From the Guidelines
Abrupt withdrawal of antipsychotic medications is a well-established cause of chorea, a condition characterized by involuntary, irregular movements, due to the development of dopamine receptor hypersensitivity. This condition is often referred to as withdrawal-emergent dyskinesia or tardive dyskinesia 1. The exact mechanism involves the blockade of dopamine receptors by antipsychotics, leading to a compensatory increase in dopamine receptor density and sensitivity. When these medications are suddenly discontinued, the increased receptor density and sensitivity can lead to an overactive dopaminergic signal, resulting in the characteristic involuntary movements of chorea.
To manage this condition, a gradual tapering of the antipsychotic medication is recommended, rather than abrupt discontinuation. The tapering schedule should extend over a period of greater than 1 month to minimize potential discontinuation effects, including dyskinesias, parkinsonian symptoms, dystonias, and neuroleptic malignant syndrome 1. In cases where chorea has already developed due to abrupt withdrawal, reinstating the previously used antipsychotic at a low dose and then tapering it slowly over weeks to months may be necessary. Nonpharmacological psychosocial interventions, such as redirection and reorientation techniques, environmental interventions, and ensuring social engagement, can also be effective in reducing antipsychotic medication and mitigating behavioral symptoms 1.
Key considerations in managing chorea resulting from antipsychotic withdrawal include:
- Gradual tapering of antipsychotic medications over more than 1 month to prevent discontinuation effects
- Reinstating the previously used antipsychotic at a low dose and then tapering it slowly if chorea has developed
- Utilizing nonpharmacological psychosocial interventions to reduce antipsychotic medication and mitigate behavioral symptoms
- Monitoring patients for at least several weeks after discontinuation as withdrawal symptoms can appear delayed 1.
From the FDA Drug Label
Withdrawal Emergent Neurological Signs Generally, patients receiving short-term therapy experience no problems with abrupt discontinuation of antipsychotic drugs. However, some patients on maintenance treatment experience transient dyskinetic signs after abrupt withdrawal In certain of these cases the dyskinetic movements are indistinguishable from the syndrome described below under “Tardive Dyskinesia” except for duration
The cause of chorea resulting from the abrupt withdrawal of antipsychotic medications is not explicitly stated in the label, but it can be inferred that transient dyskinetic signs, which may include chorea, can occur after abrupt withdrawal of antipsychotic drugs, particularly in patients on maintenance treatment 2.
From the Research
Cause of Chorea due to Antipsychotic Withdrawal
- The exact cause of chorea resulting from the abrupt withdrawal of antipsychotic medications is not explicitly stated in the provided studies.
- However, it can be inferred that the sudden discontinuation of antipsychotics may lead to an imbalance in dopamine and serotonin levels in the brain, potentially causing chorea 3, 4.
- Antipsychotics block dopamine D₂ receptors, and their abrupt withdrawal may result in a rebound effect, leading to an overactivation of these receptors and causing chorea 3.
- Additionally, the use of antipsychotics can also affect other neurotransmitter systems, such as serotonin and histamine, which may contribute to the development of chorea upon withdrawal 3.
Related Studies
- A study on clozapine discontinuation withdrawal symptoms in schizophrenia found that abrupt discontinuation of antipsychotics can cause an array of withdrawal symptoms, including psychosis, cholinergic rebound, catatonia, and serotonergic discontinuation symptoms 4.
- Another study on the impact of abrupt interruption of home psychotropic medications at ICU admission found that patients with psychotropic interruption had a longer ICU length of stay and greater incidence of ICU delirium, but withdrawal-related complications were similar between groups 5.
Treatment Options
- The treatment options for chorea include inhibitors of presynaptic vesicular monoamine transporter type 2 (VMAT2), such as tetrabenazine, deutetrabenazine, and valbenazine, which are considered the treatment of choice in patients with chorea 6.
- Dopamine receptor blockers, such as antipsychotics, and other drugs, including anti-epileptics and anti-glutamatargics, may also be used to treat chorea 6.