Extrapyramidal symptoms (EPS) are involuntary movements that can arise as a side effect of certain medications. These symptoms affect a person’s motor control, leading to various physical manifestations. Recognizing these medication-induced movement disorders is important for managing their impact.
The Underlying Cause of Symptoms
Extrapyramidal symptoms arise from disruptions within the brain’s extrapyramidal system, a network of pathways that regulate involuntary motor control, posture, and muscle tone. This system relies on a delicate balance of neurotransmitters, particularly dopamine, to function smoothly. When this balance is disturbed, unintended movements can occur.
The primary cause of this disruption is often the blockade of dopamine D2 receptors in the brain, especially within the nigrostriatal pathway. This pathway is part of the extrapyramidal system responsible for coordinating movement. Medications that block these receptors reduce dopamine’s activity, leading to an imbalance that can manifest as EPS.
First-generation, or typical, antipsychotic medications are a common cause of these symptoms due to their strong dopamine D2 receptor blocking action. Some second-generation, or atypical, antipsychotics can also induce EPS, though at a lower rate due to their differing receptor profiles, such as weaker D2 receptor affinity or additional serotonin 5-HT2A receptor activity. Other drugs, including the anti-nausea medication metoclopramide, can also cause EPS by similarly blocking dopamine D2 receptors in the central nervous system.
Types of Extrapyramidal Symptoms
Extrapyramidal symptoms manifest in several distinct ways, each presenting with characteristic involuntary movements or sensations. These forms can appear at various times after medication initiation and vary in their impact on motor control.
Acute Dystonia
Acute dystonia involves sudden, sustained, and often painful muscle contractions leading to abnormal postures or repetitive movements. These reactions emerge shortly after starting a new medication or increasing its dosage, within hours to a few days. Common presentations include torticollis, where the neck twists to one side, or oculogyric crisis, which involves the eyes rolling upward and becoming fixed in that position. Other affected areas include the jaw, tongue, and larynx, potentially causing difficulty speaking or breathing. While transient, these episodes can cause considerable distress due to their intensity and unexpected nature.
Akathisia
Akathisia is characterized by an intense inner restlessness and a compelling, uncontrollable urge to move. Individuals describe a sense of tension or discomfort, particularly in their lower limbs, making it difficult to sit or stand still. Observable signs include constant fidgeting, rocking back and forth, pacing, or shifting weight from one foot to another. This subjective feeling of unease can be distressing and may be mistaken for anxiety or agitation due to its restless presentation. Symptoms appear within weeks of starting or increasing the dose of an offending medication.
Drug-Induced Parkinsonism
Drug-induced parkinsonism presents with symptoms closely resembling Parkinson’s disease, resulting from medication-induced dopamine blockade. Common manifestations include tremor, a resting tremor that subsides with movement, and rigidity, a stiffness or resistance to passive movement in the limbs or torso. Bradykinesia, or a general slowness of movement, is also a prominent feature, affecting tasks like walking, speaking, and fine motor skills such as buttoning clothes. Unlike idiopathic Parkinson’s disease, drug-induced parkinsonism affects both sides of the body equally and may lack some non-motor symptoms associated with the progressive neurological condition.
Tardive Dyskinesia (TD)
Tardive dyskinesia is a neurological syndrome characterized by involuntary, repetitive movements that emerge after prolonged use of certain medications, though it can occur after shorter exposures. “Tardive” signifies its delayed onset, developing months or years after starting the medication, or even after a dose reduction or discontinuation. Common symptoms involve the facial muscles, such as lip-smacking, puckering, grimacing, or involuntary tongue protrusion and chewing motions. Movements can also affect the limbs and trunk, manifesting as sudden jerking, writhing, swaying, or “piano-playing” finger movements. TD is less reversible than other acute EPS types.
Identification and Management
Recognizing extrapyramidal symptoms involves a careful clinical assessment, primarily based on a detailed review of the patient’s medical history and a thorough physical examination. Healthcare providers inquire about any medications being taken, particularly antipsychotics or other drugs known to affect dopamine pathways. Observing characteristic involuntary movements or restless behaviors during the examination helps confirm EPS. Standardized rating scales can also assess the severity and specific types of movements.
Management strategies aim to alleviate symptoms and improve comfort and function. The initial approach involves reducing the dosage of the medication causing the symptoms or, if appropriate, discontinuing it. Another common strategy is to switch to an alternative medication with a lower risk of extrapyramidal side effects, such as certain atypical antipsychotics.
For specific EPS types, targeted pharmacological interventions may be used. Acute dystonia, characterized by sudden muscle spasms, responds rapidly to anticholinergic medications like benztropine or diphenhydramine, providing quick relief. Drug-induced parkinsonism may be addressed by adding anticholinergic agents or amantadine, alongside dose adjustments of the offending drug. Akathisia, with its intense inner restlessness, can be managed with beta-blockers, such as propranolol, or benzodiazepines. Tardive dyskinesia, due to its delayed onset and potentially persistent nature, is managed differently, with newer medications called VMAT2 inhibitors, such as valbenazine or deutetrabenazine. Long-term use of prophylactic anticholinergics is discouraged due to potential side effects.