Trazodone and valproate in patients discontinuing long-term benzodiazepinetherapy: effects on withdrawal symptoms and taper outcome

Recent uncontrolled research suggested that trazodone and sodium valproate may be helpful in benzodiazepine (BZ) discontinuation. We therefore underto ok a double-blind study to assess whether trazodone and valproate, as compa red to placebo, would attenuate withdrawal and facilitate discontinuation i n BZ-dependent patients with a minimum of 1 year daily BZ use. Seventy-eigh t patients, taking a mean dose of 19 +/- 17 mg/day of diazepam (or its equi valent), were stabilized for several weeks on their BZ (16 diazepam, 25 lor azepam, 37 alprazolam) and then for 1-2 weeks, pretreated with trazodone, s odium valproate or placebo before being tapered at 25% per week. All treatm ents were continued for 5 weeks post-taper. BZ-free status was assessed aft er 5 and 12 weeks post-taper. Neither trazodone nor valproate had any signi ficant effect on withdrawal severity. Peak physician withdrawal checklist c hange from baseline to peak severity was 16.4 for trazodone, 18.04 sodium v alproate and 18.24 placebo (F = 0.10; NS). Taper success rates were signifi cantly effected by both active agents at the 5-week, but not 12-week, asses sment. At 5 weeks post-taper, 79% of sodium valproate and 67% of trazodone, but only 31% of placebo patients were BZ-free (chi(2) = 7.34; df 2; P < 0. 03). Major adverse events for trazodone were sedation and dry mouth, and fo r valproate, diarrhea, nausea and headaches.