n our previous center, the efficacy of the SSR[ sertraline alone and augmented with the dopamine-reuptakeinhibitor bupropionin depressed, recently-abstinent cocaine abusers was examined. Preliminary findings arethat the likelihood of cocaine-positive urines was significantly decreased relative to placebo in the sertralinealone and sertraline-bupropiongroups, an effect that was not sustained for the entire trial in,the sertralinealone group. In this proposal, the efficacy of sertraline alone and sertraline augmentation will be exploredfurther using agents with GABAergic activity, based on evidence suggesting that GABAergic activity, inaddition to dopaminergic and serotonergic activity, may play a role in treating cocaine dependent patients,particularly those with concurrent depression. For instance, increases in GABA are associated with decreasesin depressive symptoms and we have preliminarydata showing efficacy of a GABAergic agent infacilitatingcocaine abstinence in cocaine-abusing methadone-stabilized patients. Thus, this project will examine theclinical efficacy of sertraline alone and in combination with either the GABA transporter inhibitor tiagabineor the GABAergic agent gabapentin in depressed cocaine abusers. This 12-wk, double-blind, randomizedclinical trial will provide treatment for 140depressed, cocaine-dependent individuals (18-65 yrs) over a five-year period. Participants first will reside in a residential ward at the VA CT Healthcare System to initiateinitial cocaine abstinence, be randomized by depressive symptom severity and genetic polymorphism at thesertraline transporter, and be assigned to receive one of the following: placebo, sertraline (200 ing/day),sertraline plus tiagabine (12 mg/day), or sertraline plus gabapentin (1200mg/day). Then participants transferto the OutpatientTreatment Research Program and continue to receive study medication for weeks3-12.During the outpatient portion of the trial, subjects participate in weekly individual cognitive behavioraltherapy and are given monetary incentives for complying with study requirements. At the end of 12 weeks,patients will be tapered off the study medication and referred to an appropriate treatment program. Efficacywill be determined by length of time in treatment, length of time to relapse, by self-report and urinetoxicology, depressive symptom severity and psychosocial functioning. Prognostic relevance of factors suchas depressive symptom severity, sex,prolactin levels, genetic polymorphisms at the, e.g., sertraline,donamine. and GARA transporters, and response to transcranial magnetic stimulation will he examined.
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