Extrapyramidal symptoms, or EPS, are movement-related side effects from certain medications. These symptoms are linked to the extrapyramidal system, a part of the brain that helps regulate posture and muscle tone. When medications interfere with this system, it can lead to involuntary or uncontrollable movements. While distressing, these side effects are a known possibility with specific drugs and are manageable once identified.
Identifying Extrapyramidal Symptoms
One type of EPS is acute dystonia, which involves involuntary and sometimes painful muscle contractions. These spasms affect the muscles of the face, neck, jaw, or eyes, leading to abnormal postures like a tilted head or upward-deviating eyes. Dystonic reactions can also impact the trunk, causing the back to arch, or the tongue, resulting in speech or swallowing difficulties. These symptoms appear shortly after starting a new medication or increasing the dose.
Another symptom is akathisia, characterized by a powerful feeling of inner restlessness and an inability to stay still. Individuals with akathisia feel a compelling urge to move, manifesting as constant fidgeting, pacing, or shifting weight. This sensation is often accompanied by feelings of anxiety and tension, making it very uncomfortable.
Some medications can induce parkinsonism, a cluster of symptoms that mimic Parkinson’s disease. This includes a tremor most noticeable when the hands are at rest and bradykinesia, or a slowness of movement. People experiencing drug-induced parkinsonism might also have muscle stiffness (rigidity), a shuffling walk, and reduced facial expression. Unlike Parkinson’s disease, these symptoms are a direct result of medication.
A different type of EPS that can develop after long-term medication use is tardive dyskinesia (TD). The term “tardive” means delayed, as these symptoms appear after months or years of treatment. TD involves repetitive, involuntary movements, most commonly affecting the face, such as lip-smacking, tongue protrusion, or rapid blinking. In some cases, the arms, legs, or torso may also be affected with movements like finger-tapping or swaying.
Medications That Can Cause EPS
The most common cause of EPS is a class of drugs called antipsychotics. These medications work by blocking dopamine receptors in the brain, which is therapeutic for psychosis but can disrupt the dopamine pathways that control movement. First-generation antipsychotics (FGAs), like haloperidol, have a higher likelihood of causing EPS because of their strong affinity for D2 dopamine receptors.
Second-generation antipsychotics (SGAs), or atypical antipsychotics, were developed partly to reduce this risk. While they also affect dopamine, they have a lower binding affinity for D2 receptors and interact with serotonin receptors, which is thought to mitigate movement-related side effects. However, the risk is not eliminated; some SGAs, like risperidone, carry a higher risk of EPS than others, such as clozapine.
Beyond antipsychotics, other medications can also induce these symptoms by affecting dopamine. Certain anti-nausea medications (antiemetics), particularly metoclopramide, are known for causing EPS, including acute dystonic reactions. Some antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), have also been linked to EPS, although this is less common.
Treatment Approaches for EPS
Managing EPS begins with a healthcare provider reviewing the patient’s medication regimen. The most direct approach is to adjust the dosage of the drug suspected of causing the symptoms. Lowering the dose can alleviate the side effects while preserving the medication’s therapeutic benefits. If reducing the dose is not effective, a doctor may switch to a different medication, such as transitioning from an FGA to an SGA with a lower EPS risk.
When medication adjustments are not sufficient, doctors may prescribe additional medications to counteract EPS. For acute dystonia and drug-induced parkinsonism, anticholinergic drugs like benztropine are a primary treatment. These work by helping restore the balance between dopamine and acetylcholine in the brain, which relieves muscle stiffness and spasms. For severe dystonic reactions, an injection of an anticholinergic or the antihistamine diphenhydramine provides rapid relief.
The treatment for akathisia differs from other acute forms of EPS, as anticholinergic medications are not effective for its intense restlessness. Instead, beta-blockers, with propranolol being a common choice, are a first-line treatment. Benzodiazepines, such as lorazepam, may also be prescribed to help manage the severe anxiety and agitation that can accompany akathisia.
For drug-induced parkinsonism that persists despite adjustments to the primary medication, another option is amantadine. This medication can increase dopamine activity in the brain, offering an alternative to anticholinergics. It is particularly useful for individuals who may not tolerate the side effects of those drugs.
Managing Long-Term and Severe Symptoms
While many forms of EPS resolve with medication changes, tardive dyskinesia (TD) presents a more complex challenge. Unlike acute symptoms, TD can be persistent and may even be permanent, continuing after the causative medication is stopped. The risk of TD increases with the duration of exposure to dopamine-blocking agents.
The primary treatments for TD are different from those for other EPS. The main class of drugs approved for TD are vesicular monoamine transporter 2 (VMAT2) inhibitors, such as valbenazine and deutetrabenazine. These medications work by reducing the amount of dopamine released in the brain, which helps lessen the involuntary movements of TD. Tetrabenazine, an older VMAT2 inhibitor, has also been used but is associated with a different side effect profile.
Managing long-term symptoms requires ongoing communication with a healthcare provider. Regular monitoring, sometimes using tools like the Abnormal Involuntary Movement Scale (AIMS), helps in the early detection and tracking of TD. This allows for timely intervention, which may involve adjusting medications or starting a VMAT2 inhibitor to control symptoms.