Does Rexulti Cause Tardive Dyskinesia?
Yes, Rexulti (brexpiprazole) can cause tardive dyskinesia, a potentially irreversible movement disorder, though the risk appears lower compared to older antipsychotics.
Understanding the Risk
According to the FDA drug label, tardive dyskinesia is a recognized serious adverse effect of Rexulti 1. The label explicitly states that tardive dyskinesia consists of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotic drugs 1. The risk increases with:
- Duration of treatment - longer exposure increases risk
- Cumulative dose - higher total doses increase risk
- Elderly patients, especially elderly women - highest risk group
- Continued treatment - the syndrome can develop even after relatively brief treatment periods at low doses 1
Importantly, tardive dyskinesia may also begin after discontinuation of treatment 1.
Clinical Context: Atypical vs. Typical Antipsychotics
While all antipsychotics carry some risk of tardive dyskinesia, atypical agents like Rexulti are theoretically less likely to cause extrapyramidal side effects (including tardive dyskinesia) compared to conventional neuroleptics 2. However, this does not mean the risk is absent—it is reduced but still present.
Guidelines note that tardive dyskinesia is typically associated with long-term use of neuroleptics and represents a major public health concern with both clinical and medicolegal implications 2. In youth receiving neuroleptics, as many as 50% may experience some form of tardive or withdrawal dyskinesia 2.
Preclinical Evidence for Brexpiprazole
Research suggests brexpiprazole may have a lower propensity for tardive dyskinesia compared to some other antipsychotics. Preclinical studies demonstrate that brexpiprazole has a low risk of dopamine D2 receptor sensitization after repeated administration 3, 4. This is clinically relevant because D2 receptor sensitization is thought to underlie tardive dyskinesia development.
However, the actual long-term risk in clinical practice warrants assessment by specifically designed long-term, controlled trials 5, which are currently lacking.
Management Algorithm
Before starting Rexulti:
- Obtain informed consent specifically discussing tardive dyskinesia risk 2
- Document baseline abnormal movements using the Abnormal Involuntary Movement Scale (AIMS) 2
During treatment:
- Monitor for dyskinesias every 3 to 6 months using AIMS 2
- Prescribe the lowest effective dose for the shortest duration needed 1
- Periodically reassess the need for continued treatment 1
If tardive dyskinesia develops:
- Consider drug discontinuation immediately 1
- If the patient is in full remission and any medication change would likely precipitate relapse, continuing at the current dose may be justified 2
- Otherwise, attempt to lower the dose or switch to another medication 2
- For moderate to severe or disabling tardive dyskinesia, treat with a reversible VMAT2 inhibitor 6
Critical Caveats
- Antipsychotic treatment itself may mask tardive dyskinesia symptoms by suppressing the signs, potentially obscuring the underlying progression 1
- Tardive dyskinesia may remit partially or completely if treatment is discontinued, but it can also persist indefinitely 1
- The syndrome's appearance does not always necessitate stopping Rexulti—some patients may require continued treatment despite the presence of tardive dyskinesia 1
- There is no specific curative treatment for tardive dyskinesia other than discontinuation, making prevention and early detection paramount 2
The concern over tardive dyskinesia should not outweigh the potential benefits of antipsychotics for patients with conditions like schizophrenia or treatment-resistant depression, but it demands vigilant monitoring and informed decision-making 2.