Abstract：
There is currently no standard of care for pharmacological treatment of amphetamine-type stimulant (ATS) use disorder (ATSUD). This systematic review with meta-analysis (PROSPERO CRD42022354492) aimed to pool results from randomized placebo-controlled trials (RCTs) to evaluate efficacy and safety of prescription psychostimulants (PPs) for ATSUD.
Major indexing sources and trial registries were searched to include records published before 29 August 2022. Eligible studies were RCTs evaluating efficacy and safety of PPs for ATSUD. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. Risk ratio (RR) and risk difference were calculated for random-effect meta-analysis of dichotomous variables. Mean difference and standardized mean difference (SMD) were calculated for random-effect meta-analysis of continuous variables.
Ten RCTs (n = 561 participants) were included in the meta-analysis. Trials studied methylphenidate (n = 7), with daily doses of 54-180 mg, and dextroamphetamine (n = 3), with daily doses of 60-110 mg, for 2-24 weeks. PPs significantly decreased end-point craving [SMD -0.29; 95% confidence interval (CI) = -0.55, -0.03], while such a decrease did not reach statistical significance for ATS use, as evaluated by urine analysis (UA) (RR = 0.93; 95% CI = 0.85-1.01). No effect was observed for self-reported ATS use, retention in treatment, dropout following adverse events, early-stage craving, withdrawal and depressive symptoms. In a sensitivity analysis, treatment was associated with a significant reduction in UA positive for ATS (RR = 0.89; 95% CI = 0.79-0.99) after removing studies with a high risk of bias. In subgroup analyses, methylphenidate and high doses of PPs were negatively associated with ATS use by UA, while higher doses of PPs and treatment duration (≥ 20 weeks) were positively associated with longer retention.
Among individuals with amphetamine-type stimulant use disorder, treatment with prescription psychostimulants may decrease ATS use and craving. While effect size is limited, it may increase with a higher dosage of medications.
Major indexing sources and trial registries were searched to include records published before 29 August 2022. Eligible studies were RCTs evaluating efficacy and safety of PPs for ATSUD. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. Risk ratio (RR) and risk difference were calculated for random-effect meta-analysis of dichotomous variables. Mean difference and standardized mean difference (SMD) were calculated for random-effect meta-analysis of continuous variables.
Ten RCTs (n = 561 participants) were included in the meta-analysis. Trials studied methylphenidate (n = 7), with daily doses of 54-180 mg, and dextroamphetamine (n = 3), with daily doses of 60-110 mg, for 2-24 weeks. PPs significantly decreased end-point craving [SMD -0.29; 95% confidence interval (CI) = -0.55, -0.03], while such a decrease did not reach statistical significance for ATS use, as evaluated by urine analysis (UA) (RR = 0.93; 95% CI = 0.85-1.01). No effect was observed for self-reported ATS use, retention in treatment, dropout following adverse events, early-stage craving, withdrawal and depressive symptoms. In a sensitivity analysis, treatment was associated with a significant reduction in UA positive for ATS (RR = 0.89; 95% CI = 0.79-0.99) after removing studies with a high risk of bias. In subgroup analyses, methylphenidate and high doses of PPs were negatively associated with ATS use by UA, while higher doses of PPs and treatment duration (≥ 20 weeks) were positively associated with longer retention.
Among individuals with amphetamine-type stimulant use disorder, treatment with prescription psychostimulants may decrease ATS use and craving. While effect size is limited, it may increase with a higher dosage of medications.
摘要：
目的：目前尚无苯丙胺类兴奋剂（ATS）使用障碍（ATSUD）的药物治疗标准。这项系统的荟萃分析（PROSPEROCRD42022354492）旨在汇集随机安慰剂对照试验（RCT）的结果，以评估处方精神兴奋剂（PPs）对ATSUD的疗效和安全性。
方法：搜索主要索引来源和试验注册中心，以包括2022年8月29日之前发布的记录。合格的研究是评估PPs对ATSUD的有效性和安全性的RCT。使用CochraneRoB2工具评估偏倚风险(RoB)。计算风险比（RR）和风险差异，用于二分变量的随机效应荟萃分析。计算平均差和标准化平均差（SMD），用于连续变量的随机效应荟萃分析。
结果：10项随机对照试验（n=561名参与者）纳入荟萃分析。试验研究了哌醋甲酯(n=7)，每日剂量为54-180毫克，和右苯丙胺（n=3），每日剂量为60-110毫克，2-24周。PPs显著降低终点渴望[SMD-0.29；95%置信区间(CI)=-0.55，-0.03]，虽然这种减少对于苯丙胺类兴奋剂的使用没有达到统计学意义，通过尿液分析（UA）评估（RR=0.93；95％CI=0.85-1.01）。自我报告使用ATS没有观察到效果，保留在治疗中，不良事件后退出，早期的渴望，戒断和抑郁症状。在敏感性分析中，在移除有高偏倚风险的研究后,治疗与ATS阳性UA显著降低相关(RR=0.89;95%CI=0.79~0.99).在亚组分析中，哌醋甲酯和高剂量的PPs与UA使用ATS呈负相关，而较高剂量的PPs和治疗持续时间(≥20周)与较长的滞留时间呈正相关.
结论：在苯丙胺类兴奋剂使用障碍患者中，处方精神兴奋剂治疗可能会减少ATS的使用和渴望。虽然效果大小有限，随着药物剂量的增加，它可能会增加。
方法：搜索主要索引来源和试验注册中心，以包括2022年8月29日之前发布的记录。合格的研究是评估PPs对ATSUD的有效性和安全性的RCT。使用CochraneRoB2工具评估偏倚风险(RoB)。计算风险比（RR）和风险差异，用于二分变量的随机效应荟萃分析。计算平均差和标准化平均差（SMD），用于连续变量的随机效应荟萃分析。
结果：10项随机对照试验（n=561名参与者）纳入荟萃分析。试验研究了哌醋甲酯(n=7)，每日剂量为54-180毫克，和右苯丙胺（n=3），每日剂量为60-110毫克，2-24周。PPs显著降低终点渴望[SMD-0.29；95%置信区间(CI)=-0.55，-0.03]，虽然这种减少对于苯丙胺类兴奋剂的使用没有达到统计学意义，通过尿液分析（UA）评估（RR=0.93；95％CI=0.85-1.01）。自我报告使用ATS没有观察到效果，保留在治疗中，不良事件后退出，早期的渴望，戒断和抑郁症状。在敏感性分析中，在移除有高偏倚风险的研究后,治疗与ATS阳性UA显著降低相关(RR=0.89;95%CI=0.79~0.99).在亚组分析中，哌醋甲酯和高剂量的PPs与UA使用ATS呈负相关，而较高剂量的PPs和治疗持续时间(≥20周)与较长的滞留时间呈正相关.
结论：在苯丙胺类兴奋剂使用障碍患者中，处方精神兴奋剂治疗可能会减少ATS的使用和渴望。虽然效果大小有限，随着药物剂量的增加，它可能会增加。
