From the Guidelines
Tardive dyskinesia is primarily caused by long-term use of dopamine receptor blocking agents, most commonly antipsychotic medications, with first-generation antipsychotics carrying the highest risk and second-generation antipsychotics having a lower but still significant risk. The condition develops due to dopamine receptor hypersensitivity following chronic blockade, leading to an imbalance in the basal ganglia circuits that control movement 1. Other medications that can cause tardive dyskinesia include metoclopramide, prochlorperazine, and certain antidepressants.
Risk Factors and Prevention Strategies
Risk factors for tardive dyskinesia include:
- Longer duration of medication use
- Higher doses
- Older age
- Female gender
- Mood disorders
- Cognitive impairment
- Possibly genetic predisposition
Prevention strategies include:
- Using the lowest effective dose of antipsychotics
- Regular monitoring for early signs of movement disorders
- Considering atypical antipsychotics when possible
- Discontinuing unnecessary dopamine-blocking medications
- Periodic attempts at dose reduction for patients requiring long-term antipsychotic treatment 2.
Medications and Their Risks
Some medications have a higher risk of causing tardive dyskinesia, including:
- First-generation antipsychotics like haloperidol, chlorpromazine, and fluphenazine
- Second-generation antipsychotics like risperidone, olanzapine, and quetiapine, although to a lesser extent
- Other medications like metoclopramide and prochlorperazine 3, 4.
Importance of Early Recognition
Early recognition of tardive dyskinesia is crucial as it can become permanent even after medication discontinuation 1. Regular monitoring and prompt intervention can help minimize the risk and improve patient outcomes.
From the FDA Drug Label
Tardive Dyskinesia: Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs 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 Both the risk of developing the syndrome 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.
The causes of tardive dyskinesia are not fully understood, but it is believed to be associated with:
- Long-term treatment with antipsychotic drugs
- High cumulative doses of antipsychotic drugs
- Elderly patients, especially elderly women, are at higher risk
- Duration of treatment, the longer the treatment, the higher the risk The exact cause of tardive dyskinesia is unknown, but it is thought to be related to the use of antipsychotic drugs 5, 6, 7.
From the Research
Causes of Tardive Dyskinesia
The causes of tardive dyskinesia are complex and multifactorial. Some of the key factors that contribute to the development of tardive dyskinesia include:
- The use of dopamine receptor blocking agents (DRBAs), such as antipsychotics, which can cause dopamine receptor hypersensitivity 8, 9
- The duration of treatment with DRBAs, with longer treatment durations increasing the risk of developing tardive dyskinesia 10, 11
- The type of antipsychotic used, with first-generation antipsychotics carrying a higher risk of tardive dyskinesia than second-generation antipsychotics 8, 9
- Advanced age, with older adults being at increased risk of developing tardive dyskinesia 10, 11
- Genetic susceptibility, with certain genetic variants increasing the risk of developing tardive dyskinesia 8
Pathophysiology of Tardive Dyskinesia
The pathophysiology of tardive dyskinesia is not fully understood, but several theories have been proposed, including:
- Dopamine receptor supersensitivity, which occurs when dopamine receptors become overactive due to chronic blockade by DRBAs 8, 9
- Oxidative stress, which can damage brain cells and contribute to the development of tardive dyskinesia 8, 9
- Maladaptive synaptic plasticity, which can lead to abnormal brain function and contribute to the development of tardive dyskinesia 8
Risk Factors for Tardive Dyskinesia
Several risk factors have been identified for tardive dyskinesia, including: