Extrapyramidal Side Effect

Aka: Extrapyramidal Side Effect, Extrapyramidal Reaction, Extrapyramidal Effect, Drug-Induced Dyskinesia, Akinesia, Dystonic Reaction, Dyskinesia, Tardive Dyskinesia, Oculogyric Crisis

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II. Pathophysiology

  1. Typically caused by antipyschotic agents, which may over-blockade Dopaminergic Receptors
  2. Results in excess Cholinergic Activity due to a loss of typical Dopamine-mediated inhibition

III. Symptoms

  1. Akathisia
    1. Motor restlessness
    2. Differentiate medication side effect from mania or Anxiety Disorder
  2. Parkinsonian Effects (longstanding Antipsychotic use)
    1. Shuffling gait
    2. Cogwheel rigidity
    3. Psychomotor retardation
  3. Dystonias
    1. Involuntary major Muscle Contractions
    2. Acute laryngospasm may occur
    3. Spasmodic Torticollis (spasm of neck Muscles, esp. sternocleidomastoid Muscle)
    4. Oculogyric Crisis (eyes fixed, staring upward or rolling back in head)

IV. Causes: Extrapyramidal Side Effects - Antipsychotics

  1. Haloperidol (Haldol) or Haloperidol Decanoate
  2. Perphenazine (Trilafon)
  3. Thiothixene HCl (Navane)
  4. Fluphenazine HCl (Prolixin)
  5. Trifluoperazine (Stelazine)
  6. Risperidone (Risperdal)

V. Causes: Tardive Dyskinesia

  1. Antipsychotics
    1. Longterm use of high dose, high potency agents (e.g. Haloperidol)
    2. Atypical Antipsychotics
  2. Other medications (esp. Dopamine blockers)
    1. Antiparkinsonism agents (e.g. Levodopa)
    2. Metoclopramide (Reglan)
    3. Anticonvulsants (e.g. Phenytoin)
    4. Antidepressants
      1. Tricyclic Antidepressants (e.g. Amitriptyline)
      2. Serotonin Reuptake Inhibitors or SSRI (e.g. Fluoxetine, Sertraline)

VI. Adverse Effects: Reversible Extrapyramidal signs and symptoms

  1. Conditions responsive to anti-Parkinsons Agents
    1. Akinesia (lack of movement, Parkinson-like)
    2. Dystonic Reaction (facial Muscle spasm, neck, back)
    3. Dyskinesia (Blinking or twitches)
    4. Akathisia (Can not to sit still, inner restlessness)
    5. Perioral Tremor (Rabbit Syndrome)
  2. Neuroleptic Malignant Syndrome
    1. Presents as Catatonia, fever, unstable Blood Pressure
    2. Life-threatening; Stop Antipsychotic immediately

VII. Adverse Effects: Irreversible (Tardive Dyskinesia)

  1. Evaluate for these signs monthly while on Antipsychotic (see prevention as below)
  2. Higher risk in elderly, cardiovascular disease risk, HIV Infection, neurologic disorders
  3. Tardive Dyskinesia
    1. Hyperkinesia (lingual or facial)
      1. Blinking
      2. Lip smacking
      3. Sucking or chewing
      4. Rolls or protrudes Tongue
      5. Grimaces
    2. Choreoathetoid extremity movement
      1. Clonic jerking fingers, ankles, toes
    3. Tonic contractions of neck or back

VIII. Management

  1. Reversible Extrapyramidal Effects
    1. Tolerance to affect
    2. Decrease or Increase OR discontinue drug dose
    3. Shift patient to an agent without Extrapyramidal Side Effects
    4. Anticholinergic Agents may decrease Dystonia or Parkinsonism effects
      1. Benztropine (Cogentin)
      2. Antihistamine (Benadryl)
    5. Consider Beta Blockers for Akathisia
      1. Propranolol
  2. Tardive Dyskinesia
    1. Lower dose or discontinue medication
      1. Consider Clozapine as alternative Antipsychotic
    2. Avoid adding Anticholinergic Agent (e.g. Benztropine)
      1. May worsen Tardive Dyskinesia (despite benefit in acute Dystonia)
    3. Reversible Vesicular monoamine transporter 2 Inhibitors (VMAT2)
      1. Deutetrabenazine (Austedo)
      2. Ingrezza (Valbenazine)
        1. Decreases Dopamine in nerve endings
        2. Reduces symptoms by 50% with 6 weeks of treatment (Number Needed to Treat: 4)
        3. Very expensive ($5000 per month)
    4. Other symptomatic management
      1. Vitamin E supplementation
      2. Vitamin B6 Supplementation
      3. Amantadine

IX. Prevention

  1. Clinicians should be alert for Extrapyramidal Side Effects (and modify therapy to reduce adverse effects)
  2. Perform Abnormal Involuntary Movement Scale (AIMS) at least every 6 months while on Antipsychotic Medications
    1. https://dmh.mo.gov/media/21821/download

X. References

  1. (2017) Presc Lett 24(6): 36
  2. Mason, Swadron and Herbert in Herbert (2019) EM:Rap C3 3(2): 8

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Related Studies

Ontology: Dyskinetic syndrome (C0013384)

Definition (CHV) a disease characterized by abnormal involuntary movements of muscles
Definition (NCI_FDA) Difficulty moving; distortion or impairment of voluntary movement, as in tic, spasm, or myoclonus.
Definition (NCI) Difficulty moving; distortion or impairment of voluntary movement, as in tic, spasm, or myoclonus.
Definition (MSH) Abnormal involuntary movements which primarily affect the extremities, trunk, or jaw that occur as a manifestation of an underlying disease process. Conditions which feature recurrent or persistent episodes of dyskinesia as a primary manifestation of disease may be referred to as dyskinesia syndromes (see MOVEMENT DISORDERS). Dyskinesias are also a relatively common manifestation of BASAL GANGLIA DISEASES.
Definition (PSY) Abnormal involuntary motor processes that occur due to underlying disease processes.
Concepts Disease or Syndrome (T047)
MSH D020820
ICD10 G24 , G24.9
SnomedCT 206824003, 9748009, 229694001
English Dyskinesias, DYSKINETIC SYNDROME, [D]Dyskinesia, Dyscinesia, Dyskinesis, Dyskinetic syndrome, Syndrome dyskinetic, Abnormal Movement, Abnormal Movements, Movement, Abnormal, Movements, Abnormal, Dyskinesia NOS, Dyskinesias [Disease/Finding], dyskinesia, DYSKINESIA, Dyskinesia, Dyskinesia (finding), Dyskinesia (finding) #09
French DYSKINESIE, Syndrome dyskinétique, Mouvement anormal, Mouvements anormaux, Dyscinésies, SYNDROME DE DYSKINESIE, Dyskinésie, Dyskinésies
Spanish DISCINESIA, Síndrome discinético, DISCINETICO, SINDROME, Disquinesias, discinesia (hallazgo), discinesia, Discinesia, Discinesias
Italian Discinesia, Sindrome discinetica, Movimenti anormali, Discinesie
Dutch dyskinetisch syndroom, syndroom dyskinetisch, dyskinesie, Dyskinesie
German Dyskinetisches Syndrom, Syndrom dyskinetisch, DYSKINESIE, DYSKINETISCHES SYNDROM, Dyskinesie, Dyskinesien
Portuguese Síndrome disquinética, DISQUINESIA, SINDROME DE DISQUINESIA, Discinesia, Discinesias
Swedish Dyskinesi
Czech dyskinézy, Dyskineze, Dyskinetický syndrom
Finnish Dyskinesiat
Russian DVIZHENIIA NEPROIZVOL'NYE, TREMOR DISKINETICHESKII, DISKINEZII, ДВИЖЕНИЯ НЕПРОИЗВОЛЬНЫЕ, ДИСКИНЕЗИИ, ТРЕМОР ДИСКИНЕТИЧЕСКИЙ
Japanese 強制運動, 羽ばたき振戦, 半側バリスム, 片側バリスム, ジスキネジー, バリスムス, 羽ばたき振せん, 固定姿勢不能症, バリスム, 振戦-羽ばたき, 片側バリズム, 異常運動症, 固定姿勢不能, ルイス体症候群, 異常運動, ジスキネジア, ジスキネジア症候群, ｼﾞｽｷﾈｼﾞｱ, ｼﾞｽｷﾈｼﾞｱｼｮｳｺｳｸﾞﾝ
Croatian Not Translated[Dyskinesias]
Polish Zaburzenia ruchów dowolnych, Ruchy mimowolne, Dyskinezy
Hungarian Dyskinesia, Dyskinetikus syndroma, Dyskinetikus tünetegyüttes
Norwegian Dyskinesier, Dyskinesi
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Dyskinesia, Drug-Induced (C0013386)

Definition (MSH) Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)
Concepts Disease or Syndrome (T047)
MSH D004409
SnomedCT 102448004, 38941006
English Drug-Induced Dyskinesia, Drug-Induced Dyskinesias, Dyskinesia, Drug Induced, Dyskinesia, Drug-Induced, Dyskinesias, Drug-Induced, DYSKINESIA DRUG IND, Dyskinesia, Drug-Induced [Disease/Finding], drug dyskinesias induced, Drug-induced dyskinesia, Drug-induced dyskinesia (disorder)
Swedish Dyskinesi, läkemedelsframkallad
Czech dyskinéze léková
Portuguese Discinesia Induzida por Medicamentos, Discinesia Induzida por Drogas
Spanish Discinesia Inducida por Medicamentos, Discinesia Inducida por Drogas, discinesia medicamentosa (trastorno), discinesia medicamentosa
Finnish Lääkkeen aiheuttama dyskinesia
Russian DISKINEZIIA LEKARSTVENNAIA, ДИСКИНЕЗИЯ ЛЕКАРСТВЕННАЯ
Japanese 運動異常症-薬物誘発性, ジスキネジア-遅発性, 薬物性運動異常症, 薬物性ジスキネジー, 運動障害-薬物誘発性, ジスキネジー-薬物性, 薬物誘発性ジスキネジア, 遅発性ジスキネジア, 薬物誘発性運動異常症, 晩発性運動異常症, 薬剤誘発性運動異常症, 運動異常症-薬物性, 運動異常症-晩発性, ジスキネジア-薬物誘発性
Polish Dyskineza polekowa
Norwegian Dyskinesi, legemiddelutløst, Legemiddelutløst dyskinesi
German Dyskinesia tarda, Dyskinesie, arzneimittelinduzierte, Dyskinesie, tardive, Tardive Dyskinesie
Italian Discinesia indotta da farmaci
Dutch Dyskinesie, geneesmiddelgeïnduceerde, Geneesmiddelgeïnduceerde dyskinesie
French Dyskinésie due aux médicaments, Dyskinésie induite par les médicaments
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Akinesia (C0085623)

Concepts Disease or Syndrome (T047)
SnomedCT 33994004
English AKINESIA, akinesias, akinesia, Akinesia, Akinesia (finding)
Italian Acinesia
Portuguese ACINESIA, Acinesia
Spanish ACINESIA, acinesia (hallazgo), acinesia, aquinesia, Acinesia
German AKINESE, Akinesie
French AKINESIE, Akinésie
Czech Akineze
Japanese 無動, ﾑﾄﾞｳ
Hungarian Akinesia
Dutch akinesie
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Dystonic reaction (C0541919)

Concepts Finding (T033)
Dutch dystonische reactie
French Réaction dystonique
German dystonische Reaktion
Italian Reazione distonica
Portuguese Reacção distónica
Spanish Reacción distónica
Czech Dystonická reakce
English Dystonic reaction, dystonic reaction, dystonic reactions
Hungarian Dystoniás reakció
Japanese ジストニア反応, ｼﾞｽﾄﾆｱﾊﾝﾉｳ
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Tardive Dyskinesia (C0686347)

Definition (CSP) iatrogenic extrapyramidal disorder produced by long-term administration of antipsychotic drugs; characterized by oral/lingual/buccal dyskinesias and choreoathetoid movements of the extremities.
Concepts Disease or Syndrome (T047)
ICD10 G24.01
SnomedCT 123304005, 267689009, 155007009, 192861006, 38941006
English Tardive dyskinesia, DYSKINESIA TARDIVE, Tardive Dyskinesia, TARDIVE DYSKINESIA, tardive dyskinesia (diagnosis), tardive dyskinesia, Dyskinesia tardive, dyskinesia tardive, dyskinesias tardive, Tardive dyskinesia (disorder), Tardive dyskinesia -RETIRED-
Portuguese DISCINESIA TARDIA, Disquinésia tardia, Discinesia tardia
Spanish DISCINESIA TARDIA, discinesia oral tardía - RETIRADO -, discinesia oral tardía - RETIRADO - (concepto no activo), Discinesia tardía
Italian Discinesia tardiva
Dutch dyskinesie tardief, tardieve dyskinesie
German Dyskinesie tardiv, DYSKINESIE TARDIV, tardive Dyskinesie
French DYSKINESIE TARDIVE, Dyskinésie tardive
Czech Tardivní dyskineze
Hungarian Tardiv dyskinesia
Japanese 遅発性ジスキネジア, ﾁﾊﾂｾｲｼﾞｽｷﾈｼﾞｱ
Derived from the NIH UMLS (Unified Medical Language System)

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