Extrapyramidal symptoms (EPS) are

symptoms Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showi ...

that are archetypically associated with the extrapyramidal system of the brain's

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting o ...

. When such symptoms are caused by

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field an ...

s or other drugs, they are also known as extrapyramidal side effects (EPSE). The symptoms can be acute (short-term) or chronic (long-term). They include movement dysfunction such as dystonia (continuous spasms and muscle contractions), akathisia (may manifest as motor restlessness), parkinsonism characteristic symptoms such as rigidity, bradykinesia (slowness of movement), tremor, and

tardive dyskinesia Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movemen ...

(irregular, jerky movements). Extrapyramidal symptoms are a reason why subjects drop out of

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s of

antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range o ...

s; of the 213 (14.6%) subjects that dropped out of one of the largest clinical trials of antipsychotics (the CATIE trial (Clinical Antipsychotic Trials for Intervention Effectiveness), which included 1460 randomized subjects), 58 (27.2%) of those discontinuations were due to EPS.

Causes

Medications

Extrapyramidal symptoms are most commonly caused by typical antipsychotic drugs that antagonize dopamine D2 receptors. The most common typical antipsychotics associated with EPS are haloperidol and fluphenazine. Atypical antipsychotics have lower D2 receptor affinity or higher serotonin 5-HT2A receptor affinity which lead to lower rates of EPS. Other anti-dopaminergic drugs, like the antiemetic metoclopramide, can also result in extrapyramidal side effects. Short and long-term use of antidepressants such as

selective serotonin reuptake inhibitors Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracell ...

(SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), and norepinephrine-dopamine reuptake inhibitors (NDRI) have also resulted in EPS. Specifically, duloxetine, sertraline, escitalopram, fluoxetine, and bupropion have been linked to the induction of EPS.

Non-medication-related

Other causes of extrapyramidal symptoms can include brain damage and meningitis. However, the term "extrapyramidal symptoms" generally refers to medication-induced causes in the field of psychiatry.

Diagnosis

Since it is difficult to measure extrapyramidal symptoms, rating scales are commonly used to assess the severity of movement disorders. The Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), Abnormal Involuntary Movement Scale (AIMS), and Extrapyramidal Symptom Rating Scale (ESRS) are rating scales frequently used for such assessment and are not weighted for diagnostic purposes; these scales can help clinicians weigh the benefit/expected benefit of a medication against the degree of distress which the side effects are causing the patient, aiding in the decision to maintain, reduce, or discontinue the causative medication(s).

Classification

* Acute dystonic reactions: painful, muscular spasms of neck, jaw, back, extremities, eyes, throat, and tongue; highest risk in young men. ** Oculogyric crisis is a kind of acute dystonic reaction that involves the prolonged involuntary upward deviation of the eyes. * Akathisia: A feeling of internal motor restlessness that can present as tension, nervousness, or anxiety. Clinical manifestations include pacing and an inability to sit still. *

Pseudoparkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), Rigidity (neurology), rigidity, and balance disorder, postural instability. These are the four Parkinson's disease#Motor, motor symptoms found in Parkins ...

: drug-induced parkinsonism (rigidity, bradykinesia, tremor, masked

facies In geology, a facies ( , ; same pronunciation and spelling in the plural) is a body of rock with specified characteristics, which can be any observable attribute of rocks (such as their overall appearance, composition, or condition of formatio ...

, shuffling gait, stooped posture, sialorrhoea, and seborrhoea; greater risk in the elderly). Although

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

is primarily a disease of the nigrostriatal pathway and not the extrapyramidal system, loss of dopaminergic neurons in the substantia nigra leads to dysregulation of the extrapyramidal system. Since this system regulates posture and skeletal muscle tone, a result is the characteristic bradykinesia of Parkinson's. *

Tardive dyskinesia Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movemen ...

: involuntary muscle movements in the lower face and distal extremities; this can be a chronic condition associated with long-term use of antipsychotics.

Treatment

Medications are used to reverse the symptoms of extrapyramidal side effects caused by antipsychotics or other drugs, either by directly or indirectly inhibiting dopaminergic neurotransmission. The treatment varies by the type of the EPS, but may involve

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous syste ...

agents such as procyclidine, benztropine, diphenhydramine, and trihexyphenidyl. Certain medications such as dopamine agonists are not used, as they may worsen psychotic symptoms to those taking neuroleptic drugs. If the EPS are induced by an

, EPS may be reduced by decreasing the dose of the antipsychotic or by switching from a typical antipsychotic to an (or to a different)

atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...

, such as aripiprazole, ziprasidone,

quetiapine Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its ...

, olanzapine, risperidone, or

clozapine Clozapine is a psychiatric medication and is the first atypical antipsychotic (also called second-generation antipsychotic). It is primarily used to treat people with schizophrenia and schizoaffective disorders who have had an inadequate resp ...

. These medications possess an additional mode of action that is believed to mitigate their effect on the nigrostriatal pathway, which means they are associated with fewer extrapyramidal side-effects than "conventional" antipsychotics ( chlorpromazine, haloperidol, etc.)

Dystonia

Anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous syste ...

medications are used to reverse acute dystonia. If the symptoms are particularly severe, the anticholinergic medication may be administered by injection into a muscle to rapidly reverse the dystonia.

Akathisia

Certain second-generation antipsychotics, such as lurasidone and the partial D2-agonist aripiprazole, are more likely to cause akathisia compared to other second-generation antipsychotics. If akathisia occurs, switching to an antipsychotic with a lower risk of akathisia may improve symptoms.

Beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack ( secondary prevention). They are ...

s (like propranolol) are frequently used to treat akathisia. Other medications that are sometimes used include

clonidine Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, an ...

, mirtazapine, or even

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

s. Anticholinergic medications are not helpful for treating akathisia.

Pseudoparkinsonism

Medication interventions are generally reserved for cases in which withdrawing the medication that caused the pseudoparkinsonism is either ineffective or infeasible.

medications are sometimes used to treat pseudoparkinsonism, but they can be difficult to tolerate when given chronically. Amantadine is sometimes used as well. It is rare for dopamine agonists to be used for antipsychotic-induced EPS, as they may exacerbate psychosis.

Tardive dyskinesia

When other measures fail or are not feasible, medications are used to treat tardive dyskinesia. These include the vesicular monoamine transporter 2 inhibitors tetrabenazine and deutetrabenazine.

History

Extrapyramidal symptoms (also called extrapyramidal side effects) get their name because they are symptoms of disorders in the extrapyramidal system, which regulates posture and skeletal muscle tone. This is in contrast to symptoms originating from the pyramidal tracts.

References

External links

{{Medical resources , ICD9 = {{ICD9, 333.90 , ICDO = , OMIM = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = * Extrapyramidal and movement disorders Syndromes