Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Feb 7:16:1483770.
doi: 10.3389/fphar.2025.1483770. eCollection 2025.

Does pregabalin offer potential as a first-line therapy for generalized anxiety disorder? A meta-analysis of efficacy, safety, and cost-effectiveness

Narcis Cardoner  1   2   3   4 , Luis Gutiérrez-Rojas  5   6 , Pilar Saiz  7   8   9   10   11 , Guillermo Lahera  8   12   13   14 , Miguel Ángel Álvarez-Mon  8   15   16   17 , Pino Alonso Ortega  8   18   19   20 , María Pérez-Páramo  21
Affiliations

Does pregabalin offer potential as a first-line therapy for generalized anxiety disorder? A meta-analysis of efficacy, safety, and cost-effectiveness

Narcis Cardoner et al. Front Pharmacol. .

Abstract

Introduction: Generalized Anxiety Disorder (GAD) is a mental health condition with a recent increase in prevalence. GAD is often underdiagnosed, leading to negative consequences for individuals, healthcare systems, and society. The economic burden and impaired quality of life associated with GAD underscores the need for effective treatment. Pregabalin has shown promise in reducing anxiety symptoms; however, further research is needed to evaluate its efficacy and compare it with other treatment options. This study aimed to assess the efficacy, safety, and optimal pregabalin dosage for the treatment of GAD.

Methods: This meta-analysis followed PRISMA guidelines. Pregabalin-treated patients comprised the intervention group, whereas the comparator group received benzodiazepines, SSRIs, SNRIs, or placebo. Efficacy and safety were evaluated using various scales and adverse events (AEs). Randomized clinical trials were included in the study. Four major databases were used for this study. Outcome measures included the Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression Improvement Scale (CGI-I), discontinuation rates, costs, and quality-adjusted life-years (QALYs). Meta-analyses were conducted using Review Manager 5.4 software, employing odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed based on follow-up and dosage.

Results: Fourteen studies involving 4,822 patients were analyzed. Pregabalin demonstrated superior efficacy in reducing HAM-A global scores at 2 weeks (MD -1.23, 95% CI -1.79 to -0.66), 4 weeks (MD -1.12, 95% CI -1.60 to -0.63), 8 weeks (MD -2.50, 95% CI -4.21 to -0.79), 12 weeks (MD 0.99, 95% CI 0.35-1.63), and 6 months to 1 year (MD -3.31, 95% CI -4.30 to -2.31). Pregabalin also showed a higher response rate to HAM-A (OR 1.51, 95% CI 1.31 1.75). CGI-I scores favored pregabalin (MD -0.25, 95% CI -0.38 to -0.12), with a higher response rate (OR 1.33, 95% CI 1.15-1.55). The discontinuation rates were lower with pregabalin (OR 0.80, 95% CI 0.70, 0.91). Adverse events favored pregabalin over SSRIs/SNRIs and benzodiazepines at different doses. Pregabalin was associated with higher cost-effectiveness (MD 0.02, 95% CI 0.01, 0.03).

Conclusion: Pregabalin is an effective and well-tolerated treatment for generalized anxiety disorder, showing superior efficacy and safety compared with first-line medications.

Systematic review registration: PROSPERO CRD42024556152.

Keywords: SNRIs generalized anxiety disorder; SSRIs; benzodiazepines; efficacy; pregabalin; safety.

PubMed Disclaimer

Conflict of interest statement

Author MP-P was employed by Viatris. GL has been a consultant to and/or has received honoraria or grants from Adamed, Angelini Pharma, CIBERSAM, Instituto de Salud Carlos III, Johnson & Johnson, Lundbeck, Otsuka and Viatris España. PS has been a consultant to and/or has received honoraria or grants from Adamed, Alter Medica, Angelini Pharma, CIBERSAM, Ethypharm Digital Therapy, European Commission, Government of the Principality of Asturias, Instituto de Salud Carlos III, Johnson & Johnson, Lundbeck, Otsuka, Pfizer, Plan Nacional Sobre Drogas, Servier, and Viatris España. PAO has been a consultant to and/or has received honoraria or grants from Instituto de Salud Carlos III, Johnson & Johnson, Viatris España, Casen recordati, Boston Scientific and Medtronic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Viatris, which funded the statistical analysis and the medical writing services. The funder had the following involvement in the study: data collection and analysis, decision to publish and preparation of the manuscript. No financial compensation was provided to the physicians for their contributions as authors of this publication. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Study selection flow diagram (Preferred Reporting Items for Systematic reviews and meta-analyses).
FIGURE 2
FIGURE 2
Risk of bias (green = low risk; red = high risk; yellow = unknown).
FIGURE 3
FIGURE 3
Forest plot depicting response rate based on HAM-A scale. The response rate was significantly higher in the pregabalin group (OR: 1.51; 95% CI 1.31: 1.75).
FIGURE 4
FIGURE 4
Forest plot illustrating a significant improvement in CGI-I at the end of follow-up in the pregabalin group (A). The response rate to CGI-I at the end of the follow-up was significantly higher in the pregabalin group (OR 1.33, 95% CI 1.15–1.55) (B).
FIGURE 5
FIGURE 5
A forest plot demonstrating a significantly lower discontinuation rate in the pregabalin group (OR 0.80, 95% CI 0.70, 0.91).
FIGURE 6
FIGURE 6
Forest plots presenting the cost analysis. The total costs were significantly higher in the pregabalin group than in the SSRI/SNRI group (A). Furthermore, drug costs were significantly higher in the pregabalin group than in the SSRI/SNRI group (B). QALYs were significantly higher in the pregabalin group than in the SSRI/SNRI group (C).
FIGURE 7
FIGURE 7
Funnel plot demonstrating the presence of publication bias.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Alles S. R. A., Cain S. M., Snutch T. P. (2020). Pregabalin as a pain therapeutic: beyond calcium channels. Front. Cell. Neurosci. 14, 83. 10.3389/fncel.2020.00083 - DOI - PMC - PubMed
    1. Álvarez E., Olivares J. M., Carrasco J. L., López-Gómez V., Rejas J. (2015). Clinical and economic outcomes of adjunctive therapy with pregabalin or usual care in generalized anxiety disorder patients with partial response to selective serotonin reuptake inhibitors. Ann. general psychiatry 14 (1), 2. 10.1186/s12991-014-0040-0 - DOI - PMC - PubMed
    1. Armbrecht E., Shah R., Poorman G. W., Luo L., Stephens J. M., Li B., et al. (2021). Economic and humanistic burden associated with depression and anxiety among adults with non-communicable chronic diseases (NCCDs) in the United States. J. Multidiscip. Healthc. 14, 887–896. 10.2147/JMDH.S280200 - DOI - PMC - PubMed
    1. Arnold L. M., Sarzi-Puttini P., Arsenault P., Khan T., Bhadra Brown P., Clair A., et al. (2015). Efficacy and safety of pregabalin in patients with fibromyalgia and comorbid depression taking concurrent antidepressant medication: a randomized, placebo-controlled study. J. rheumatology 42 (7), 1237–1244. 10.3899/jrheum.141196 - DOI - PubMed
    1. Bereza B. G., Machado M., Einarson T. R. (2009). Systematic review and quality assessment of economic evaluations and quality-of-life studies related to generalized anxiety disorder. Clin. Ther. 31 (6), 1279–1308. 10.1016/j.clinthera.2009.06.004 - DOI - PubMed

Publication types