An overview of the pharmacotherapeutics for dystonia: advances over the past decade

ABSTRACT

Introduction

Dystonia is the third most common movement disorder, impacting quality of life and work productivity. Its pathogenesis is heterogeneous, and many pharmacotherapeutics have been suggested for its treatment. The mainstay of management for focal dystonia is botulinum toxin. Oral pharmacotherapeutics usually are nonspecific and associated with risk of unwanted side effects such as drowsiness and lethargy. There is tremendous need for robust clinical trials for new pharmacotherapeutics as we deepen our understanding of dystonia.

Areas covered

This review will focus on the advances and research in the pharmacologic treatment of dystonia from January 2012 to April 2022. We performed a systematic database search on PubMed for the period mentioned.

Expert opinion

Botulinum toxins remain the mainstay of focal dystonia treatment but may be insufficient for treatment of patients with more widespread dystonia manifestations. The most novel emerging therapies include daxibotulinumtoxinA, dipraglurant, and sodium oxybate. There is a strong clinical need for more effective therapeutic options in dystonia, which may involve the development of individualized treatment options based on dystonia subtype, etiology, or novel mechanisms of action that target specific underlying contributing features.

KEYWORDS:

• Dystonia
• focal dystonia
• pharmacotherapy
• botulinum toxin
• GABA
• NMDA receptor

Article highlights

• The bulk of robust investigations into dystonia therapeutics over the past decade relates to the use of botulinum toxin, including novel formulations (e.g. daxibotulinumtoxinA, with a proposed extended duration of action).

• Evidence for efficacy of non-toxin pharmacotherapeutics is mostly derived from descriptions in case reports or small case series.

• Antiepileptic medications have been studied in small randomized controlled trials, though their mechanistic role in treating dystonia remains unclear.

• Cannabinoids and repurposing of agents previously developed for non-dystonia indications such as 5HT receptor agonists, certain gaba-ergic medications (e.g. zolpidem and sodium oxybate), and glutamate modulating treatments may be viable alternatives to conventional dystonia pharmacotherapeutics.

• Dipraglurant and sodium oxybate represent the most novel and promising pharmacotherapeutics in the last decade, due to their distinct mechanisms of action.

• The ongoing development of animal models of dystonia will facilitate testing of novel experimental therapeutics, as well as discovery of additional relevant and modifiable biochemical pathways.

This box summarizes key points contained in the article.

Declaration of interest

J Jimenez-Shahed has been supported by Medtronic, Bracket, Blue Rock Therapeutics, Teva, PhotoPharmics, St. Jude Medical and Amneal and has received consulting fees from Abbvie for work unrelated to this article. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are a consultant for Medtronic and have provided a presentation supported by Merz. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.