The clinical efficacy of promising cocaine anti-craving medications was examined in combination with buprenorphine. Twenty-one opioid-dependent cocaine abusers were enrolled in a double-blind, 12-week trial in which they received on a daily basis buprenorphine (8 mg, s.l.) plus either desipramine (150 mg, p.o.), amantadine (300 mg, p.o.), or fluoxetine (60 mg, p.o.). Urine samples and self-reported drug use were obtained 1-3 times/week. The order of greatest patient retention across the 12 weeks was desipramine (83.3%) > amantadine (66.7%) > fluoxetine (20.0%). The desipramine and amantadine groups appeared to have greater increases in opioid- and cocaine-free urines than the fluoxetine group. These results suggest that desipramine and amantadine may facilitate greater opioid and cocaine abstinence than fluoxetine.