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The adverse event profile of pregabalin across different disorders: a meta-analysis

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Abstract

Purpose

In a recent meta-analysis of 38 double-blind randomized controlled trials (RCTs) comparing pregabalin (PGB) to placebo, we found 20 adverse events (AEs) to be significantly associated with PGB treatment. In the present study, we evaluated whether the incidence of these 20 AEs differs across distinct disorders in which PGB was investigated.

Methods

Among the 38 previously identified RCTs of PGB, we selected only those including a PGB 600 mg/day arm and subsequently classified them into four distinct groups according to the disorder in which PGB was investigated: (1) drug-resistant partial epilepsy, (2) psychiatric disorders, (3) fibromyalgia, and (4) neuropathic pain. We used risk differences (RDs) to quantify the placebo-corrected proportion of subjects discontinuing PGB due to intolerable AEs and to determine the placebo-corrected incidence of each of the 20 PGB AEs across the four disorders.

Results

Twenty-two RCTs were included in this study. Neither the proportion of subjects discontinuing PGB due to intolerable AEs nor the incidence of PGB AEs (with the exception of ataxia) differed significantly across the four disorders. Ataxia was more common in drug-resistant partial epilepsy compared to fibromyalgia. When limiting analyses to subjects on placebo, most vestibulo-cerebellar AEs (ataxia, diplopia, and blurred vision) were found to be more common in drug-resistant partial epilepsy compared to all other disorders. Diplopia and blurred vision were more common in epilepsy than in neuropathic pain; and ataxia had a higher incidence in epilepsy than in anxiety disorder and fibromyalgia. Among other CNS AEs, somnolence was more common in epilepsy compared to neuropathic pain and in anxiety disorders alone compared to neuropathic pain and fibromyalgia. Asthenia was also more common in epilepsy than in neuropathic pain and fibromyalgia.

Conclusions

Although drug-resistant partial epilepsy is associated with a higher probability of developing vestibulo-cerebellar AEs, the risk for PGB toxicity does not differ across distinct disorders.

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Acknowledgments

We are grateful to Ettore Beghi for his valuable comments.

Funding

The authors received no funding for this study.

Disclosure

G.Z. has received speaker’s or consultancy fees from EISAI, Jansen-Cilag, Novartis, Sanofi-Aventis, and UCB Pharma. P.P. is the recipient of the Susan S. Spencer Clinical Research Training Fellowship in Epilepsy supported by the American Academy of Neurology Foundation, the American Epilepsy Society, and the Epilepsy Foundation. P.G. reports no disclosures.

Author information

Authors and Affiliations

  1. U.O. Neurologia, Azienda Sanitaria di Firenze, Firenze, Italy

    Gaetano Zaccara

  2. Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

    Piero Perucca

  3. Anffas Rehabilitation Institute, Firenze, Italy

    Pier Franco Gangemi

  4. Unit of Neurology, San Giovanni di Dio Hospital, Azienda Sanitaria di Firenze, Italy

    Gaetano Zaccara

Authors
  1. Gaetano Zaccara
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  2. Piero Perucca
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  3. Pier Franco Gangemi
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Corresponding author

Correspondence to Gaetano Zaccara.

Appendices

Appendix 1

Table 2 compares the placebo-corrected incidence of PGB AEs across four distinct disorders.

Table 2 Comparison of the placebo-corrected incidence of pregabalin adverse events (AEs) across four distinct disorders. Values are risk differences (95% CI)
Full size table

Appendix 2

Table 3 presents the incidence of adverse events (AEs) in subjects taking placebo across four distinct disorders.

Table 3 Incidence of adverse events (AEs) in subjects taking placebo across four distinct disorders (epilepsy, anxiety disorders, fibromyalgia, and neuropathic pain). Values are percentages (95% CI)
Full size table

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Zaccara, G., Perucca, P. & Gangemi, P.F. The adverse event profile of pregabalin across different disorders: a meta-analysis. Eur J Clin Pharmacol 68, 903–912 (2012). https://doi.org/10.1007/s00228-012-1213-x

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  • DOI: https://doi.org/10.1007/s00228-012-1213-x

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