Is hypnotic withdrawal facilitated by the transitory use of a substitute drug?

Long-term consumption of hypnotics may lead to various side-effects, including impaired daytime and cognitive functioning and increased risk of accidents. Unfortunately, few guidelines exist for physicians to apply when attempting to withdraw hypnotics from patients. This study investigated whether withdrawal is facilitated by using zopiclone as a substitute drug and evaluated abrupt and gradual substitution techniques.

This open, multicentre and randomized study involved 1,002 male and female outpatients aged 18 years or over recruited by psychiatrists in Lyon, France. Patients had a mean age of 44 years, and 65.9% were women. Outpatients were chronic insomniacs being treated with a hypnotic for at least three weeks. The study included a substitution (D0-D35) and a withdrawal (D36-D56) stage. Patients were randomly drawn into three parallel groups: Group A underwent gradual substitution of zopiclone for the initial BZD; Group B was subjected to complete and immediate withdrawal of the initial BZD in favor of zopiclone; and Group C remained on the initial BZD, though told otherwise. The withdrawal stage began on D36 with a 50% reduction in medication and ended on D50 with complete withdrawal.

Groups A (gradual substitution) and B (abrupt substitution) presented a net improvement in sleep during the substitution stage. However, Group B displayed a better improvement in sleep-onset period, a decrease in nocturnal awakenings and an increased quantity of sleep. In the withdrawal stage, Groups A and B were similar but Group C displayed a deterioration in sleep. Following the withdrawal stage, 29% of patients in Group C, 18% in Group A and 19% in Group B resumed hypnotic use.

Discontinuation of this type of medication is possible in over three quarters of cases, provided that the prescribing physician adheres to a precise withdrawal protocol. Patients on zopiclone were less likely to resume consumption of hypnotics during the week of full withdrawal and were more satisfied with sleep than when treated with a BZD hypnotic. Finally, the results of the study showed that abrupt substitution yielded better results for chronic users of hypnotics.