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Dispensability of Annual Laboratory Follow-Up After More than 2 Years of Valproic Acid Use: A Systematic Review

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Abstract

Background

The necessity of annual laboratory follow-up in patients treated with valproic acid (VPA) is controversial.

Objective

We investigated the need for annual laboratory follow-up of liver enzymes, electrolytes, and full blood count (FBC) in patients treated with VPA.

Patients and methods

A systematic search in Evidence-Based Medicine Reviews (EBMR), MEDLINE, and EMBASE was undertaken in December 2016 to identify all published articles investigating or citing valproic acid, liver function disorders, electrolyte disorders, and FBC deviations.

Results

This review included 108 articles. As the number of participants and duration of the study was not adequate in most studies to detect rare adverse events, studies did not demonstrate a clear prevalence of hepatotoxicity. While a transient increase of transaminases is common and seldom harmful, severe hepatotoxicity is a rare phenomenon and is not prevented by routine laboratory monitoring. VPA had no relevant effect on serum calcium, sodium, potassium, and albumin. The prevalence of FBC varied from 0.6 to 27.8%, occurred mostly in the first 2 years of therapy, and was usually asymptomatic.

Conclusions

Long-term monitoring in VPA treatment is only necessary when there have been dose adjustments, co-medication switches, or co-morbidity. In uncomplicated cases, annual laboratory follow-up may be discontinued after 2 years of VPA treatment. Encouraging patients to be vigilant is more effective in the detection of hepatotoxicity than laboratory testing. Follow-up of FBC at 3–6 months, 1 year, and 2 years after start or after a dose increase of VPA or interacting medication is sufficient.

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Authors and Affiliations

  1. Midden-Brabant Hospital Pharmacy, Elisabeth-TweeSteden Hospital, Dr. Deelenlaan 5, 5042 AD, Tilburg, The Netherlands

    Rosanne W. Meijboom

  2. Reinier van Arkel Mental Health Institute, ‘s Hertogenbosch, The Netherlands

    Koen P. Grootens

  3. Radboud University Medical Centre, Nijmegen, The Netherlands

    Koen P. Grootens

Authors
  1. Rosanne W. Meijboom
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  2. Koen P. Grootens
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Correspondence to Rosanne W. Meijboom.

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Rosanne W. Meijboom and Koen P. Grootens have no conflicts of interest to declare.

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No funding was received for this study.

Appendices

Appendices

1.1 Appendix 1

See Table 8.

Table 8 MeSH terms used
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1.2 Appendix 2

See Fig. 1.

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Meijboom, R.W., Grootens, K.P. Dispensability of Annual Laboratory Follow-Up After More than 2 Years of Valproic Acid Use: A Systematic Review. CNS Drugs 31, 939–957 (2017). https://doi.org/10.1007/s40263-017-0479-z

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