From the Guidelines
Tardive dyskinesia should be managed with a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2) for patients with moderate to severe or disabling symptoms, as recommended by the American Psychiatric Association 1.
Introduction to Tardive Dyskinesia
Tardive dyskinesia is a neurological disorder characterized by involuntary, repetitive movements, typically affecting the face, mouth, tongue, and sometimes the limbs. It's primarily caused by long-term use of dopamine receptor blocking medications, especially first-generation antipsychotics like haloperidol and chlorpromazine, though it can also occur with some second-generation antipsychotics, antiemetics like metoclopramide, and other medications.
Causes and Development
The condition develops because these drugs block dopamine receptors, leading to receptor hypersensitivity over time. This hypersensitivity can result in the involuntary movements characteristic of tardive dyskinesia. The risk of developing tardive dyskinesia is significant, with up to 50% of youth receiving neuroleptics experiencing some form of tardive or withdrawal dyskinesia, as noted in earlier studies 1.
Management and Treatment
Management includes medication adjustment when possible, with consideration of switching to antipsychotics with lower risk profiles such as quetiapine or clozapine. For established tardive dyskinesia, FDA-approved treatments include valbenazine and deutetrabenazine, which are VMAT2 inhibitors that regulate dopamine release. The American Psychiatric Association recommends treating patients with moderate to severe or disabling tardive dyskinesia associated with antipsychotic therapy with a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2) 1.
Prevention
Prevention is crucial through using the lowest effective dose of antipsychotics, regular monitoring for early symptoms, and considering drug holidays when clinically appropriate. The Abnormal Involuntary Movement Scale is a useful measure for monitoring this problem, as suggested in earlier guidelines 1. Once established, tardive dyskinesia can be persistent even after medication discontinuation, highlighting the importance of early recognition and intervention.
Key Considerations
- Medication Adjustment: Consider switching to antipsychotics with lower risk profiles.
- VMAT2 Inhibitors: Valbenazine and deutetrabenazine are FDA-approved for treating tardive dyskinesia.
- Prevention: Use the lowest effective dose of antipsychotics and monitor regularly for early symptoms.
- Monitoring: Utilize the Abnormal Involuntary Movement Scale for monitoring.
From the FDA Drug Label
Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses or may even arise after discontinuation of treatment. Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment is withdrawn Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. If signs and symptoms of tardive dyskinesia appear in a patient on quetiapine, drug discontinuation should be considered. However, some patients may require treatment with quetiapine despite the presence of the syndrome.
Tardive Dyskinesia is a potential side effect of antipsychotic drugs, including quetiapine. The risk of developing tardive dyskinesia increases with:
- Duration of treatment
- Total cumulative dose of antipsychotic drugs However, it can also occur after brief treatment periods at low doses or even after discontinuation of treatment. Discontinuation of treatment may lead to remission of tardive dyskinesia, but antipsychotic treatment can also mask the underlying process. If tardive dyskinesia occurs, drug discontinuation should be considered, but some patients may still require treatment with quetiapine despite the presence of the syndrome 2.
Tardive dyskinesia (TD) has occurred in patients treated with antipsychotic drugs, including clozapine. The syndrome consists of potentially irreversible, involuntary, dyskinetic movements. The risk of TD and the likelihood that it will become irreversible are believed to increase with greater durations of treatment and higher total cumulative doses However, the syndrome can develop after relatively brief treatment periods at low doses. Prescribe clozapine in a manner that is most likely to minimize the risk of developing TD. Use the lowest effective dose and the shortest duration necessary to control symptoms. Periodically assess the need for continued treatment. Consider discontinuing treatment if TD occurs However, some patients may require treatment with clozapine despite the presence of the syndrome.
Tardive Dyskinesia is also a potential side effect of clozapine, with a risk that increases with:
- Duration of treatment
- Total cumulative dose The syndrome can be potentially irreversible and consists of involuntary, dyskinetic movements. To minimize the risk, clozapine should be prescribed with the lowest effective dose and shortest duration necessary, and discontinuation should be considered if tardive dyskinesia occurs 3.
From the Research
Definition and Overview of Tardive Dyskinesia
- Tardive dyskinesia (TD) is a movement disorder characterized by irregular, stereotyped, and choreiform movements associated with the use of antipsychotic medication 4.
- It is a late-appearing extrapyramidal disorder of involuntary, choreoathetoid movements that may appear during chronic treatment with classical neuroleptics or a short time after its prolonged administration is interrupted 5.
Prevention and Management of Tardive Dyskinesia
- Preventing TD is of primary importance, and clinicians should follow best practice for prescribing antipsychotic medication, including limiting the prescription for specific indications, using the minimum effective dose, and minimizing the duration of therapy 4.
- The first-line management of TD is the withdrawal of antipsychotic medication if clinically feasible 4.
- Switching from a first-generation to a second-generation antipsychotic with a lower D2 affinity, such as clozapine or quetiapine, may be effective in reducing TD symptoms 4, 5.
Treatment Options for Tardive Dyskinesia
- The strongest evidence for a suitable co-intervention to treat TD comes from tests with the new VMAT inhibitors, deutetrabenazine and valbenazine 4, 6.
- Quetiapine has been shown to be effective in the treatment of TD, with early and lasting improvement in symptoms 5.
- Other treatment options include benzodiazepines, anticholinergic drugs, botulinum toxin injections, and tetrabenazine, although their use is often limited by side effects 7.
- Non-pharmacological approaches, such as deep brain stimulation and repetitive transcranial magnetic stimulation, are also being explored as potential treatment options for TD 8.