Effects of the combination of metyrapone and oxazepam on cocaine craving and cocaine taking: a double-blind, randomized, placebo-controlled pilot study

被引:25
作者
Kablinger, Anita S. [2 ]
Lindner, Marie A. [3 ]
Casso, Stephanie [4 ]
Hefti, Franz [5 ]
DeMuth, George [6 ]
Fox, Barbara S. [5 ]
McNair, Lindsay A. [7 ]
McCarthy, Bruce G. [8 ]
Goeders, Nicholas E. [1 ,5 ]
机构
[1] Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol Toxicol & Neurosci, Shreveport, LA 71130 USA
[2] Virginia Tech, Caril Sch Med, Roanoke, VA USA
[3] BioAdvance, Philadelphia, PA USA
[4] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA
[5] Embera NeuroTherapeut Inc, Shreveport, LA USA
[6] Stat Tech Serv, Chapel Hill, NC USA
[7] Equipoise Consulting LLC, Allston, MA USA
[8] Afferent Pharmaceut, San Mateo, CA USA
关键词
Benzodiazepine; cocaine; cortisol; craving; HPA axis; metyrapone; oxazepam; stress; PITUITARY-ADRENAL AXIS; MAJOR-DEPRESSION; INDUCED REINSTATEMENT; CONTROLLED TRIAL; RATS; KETOCONAZOLE; DEPENDENCE; STRESS; INHIBITION; THERAPY;
D O I
10.1177/0269881111430745
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Although cocaine dependence affects an estimated 1.6 million people in the USA, there are currently no medications approved for the treatment of this disorder. Experiments performed in animal models have demonstrated that inhibitors of the stress response effectively reduce intravenous cocaine self-administration. This exploratory, double-blind, placebo-controlled study was designed to assess the safety and efficacy of combinations of the cortisol synthesis inhibitor metyrapone, and the benzodiazepine oxazepam, in 45 cocaine-dependent individuals. The subjects were randomized to a total daily dose of 500 mg metyrapone/20 mg oxazepam (low dose), a total daily dose of 1500 mg metyrapone/20 mg oxazepam (high dose), or placebo for 6 weeks of treatment. The outcome measures were a reduction in cocaine craving and associated cocaine use as determined by quantitative measurements of the cocaine metabolite benzoylecgonine (BE) in urine at all visits. Of the randomized subjects, 49% completed the study. The combination of metyrapone and oxazepam was well tolerated and tended to reduce cocaine craving and cocaine use, with significant reductions at several time points when controlling for baseline scores. These data suggest that further assessments of the ability of the metyrapone and oxazepam combination to support cocaine abstinence in cocaine-dependent subjects are warranted.
引用
收藏
页码:973 / 981
页数:9
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