Extrapyramidal Side Effects (EPS) are a collection of drug-induced, involuntary movement disorders caused by certain medications. These effects involve a disruption of the body’s motor control systems, meaning a person cannot consciously control them. Recognizing EPS is important because the symptoms can significantly impair a person’s quality of life and compliance with treatment. This article explains the underlying biology of EPS and details the standard approaches to managing these reactions.
How Medications Affect Movement Control
EPS is directly linked to how certain medications interact with the brain’s motor circuit, the extrapyramidal system. This system includes the basal ganglia, a neural network responsible for regulating motor commands and coordination. Proper function requires a balanced supply of the neurotransmitter dopamine.
Many medications, particularly those used to treat conditions involving psychosis, work by blocking dopamine receptors. This action is intended to modulate brain activity, but when the blockade occurs in the nigrostriatal pathway—a specific section of the extrapyramidal system—it disrupts the normal balance of motor control. Reducing dopamine signaling causes the indirect pathway, which normally inhibits movement, to become relatively overactive. This imbalance results in the involuntary or abnormal movements that characterize Extrapyramidal Side Effects.
Identifying the Main Types of EPS
The manifestations of EPS are categorized into four main types, differing in presentation and time frame. Some are acute, arising quickly after starting a medication, while others are chronic, developing after prolonged exposure.
Acute dystonia is one of the earliest forms of EPS, often occurring within the first 96 hours of medication use or dose increase. This condition involves sudden, sustained, involuntary muscle contractions leading to twisting movements or abnormal postures. Common presentations include torticollis (twisting of the neck) or oculogyric crisis (involuntary upward deviation of the eyes). Acute dystonia can be painful and potentially dangerous if throat muscles are involved, which can compromise breathing.
Drug-induced parkinsonism is another acute form, closely mimicking the symptoms of idiopathic Parkinson’s disease. Symptoms include a resting tremor, muscle rigidity, and bradykinesia (generalized slowing of movement). This condition typically develops gradually within the first three months of starting the causative medication.
Akathisia is characterized by a subjective feeling of inner restlessness and an intense urge to move. Individuals often exhibit repetitive movements such as pacing or constantly shifting position. This symptom is distressing and is a frequent reason for patients to stop taking their medication, as it may be misinterpreted as anxiety.
Tardive dyskinesia (TD) is a chronic, late-onset condition usually appearing after six months or longer of medication use. TD is characterized by repetitive, involuntary movements, most commonly affecting the face, mouth, and tongue, such as lip smacking or tongue thrusting. Unlike acute forms, TD can be persistent and may not fully resolve even after the causative medication is discontinued.
Drugs Commonly Associated with EPS
Extrapyramidal Side Effects are most strongly associated with medications that block dopamine receptors, particularly those developed to treat psychotic disorders. Typical, or first-generation, antipsychotics carry the highest risk because they produce a potent blockade of dopamine D2 receptors. Medications such as haloperidol have a higher propensity for inducing EPS compared to newer agents.
Atypical, or second-generation, antipsychotics generally present a lower risk of EPS, especially tardive dyskinesia. This reduced risk is attributed to their differing receptor profiles, often involving weaker D2 receptor binding or a higher affinity for serotonin receptors. However, even these newer drugs can still cause EPS, particularly akathisia, and the risk increases with higher doses. Non-antipsychotic drugs that block dopamine can also induce acute EPS, including certain antiemetics used to treat nausea, such as metoclopramide.
Treatment and Mitigation Strategies
The primary approach to managing EPS is to reduce the dosage of the offending medication or to switch the patient to an alternative drug with a lower risk profile. For acute EPS, specific pharmacological interventions can provide rapid relief by addressing the underlying neurotransmitter imbalance. Acute dystonia is often treated effectively with anticholinergic agents, such as benztropine or diphenhydramine, which help restore the balance between dopamine and acetylcholine signaling.
Managing akathisia, particularly the severe inner restlessness, can be more challenging, and anticholinergic drugs are often not effective. Beta-blockers, such as propranolol, are frequently used to help reduce the motor and subjective symptoms associated with akathisia. For drug-induced parkinsonism, anticholinergic medications may also be used, but physicians must weigh their benefit against potential side effects like confusion.
Treating chronic tardive dyskinesia requires a different strategy since the symptoms may persist even after the causative drug is discontinued. The contemporary approach involves the use of Vesicular Monoamine Transporter 2 (VMAT2) inhibitors. These agents, such as valbenazine, work by modulating the release of dopamine, which helps to stabilize the overactive motor system that drives the involuntary movements of TD.