评价和荟萃分析的首选报告项目指南进行了系统综述。该方案已在国际前瞻性系统评价注册库（CRD42021243484）注册。符合条件的研究为纵向观察性研究，包括队列研究或病例对照研究，以英文发表，报告了PS暴露与精神病事件或疾病的风险。使用ROBINS-I工具进行偏倚风险评估。
共筛选了10736份报告，最终纳入8份（n = 232567名患者）：4项回顾性队列研究、1项巢式病例对照研究、2项自身对照病例系列研究和1项前瞻性队列研究。与苯丙胺（AMPH）相比，对哌甲酯（MPH）暴露的研究更为常见。在偏倚风险最低的3项研究中，MPH暴露对精神病风险没有影响，但在1项研究中有证据表明AMPH会增加风险。
启示/结论：我们得出结论，观察性研究不支持规定剂量的MPH对精神病风险有明确影响，但对AMPH的研究较少，它可能会增加精神病风险。
