Newton Thomas F, Roache John D, De La Garza Richard, Fong Tim, Wallace Christopher L, Li Shou-Hua, Elkashef Ahmed, Chiang Nora, Kahn Roberta
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Psychopharmacology (Berl). 2005 Nov;182(3):426-35. doi: 10.1007/s00213-005-0102-8. Epub 2005 Oct 19.
Methamphetamine dependence is a growing problem for which no medication treatments have proven effective.
We evaluated bupropion, an antidepressant with beneficial effects for the treatment of nicotine dependence, in patients with methamphetamine dependence, to assess the safety and tolerability of methamphetamine administration during bupropion treatment.
Twenty-six participants entered the study and 20 completed the protocol. Participants received intravenous methamphetamine (0, 15, and 30 mg) before and after randomization to twice-daily bupropion (150 mg SR) or matched placebo. Dependent measures included cardiovascular effects of methamphetamine, methamphetamine and amphetamine pharmacokinetics, and peak and trough plasma concentrations of bupropion and its metabolites.
Bupropion treatment was well tolerated, with bupropion- and placebo-treated groups reporting similar rates of adverse events. Methamphetamine administration was associated with expected stimulant cardiovascular effects, and these were not accentuated by bupropion treatment. Instead, there was a trend for bupropion to reduce methamphetamine-associated increases in blood pressure and a statistically significant reduction in methamphetamine-associated increases in heart rate. Pharmacokinetic analysis revealed that bupropion treatment reduced the plasma clearance of methamphetamine and also reduced the appearance of amphetamine in the plasma. Methamphetamine administration did not alter the peak and trough plasma concentrations of bupropion or its metabolites.
Methamphetamine administration was well tolerated during bupropion treatment. There was no evidence of additive cardiovascular effects when the drugs were coadministered. This study provides initial evidence for the safety of prescribing bupropion for the treatment of methamphetamine abuse and dependence. The impact of bupropion treatment in patients who abuse larger doses of methamphetamine remains undetermined.
甲基苯丙胺成瘾是一个日益严重的问题，尚无药物治疗被证明有效。
我们评估了安非他酮，一种对治疗尼古丁成瘾有有益作用的抗抑郁药，用于甲基苯丙胺成瘾患者，以评估在安非他酮治疗期间给予甲基苯丙胺的安全性和耐受性。
26名参与者进入研究，20名完成了方案。参与者在随机分组接受每日两次的安非他酮（150mg缓释片）或匹配的安慰剂之前和之后接受静脉注射甲基苯丙胺（0、15和30mg）。相关测量包括甲基苯丙胺的心血管效应、甲基苯丙胺和苯丙胺的药代动力学，以及安非他酮及其代谢物的血浆峰浓度和谷浓度。
安非他酮治疗耐受性良好，安非他酮治疗组和安慰剂治疗组报告的不良事件发生率相似。给予甲基苯丙胺与预期的兴奋剂心血管效应相关，且这些效应未因安非他酮治疗而加重。相反，安非他酮有降低甲基苯丙胺相关血压升高的趋势，且在统计学上显著降低甲基苯丙胺相关的心率升高。药代动力学分析显示，安非他酮治疗降低了甲基苯丙胺的血浆清除率，也减少了苯丙胺在血浆中的出现。给予甲基苯丙胺未改变安非他酮及其代谢物的血浆峰浓度和谷浓度。
在安非他酮治疗期间给予甲基苯丙胺耐受性良好。联合用药时没有累加心血管效应的证据。本研究为开具安非他酮治疗甲基苯丙胺滥用和成瘾的安全性提供了初步证据。安非他酮治疗对滥用大剂量甲基苯丙胺患者的影响仍未确定。
