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Tardive Dyskinesia CT
Tardive Dyskinesia in People With Mood Disorders

Released: August 06, 2025

Stanley N. Caroff
Stanley N. Caroff, MD
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Key Takeaways
  • TD is often mischaracterized as a disorder only affecting patients with schizophrenia, but patients with mood disorders are also at risk, even when treated with newer antipsychotics at lower doses or intermittently.
  • Age, treatment pattern, and drug exposure are major risk factors that warrant careful attention in patients with bipolar and depressive disorders.
  • Proactive screening and treatment with VMAT2 inhibitors can significantly reduce the burden of TD and improve patient outcomes.

With expanding use of antipsychotics for mood disorders, the number of people at risk for tardive dyskinesia (TD) has increased dramatically. At the same time, the risk for TD may be underestimated because of mistaken notions that TD occurs only in people with schizophrenia or other chronic psychotic disorders, that it occurs only after a year or more of treatment, and that it is not a risk with newer antipsychotic agents. However, patients with mood disorders treated with any dopamine receptor–blocking antipsychotics are at significant risk for TD and its adverse impact on their lives.

Increasing Use of Antipsychotics in Mood Disorders
Antipsychotics have long been an essential tool in the treatment of mood disorders. First-generation antipsychotics were commonly used to treat psychotic symptoms or agitation during acute manic or depressive episodes with the proviso that the antipsychotic would be tapered off, in part to avoid risk of TD, once remission had been achieved using mood stabilizers or antidepressants. Currently, antipsychotics are prescribed in more than one half of patients with bipolar disorder, surpassing use of mood stabilizers. Antipsychotics are often used in combination with other agents for extended periods of time in this patient population. Approximately one fifth of patients with major depressive disorder receive antipsychotics, most often for psychotic symptoms, for agitation, or as adjunctive agents for antidepressant resistance. For patients with bipolar disorder or major depression, antipsychotic treatment is often maintained even after an acute episode has resolved.

Several newer antipsychotics are approved by the FDA for treatment as monotherapy or as adjuncts in unipolar or bipolar depression, or for manic and mixed states. Although indications are restricted, they are nevertheless widely advertised, likely overprescribed and used off-label for unapproved indications. Although mood stabilizers or antidepressants remain the gold-standard treatment for acute episodes and maintenance of mood disorders in treatment guidelines, second-generation antipsychotics are increasingly recognized as adjunctive or monotherapy first-line or second-line interventions for mania, bipolar depression, or treatment-resistant depression.

Although maintenance treatment usually extends successful acute regimens, simplifying pharmacotherapy to a mood stabilizer or antidepressant only is preferable in long-term care whenever possible. Evidence on use of antipsychotics for maintenance treatment of mood disorders at least up to 2 years (including long-acting injectables) is more limited than for acute care but suggests a role in treating patients with unstable illness, in preventing recurrent manic more than depressive episodes in patients with bipolar disorder, in patients resistant to or intolerant of mood stabilizers or antidepressants, or when nonadherence with oral medications is a problem. Long-term use of antipsychotics in unipolar nonpsychotic depression requires further research because of insufficient evidence for their effectiveness in preventive maintenance treatment.

Risk Factors for TD in Patients With Mood Disorders
At the same time, the risk of TD in patients with mood disorders undergoing sustained antipsychotic treatment has been amply demonstrated. Prevalence rates of TD among patients with bipolar disorder average 5% to 10% but have ranged up to 42% depending on risk factors in the sample population, whereas rates of TD in patients with depression are less well established. As in other populations, age is the strongest predictor of TD risk, which rises in linear fashion after the age of 40 years. Sex, race, comorbid medical illness, and drug class, cumulative dosage, or duration of antipsychotic treatment may also influence risk. Long-acting injectables are associated with no greater risk than oral antipsychotics. Past evidence with older drugs suggested that patients with mood disorders are at increased risk of TD, which may reflect the fact that patients with mood disorders as a group are older, and people with episodic depressive or manic episodes are likely to receive antipsychotics intermittently with drug-free periods during remission, both conditions which are recognized as risk factors for TD. On the other hand, patients with mood disorders are more likely than patients with schizophrenia to receive newer antipsychotics and at lower doses, factors which reduce TD risk. The bottom line is that anyone who receives any dopamine-blocking antipsychotic for any reason and for any sustained length of time is at risk for TD.

Burden of TD in Patients With Mood Disorders
Severe TD symptoms can cause significant physical disability in patients with mood disorders as in other patient populations. However, even mild symptoms can cause significant social, psychological, and occupational dysfunction affecting quality of life. People with recurrent mood episodes and periods of remission, who are able to function at a high level between episodes, may be particularly embarrassed and affected by even mild signs of TD, increasing the need for early diagnosis and specific treatment.

Best Practices for Managing TD in Patients With Mood Disorders
Therefore, it is essential that healthcare professionals incorporate best practices for screening, detection, diagnosis, and management of TD for their patients with mood disorders. To limit the risk of TD, selecting drugs with reduced risk and prescribing the lowest effective doses for proper indications are important practices. It is prudent to document the indication for prescribing an antipsychotic for a mood disorder, the reason for selecting a specific drug, and the discussion with patients and caregivers of the risk of TD, while also counseling patients and caregivers to self-examine and report any abnormal movements. Although formal Abnormal Involuntary Movement Scale (AIMS) examinations can be documented every 6-12 months, effective screening for any abnormal movements and their functional impact requires brief patient questioning and visual inspection as part of the mental status examination at every visit at least every 3 months. Consideration of the differential diagnosis for abnormal movements is in order as well, followed by reassessment of pharmacotherapy with antipsychotics and anticholinergics. Resolution of TD symptoms may be possible in some patients if mild incipient signs of TD are detected early, especially in younger patients, and if adjunctive antipsychotics can be safely discontinued in nonpsychotic patients, relying instead on maintenance treatment with mood stabilizers or antidepressants alone. However, evidence regarding reversibility of TD is limited and remains controversial, whereas modifying antipsychotic treatment in a stable patient always carries the serious risk of psychotic relapse.

Finally, prescribing a VMAT2 inhibitor is recommended for moderate to severe TD, or even mild TD that significantly affects functioning and quality of life. The VMAT2 inhibitors valbenazine and deutetrabenazine have been shown to be safe and effective in people with mood disorders. Valbenazine is started at 40 mg daily and can be increased to 80 mg if tolerated after 1 week. Deutetrabenazine can be started at 12 mg daily and increased in smaller increments at the rate of 6 mg daily every week up to a dose of 48 mg. Both drugs can be taken once daily with or without food (using the extended-release formulation for deutetrabenazine), and both drugs can be taken without the need to modify concurrent antipsychotic, mood stabilizer, or antidepressant treatment. However, dosing modifications should be considered when drug interactions may occur with CYP2D6 (antidepressants fluoxetine, paroxetine, bupropion, duloxetine) or CYP3A4 (grapefruit juice, certain antibiotics and antifungals) inhibitors and when concurrent medications may prolong the QTc interval (several antipsychotics and antidepressants). Patients should be warned and monitored closely for emerging signs of depression or suicidal risk during VMAT2 inhibitor treatment which is contraindicated in patients who are suicidal or have inadequately treated depression at baseline. If one VMAT2 inhibitor is ineffective, the other can be tried. If both fail, there are other agents that can be tried empirically although none has achieved the threshold for FDA approval. VMAT2 inhibitors are suppressive but not curative, such that improvement of TD symptoms is sustained as long as the treatment is continued.

Your Thoughts?
When considering antipsychotic agents for the treatment of mood disorders, how do you discuss the risk of TD with patients? Get involved in the conversation by answering the polling question or posting a comment below.

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I evaluate TD risk as a factor when considering treatment with an antipsychotic agent for patients with mood disorders:

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