PROGESTERONE COADMINISTRATION IN PATIENTS DISCONTINUING LONG-TERM BENZODIAZEPINE THERAPY - EFFECTS ON WITHDRAWAL SEVERITY AND TAPER OUTCOME

Since recent research has suggested that the major metabolites of prog esterone are barbiturate-like modulators of GABAergic function, we und ertook a pilot study of the efficacy of micronized progesterone in att enuating withdrawal and facilitating discontinuation in benzodiazepine -dependent patients with a minimum of 1 year of continuous daily use. Forty-three patients taking a mean daily dose of 16.2 mg of diazepam ( or its equivalent) were assigned, double-blind, to treatment with eith er placebo (n = 13) or progesterone (n = 30). Progesterone was titrate d to a mean daily dose of 1983 mg, and was co-administered for 3 weeks , after which the benzodiazepine was tapered by 25% per week. Progeste rone (or placebo) was then continued for 4 weeks before being disconti nued. There was no progesterone versus placebo difference in the sever ity of taper withdrawal. Withdrawal checklist change scores were 17.3 for progesterone and 16.5 for placebo (F 0.63; df 2,31; n.s.), and the Hamilton rating scale for anxiety change scores were 7.8 for progeste rone and 6.3 for placebo (F 0.22; df 2,30; n.s.). There was no differe nce in ability to remain drug-free at 12 weeks post-taper, with 57% of progesterone-treated patients, and 58% of placebo-treated patients ha ving a successful outcome.