Thank you for your interest in CCO content. As a guest, please complete the following information fields. These data help ensure our continued delivery of impactful education.
Become a member (or login)? Member benefits include accreditation certificates, downloadable slides, and decision support tools.
Anticholinergics are efficacious in treating parkinsonism, but they generally worsen TD. It is a common mistake for HCPs to prescribe them for the abnormal involuntary movements associated with TD, although they may be of some benefit in tardive dystonia.3
TD is thought to result from nigrostriatal D2 blockade leading to postsynaptic upregulation/hypersensitivity. These supersensitive receptors then overreact to dopamine, leading to abnormal involuntary movements. Parkinsonism, on the other hand, is due to low postsynaptic dopamine stimulation. Medications that increase dopamine release (eg, anticholinergics) exacerbate TD.4,5
Second-generation antipsychotics have been associated with a significant reduction in the risk of TD,6 but TD still can occur with these agents. In addition, although switching from first-generation to second-generation medications initially was hoped to be helpful, meta-analysis suggests that such switching did not improve TD.7 Clozapine has been shown to be of some benefit in moderate to severe cases of TD, but there is considerable variability in response.8
VMAT is a protein integrated into the membrane of synaptic vesicles of presynaptic neurons that transports monoamine neurotransmitters (dopamine, 5-hydroxytryptamine, norepinephrine, epinephrine, and histamine) into vesicles. There are 2 forms: VMAT1 and VMAT2. VMAT1 is expressed mainly in the peripheral nervous system, and VMAT2 is expressed mainly in monoaminergic cells of the central nervous system.1 Deutetrabenazine and valbenazine both are VMAT2 inhibitors that were approved by the FDA for the treatment of TD in 2017; deutetrabenazine also is approved by the FDA for Huntington disease. Deutetrabenazine and valbenazine have been shown to be effective in well-designed clinical trials,9,10 with good long-term safety and efficacy.11,12 With both medications, there is some reemergence of involuntary movements after discontinuation, so continued therapy is likely needed.11,13 Valbenazine is dosed once daily with a 1-week titration from 40 mg/day to 80 mg/day. Deutetrabenazine requires twice-daily dosing with food, with a longer titration period to reach the effective dose range of 36-48 mg/day. There are no direct head-to-head comparisons of these agents.
In summary, TD remains a persistent clinical problem due to the widespread use of second-generation antipsychotics. HCPs should be cautious in the use of antipsychotic medications, reserving them for situations in which they are clearly indicated and beneficial. TD is generally not reversible, even with antipsychotic discontinuation. There is limited benefit with switching to clozapine, but not to other second-generation antipsychotics. HCPs must learn to recognize TD and identify other movement disorders commonly seen with psychotropic treatment. Anticholinergics used for parkinsonism exacerbate TD. VMAT2 inhibitors represent the first class of medications with regulatory approval for the treatment of TD.