Division of Clinical Pharmacology and Medical Toxicology, Uniformed Services University of Health Sciences, Bethesda, MD, USA.
J Addict Med. 2012 Dec;6(4):265-73. doi: 10.1097/ADM.0b013e31826b767f.
Atomoxetine has been considered as an agonist replacement therapy for cocaine. We investigated the safety of the interaction of atomoxetine with cocaine and also whether cognitive function was affected by atomoxetine during short-term administration.
In a double-blind placebo-controlled inpatient study of 20 cocaine-dependent volunteers, participants received atomoxetine 80 mg daily followed by 100 mg daily for 5 days each. On the fourth and fifth day at each dose, cocaine (20 and 40 mg) was infused intravenously in sequential daily sessions.
Preinfusion mean systolic pressures showed a small but statistically significant difference between placebo and both doses of atomoxetine. Preinfusion mean diastolic pressures were significant between placebo and atomoxetine 80 mg only. The diastolic pressure response to 40 mg cocaine was statistically significant only between the 80- and 100-mg atomoxetine doses. All electrocardiogram parameters were unchanged. Visual Analog Scale (VAS) scores for "bad effect" in the atomoxetine group were significantly higher at baseline, then declined, and for "likely to use" declined with atomoxetine treatment. On the Addiction Research Center Inventory, the atomoxetine group scored significantly lower on amphetamine, euphoria, and energy subscales (P < 0.0001). Other VAS descriptors, Brief Substance Craving Scale, Profile of Moods State, and Brief Psychiatric Rating Scale showed no differences. Atomoxetine did not affect cocaine pharmacokinetics. In tests of working memory, sustained attention, cognitive flexibility, and decision-making, atomoxetine improved performance on the visual n-back task. There were no differences in any pharmacokinetic parameters for cocaine with atomoxetine.
Atomoxetine was tolerated safely by all participants. Certain cognitive improvements and a dampening effect on VAS scores after cocaine were observed, but should be weighed against small but significant differences in hemodynamic responses after atomoxetine.
阿托西汀被认为是可卡因的激动剂替代治疗药物。我们研究了阿托西汀与可卡因相互作用的安全性，以及阿托西汀在短期给药期间是否会影响认知功能。
在一项 20 名可卡因依赖志愿者的双盲安慰剂对照住院研究中，参与者每天接受 80mg 阿托西汀，然后每天接受 100mg，每种剂量连续 5 天。在每个剂量的第 4 天和第 5 天，在每日序贯的静脉内输注 20mg 和 40mg 可卡因。
在预输注时，收缩压的平均值在安慰剂和两种剂量的阿托西汀之间存在微小但统计学显著的差异。只有在安慰剂和 80mg 阿托西汀之间，舒张压的平均值才有统计学差异。只有在 80mg 和 100mg 阿托西汀剂量之间，对 40mg 可卡因的舒张压反应才有统计学意义。所有心电图参数均未改变。在阿托西汀组中，“不良影响”的视觉模拟量表（VAS）评分在基线时显著较高，然后下降，而“可能使用”的评分随着阿托西汀的治疗而下降。在成瘾研究中心清单上，阿托西汀组在安非他命、欣快和能量子量表上的评分显著较低（P < 0.0001）。其他 VAS 描述符、简短物质渴求量表、心境状态剖面图和简短精神病评定量表没有差异。阿托西汀对可卡因的药代动力学没有影响。在工作记忆、持续注意力、认知灵活性和决策测试中，阿托西汀改善了视觉 n 回任务的表现。在与阿托西汀一起使用时，可卡因的任何药代动力学参数都没有差异。
所有参与者均耐受阿托西汀治疗。在服用可卡因后，观察到某些认知改善和 VAS 评分的抑制作用，但应权衡与阿托西汀后出现的血流动力学反应的微小但显著差异。
