Our clinic has fortuitously developed the therapeutic use of the association of mianserin (maximum daily dose 90 mg) and carbamazepine (maximum daily dose 400 mg) in opiate withdrawal management. If animal studies have suggested efficacy of mianserin in such indication, no human studies have been performed. To test the efficacy of such an association, a comparison was made to clonidine (maximum daily dose 0.600 mg) in a one week treatment period according to a double blind pilot study design. Thirty-two patients were included (16 in each treatment group). The two treatments did not differ in the intensity of the withdrawal, according to the rate of retention in treatment and symptoms, and the psychic distress which were auto-evaluated every other day with the Opiate Withdrawal Questionnaire and several Visual Analog Scales (VAS). The clonidine group, however, scored significantly higher (P < 0.05) on the VAS rating of the global feeling of satisfaction on the last day. The patients in the mianserin group fortuitously had a moderately lower number of daily heroin intakes but there was no significant correlation between this variable and the global OWQ scores on Days 1, 3, 5 and 7. Given the size of the groups, we cannot conclude that the association carbamazepine-mianserin is as effective as clonidine, but a real effectiveness is probable. A study versus placebo would be necessary to draw more definitive conclusions.