Differential symptom reduction in depressed cocaine abusers treated with psychotherapy and pharmacotherapy.
ABSTRACT We evaluated treatment response for depressed versus nondepressed ambulatory cocaine abusers in a 12-week randomized controlled trial of desipramine and cognitive-behavioral treatment, alone and in combination. Subjects with depressive symptomatology at baseline tended to have better retention and better cocaine outcomes compared with nondepressed subjects. Desipramine was an effective antidepressant in this sample and was associated with significantly greater reduction in depressive symptoms than was placebo; however, desipramine treatment was not associated with greater reductions in cocaine use for either the depressed or euthymic subgroup. Cognitive-behavioral relapse prevention treatment was associated with significantly longer periods of consecutive abstinence and better retention compared with supportive clinical management for the depressed subgroup, but psychotherapy condition did not have an effect on depressive symptoms. These data point to differential symptom reduction in depressed cocaine addicts and underscore the importance of evaluating combined psychotherapy-pharmacotherapy approaches for this population.
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ABSTRACT: N-Substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines are a class of pure opioid receptor antagonists with a novel pharmacophore. This opioid receptor antagonist pharmacophore was used as a lead structure to design and develop several interesting and useful opioid receptor antagonists. In this review we describe: 1) early SAR studies that led to the discovery of LY255582 and analogues that are nonselective opioid receptor antagonists developed for the treatment of obesity; 2) the discovery and commercialization of LY246736 (alvimopan; ENTEREG®), a peripherally selective opioid receptor antagonist that accelerates the time to upper and lower GI recovery following surgeries that include partial bowel resection with primary anastomosis; and 3) the discovery and development of the potent and selective κ opioid receptor antagonist JDTic and analogues as potential pharmacotherapies for treating depression, anxiety, and substance abuse (nicotine, alcohol, and cocaine). In addition, the use of JDTic for obtaining the X-ray structure of the human κ opioid receptor is discussed.ChemMedChem 06/2014; DOI:10.1002/cmdc.201402142 · 3.05 Impact Factor