Valproate-associated Movement Disorder: A Literature Review.

Jamir Pitton Rissardo,Ana Letícia Fornari Caprara,Ícaro Durante

doi:10.14712/23362936.2021.14

Jamir Pitton Rissardo, Ana Letícia Fornari Caprara + Show 1 more

Open Access

https://doi.org/10.14712/23362936.2021.14

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Abstract

Valproate (VPA) was first synthesized in 1882, but it was only in the early 1960s that its anticonvulsant properties were discovered. The aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms, and management of VPA-associated movement disorder (MD). Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 138 reports containing 362 cases of subjects who developed a MD secondary to VPA were reported. The MD identified were parkinsonism (PKN) (252), myoclonus (MCL) (54), dystonia (DTN) (17), dyskinesia (DKN) (16), stutters (4), tics (3), akathisia (AKT) (1). In the not clearly defined group, 15 extrapyramidal symptoms, 3 AKT, 2 DTN, 1 rigidity, 1 unstable gait were assessed. The mean and median age was 55.8 (SD: 16.58) and 61 years (range: 4-87 years). The most common VPA-indication was epilepsy, and 51.36% were males. The mean and median time from the VPA start to the MD onset was 32.75 (SD: 30.05) and 21.15 months (range: 1 day - 20 years). The mean and median time from the VPA withdrawal until the MD recovery was 2.89 (SD: 2.79) and 3 months (1 day - 12 months). The most common management was drug withdrawal. A complete recovery was obtained in 80.61%. VPA-associated MD was extensively reported in the literature. PKN was the most well-described. Future studies need to clearly report the clinical history of the patient, considering the full investigation of other adverse events during their entire life.

Highlights

Valproate (VPA), and its pharmacological forms such as valproic acid, sodium valproate, and valproate semisodium are anticonvulsants (Figure 1)
VPA-associated movement disorder (MD) was extensively reported in the literature
In sum, VPA-associated MD was extensively reported in the literature probably due to availability, costs, and some historical factors of VPA

Summary

Introduction

Valproate (VPA), and its pharmacological forms such as valproic acid, sodium valproate, and valproate semisodium are anticonvulsants (Figure 1). Pierre Eymard, in the early 1960s, during animal studies to develop a new antiepileptic drug, noted that the substances dissolved in VPA had apparently better anticonvulsant properties (Henry, 2003). After this observation, many clinical studies showed the efficacy and safety of VPA for the management of focal seizures (Brugger et al, 2016). German clinical trials followed by North American studies supported the hypothesis of Lambert et al In 1995, VPA was approved as monotherapy during manic episodes by the FDA (Lempérière, 2001)

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