Extrapyramidal Symptoms & Risk Factors

Extrapyramidal Symptoms: Identifying Neurological Side Effects of Antipsychotic Medications

Extrapyramidal Symptoms (EPS) refer to movement disorders triggered by medications, particularly antipsychotics. Symptoms occur as a consequence of the blockade of the brain's nigrostriatal dopamine transmission. Dopamine blockade increases cholinergic activity responsible for acute dystonia, akathisia, antipsychotic-induced parkinsonism, and late-emerging disturbances like tardive dyskinesia (TD), tardive dystonia, and tardive akathisia.

In some individuals, these symptoms can be so severe that they disrupt routine life, making movement difficult, hindering communication, and interfering with daily tasks at home, work, or school. Most people improve with treatment, but some effects last for a while. Treatment outcomes are best when they begin early.

Keep reading to learn more about extrapyramidal symptoms!

What are Extrapyramidal Symptoms?

EPS can affect both children and adults, sometimes with high intensity. These early warning signs may appear shortly after being administered the first dose of a new drug. They usually happen a few hours later, but also at random times during any interval in the first couple of weeks of medication treatment.

It varies depending on the sign, and at times, only symptoms develop following extended exposure to the drug.

Here is a detailed overview of extrapyramidal symptoms:

1. Akathisia

Akathisia involves severe restlessness and an irresistible urge to move. Adults will develop tension or internal distress, whereas children will develop irritability, anxiety, or restless activity.

• You may find temporary relief by pacing, bouncing your legs, swaying, or rubbing parts of your body, like your face.
• It has been found that the risk of developing akathisia is increased with increasing doses of medication.
• Notably, patients developing akathisia are at increased risk of developing tardive dyskinesia in the future.
• It has been found that 5% to 36% of patients treated with antipsychotic medications can develop akathisia.
   

Treatment may involve reducing the dose of the antipsychotic or adding medications such as beta-blockers to minimise symptoms.

2. Acute Dystonia

Dystonia involves spasmodic contraction of the muscles, causing repetitive twisting movements.

• Symptoms may include forceful blinking, eye spasms, twisting of the head or neck, tongue protrusion, and jaw or neck stiffness.
• While transient, the movements have a remarkable impact on posture or cause muscle rigidity.
• Although dystonia often affects the head and neck, other parts of the body may be involved.
• These spasms are painful and can cause swallowing or breathing blockages if the muscles of the throat are involved.
• Acute dystonia occurs in approximately 2–10% of patients on antipsychotics, with higher rates in young males and those new to treatment.
   

This is a condition that usually happens within 48 hours of starting an antipsychotic drug. It is generally treated by reducing the dose. Sometimes, medicines like antihistamines or anti-Parkinson medications can be used to alleviate the symptoms.

3. Parkinsonism

Parkinsonism refers to a group of symptoms that can be similar to Parkinson's disease because there is a loss of function of dopamine.

• The cause of the most noticeable symptom is stiffness of the muscles, particularly the limbs.
• Some other symptoms could be tremors, slowness of movement (bradykinesia), salivation, and altered posture or gait.
• Between 20% and 40% of people taking antipsychotic medications may develop Parkinsonian symptoms.
• These symptoms usually begin subtly, often within a few days after starting the drug. The likelihood of experiencing Parkinsonism increases with higher doses.
• Although the symptoms are generally mild to moderate in severity, they do affect daily functioning.
• In a few cases, they will resolve spontaneously over time, but some forms of therapy are usually required.
   

Treatment usually involves a reduction in the dose of an antipsychotic or a change to a different drug. In a few cases, medications used for Parkinson's disease are administered to alleviate EPS.

4. Neuroleptic Malignant Syndrome (NMS)

Neuroleptic Malignant Syndrome is a rare yet potentially lethal side effect of antipsychotic treatment.

• Symptoms initially tend to be severe muscle rigidity and high fever, with confusion or severe drowsiness later on.
• In more serious cases, seizures may occur, and overall nervous system function can deteriorate rapidly.
• Symptoms usually occur immediately, in some cases within hours of starting treatment.
• Though extremely rare, in fewer than 0.02% of patients, NMS can lead to serious complications such as renal failure, coma, or death.
• NMS has been observed after starting a new antipsychotic or making abrupt changes to existing treatment.
• Managing NMS involves stopping the offending drug immediately and providing supportive care, often in a hospital setting.
   

When treated promptly, full recovery is possible, although the healing process may take two weeks or longer.

5. Tardive Dyskinesia

Tardive dyskinesia is only one of the extrapyramidal side effects of long-term antipsychotic use.

• It manifests as uncontrolled, repetitive movements, especially in the face.
• These may include lip smacking, tongue-twisting, grimacing, puffing of the cheeks, or chewing-like motions.
• Some individuals also develop jerky arm or leg movements, altered walking patterns, or habitual shoulder shrugging.
• This disorder is not usually noted until after six or more months of treatment with an antipsychotic.
• In some cases, the symptoms persist despite drug withdrawal.
• Women have a greater risk of developing tardive dyskinesia, and predisposing factors are old age, diabetes, and negative symptoms of schizophrenia that disrupt normal functioning.
   

Studies indicate that as many as 30% of individuals on first-generation antipsychotics can develop this disorder. Discontinuation of the antipsychotic or a decrease in dosage may be a part of the treatment or a change to a different drug. Clozapine has been noted to offer relief. Deep brain stimulation (DBS) is sometimes an option for more severe or chronic cases.

Subtypes of Tardive Dyskinesia

1. Tardive Dystonia: A more intense form of dystonia, this type involves slower, twisting movements that typically affect larger parts of the body, such as the neck or torso.
    
2. Persistent or Chronic Akathisia: This variant is distinguished from acute akathisia and includes long-standing restlessness, e.g., body rocking, arm swinging, or shuffling of the legs that persists for one month or longer on a stable dose of medication.

These subtypes usually emerge later in treatment and may remain despite attempts at intervention. Though both are movement disorders, the exact nature of motion differs.

In children, suddenly stopping medication may trigger withdrawal dyskinesias—erratic, repetitive movements affecting the torso, neck, and limbs. These usually subside within a few weeks. Restarting the antipsychotic and gradually tapering the dose can help manage such reactions.

What is the Treatment for Extrapyramidal Symptoms?

The initial treatment of extrapyramidal symptoms involves discontinuing the antipsychotic medication responsible for the reaction. This is combined with the administration of an oral or intramuscular anticholinergic, e.g., benztropine.

• Overall, drugs that block cholinergic activity (e.g., anti-Parkinsonian agents) or increase dopamine transmission in the striatum (e.g., some atypical antipsychotics) can reverse the acetylcholine-dopamine imbalance in the nigrostriatal pathway at the origin of EPS.
• While benztropine is very effective for the management of acute emergency dystonia, prevention or chronic use is not recommended.
• Chronic routine use has been associated with cognitive impairments, increased risk of dementia, and possible worsening of tardive dyskinesia, especially in already affected patients.
• In most situations, long-term prescriptions of benztropine can be safely discontinued without increasing the risk of recurrence.
• On the contrary, cognitive functions may even improve once benztropine is stopped.
   

Early detection and intervention are key to the best treatment outcomes regarding extrapyramidal symptoms. In this regard, having a comprehensive health insurance plan can be an ideal way to access quality medical care without creating an unnecessary burden on finances.