Objective: To retrospectively investigate whether the concomitant use of VMAT2 inhibitors and antipsychotics in individuals with Huntington’s disease (HD) is associated with an increased occurrence of extrapyramidal symptoms.

Background: Recent clinical trials have evaluated the efficacy and safety of VMAT2 inhibitors such as valbenazine and deutetrabenazine in individuals with tardive dyskinesia (TD) due to antipsychotic use. In most clinical trials using VMAT2 inhibitors to treat TD, study subjects remained on antipsychotics.  There is little to no published data on the concomitant use of VMAT2 inhibitors (tetrabenazine and deutetrabenazine both FDA approved for chorea in HD) and antipsychotics in individuals with HD. Due to the lack of data on potential side effects with this drug combination, there are no recommendations for their simultaneous use in HD.  Therefore, this study aims to retrospectively investigate whether the concomitant use of VMAT2 inhibitors and antipsychotics is associated with worsening motor symptoms.

Method: Retrospective longitudinal study including manifest HD patients from the Enroll-HD database (PDS4). The database assesses participants annually, manifest HD with at least four years of visits were included in analysis. Linear mixed models were used to assess motor, behavioral, and cognitive functioning over a series of visits in patients who have taken VMAT2 inhibitors (WHO ATC/DDD code = N07XX), antipsychotics (WHO ATC/DDD code = N05A), both or none.

Results: Participants who have taken either VMAT2 inhibitors or antipsychotics presented with worse motor scores over the four annual visits than participants who have never taken  these drugs. Patients who have taken both drugs (i.e., VMAT2 inhibitors and antipsychotics) presented with worse scores since the first (baseline) visit, thus concluding that the concomitant prescription of these drugs occurred when patients presented with greater severity of motor symptoms. The use of VMAT2 inhibitors, antipsychotics or both did not alter disease progression.

Conclusion: Patients with HD who have used both VMAT2 inhibitors and antipsychotics had more severe motor symptoms at baseline than patients who have taken these drugs separately or who have never taken any of these drugs, these differences persisted throughout a four period. The concomitant use of VMAT2 inhibitors and antipsychotics was not associated with a worsening in motor symptoms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/vmat-2-inhibitor-and-antipsychotic-use-in-individuals-with-huntingtons-disease/