Extrapyramidal symptoms


Extrapyramidal symptoms, also known as extrapyramidal side effects if drug-induced, are movement disorders, which include acute and long term symptoms. These symptoms include dystonia, akathisia, parkinsonism, bradykinesia, tremor, and tardive dyskinesia. Extrapyramidal symptoms are a reason why subjects drop out of clinical trials of antipsychotics; of the 213 subjects that dropped out of the one of the largest clinical trials of antipsychotics, 58 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, serotonin-norepinephrine reuptake inhibitors, and norepinephrine-dopamine reuptake inhibitors 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, Barnes Akathisia Rating Scale, Abnormal Involuntary Movement Scale, and Extrapyramidal Symptom Rating Scale 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.

Classification

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 agents such as procyclidine, benztropine, diphenhydramine, and trihexyphenidyl, and dopamine agonists like pramipexole.
If the EPS are induced by an antipsychotic, EPS may be reduced by decreasing the dose of the antipsychotic or by switching from a typical antipsychotic to an atypical antipsychotic, such as aripiprazole, ziprasidone, quetiapine, olanzapine, risperidone, or clozapine. 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

Dystonia

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 blockers are frequently used to treat akathisia. Other medications that are sometimes used include clonidine, mirtazapine, or even benzodiazepines. Anticholinergic medications are not helpful for treating akathisia.

Pseudoparkinonism

Medication interventions are generally reserved for cases in which withdrawing the medication that caused the pseudoparkinonism is either ineffective or infeasible. Anticholinergic medications are sometimes used to treat pseudoparkinonism, 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 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.