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Selective serotonin reuptake inhibitors and the risk of restless legs syndrome: a symmetry analysis

  • Pharmacoepidemiology and Prescription
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Largely based on case series, several drugs have been implicated in drug-induced restless legs syndrome (RLS) including selective serotonin reuptake inhibitors (SSRI). We aimed to assess the association between initiation of SSRIs and RLS in a self-controlled design.

Methods

We conducted a symmetry analysis, including Danish adults who filled in their first prescription of an SSRI in the period of 1997–2017 and initiated an RLS drug (quinine, ropinirole, pramipexole or rotigotine) 1 year prior to or after this date. A symmetrical distribution of prescriptions before and after SSRI initiation is expected if there is no association between SSRI and RLS (a sequence ratio (SR) of 1.0). The symmetry analysis design is robust to confounders that are stable over time. Subgroup analyses were conducted, restricting the population on sex, age, selected diagnoses and concurrent medication.

Results

A total of 10,875 patients filled in their first-ever prescription of both an SSRI and an RLS drug within a 1-year interval; 5341 patients filled their prescription of SSRI prior to their prescription of an RLS drug, and 5534 patients redeemed their prescriptions in the opposite order (SR 0.97, 95% CI 0.93–1.00). Restricting the outcome to dopamine agonist initiation revealed a slightly increased sequence ratio (SR 1.34, 95% CI 1.24–1.46), which was reduced when adjusting for trends in prescription (adjusted SR 1.21, 95% CI 1.12–1.32). Restricting the outcome to quinine initiation showed no association.

Conclusion

We found no association between the initiation of an SSRI and the development of RLS assessed by the prescription of an RLS drug.

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Data availability statement

The data that support the findings of this study are available from the Danish Health Data Agency, but restrictions apply to the availability of these data and so are not publicly available. Data are however available from the Danish Health Data Agency for research purposes only.

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Authors and Affiliations

  1. Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, J.B. Winsløws Vej 19, 2, 5000, Odense, Denmark

    Ann-Cathrine Dalgård Dunvald, Daniel Pilsgaard Henriksen, Jesper Hallas & Mette Marie Hougaard Christensen

  2. Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark

    Daniel Pilsgaard Henriksen, Jesper Hallas & Lars Christian Lund

  3. Department of Clinical Research, University of Southern Denmark, Odense, Denmark

    Mette Marie Hougaard Christensen

Authors
  1. Ann-Cathrine Dalgård Dunvald
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  2. Daniel Pilsgaard Henriksen
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  3. Jesper Hallas
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  4. Mette Marie Hougaard Christensen
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  5. Lars Christian Lund
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Contributions

All authors have made substantial contributions to the conception or design of the work. ACDD and DPH wrote the first draft of the manuscript. LCL performed the data analysis. All authors provided comments and edits throughout the drafting process for important intellectual content. All authors approved the final version of the manuscript and are accountable for all aspects included in it.

Corresponding author

Correspondence to Ann-Cathrine Dalgård Dunvald.

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The authors declare that they have no conflict of interest.

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Dunvald, AC.D., Henriksen, D.P., Hallas, J. et al. Selective serotonin reuptake inhibitors and the risk of restless legs syndrome: a symmetry analysis. Eur J Clin Pharmacol 76, 719–722 (2020). https://doi.org/10.1007/s00228-020-02847-7

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  • DOI: https://doi.org/10.1007/s00228-020-02847-7

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