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Effectiveness and safety of long-term benzodiazepine use in anxiety disorders

a systematic review and meta-analysis

Shinfuku, Masakia,,b; Kishimoto, Taishirob; Uchida, Hiroyukib,,d; Suzuki, Takefumic; Mimura, Masarub; Kikuchi, Toshiakib

International Clinical Psychopharmacology: September 2019 - Volume 34 - Issue 5 - p 211–221
doi: 10.1097/YIC.0000000000000276

Long-term benzodiazepines (BZDs) use is not endorsed in the treatment guidelines for anxiety disorders, but is prevalent in the real-world clinical settings. A systematic literature review was performed by using PubMed (last search: May 2019) to identify randomized controlled trials (RCTs) or maintenance studies following RCT that examined the effectiveness of BZDs in patients with anxiety disorders for a duration of 13 weeks or more. Meta-analyses were then conducted regarding changes in the Hamilton Anxiety Rating Scale (HAM-A) scores from baseline through endpoint, all-cause discontinuation, side effects, and the numbers of panic attacks at endpoint. Eight studies were identified (N = 1228). There were no significant differences in all outcomes between BZDs and antidepressants after the initial 8-week treatment. While no significant difference was noted in the HAM-A score changes between BZDs and placebo, BZDs resulted in a lower discontinuation rate and more frequent constipation and dry mouth than placebo. Our study indicates that for those who respond to an initial 8-week treatment, continuing BZDs is equivalent to antidepressants in efficacy and safety. However, the limited number of studies warranted further investigations of the long-term effectiveness and safety of BZDs.

aDepartment of Psychiatry, Tokyo Medical Center

bDepartment of Neuropsychiatry, Keio University School of Medicine, Tokyo

cDepartment of Neuropsychiatry and Clinical Ethics, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan

dGeriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

Received 15 September 2018 Accepted 23 May 2019

Correspondence to Toshiaki Kikuchi, MD, PhD, Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160–8252, Japan, Tel: +81 3 5363 3829; fax +81 3 5379 0187; e-mail:

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