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Pharmacologic predictors of benzodiazepine response trajectory in anxiety disorders: a Bayesian hierarchical modeling meta-analysis

Published online by Cambridge University Press:  01 October 2021

Julia N. Stimpfl ,
Jeffrey A. Mills  and
Jeffrey R. Strawn Open the ORCID record for Jeffrey R. Strawn [Opens in a new window]
Julia N. Stimpfl
Affiliation:
Anxiety Disorders Research Program, Department of Psychiatry and Behavioral Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA
Jeffrey A. Mills
Affiliation:
Carl H. Lindner College of Business, University of Cincinnati, Cincinnati, Ohio, USA
Jeffrey R. Strawn*
Affiliation:
Anxiety Disorders Research Program, Department of Psychiatry and Behavioral Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA Division of Clinical Pharmacology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA Division of Child and Adolescent Psychiatry, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
*
*Author for correspondence: Jeffrey R. Strawn, MD Email: strawnjr@uc.edu
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Abstract

Background

Despite frequent benzodiazepine use in anxiety disorders, the trajectory and magnitude of benzodiazepine response and the effects of benzodiazepine potency, lipophilicity, and dose on improvement are unknown.

Methods

We performed a meta-analysis using weekly symptom severity data from randomized, parallel group, placebo-controlled trials of benzodiazepines in adults with anxiety disorders. Response was modeled for the standardized change in continuous measures of anxiety using a Bayesian hierarchical model. Change in anxiety was evaluated as a function of medication, disorder, time, potency, lipophilicity, and standardized dose and compared among benzodiazepines.

Results

Data from 65 trials (73 arms, 7 medications, 7110 patients) were included. In the logarithmic model of response, treatment effects emerged within 1 week of beginning treatment (standardized benzodiazepine-placebo difference = −0.235 ± 0.024, CrI: −0.283 to −0.186, P < .001) and placebo response plateaued at week 4. Doses <6 mg per day (lorazepam equivalents) produced faster and larger improvement than higher doses (P = .039 for low vs medium dose and P = .005 for high vs medium dose) and less lipophilic benzodiazepines (beta = 0.028 ± 0.013, P = .030) produced a greater response over time. Relative to the reference benzodiazepine (lorazepam), clonazepam (beta = −0.217 ± 0.95, P = .021) had a greater trajectory/magnitude of response (other specific benzodiazepines did not statistically differ from lorazepam).

Conclusions

In adults with anxiety disorders, benzodiazepine-related improvement emerges early, and the trajectory and magnitude of improvement is related to dose and lipophilicity. Lower doses and less lipophilic benzodiazepines produce greater improvement.

Keywords

GABAanxiolyticpanic disordersocial anxietydisordergeneralized anxiety disorder
Type
Original Research
Information
CNS Spectrums , Volume 28 , Issue 1 , February 2023 , pp. 53 - 60
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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