Switching from long-term benzodiazepine therapy to pregabalin in patients with generalized anxiety disorder: a double-blind, placebo-controlled trial
Abstract
To evaluate the efficacy of pregabalin in facilitating taper off chronic benzodiazepines, outpatients (N = 106) with a lifetime diagnosis of generalized anxiety disorder (current diagnosis could be subthreshold) who had been treated with a benzodiazepine for 8-52 weeks were stabilized for 2-4 weeks on alprazolam in the range of 1-4 mg/day. Patients were then randomized to 12 weeks of double-blind treatment with either pregabalin 300-600 mg/day or placebo while undergoing a gradual benzodiazepine taper at a rate of 25% per week, followed by a 6-week benzodiazepine-free phase during which they continued double-blind study treatment. Outcome measures included ability to remain benzodiazepine-free (primary) as well as changes in Hamilton Anxiety Rating Scale (HAM)-A and Physician Withdrawal Checklist (PWC). At endpoint, a non-significant higher proportion of patients remained benzodiazepine-free receiving pregabalin compared with placebo (51.4% vs 37.0%). Treatment with pregabalin was associated with significantly greater endpoint reduction in the HAM-A total score versus placebo (-2.5 vs +1.3; p < 0.001), and lower endpoint mean PWC scores (6.5 vs 10.3; p = 0.012). Thirty patients (53%) in the pregabalin group and 19 patients (37%) in the placebo group completed the study, reducing the power to detect a significant difference on the primary outcome. The results on the anxiety and withdrawal severity measures suggest that switching to pregabalin may be a safe and effective method for discontinuing long-term benzodiazepine therapy.
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In outpatients with generalized anxiety disorder, there was no statistically significant difference in the rate of BZD cessation between pregabalin and placebo groups (51.4% vs 37.0%) after 12 weeks.
“Following 12 weeks of treatment, there was no statistically significant difference in the rate of BZD cessation between the pregabalin and placebo groups (51.4% versus 37.0%).”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [89]
Individuals receiving pregabalin reported fewer anxiety and withdrawal-related symptoms compared to those receiving placebo.
“Nonetheless, individuals receiving pregabalin reported fewer anxiety and withdrawal-related symptoms compared to those receiving placebo. 89”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [89]
Existing evidence indicates that gabapentin or pregabalin may offer benefits during BZD withdrawal, either by increasing the likelihood of successful discontinuation or by alleviating anxiety and withdrawal-related symptoms.
“Existing evidence indicates that they may offer benefits during BZD withdrawal, either by increasing the likelihood of successful discontinuation, 87 88 or by alleviating anxiety and withdrawal-related symptoms throughout the tapering process. 89”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [89]
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“88 Hadley et al. 89 (2012) examined the effectiveness of pre-gabalin in assisting BZD discontinuation among 106 outpatients with generalized anxiety disorder.”
- Authors
- Hadley, S. J., Mandel, F. S., & Schweizer, E.
- Affiliations
- Pfizer (United States) (US)
- Paladin Consulting Group, Hoboken, NJ, USA
- ORCID
- Mandel, Francine S
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2011-06-21
- Volume
- 26
- Issue
- 4
- Pages
- 461-470
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W2007168079
- Cited by
- 66
- References
- 45
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 6 · 2023: 3 · 2022: 7 · 2021: 6 · 2020: 6 · 2019: 2 · 2018: 8 · 2017: 1 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 4
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Neurocrine Biosciences
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- pregabalin, benzodiazepine tapering, benzodiazepine withdrawal, generalized anxiety disorder, alprazolam, anxiety symptoms, withdrawal symptoms
- MeSH terms
- Pregabalin, Adult, Alprazolam, Anxiety Disorders, Cognition, Double-Blind Method, Female, gamma-Aminobutyric Acid, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Psychomotor Performance, Least-Squares Analysis
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