Long-term outcome after discontinuation of benzodiazepines for insomnia: a survival analysis of relapse

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Abstract

Discontinuation of benzodiazepine (BZD) treatment for insomnia can be a difficult task. Cognitive-behavior therapy (CBT) for insomnia, combined with a supervised medication taper, can facilitate withdrawal but there is limited evidence on long-term outcome after discontinuation. The objective of this study was to examine medication-free survival time and predictors of relapse (i.e., resumed BZD hypnotics) over a 2-year period in 47 older adults (mean age 62.1 years) with persistent insomnia and prolonged BZD use (average duration of 18.9 years), who had successfully discontinued BZD following CBT for insomnia, a supervised medication taper program, or a combined approach. The Kaplan–Meier product-limit method was used to estimate survival time, defined as time between end-of-treatment and relapse or end of follow-up. By the end of the 24-month follow-up, 42.6% of the samples had resumed BZD use. Participants in the Combined (33.3%) and Taper (30.8%) groups relapsed significantly less than their counterparts from the CBT group (69.2%). Survival rates at 3 months were 61.5% (CBT), 100% (Taper), and 80.9% (Combined). At 12 months, they were 38.5%, 83.3%, and 70.8%, respectively; and, at 24 months, they were 28.9%, 64.8% and 64.9%, respectively. Mean survival time was significantly longer for both the Taper (18.6 months, SE=2.1) and Combined groups (12.6 months, SE=1.4), relative to the CBT group (8.5 months, SE=1.8). Significant predictors of relapse included treatment condition, end of treatment insomnia severity, and psychological distress. In conclusion, there is a substantial relapse rate following BZD discontinuation among prolonged users. CBT booster sessions might enhance compliance with CBT and prove useful in preventing relapse.

Introduction

Insomnia is a widespread and burdensome health complaint which increases with aging. Chronic insomnia has been associated with functional impairments, reduced quality of life, higher risk for depression, and increased utilization of health-care services (Ohayon and Caulet, 1996, Simon and VonKorff, 1997, Weissman, Greenwald, Nino-Muricia and Dement, 1997). The higher incidence of insomnia with aging is paralleled by an increased use of hypnotic drugs among older adults. Compared to prevalence rates in middle aged individuals with insomnia complaints, hypnotic use in older adults is more than twice as high (14%). These rates are even higher in elderly patients attending medical practices, with 26% of women and 6% of men using sleep medications (Hohagen, Käppler, Schramm, Rink, Weyerer, Riemann and Berger, 1994, Ohayon and Caulet, 1996).

Benzodiazepines (BZD) are efficacious in relieving insomnia and, as hypnotics, may be indicated in the treatment of acute sleep difficulties. However, this drug class is associated with potential adverse effects (e.g., memory impairments), with altered sleep structure (e.g., reduces stages 3 and 4) and with increased risks of physical and psychological dependence. Because elimination of BZD metabolites slows down with aging, long-term use exposes elderly users to an exacerbation of these risks (Tamblyn et al., 1994). BZD-related health hazards, specific to the aging population, have also been identified. They include increased risk of falls and hip fractures (Leipzig, Cumming and Tinetti, 1999, Ray, Griffin, Schaffner, Bauth and Melton, 1987, Ray, Thapa and Gideon, 2000) and road accidents by elderly drivers (Hemmelgarn, Suissa, Huang, Boivin and Pinard, 1997, Ray, Fought and Decker, 1992). According to standard prescription guidelines, hypnotic use should be restricted to a maximum of four weeks (National Institutes of Health, 1984, National Institute of Health, 1991). Despite this, a significant proportion of the population use BZDs for sleep on a chronic basis. Among these users, older adults are overly represented (Egan, Morides, Wolfson and Monette, 2000, Morgan, et al., 1988, Tamblyn et al., 1994).

Discontinuation of BZD hypnotics can be a difficult task. Relapse rates often exceeding 50% after discontinuation have been reported at follow-ups (Kirmil-Gray, Eagleston, Thorensen and Zarcone, 1985, Rickels, et al., 1991, Rickels, Schweizer, Case and Greenblatt, 1990). Cognitive-behavior therapy (CBT) has been shown helpful in aiding patients suffering from anxiety (Otto, Pollack, Sachs, Reiter, Meltzer-Brody and Rosenbaum, 1993, Sanchez-Craig, Cappell, Busto, and Kay, 1987, Spiegal, Bruce, Gregg, and Nuzzarello, 1994) and insomnia (Baillargeon, Demers and Ladouceur, 1998, Lichstein, Peterson, Ridel, Means, Epperson, and Aguillard, 1999, Morgan, Thompson, Dixon, Tomeny and Mathers, 2003, Morin, Colecchi, Ling and Sood, 1995) discontinue BZD medications. In two recent studies reporting on the use of CBT to facilitate BZD withdrawal, significantly more participants who had received CBT during taper were drug-free by the end of the treatment period compared to those who had not received it (Baillargeon, Landreville, Verreault, Beauchemin, Grégoire and Morin, 2003, Morin et al., 2004). CBT has also been shown to decrease relapse rates (return to medication use) and to facilitate long-term abstinence in patients using BZD for anxiety problems (Bruce, Spiegel, & Hegel, 1999). Few studies though have systematically investigated long-term outcome (beyond 12 months) after successful withdrawal and, to our knowledge, none has documented relapse-free survival time (time without medication use) in patients suffering from chronic insomnia.

This study aimed at examining long-term outcome (24 months), in terms of medication-free survival time among individuals with chronic insomnia who had previously discontinued BZD usage. A secondary goal was to examine predictors of relapse.

Section snippets

Method

The present report is based on follow-up data from a randomized comparative clinical trial which evaluated the effectiveness of three treatment conditions in helping patients withdraw from BZD hypnotic medication (Morin et al., 2004). In the present study, survival time between end-of-treatment and relapse or end of follow-up was examined in 47 patients who had completely discontinued BZD use in the former study. Information regarding this principal study, essential to the presentation and

Survival time

Of the total sample, 42.6% relapsed, 69.2% in the CBT, 30.8% in the Taper and 33.3% in the Combined group. A total of six patients were censured before the end of the 24-month follow-up period. Mean survival time was 8.5 months (SE=1.8) for the CBT group, 18.6 months (SE=2.1) for the Taper group and 12.6 months (SE=1.4) for the Combined group. Survival at 3 months was of 61.5% in the CBT group, 100% in the Taper group, and 80.9% in the Combined group. At 12 months, survival was of 38.5%, 83.3%,

Discussion

Results of this study showed a substantial relapse rate after BZD discontinuation. Indeed, 20 patients out of 47 (43%) relapsed during the two-year follow up. This rate is consistent with prior reports on long-term outcome after BZD withdrawal among patients suffering from anxiety disorders (Bruce, Spiegel, and Hagel, 1999, Rickels, et al., 1991, Rickels, Schweizer, Case and Greenblatt, 1990). No information regarding long-term outcome after participation in a structured BZD discontinuation

Acknowledgements

Preparation of this article was supported in part by the National Institute of Mental Health (MH55469).

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