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Multicenter Study
. 2021 Apr 14;21(1):193.
doi: 10.1186/s12888-021-03196-0.

Prevalence of and factors associated with acute withdrawal symptoms after 24 weeks of eszopiclone treatment in patients with chronic insomnia: a prospective, interventional study

Yuichi Inoue  1   2 , Yoshikazu Takaesu  3 , Michinori Koebis  4
Affiliations
Multicenter Study

Prevalence of and factors associated with acute withdrawal symptoms after 24 weeks of eszopiclone treatment in patients with chronic insomnia: a prospective, interventional study

Yuichi Inoue et al. BMC Psychiatry. .

Abstract

Background: Although long-term use of benzodiazepines and benzodiazepine receptor agonists (BZDs) has been associated with an increased risk of dependence, the incidence, details of clinical manifestations, and triggering factors of withdrawal symptoms associated with long-term BZD use at common clinical doses remain unclear.

Methods: In a multicenter, open-label study of 123 Japanese patients with insomnia, patients were given a common clinical dose of eszopiclone (2 mg) for 24 weeks, and then treatment was abruptly discontinued. Withdrawal symptoms were evaluated using the Benzodiazepine Hypnotics Withdrawal Symptom Scale (BHWSS). The Insomnia Severity Index (ISI) was used to rate insomnia severity during treatment and 2 weeks after discontinuation. Dependence and poor compliance during treatment without strict medication controls were evaluated with the Benzodiazepine Dependence Self Report Questionnaire short version (Bendep-SRQ SV) subscale sum scores for problematic use, preoccupation, and lack of compliance. Associations between the presence of clinically relevant withdrawal symptoms (BHWSS≥7) and demographic measures, ISI scores at Week 24, and Bendep-SRQ SV subscale sum scores were evaluated by multivariable stepwise logistic regression analyses.

Results: Seventy-six patients completed treatment and 2 weeks of withdrawal; eight (10.5%) had clinically relevant withdrawal symptoms. On multiple logistic regression analysis, Bendep-SRQ SV subscale sum scores were correlated with withdrawal symptoms (odds ratio, 1.650; 95% confidence interval, 1.105-2.464; p = 0.014). Exacerbation of post-discontinuation insomnia was not significantly different between patients who showed clinically relevant withdrawal symptoms and those who did not (p = 0.245).

Conclusions: Dependence and poor compliance may contribute to withdrawal symptoms with long-term BZD use. Providing guidance to ensure proper compliance is thought to be the best way to mitigate withdrawal symptoms.

Trial registration: UMIN000024462 (18/10/2016).

Keywords: Benzodiazepine dependence self report questionnaire; Benzodiazepine receptor agonists; Eszopiclone; Typical clinical dose; Withdrawal symptoms.

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Conflict of interest statement

YI reports research funding from Eisai Co., Ltd. during the conduct of the study; personal fees and honoraria from Pacific Medico Co., Ltd., Otsuka Pharmaceutical Co., Ltd., and MSD K.K.; grants, personal fees, honoraria, and research funding from Takeda Pharmaceutical Co., Ltd., Eisai Co., Ltd., Alfresa Pharma Corporation, Koike Medical Co., Ltd., and Koninklijke Philips N.V.; personal fees, honoraria and clinical trial funding from Astellas Pharma Inc.; and clinical trial funding from Janssen Pharmaceutical K.K. and Idorsia Pharma Inc., outside the submitted work. YT reports grants and personal fees from Otsuka Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd., MSD K.K., Eisai Co., Ltd., and Takeda Pharmaceutical Company Limited; and personal fees from Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, and Yoshitomi Pharmaceutical Industries, Ltd., outside the submitted work. MK is an employee of Eisai Co., Ltd.

Figures

Fig. 1
Fig. 1
Distribution of BHWSS scores among the subjects (n = 76) who had clinically relevant withdrawal symptoms. BHWSS scores of 7 and greater are considered to indicate withdrawal symptoms
Fig. 2
Fig. 2
The positivity rates for the respective BHWSS items in the withdrawal symptom-positive population (n = 8)
See this image and copyright information in PMC

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