Extrapyramidal symptoms

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Extrapyramidal symptoms
Other namesextrapyramidal manifestations;
extrapyramidal side effects (EPSE) (when caused by drugs)
Specialty Neurology

Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications 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), [1] parkinsonism characteristic symptoms such as rigidity, bradykinesia (slowness of movement), tremor, and tardive dyskinesia (irregular, jerky movements). [2] Extrapyramidal symptoms are a reason why subjects drop out of clinical trials of antipsychotics; 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. [3]

Contents

Causes

Medications

Extrapyramidal symptoms are most commonly caused by typical antipsychotic drugs that antagonize dopamine D2 receptors. [2] The most common typical antipsychotics associated with EPS are haloperidol and fluphenazine. [4] Atypical antipsychotics have lower D2 receptor affinity or higher serotonin 5-HT2A receptor affinity which lead to lower rates of EPS. [5]

Other anti-dopaminergic drugs, like the antiemetic metoclopramide, can also result in extrapyramidal side effects. [6] 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. [7] Specifically, duloxetine, sertraline, escitalopram, fluoxetine, and bupropion have been linked to the induction of EPS. [7]

Other causes of extrapyramidal symptoms can include brain damage and meningitis. [8] However, the term "extrapyramidal symptoms" generally refers to medication-induced causes in the field of psychiatry. [9]

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; [2] 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 ]

Classification

Treatment

Medications are used to reverse the symptoms of extrapyramidal side effects caused by antipsychotics or other drugs, either by 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.) [11]

Dystonia

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. [9]

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. [12] If akathisia occurs, switching to an antipsychotic with a lower risk of akathisia may improve symptoms. [13] 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. [9]

Pseudoparkinsonism

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. [9]

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. [9]

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.[ citation needed ]

See also

Related Research Articles

<span class="mw-page-title-main">Antipsychotic</span> Class of medications

Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay together with mood stabilizers in the treatment of bipolar disorder.

<span class="mw-page-title-main">Trifluoperazine</span> Chemical compound

Trifluoperazine, marketed under the brand name Stelazine among others, is a typical antipsychotic primarily used to treat schizophrenia. It may also be used short term in those with generalized anxiety disorder but is less preferred to benzodiazepines. It is of the phenothiazine chemical class.

<span class="mw-page-title-main">Haloperidol</span> Typical antipsychotic medication

Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosis, and hallucinations from alcohol withdrawal. It may be used by mouth or injection into a muscle or a vein. Haloperidol typically works within 30 to 60 minutes. A long-acting formulation may be used as an injection every four weeks by people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.

<span class="mw-page-title-main">Typical antipsychotic</span> Class of drugs

Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis. Typical antipsychotics may also be used for the treatment of acute mania, agitation, and other conditions. The first typical antipsychotics to come into medical use were the phenothiazines, namely chlorpromazine which was discovered serendipitously. Another prominent grouping of antipsychotics are the butyrophenones, an example of which is haloperidol. The newer, second-generation antipsychotics, also known as atypical antipsychotics, have largely supplanted the use of typical antipsychotics as first-line agents due to the higher risk of movement disorders in the latter.

<span class="mw-page-title-main">Atypical antipsychotic</span> Class of pharmaceutical drugs

The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, irritability in autism, and as an adjunct in major depressive disorder.

<span class="mw-page-title-main">Benzatropine</span> Group of stereoisomers

Benzatropine (INN), known as benztropine in the United States and Japan, is a medication used to treat movement disorders like parkinsonism and dystonia, as well as extrapyramidal side effects of antipsychotics, including akathisia. It is not useful for tardive dyskinesia. It is taken by mouth or by injection into a vein or muscle. Benefits are seen within two hours and last for up to ten hours.

<span class="mw-page-title-main">Akathisia</span> Movement disorder involving a feeling of inner restlessness

Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back and forth, or pace, while some may just have an uneasy feeling in their body. The most severe cases may result in aggression, violence, and/or suicidal thoughts. Akathisia is also associated with threatening behaviour and physical aggression that is greatest in patients with mild akathisia, and diminishing with increasing severity of akathisia.

<span class="mw-page-title-main">Tardive dyskinesia</span> Neurological disorder featuring involuntary, repetitive body movements

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 movements. In about 20% of people with TD, the disorder interferes with daily functioning.

Dyskinesia refers to a category of movement disorders that are characterized by involuntary muscle movements, including movements similar to tics or chorea and diminished voluntary movements. Dyskinesia can be anything from a slight tremor of the hands to an uncontrollable movement of the upper body or lower extremities. Discoordination can also occur internally especially with the respiratory muscles and it often goes unrecognized. Dyskinesia is a symptom of several medical disorders that are distinguished by their underlying cause.

<span class="mw-page-title-main">Dopamine antagonist</span> Drug which blocks dopamine receptors

A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.

<span class="mw-page-title-main">Prochlorperazine</span> Medication for nausea, psychosis, and anxiety

Prochlorperazine, formerly sold under the brand name Compazine among others, is a medication used to treat nausea, migraines, schizophrenia, psychosis and anxiety. It is a less preferred medication for anxiety. It may be taken by mouth, rectally, injection into a vein, or injection into a muscle.

<span class="mw-page-title-main">Progabide</span> Pharmaceutical drug

Progabide is an analogue and prodrug of γ-aminobutyric acid (GABA) used in the treatment of epilepsy. Via conversion into GABA, progabide behaves as an agonist of the GABAA, GABAB, and GABAA-ρ receptors.

<span class="mw-page-title-main">Amisulpride</span> Atypical antipsychotic and antiemetic medication

Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold under the brand names Barhemsys and Solian, Socian, Deniban and others. At very low doses it is also used to treat dysthymia.

<span class="mw-page-title-main">Procyclidine</span> Group of stereoisomers

Procyclidine is an anticholinergic drug principally used for the treatment of drug-induced parkinsonism, akathisia and acute dystonia, Parkinson's disease, and idiopathic or secondary dystonia.

<span class="mw-page-title-main">Asenapine</span> Medication to treat schizophrenia

Asenapine, sold under the brand name Saphris among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder as well as the medium to long-term management of bipolar disorder.

<span class="mw-page-title-main">Zuclopenthixol</span> Chemical compound

Zuclopenthixol, also known as zuclopentixol, is a medication used to treat schizophrenia and other psychoses. It is classed, pharmacologically, as a typical antipsychotic. Chemically it is a thioxanthene. It is the cis-isomer of clopenthixol. Clopenthixol was introduced in 1961, while zuclopenthixol was introduced in 1978.

<span class="mw-page-title-main">Tiapride</span> Drug

Tiapride is a drug that selectively blocks D2 and D3 dopamine receptors in the brain. It is used to treat a variety of neurological and psychiatric disorders including dyskinesia, alcohol withdrawal syndrome, negative symptoms of psychosis, and agitation and aggression in the elderly. A derivative of benzamide, tiapride is chemically and functionally similar to other benzamide antipsychotics such as sulpiride and amisulpride known for their dopamine antagonist effects.

Pleurothotonus, commonly known as Pisa syndrome, is a rare neurological disorder which occurs due to prolonged exposure to antipsychotic drugs. It is characterized by dystonia, and abnormal and sustained involuntary muscle contraction. This may cause twisting or jerking movements of the body or a body part. Although Pisa syndrome develops most commonly in those undergoing long-term treatment with antipsychotics, it has been reported less frequently in patients receiving other medications, such as an acetylcholinesterase inhibitor. However, it has also been seen in those with other diseases causing neurodegeneration and in those who are not receiving any medication. The characteristic development of Pisa syndrome consists of two types of dystonia: acute dystonia and tardive dystonia. The underlying pathology of drug-induced Pisa syndrome is very complex, and development may be due to an underlying dopaminergic-cholinergic imbalance, or serotonergic/noradrenergic dysfunction.

<span class="mw-page-title-main">Aripiprazole lauroxil</span> Chemical compound

Aripiprazole lauroxil, sold under the brand name Aristada, is a long-acting injectable atypical antipsychotic that was developed by Alkermes. It is an N-acyloxymethyl prodrug of aripiprazole that is administered via intramuscular injection once every four to eight weeks for the treatment of schizophrenia. Aripiprazole lauroxil was approved by the U.S. Food and Drug Administration (FDA) on 5 October 2015.

References

  1. ↑ Akagi, Hiroko; Kumar, T Manoj (2002-06-22). "Akathisia: overlooked at a cost". BMJ: British Medical Journal. 324 (7352): 1506–1507. doi:10.1136/bmj.324.7352.1506. ISSN   0959-8138. PMC   1123446 . PMID   12077042.
  2. 1 2 3 4 5 6 7 Pierre, JM (2005). "Extrapyramidal symptoms with atypical antipsychotics: incidence, prevention and management". Drug Safety. 28 (3): 191–208. doi:10.2165/00002018-200528030-00002. PMID   15733025. S2CID   41268164.
  3. ↑ Jeffrey A. Lieberman; T. Scott Stroup; Joseph P. McEvoy; Marvin S. Swartz; Robert A. Rosenheck; Diana O. Perkins; Richard S.E. Keefe; Sonia M. Davis; Clarence E. Davis; Barry D. Lebowitz; Joanne Severe; John K. Hsiao & for the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators (September 22, 2005). "Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia". N Engl J Med. 353 (12): 1209–1223. doi:10.1056/NEJMoa051688. PMID   16172203.
  4. ↑ Nevena Divac; Milica Prostran; Igor Jakovcevski & Natasa Cerovac (2014). "Second-Generation Antipsychotics and Extrapyramidal Adverse Effects". BioMed Research International. 2014: 6 pages. doi: 10.1155/2014/656370 . PMC   4065707 . PMID   24995318.
  5. ↑ Correll C (2014). "Mechanism of Action of Antipsychotic Medications". J Clin Psychiatry. 75 (9): e23. doi:10.4088/jcp.13078tx4c.
  6. ↑ Moos, DD.; Hansen, DJ. (October 2008). "Metoclopramide and Extrapyramidal Symptoms: A Case Report". Journal of PeriAnesthesia Nursing. 23 (5): 292–299. doi:10.1016/j.jopan.2008.07.006. PMID   18926476.
  7. 1 2 Madhusoodanan S, Alexeenko L, Sanders R, Brenner R (2010). "Extrapyramidal symptoms associated with antidepressants—A review of the literature and an analysis of spontaneous reports" (PDF). Annals of Clinical Psychiatry. 22 (3): 148–156. PMID   20680187.
  8. ↑ Ori Scott; Simona Hasal & Helly R. Goez (November 2013) [September 10, 2012]. "Basal Ganglia Injury With Extrapyramidal Presentation: A Complication of Meningococcal Meningitis". J Child Neurol. 28 (11): 1489–1492. doi:10.1177/0883073812457463. PMID   22965562. S2CID   30536341.
  9. 1 2 3 4 5 "Involuntary Movement Disorders (Ch. 18)". Kaufman's Clinical Neurology for Psychiatrists (8th ed.). Elsevier Inc.
  10. 1 2 "Be Drug Wise: Psychotherapeutic Meds". Educational Global Technologies, Inc. Retrieved 10 September 2020.
  11. ↑ Michael J. Peluso; Shôn W. Lewis; Thomas R. E. Barnes; Peter B. Jones (2012). "Extrapyramidal motor side-effects of first- and second-generation antipsychotic drugs". The British Journal of Psychiatry. 200 (5): 387–92. doi: 10.1192/bjp.bp.111.101485 . PMID   22442101.
  12. ↑ E. Thomas, Jennifer; Caballero, Joshua; A. Harrington, Catherine (13 October 2015). "The Incidence of Akathisia in the Treatment of Schizophrenia with Aripiprazole, Asenapine and Lurasidone: A Meta-Analysis". Current Neuropharmacology. 13 (5): 681–691. doi:10.2174/1570159X13666150115220221. PMC   4761637 . PMID   26467415.
  13. ↑ Salem, Haitham; Nagpal, Caesa; Pigott, Teresa; Teixeira, Antonio Lucio (15 June 2017). "Revisiting Antipsychotic-induced Akathisia: Current Issues and Prospective Challenges". Current Neuropharmacology. 15 (5): 789–798. doi:10.2174/1570159X14666161208153644. PMC   5771055 . PMID   27928948.
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