:Extrapyramidal symptoms

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.{{cite journal|author=Nevena Divac|author2=Milica Prostran|author3=Igor Jakovcevski|author4=Natasa Cerovac|name-list-style=amp|title=Second-Generation Antipsychotics and Extrapyramidal Adverse Effects|journal=BioMed Research International|volume=2014|pages=6 pages|year=2014|doi=10.1155/2014/656370|pmid=24995318|pmc=4065707|doi-access=free}} Atypical antipsychotics have lower D2 receptor affinity or higher serotonin 5-HT2A receptor affinity which lead to lower rates of EPS.{{cite journal|author=Correll C|title=Mechanism of Action of Antipsychotic Medications|journal=J Clin Psychiatry|year=2014|volume=75|issue=9|page=e23|doi=10.4088/jcp.13078tx4c}}

Other anti-dopaminergic drugs, like the antiemetic metoclopramide, can also result in extrapyramidal side effects.{{cite journal|author=Moos, DD.|author2=Hansen, DJ.|title=Metoclopramide and Extrapyramidal Symptoms: A Case Report|journal=Journal of PeriAnesthesia Nursing|volume=23|issue=5|date=October 2008|pages=292–299|doi=10.1016/j.jopan.2008.07.006|pmid=18926476}} Short and long-term use of antidepressants such as selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), and norepinephrine-dopamine reuptake inhibitors (NDRI) have also resulted in EPS.{{cite journal|vauthors=Madhusoodanan S, Alexeenko L, Sanders R, Brenner R|title=Extrapyramidal symptoms associated with antidepressants—A review of the literature and an analysis of spontaneous reports|journal=Annals of Clinical Psychiatry|year=2010|volume=22|issue=3|pages=148–156|pmid=20680187|url=https://www.aacp.com/pdf%2F0810%2F0810ACP_Madhusoodanan.pdf|access-date=2016-05-03|archive-date=2013-11-27|archive-url=https://web.archive.org/web/20131127041240/http://www.aacp.com/pdf/0810/0810ACP_Madhusoodanan.pdf|url-status=dead}} Specifically, duloxetine, sertraline, escitalopram, fluoxetine, and bupropion have been linked to the induction of EPS.

Other causes of extrapyramidal symptoms can include brain damage and meningitis.{{cite journal|author=Ori Scott|author2=Simona Hasal|author3=Helly R. Goez|name-list-style=amp|title=Basal Ganglia Injury With Extrapyramidal Presentation: A Complication of Meningococcal Meningitis|journal=J Child Neurol|date=November 2013|volume=28|issue=11|pages=1489–1492|orig-year=September 10, 2012|doi=10.1177/0883073812457463|pmid=22965562|s2cid=30536341}} However, the term "extrapyramidal symptoms" generally refers to medication-induced causes in the field of psychiatry.{{cite book |title=Kaufman's Clinical Neurology for Psychiatrists |publisher=Elsevier Inc. |edition=8th |chapter=Involuntary Movement Disorders (Ch. 18)}}

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).{{citation needed|date=July 2021}}

• 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.{{Cite web|title=Be Drug Wise: Psychotherapeutic Meds|url=https://www.edgt.com/|access-date=10 September 2020|website=Educational Global Technologies, Inc.}}
• Pseudoparkinsonism: drug-induced parkinsonism (rigidity, bradykinesia, tremor, masked facies, shuffling gait, stooped posture, sialorrhoea, and seborrhoea; greater risk in the elderly). Although Parkinson's disease 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: involuntary muscle movements in the lower face and distal extremities; this can be a chronic condition associated with long-term use of antipsychotics.

Medications are used to reverse the symptoms of extrapyramidal side effects caused by antipsychotics or other drugs, by either directly or indirectly increasing dopaminergic neurotransmission. The treatment varies by the type of the EPS, but may involve anticholinergic 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 antipsychotic, 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, 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 (chlorpromazine, haloperidol, etc.){{cite journal|title=Extrapyramidal motor side-effects of first- and second-generation antipsychotic drugs|author=Michael J. Peluso|author2=Shôn W. Lewis|author3=Thomas R. E. Barnes|author4=Peter B. Jones|journal=The British Journal of Psychiatry|year=2012|volume=200|issue=5|pages=387–92|doi=10.1192/bjp.bp.111.101485|pmid=22442101|doi-access=free}}

Anticholinergic 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.

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.{{cite journal |last1=E. Thomas |first1=Jennifer |last2=Caballero |first2=Joshua |last3=A. Harrington |first3=Catherine |title=The Incidence of Akathisia in the Treatment of Schizophrenia with Aripiprazole, Asenapine and Lurasidone: A Meta-Analysis |journal=Current Neuropharmacology |date=13 October 2015 |volume=13 |issue=5 |pages=681–691 |doi=10.2174/1570159X13666150115220221|pmid=26467415 |pmc=4761637 }} If akathisia occurs, switching to an antipsychotic with a lower risk of akathisia may improve symptoms.{{cite journal |last1=Salem |first1=Haitham |last2=Nagpal |first2=Caesa |last3=Pigott |first3=Teresa |last4=Teixeira |first4=Antonio Lucio |title=Revisiting Antipsychotic-induced Akathisia: Current Issues and Prospective Challenges |journal=Current Neuropharmacology |date=15 June 2017 |volume=15 |issue=5 |pages=789–798 |doi=10.2174/1570159X14666161208153644|pmid=27928948 |pmc=5771055 }} Beta blockers (like propranolol) 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.

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

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.

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.{{citation needed|date=July 2021}}

• Neuroleptic malignant syndrome
• Rabbit syndrome

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Category:Extrapyramidal and movement disorders

Category:Syndromes