From the Guidelines
Extrapyramidal symptoms (EPS) are neurological side effects primarily caused by medications that block dopamine receptors in the brain, especially antipsychotics, and include acute dystonia, akathisia, parkinsonism, and tardive dyskinesia. These symptoms are a significant concern in the management of patients on antipsychotic medications due to their impact on morbidity, mortality, and quality of life. According to the study published in Pediatrics 1, EPS can occur due to the use of antipsychotics, which can block dopamine receptors in the brain, leading to an imbalance between dopamine and acetylcholine and disrupting normal motor function.
Types of EPS
- Acute dystonia: characterized by involuntary muscle contractions causing abnormal postures, which can occur after the first few doses of medication or after an increase in dosage 1.
- Akathisia: a subjective feeling of restlessness, which generally occurs within the first few days of antipsychotic medication therapy 1.
- Parkinsonism: a syndrome that includes tremor, rigidity, bradykinesia, and postural instability, which can be treated by adding an anticholinergic agent, adding a dopaminergic agonist, or decreasing the dosage of a typical antipsychotic or switching to an atypical antipsychotic 1.
- Tardive dyskinesia: characterized by rapid involuntary facial movements and extremity or truncal movements, which can occur after months or years of treatment with antipsychotic medications 1.
Treatment and Management
Treatment of EPS depends on the specific symptom but may include:
- Anticholinergic medications like benztropine for parkinsonism and acute dystonia.
- Beta-blockers like propranolol for akathisia 1.
- Dose reduction of the causative medication.
- Switching to a different antipsychotic medication with a lower risk of EPS.
It is essential to note that first-generation antipsychotics like haloperidol carry a higher risk of causing EPS than newer second-generation medications. Therefore, the use of newer antipsychotic medications with a lower risk of EPS is recommended to minimize the risk of these neurological side effects. Additionally, regular monitoring of patients on antipsychotic medications for signs of EPS is crucial to ensure early detection and treatment, which can help improve morbidity, mortality, and quality of life outcomes.
From the FDA Drug Label
In the treatment of extrapyramidal disorders due to neuroleptic drugs (e.g., phenothiazines), in patients with mental disorders, occasionally there may be intensification of mental symptoms. Tardive dyskinesia may appear in some patients on long-term therapy with phenothiazines and related agents, or may occur after therapy with these drugs have been discontinued. The drug may cause complaints of weakness and inability to move particular muscle groups, especially in large doses. Mental confusion and excitement may occur with large doses, or in susceptible patients Visual hallucinations have been reported occasionally. Parkinsonism has also been observed with other VMAT2 inhibitors. In the 3 placebo-controlled clinical studies in patients with tardive dyskinesia, the incidence of parkinson-like adverse events was 3% of patients treated with INGREZZA and <1% of placebo-treated patients In a placebo-controlled clinical study in patients with chorea associated with Huntington’s disease, the incidence of parkinson-like adverse events was 4.7% in patients treated with INGREZZA and 0% in placebo-treated patients.
EPS symptoms include:
- Parkinson-like symptoms: rigidity, tremor, drooling, hypokinesia
- Tardive dyskinesia: involuntary, repetitive body movements
- Mental symptoms: confusion, excitement, visual hallucinations
- Muscle weakness: inability to move particular muscle groups
- Parkinsonism: gait disturbances, falls, hypokinesia 2 3
From the Research
EPS Symptoms
The extrapyramidal symptoms (EPS) include:
- Acute dyskinesias and dystonic reactions
- Tardive dyskinesia
- Parkinsonism
- Akinesia
- Akathisia
- Neuroleptic malignant syndrome 4 EPS are caused by dopamine blockade or depletion in the basal ganglia, which can mimic idiopathic pathologies of the extrapyramidal system.
Types of EPS
Some specific types of EPS are:
- Drug-induced parkinsonism (DIP), which often presents as bradykinesia and rigidity, as well as rhythmic tremor 5
- Tardive dyskinesia (TD), which typically appears after at least 3 months or longer of treatment, and patients will commonly present with involuntary, abnormal facial movements such as lip smacking, puckering, chewing, or tongue protrusion 5
- Akathisia, which is characterized by subjective feelings of restlessness and objective signs of agitation 6
- Tardive dystonia, which is a rare but potentially debilitating side effect of long-term antipsychotic treatment 7
Prevalence of EPS
EPS are common in clinical practice, partly due to lack of screening by health professionals 6. The prevalence of EPS can range from approximately 20 to 35% among antipsychotic users 5. Almost 30% of patients may suffer from two or more EPS 7.
Diagnosis and Treatment
Accurate diagnosis and appropriate treatment of EPS are imperative, as its symptoms can be highly disruptive to both patients and their caregivers 8. The differential diagnosis of EPS is based on history of dopamine receptor blocking agent exposure, recent discontinuation or dose reduction of a dopamine receptor blocking agent, and movement phenomenology 8. Treatment options should be reviewed with the patient and caregivers after documentation of the phenomenology, severity, and distribution of EPS movements 8.