약물 유발 움직임 이상증 탐구(파킨슨 증상의 이해를 위해)...

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Extrapyramidal Symptoms

Ryan S. D'Souza; W M. Hooten.
Author Information and AffiliationsLast Update: July 31, 2023.

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Continuing Education Activity

Extrapyramidal side effects (EPS), commonly referred to as drug-induced movement disorders are among the most common adverse drug effects patients experience from dopamine-receptor blocking agents. A variety of movement phenotypes has since been described along the EPS spectrum, including dystonia, akathisia, and parkinsonism, which occur more acutely, as well as more chronic manifestations of tardive akathisia and tardive dyskinesia. This activity reviews the cause, pathophysiology, and presentation of EPS and highlights the role of the interprofessional team in its management.

추체외로 부작용 Extrapyramidal side effects (EPS)은

일반적으로 약물 유발 운동 장애로 불리며,

도파민 수용체 차단제로 인해

환자가 경험하는 가장 흔한 약물 부작용 중 하나입니다.

이후 EPS 스펙트럼을 따라

근긴장 이상증 dystonia,

운동 실조증(좌불안석증) akathisia,

파킨슨병 등 다양한 운동 표현형이 설명되었으며,

dystonia,

akathisia

이는

보다 급성으로 발생하는

운동 이상증과 지체성 운동 실조증 및 지체성 운동 이상증의 만성 증상을 포함합니다.

akathisia and tardive dyskinesia

이 활동에서는

EPS의 원인,

병태생리 및 증상을 검토하고

관리에서 전문가 간 팀의 역할을 강조합니다.

Objectives:

• Outline the types of drugs known to cause EPS.
• Differentiate the types of EPS symptoms.
• Summarize the treatment of EPS.
• Review the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by EPS.

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Introduction

Extrapyramidal side effects (EPS), commonly referred to as drug-induced movement disorders are among the most common adverse drug effects patients experience from dopamine-receptor blocking agents. It was first described in 1952 after chlorpromazine-induced symptoms resembling Parkinson disease.[1] A variety of movement phenotypes has since been described along the EPS spectrum, including dystonia, akathisia, and parkinsonism, which occur more acutely, as well as more chronic manifestations of tardive akathisia and tardive dyskinesia. The symptoms of EPS are debilitating, interfering with social functioning and communication, motor tasks, and activities of daily living. This is often associated with poor quality of life and abandonment of therapy, which may result in disease relapse and re-hospitalization, particularly in schizophrenic patients stopping pharmacologic therapy.[2]

추체외로 부작용(EPS)은

흔히 약물로 인한 운동 장애 drug-induced movement disorders 로 불리는데,

도파민 수용체 차단제로 인해

환자가 경험하는 가장 흔한 약물 부작용 중 하나입니다.

1952년 클로르프로마진으로 인해

파킨슨병과 유사한 증상이 나타난 후 처음 설명되었습니다.[1]

A variety of movement phenotypes has since been described along the EPS spectrum, including dystonia, akathisia, and parkinsonism, which occur more acutely, as well as more chronic manifestations of tardive akathisia and tardive dyskinesia. 

이후 EPS 스펙트럼을 따라

보다 급성적으로 발생하는 운동 이상증인

근긴장 이상증,

운동 실조증, 파킨슨증 등

다양한 운동 표현형이 설명되었으며,

뿐만아니라

만성적으로 나타나는

지체성 운동 실조증 tardive akathisia ,

지체성 운동 이상증 tardive dyskinesia이 있습니다.

The symptoms of EPS are debilitating, interfering with social functioning and communication, motor tasks, and activities of daily living. This is often associated with poor quality of life and abandonment of therapy, which may result in disease relapse and re-hospitalization, particularly in schizophrenic patients stopping pharmacologic therapy.

EPS의 증상은

쇠약해지고 사회적 기능과 의사소통,

운동 작업 및 일상 생활 활동을 방해합니다.

이는 종종 삶의 질 저하 및 치료 포기와 관련이 있으며,

특히 약물 치료를 중단하는 조현병 환자의 경우

질병 재발 및 재입원을 초래할 수 있습니다[2].

Etiology

Centrally-acting, dopamine-receptor blocking agents, namely the first-generation antipsychotics haloperidol and phenothiazine neuroleptics, are the most common medications associated with EPS. While EPS occurs less frequently with atypical antipsychotics, the risk of EPS increases with dose escalation.[3] Other agents that block central dopaminergic receptors have also been identified as causative of EPS, including antiemetics (metoclopramide, droperidol, and prochlorperazine),[4][5] lithium,[6] serotonin reuptake inhibitors (SSRIs),[7] stimulants,[8] and tricyclic antidepressants (TCAs).[7] In rare situations, antivirals, antiarrhythmics, and valproic acid have also been implicated.[9]

병인

중추 작용 도파민 수용체 차단제,

즉 1세대 항정신병약물인 할로페리돌과 페노티아진 신경 이완제(neuroleptics)는

EPS와 관련된 가장 흔한 약물입니다.

비정형 항정신병 약물의 경우 EPS 발생 빈도는 낮지만,

약물의 용량이 증가함에 따라

EPS의 위험은 증가합니다. [3]

항구토제(메토클로프라미드, 드로페리돌, 프로클로페라진),[4][5 ]

리튬,[6]

세로토닌 재흡수 억제제(SSRI),[7]

각성제,[8]

삼환계 항우울제(TCA) 등

중앙 도파민 수용체를 차단하는 다른 약물도

EPS의 원인으로 확인된 바 있습니다. [7]

드물게

항바이러스제,

항부정맥제,

발프로산도 관련되어 있습니다[9].

Epidemiology

Rates of EPS are dependent on the class of medication administered. First-generation neuroleptics were associated with EPS in 61.6% of patients in a study of institutionalized patients with schizophrenia.[10] Rates of EPS have declined with atypical antipsychotics with clozapine having the lowest risk and risperidone the highest.[11] In terms of antiemetics with a dopamine D2 receptor antagonist effect, EPS incidence is cited to be between 4% to 25% with metoclopramide[12][13][14] and between 25% to 67% with prochlorperazine.[15][16]
Risks factors include a history of prior EPS and high medication dose.[17] Elderly females are more susceptible to drug-induced parkinsonism and tardive dyskinesia,[18][19] while young males manifest with more dystonic reactions.[20]

역학

EPS의 비율은

투여되는 약물의 종류에 따라 달라집니다.

1세대 신경 이완제는

정신분열증 환자를 대상으로 한 연구에서

환자의 61.6%에서 EPS와 관련이 있었습니다.[10]

비정형 항정신병 약물의 경우

클로자핀이 가장 위험이 낮고

리스페리돈이 가장 높은 것으로 나타나면서

EPS 발생률이 감소했습니다. 11]

도파민 D2 수용체 길항 효과가 있는 항구토제의 경우,

메토클로프라미드[12][13][14] 는 4%에서 25%,

프로클로페라진[15][16]은 25%에서 67% 사이의 EPS 발생률을

보이는 것으로 알려져 있습니다[15][16].

위험 요인으로는

이전 EPS 병력과 고용량의 약물이 있습니다.[17]

노인 여성은

약물로 인한 파킨슨병과

지체성 운동 이상증에 더 취약하며[18][19]

젊은 남성은

근긴장 이상 반응이 더 많이 나타납니다[20].

Pathophysiology

The mechanism of EPS is thought to be due to the antagonistic binding of dopaminergic D2 receptors within the mesolimbic and mesocortical pathways of the brain. However, the antidopaminergic action in the caudate nucleus and other basal ganglia may also contribute significantly to the occurrence of EPS.[21]

병태생리학

EPS의 메커니즘은

뇌의 중변연계 및 중피질 경로 내에서

도파민성 D2 수용체의 길항 결합에 기인하는 것으로 생각됩니다.

그러나

꼬리핵 및 기타 기저핵의 항 도파민 작용도

EPS 발생에 크게 기여할 수 있습니다[21].

Toxicokinetics

Researchers previously hypothesized that the faster dissociation of atypical antipsychotics from the dopamine receptor, compared to typical antipsychotics, explained the reduced incidence of EPS. However, a recent study by Sykes utilized a novel time-resolved fluorescence energy transfer assay to demonstrate that binding kinetics and association rates, not dissociation, correlate more with EPS.[22]

독성 동력학

연구자들은

이전에 도파민 수용체에서

비정형 항정신병 약물이 일반적인 항정신병 약물에 비해

더 빨리 해리되는 것이 EPS 발생률 감소를 설명한다고 가설을 세웠습니다.

그러나 Sykes의 최근 연구에서는

새로운 시간 분해 형광 에너지 전달 분석법을 활용하여

해리가 아닌 결합 동역학 및 결합 속도가 EPS와 더 관련이 있음을 입증했습니다.[22]

History and Physical

There is a wide spectrum of EPS presentations. Dystonia most often occurs within 48 hours of drug exposure in 50% of cases, and within five days in 90% of cases.[23] On physical exam, dystonia manifests with involuntary muscle contractions resulting in abnormal posturing or repetitive movements. It may affect muscles in different body parts, including the back and extremities (opisthotonus), neck (torticollis), jaw (trismus), eyes (oculogyric crisis), abdominal wall, and pelvic muscles (tortipelvic crisis), and facial and tongue muscles (buccolingual crisis).[24] The provider must eval‎uate these patients for pain and particularly difficulty in breathing, swallowing, and speech.

Akathisia is characterized by a subjective feeling of internal restlessness and a compelling urge to move, leading to the objective observation of repetitive movements comprising leg crossing, swinging, or shifting from one foot to another.[19] The onset is usually within four weeks of starting or increasing the dosage of the offending medication. Due to its often vague and non-specific presentation of nervousness and discomfort, akathisia is often misdiagnosed as anxiety, restless leg syndrome, or agitation. In an attempt to treat these incorrect diagnoses, the provider may subsequently increase anti-psychotic or SSRI medications, further exacerbating akathisia.[19][25] This failure to correctly diagnose can be detrimental as the severity of akathisia is linked to suicidal ideation, aggression, and violence.[26] The provider must also note that withdrawal akathisia may occur with discontinuation or dose reduction of antipsychotic medication, and is typically self-limited lasting within six weeks.[19]
Drug-induced parkinsonism presents as tremor, rigidity, and slowing of motor function in the truncal region and extremities. The classic appearance is an individual with masked facies, stooped posture, and a slow shuffling gait. Gait imbalance and difficulty rising from a seated position are often noted.[9][27]
Finally, tardive dyskinesia manifests as involuntary choreoathetoid movements affecting orofacial and tongue muscles, and less commonly the truncal region and extremities. While symptoms are typically not painful, they may impede social interaction and cause difficulty in chewing, swallowing, and talking.[28]

역사 및 물리

EPS는

다양한 스펙트럼으로 나타납니다.

근긴장 이상증은

약물 노출 후 48시간 이내에 50%에서,

5일 이내에 90%에서 가장 자주 발생합니다.[23]

신체 검사에서

근긴장 이상증은

불수의적인 근육 수축으로 나타나 비정상적인 자세나 반복적인 동작을 초래합니다.

등 및 사지(사경),

목(사경),

턱(사경),

눈(안구 위기),

복벽 및 골반 근육(사골 위기),

안면 및 혀 근육(협측 위기) 등

다양한 신체 부위의 근육에 영향을 미칠 수 있습니다.[24]

It may affect muscles in different body parts, including the back and extremities (opisthotonus), neck (torticollis), jaw (trismus), eyes (oculogyric crisis), abdominal wall, and pelvic muscles (tortipelvic crisis), and facial and tongue muscles (buccolingual crisis)

의료진은

이러한 환자의 통증과 특히

호흡, 삼킴, 언어 장애에 대해 평가해야 합니다.

운동실조증은

주관적인 내적 불안감과 움직이고 싶은 강한 충동으로 인해

다리를 꼬거나 흔들거나 한 발에서 다른 발로 옮기는 등의

반복적인 움직임이 객관적으로 관찰되는 것이 특징입니다.[19]

objective observation of repetitive movements 

일반적으로

발병 시기는

문제 약물의 복용량을 시작하거나 늘린 후

4주 이내입니다.

긴장감과 불편함을 모호하고

비특이적으로 표현하는 경우가 많기 때문에

무감각증은 불안, 하지 불안 증후군 또는

초조증으로 오진되는 경우가 많습니다.

이러한

잘못된 진단을 치료하기 위해

의료진은 항정신병 약물 또는 SSRI 약물을 증량하여

운동실조증을 더욱 악화시킬 수 있습니다.[19][25]

이러한 정확한 진단 실패는

운동실조증의 심각성이 자살 생각,

공격성 및 폭력과 관련이 있기 때문에 해로울 수 있습니다.[26]

또한

의료진은 항정신병 약물의 중단 또는

용량 감소로 금단 운동실조증이 발생할 수 있으며

일반적으로 6주 이내에 자체 제한적으로 지속된다는 점에 유의해야합니다.

약물로 인한 파킨슨병은

떨림, 경직, 사지 운동 기능 둔화 등의 증상이 나타납니다.

전형적인 증상은

얼굴을 가리고 구부정한 자세를 취하며

걸음걸이가 느리게 뒤섞이는 것입니다.

보행 불균형과 앉은 자세에서 일어나는 데

어려움이 종종 나타납니다.[9][27]

마지막으로

지체성 운동 이상증은

구강안면 및 혀 근육에 영향을 미치는 불수의적인 안무성 운동 이상증으로 나타나며,

덜 흔하게는 관골 부위와 사지에 영향을 미칩니다.

증상은 일반적으로 고통스럽지는 않지만

사회적 상호 작용을 방해하고

씹고 삼키고 말하는 데 어려움을 겪을 수 있습니다[28].

Eval‎uation

In most cases, laboratory and imaging tests are not required. The diagnosis is apparent from an accurate history and physical exam, especially noting a history of medication exposure.

Treatment / Management

If a patient is experiencing acute onset of EPS, particularly dystonia, the provider must assess if an emergency airway intervention is necessary as laryngeal and pharyngeal dystonic reactions may increase the risk of imminent respiratory arrest. Dystonic reactions are rarely life-threatening, and the provider should discontinue the offending agent and manage pain if present. If the causative medication is a typical first-generation antipsychotic, switching to an atypical antipsychotic may be trialed. Administration of an antimuscarinic agent (benztropine, trihexyphenidyl) or diphenhydramine may relieve dystonia within minutes.[21] In cases of tardive dystonia, additional therapeutic strategies include administration of benzodiazepine,[21] injection of botulinum toxin for facial dystonia,[29][30] trial of muscle relaxant (e.g., baclofen),[30] trial of dopamine-depleting agents (e.g. tetrabenazine),[30] and consideration of deep-brain stimulation or pallidotomy for refractory cases.[30][31]
For the treatment of akathisia, strategies similar to managing dystonia are employed, including stopping or reducing the dosage of the offending medication, switching to an atypical antipsychotic if a typical first-generation antipsychotic was the offending drug, and administering anti-muscarinic agents. Additional therapeutic strategies more specific to akathisia include administration of a beta-blocker (most commonly propranolol), amantadine, clonidine, benzodiazepines, mirtazapine, mianserin (tetracyclic antidepressant), cyproheptadine, and propoxyphene.[32][33]
Tardive dyskinesia is treated by withdrawal or dose reduction of the causative medication, switching to an atypical antipsychotic, withdrawal of concurrent antimuscarinic medications (although trihexyphenidyl has been reported to be therapeutic[34]), injection of botulinum toxin for facial dyskinesia,[35] benzodiazepines,[36] amantadine,[36] and trial of dopamine-depleting medications (e.g. tetrabenazine[37]). Interestingly, the trial of levetiracetam, zonisamide, pregabalin, vitamin B6, and vitamin E have also been reported as therapeutic.[28][38]
Drug-induced parkinsonism is treated with discontinuation or dose reduction of the causative medication, switching to an atypical antipsychotic, and administration of medications used for Parkinson disease, including amantadine, antimuscarinic agents, dopamine agonists, and levodopa.[27]

평가

대부분의 경우 실험실 및 영상 검사는 필요하지 않습니다. 진단은 정확한 병력과 신체 검사, 특히 약물 노출 이력을 통해 알 수 있습니다.

치료/관리

환자가 급성 EPS,

특히 근긴장이상증을 경험하는 경우

후두 및 인두 근긴장 이상 반응이 임박한

호흡 정지 위험을 높일 수 있으므로

의료진은 응급 기도 확보가 필요한지 평가해야 합니다.

근긴장 이상 반응은

생명을 위협하는 경우는 드물며,

의료진은 원인 약물의 투여를 중단하고

통증이 있는 경우 통증을 관리해야 합니다.

원인 약물이 전형적인 1세대 항정신병약물인 경우 비정형 항정신병약물로 전환을 시도해 볼 수 있습니다.

항무스카린제(벤즈트로핀, 트리헥시페니딜) 또는 디펜히드라민을 투여하면

몇 분 내에 근긴장 이상을 완화할 수 있습니다.[21]

지연성 근긴장 이상증의 경우,

추가적인 치료 전략으로는 벤조디아제핀 투여,[21]

안면 근긴장 이상증에 대한 보툴리눔 톡신 주사,[29][30 ]

근육 이완제(예, 바클로펜),[30]

도파민 고갈제(예: 테트라베나진)

시험,[30] 불응성 사례에 대한 뇌심부 자극 또는 구개 절제술 고려[30][31][32]

운동 실조증의 치료를 위해,

문제가되는 약물의 복용량을 중단하거나 줄이고,

전형적인 1 세대 항 정신병 약물이 문제가되는 약물 인 경우 비정형 항 정신병 약으로 전환하고,

항 무스카린 제제를 투여하는 등 근긴장 이상 관리와 유사한 전략이 사용됩니다.

운동 이상증에 더 특화된 추가 치료 전략으로는

베타 차단제(가장 일반적으로 프로프라놀롤), 아만타딘, 클로니딘, 벤조디아제핀, 미르타자핀, 미안세린(테트라사이클릭 항우울제), 사이프로헵타딘 및 프로폭시펜의 투여[32][33] 등이 있습니다.

지체성 운동 이상증은 원인 약물의 중단 또는 용량 감소, 비정형 항정신병 약물로 전환, 동시 복용하는 항무스카린 약물 중단(트리헥시페니딜이 치료 효과가 있다고 보고되었지만[34]), 안면 운동 이상증에 보툴리눔 독소 주사,[35] 벤조디아제핀,[36] 아만타딘,[36] 도파민 고갈 약물(예: 테트라베나진[37]) 시험으로 치료할 수 있습니다. 흥미롭게도 레베티라세탐, 조니사미드, 프레가발린, 비타민 B6 및 비타민 E의 시험도 치료제로 보고되었습니다.[28][38]
약

물 유발 파킨슨병은 원인 약물의 중단 또는 용량 감소, 비정형 항 정신병 약으로 전환, 아만 타딘, 항 무스카린 제, 도파민 작용제 및 레보도파를 포함한 파킨슨 병에 사용되는 약물 투여로 치료됩니다.[27]

Differential Diagnosis

EPS may be challenging to distinguish from other idiopathic movement disorders. Muscle rigidity and tension are nonspecific symptoms that may be observed in neuroleptic malignant syndrome, serotonin syndrome, and other movement disorders. Chorea and athetosis are also present in Huntington disease (distinguished based on family history and genetic testing), Sydenham chorea (identified with a history of streptococcal infection), Wilson disease (adolescent-onset with a defect in copper metabolism), and cerebrovascular lesions.[39][40] The flat facial expression‎, psychomotor slowing, and low energy level in akathisia may mimic the negative symptoms of schizophrenia. In addition, restlessness in akathisia may also appear similar to anxiety and psychotic agitation.[41] If dementia accompanies parkinsonian signs and other motor abnormalities, the provider should eval‎uate the patient for Parkinson disease, Lewy body dementia, vascular dementia, and frontotemporal dementia.[40] Interestingly, up to a third of new-onset schizophrenic patients who have never been medicated may present with parkinsonian signs.[42]

감별 진단

근긴장 이상증은 다른 특발성 운동 장애와 구별하기 어려울 수 있습니다.

근육 경직과 긴장은

신경 이완성 악성 증후군,

세로토닌 증후군 및 기타 운동 장애에서 관찰될 수 있는 비특이적 증상입니다.

헌팅턴병(가족력 및 유전자 검사로 구분), 시덴햄 무도병(연쇄상구균 감염 병력으로 확인), 윌슨병(구리 대사에 결함이 있는 청소년기 발병), 뇌혈관 병변에서도 무도증과 무력증이 나타납니다.[39][40] 무운동증의 평평한 표정, 정신 운동 둔화, 낮은 에너지 수준은 조현병의 부정적인 증상을 모방할 수 있습니다. 또한 운동 실조증의 불안은 불안 및 정신병 적 동요와 유사하게 나타날 수 있습니다.[41] 치매가 파킨슨 병 징후 및 기타 운동 이상을 동반하는 경우 의료진은 환자에게 파킨슨 병, 루이체 치매, 혈관성 치매 및 전두 측두엽 치매가 있는지 평가해야합니다.[40]

흥미롭게도

약을 복용 한 적이없는

신규 발병 정신 분열증 환자의 최대 1/3이

파킨슨 징후를 보일 수 있습니다.[42]

Prognosis

EPS typically resolve spontaneously or improve with pharmacologic interventions. Acute dystonic reactions are often transient, but late-onset and persistent tardive dystonia have been described in the literature where symptoms persisted for years.[43] A study of 107 cases of tardive dystonia reported that only 14% of patients achieved remission over a mean follow-up period of 8.5 years.[44] Similarly, while acute akathisia may spontaneously resolve or improve with appropriate medication, studies have reported cases of tardive akathisia persisting over many years.[45] Tardive dyskinesia also persists chronically with a cumulative persistence rate as high as 82% in a study of patients with schizophrenia.[46]

예후

근긴장 이상 반응은

일반적으로 자연적으로 해결되거나

약학적 개입을 통해 개선됩니다.

급성 긴장 이상 반응은 일시적인 경우가 많지만,

증상이 수년간 지속되는 지연성 긴장 이상증도 문헌에 기술되어 있습니다.[43]

107건의 지연성 긴장 이상증 사례에 대한 연구에 따르면

평균 8.5년의 추적 관찰 기간 동안

환자의 14%만이 완화에 도달한 것으로 보고되었습니다. [44]

마찬가지로 급성 운동 이상증은 적절한 약물 치료로 자연적으로 해결되거나 개선될 수 있지만, 지체성 운동 이상증은 수년 동안 지속되는 사례가 보고되었습니다.[45]

지체성 운동 이상증은 또한 조현병 환자를 대상으로 한 연구에서

누적 지속률이 82%에 달하는 등

만성적으로 지속됩니다.[46]

Complications

Antipsychotic-induced and metoclopramide-induced laryngeal dystonia has been reported predominantly in young males.[47] Rhabdomyolysis is a rare complication of drug-induced dystonia, especially if prolonged dystonia is present.[48] While dystonic storm typically occurs in patients with primary known dystonia (e.g., Wilson disease, DYT1 dystonia), triggers typically include infection and medication adjustment in a significant number of cases.[49] A dystonic storm is a life-threatening situation that manifests with fever, tachycardia, tachypnea, hypertensive crisis, diaphoresis, dysphagia, and respiratory failure.[49] The manifestation of EPS in schizophrenic patients is associated with poor compliance with other atypical antipsychotic medications, which may subsequently lead to a relapse of schizophrenia and hospitalization.[2] Failure to correctly diagnose and treat EPS is linked to suicidal ideation, aggression, and violence.[26]

합병증

항 정신병 약 유발 및 메토 클로 프라 미드 유발 후두 긴장 이상증 주로 젊은 남성에서보고되었습니다.[47] 횡문근 융해증 특히 장기간의 긴장 이상증이있는 경우 약물 유발 긴장 이상증의 드문 합병증입니다.[48] 긴장성 폭풍은 일반적으로 알려진 1 차 근긴장 이상이있는 환자에서 발생하지만 (예 :, 윌슨병, DYT1 근긴장 이상증), 유발 요인에는 일반적으로 상당수의 경우 감염 및 약물 조정이 포함됩니다.[49] 근긴장성 폭풍은 발열, 빈맥, 빈호흡, 고혈압 위기, 발한, 연하곤란 및 호흡 부전으로 나타나는 생명을 위협하는 상황입니다. [49] 조현병 환자에서 EPS의 증상은 다른 비정형 항정신병 약물의 순응도 저하와 관련이 있으며, 이는 이후 조현병 재발 및 입원으로 이어질 수 있습니다.[2] EPS를 정확하게 진단하고 치료하지 못하면 자살 생각, 공격성, 폭력성과 관련이 있습니다.[26]

Consultations

While some drug-induced movement disorders may last a few minutes, others may last long-term for weeks to years, and may potentially lead to contractures, bony deformities, or significant motor impairment. Physical medicine and rehabilitation consultation may provide useful treatment modalities that have shown efficacy in alleviating dystonia, including relaxation training, biofeedback, transcutaneous electrical nerve stimulation (TENS), and percutaneous dorsal column stimulation.[50] Physical and occupational therapy is paramount, leading to improvement in gait and mobility. In patients with oromandibular or laryngeal involvement, speech therapy may assist with dysphagia and communication barriers. In presentations of EPS refractory to pharmacologic management, neurosurgical consultation may be beneficial to explore deep brain stimulation, thalamotomy, and pallidotomy.

Enhancing Healthcare Team Outcomes

The spectrum of acute symptoms in EPS is distressing, especially with painful torticollis, oculogyric crisis, and bulbar type of speech. If left untreated, it may cause dehydration, infection, pulmonary embolism, rhabdomyolysis, respiratory stridor, and obstruction.[4][24][51][52] To this end, studies investigating the administration of prophylactic anticholinergic medications to prevent or reduce EPS have been performed. Authors have cautioned that prophylactic anticholinergic medications have distressing peripheral side-effects, including dry mouth, urinary disturbances, and constipation, as well as undesirable central effects comprising cognitive dysfunction and delirium.[53] This long-term prophylactic administration of anticholinergic medications in schizophrenia patients taking antipsychotics may worsen underlying cognitive impairment and subsequently worsen the quality of life.[53] Thus, while current guidelines generally do not recommend the prophylactic or long-term use of anticholinergics in schizophrenic patients taking antipsychotics, this decision should be made on a case-by-case basis with meticulous risk-benefit analysis. In the emergency medicine realm, a meta-analysis demonstrated that prophylactic diphenhydramine reduces EPS in patients receiving bolus administration of antiemetic (with a dopamine D2 antagonist effect), but not when the antiemetic was given as an infusion; thus, this meta-analysis concluded that the most effective strategy would be to administer the antiemetic as an infusion without anticholinergic prophylaxis.
While typical, first-generation antipsychotics are used less frequently today, the provider must also be cognizant that even second-generation atypical antipsychotics may lead to EPS, although at a lower incidence. Abouzaid and colleagues recently assessed the economic burden of EPS due to atypical antipsychotics in schizophrenia patients. During a 12-month follow-up period, 12.6% of patients experienced EPS. Compared to those without EPS, patients who did experience EPS had more schizophrenia-related and all-cause hospitalizations, schizophrenia-related emergency room visits, and higher schizophrenia-related and all-cause total healthcare, inpatient, and prescription medication costs.[54]
Psychiatric nurses and pharmacists should educate patients about EPS. Nurses monitor patients and consult with the team if issues persist. Pharmacists review acute and chronic medications for doses and interactions. [Level 5]

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Figure

Parkinson Gait, Involuntary Movement, Festinant Gait Contributed by RS Kumar, MD

Figure

Simulation of Cogwheel Rigidity, Parkinson's Disease, Tremor, Stop and Go effect during a range of motion maneuver Contributed by Dr. Raju S. Menon (https://www.youtube.com/watch?v=8xxe2WWWoYI)

Figure

Shuffling gait in parkinson disease Image courtesy S Bhimji MD

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References1.Rifkin A. Extrapyramidal side effects: a historical perspective. J Clin Psychiatry. 1987 Sep;48 Suppl:3-6. [PubMed]2.Frances A, Weiden P. Promoting compliance with outpatient drug treatment. Hosp Community Psychiatry. 1987 Nov;38(11):1158-60. [PubMed]3.Farah A. Atypicality of atypical antipsychotics. Prim Care Companion J Clin Psychiatry. 2005;7(6):268-74. [PMC free article] [PubMed]4.D'Souza RS, Mercogliano C, Ojukwu E, D'Souza S, Singles A, Modi J, Short A, Donato A. Effects of prophylactic anticholinergic medications to decrease extrapyramidal side effects in patients taking acute antiemetic drugs: a systematic review and meta-analysis. Emerg Med J. 2018 May;35(5):325-331. [PubMed]5.Miller LG, Jankovic J. Metoclopramide-induced movement disorders. Clinical findings with a review of the literature. Arch Intern Med. 1989 Nov;149(11):2486-92. [PubMed]6.Kane J, Rifkin A, Quitkin F, Klein DF. Extrapyramidal side effects with lithium treatment. Am J Psychiatry. 1978 Jul;135(7):851-3. [PubMed]7.Madhusoodanan S, Alexeenko L, Sanders R, Brenner R. Extrapyramidal symptoms associated with antidepressants--a review of the literature and an analysis of spontaneous reports. Ann Clin Psychiatry. 2010 Aug;22(3):148-56. [PubMed]8.Asser A, Taba P. Psychostimulants and movement disorders. Front Neurol. 2015;6:75. [PMC free article] [PubMed]9.Bohlega SA, Al-Foghom NB. Drug-induced Parkinson`s disease. A clinical review. Neurosciences (Riyadh). 2013 Jul;18(3):215-21. [PubMed]10.Janno S, Holi M, Tuisku K, Wahlbeck K. Preval‎ence of neuroleptic-induced movement disorders in chronic schizophrenia inpatients. Am J Psychiatry. 2004 Jan;161(1):160-3. [PubMed]11.Divac N, Prostran M, Jakovcevski I, Cerovac N. Second-generation antipsychotics and extrapyramidal adverse effects. Biomed Res Int. 2014;2014:656370. [PMC free article] [PubMed]12.Ganzini L, Casey DE, Hoffman WF, McCall AL. The preval‎ence of metoclopramide-induced tardive dyskinesia and acute extrapyramidal movement disorders. Arch Intern Med. 1993 Jun 28;153(12):1469-75. [PubMed]13.Parlak I, Atilla R, Cicek M, Parlak M, Erdur B, Guryay M, Sever M, Karaduman S. Rate of metoclopramide infusion affects the severity and incidence of akathisia. Emerg Med J. 2005 Sep;22(9):621-4. [PMC free article] [PubMed]14.Parlak I, Erdur B, Parlak M, Ergin A, Turkcuer I, Tomruk O, Ayrik C, Ergin N. Intravenous administration of metoclopramide by 2 min bolus vs 15 min infusion: does it affect the improvement of headache while reducing the side effects? Postgrad Med J. 2007 Oct;83(984):664-8. [PMC free article] [PubMed]15.Saadah HA. Abortive headache therapy in the office with intravenous dihydroergotamine plus prochlorperazine. Headache. 1992 Mar;32(3):143-6. [PubMed]16.Taylor WB, Bateman DN. Preliminary studies of the pharmacokinetics and pharmacodynamics of prochlorperazine in healthy volunteers. Br J Clin Pharmacol. 1987 Feb;23(2):137-42. [PMC free article] [PubMed]17.Hedenmalm K, Güzey C, Dahl ML, Yue QY, Spigset O. Risk factors for extrapyramidal symptoms during treatment with selective serotonin reuptake inhibitors, including cytochrome P-450 enzyme, and serotonin and dopamine transporter and receptor polymorphisms. J Clin Psychopharmacol. 2006 Apr;26(2):192-7. [PubMed]18.Jeste DV. Tardive dyskinesia rates with atypical antipsychotics in older adults. J Clin Psychiatry. 2004;65 Suppl 9:21-4. [PubMed]19.Salem H, Nagpal C, Pigott T, Teixeira AL. Revisiting Antipsychotic-induced Akathisia: Current Issues and Prospective Challenges. Curr Neuropharmacol. 2017;15(5):789-798. [PMC free article] [PubMed]20.Kondo T, Otani K, Tokinaga N, Ishida M, Yasui N, Kaneko S. Characteristics and risk factors of acute dystonia in schizophrenic patients treated with nemonapride, a selective dopamine antagonist. J Clin Psychopharmacol. 1999 Feb;19(1):45-50. [PubMed]21.Kamin J, Manwani S, Hughes D. Emergency psychiatry: extrapyramidal side effects in the psychiatric emergency service. Psychiatr Serv. 2000 Mar;51(3):287-9. [PubMed]22.Sykes DA, Moore H, Stott L, Holliday N, Javitch JA, Lane JR, Charlton SJ. Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors. Nat Commun. 2017 Oct 02;8(1):763. [PMC free article] [PubMed]23.Pasricha PJ, Pehlivanov N, Sugumar A, Jankovic J. Drug Insight: from disturbed motility to disordered movement--a review of the clinical benefits and medicolegal risks of metoclopramide. Nat Clin Pract Gastroenterol Hepatol. 2006 Mar;3(3):138-48. [PubMed]24.Low LC, Goel KM. Metoclopramide poisoning in children. Arch Dis Child. 1980 Apr;55(4):310-2. [PMC free article] [PubMed]25.Peitl MV, Prološčić J, Blažević-Zelić S, Skarpa-Usmiani I, Peitl V. Symptoms of agitated depression and/or akathisia. Psychiatr Danub. 2011 Mar;23(1):108-10. [PubMed]26.Lipinski JF, Mallya G, Zimmerman P, Pope HG. Fluoxetine-induced akathisia: clinical and theoretical implications. J Clin Psychiatry. 1989 Sep;50(9):339-42. [PubMed]27.Shin HW, Chung SJ. Drug-induced parkinsonism. J Clin Neurol. 2012 Mar;8(1):15-21. [PMC free article] [PubMed]28.Cornett EM, Novitch M, Kaye AD, Kata V, Kaye AM. Medication-Induced Tardive Dyskinesia: A Review and Update. Ochsner J. 2017 Summer;17(2):162-174. [PMC free article] [PubMed]29.Vogt T, Lüssi F, Paul A, Urban P. [Long-term therapy of focal dystonia and facial hemispasm with botulinum toxin A]. Nervenarzt. 2008 Aug;79(8):912-7. [PubMed]30.Cloud LJ, Jinnah HA. Treatment strategies for dystonia. Expert Opin Pharmacother. 2010 Jan;11(1):5-15. [PMC free article] [PubMed]31.Vidailhet M, Vercueil L, Houeto JL, Krystkowiak P, Benabid AL, Cornu P, Lagrange C, Tézenas du Montcel S, Dormont D, Grand S, Blond S, Detante O, Pillon B, Ardouin C, Agid Y, Destée A, Pollak P., French Stimulation du Pallidum Interne dans la Dystonie (SPIDY) Study Group. Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia. N Engl J Med. 2005 Feb 03;352(5):459-67. [PubMed]32.Miller CH, Fleischhacker WW. Managing antipsychotic-induced acute and chronic akathisia. Drug Saf. 2000 Jan;22(1):73-81. [PubMed]33.Inada T. [Drug-Induced Akathisia]. Brain Nerve. 2017 Dec;69(12):1417-1424. [PubMed]34.Kang UJ, Burke RE, Fahn S. Natural history and treatment of tardive dystonia. Mov Disord. 1986;1(3):193-208. [PubMed]35.Alabed S, Latifeh Y, Mohammad HA, Rifai A. Gamma-aminobutyric acid agonists for neuroleptic-induced tardive dyskinesia. Cochrane Database Syst Rev. 2011 Apr 13;(4):CD000203. [PubMed]36.Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor Other Hyperkinet Mov (N Y). 2013;3 [PMC free article] [PubMed]37.Kenney C, Jankovic J. Tetrabenazine in the treatment of hyperkinetic movement disorders. Expert Rev Neurother. 2006 Jan;6(1):7-17. [PubMed]38.Cloud LJ, Zutshi D, Factor SA. Tardive dyskinesia: therapeutic options for an increasingly common disorder. Neurotherapeutics. 2014 Jan;11(1):166-76. [PMC free article] [PubMed]39.Handley A, Medcalf P, Hellier K, Dutta D. Movement disorders after stroke. Age Ageing. 2009 May;38(3):260-6. [PubMed]40.Sanders RD, Gillig PM. Extrapyramidal examinations in psychiatry. Innov Clin Neurosci. 2012 Jul;9(7-8):10-6. [PMC free article] [PubMed]41.Kane JM. Extrapyramidal side effects are unacceptable. Eur Neuropsychopharmacol. 2001 Oct;11 Suppl 4:S397-403. [PubMed]42.Peralta V, Basterra V, Campos MS, de Jalón EG, Moreno-Izco L, Cuesta MJ. Characterization of spontaneous Parkinsonism in drug-naive patients with nonaffective psychotic disorders. Eur Arch Psychiatry Clin Neurosci. 2012 Mar;262(2):131-8. [PubMed]43.Burke RE, Fahn S, Jankovic J, Marsden CD, Lang AE, Gollomp S, Ilson J. Tardive dystonia: late-onset and persistent dystonia caused by antipsychotic drugs. Neurology. 1982 Dec;32(12):1335-46. [PubMed]44.Kiriakakis V, Bhatia KP, Quinn NP, Marsden CD. The natural history of tardive dystonia. A long-term follow-up study of 107 cases. Brain. 1998 Nov;121 ( Pt 11):2053-66. [PubMed]45.Burke RE, Kang UJ, Jankovic J, Miller LG, Fahn S. Tardive akathisia: an analysis of clinical features and response to open therapeutic trials. Mov Disord. 1989;4(2):157-75. [PubMed]46.Tenback DE, van Harten PN, Slooff CJ, van Os J. Incidence and persistence of tardive dyskinesia and extrapyramidal symptoms in schizophrenia. J Psychopharmacol. 2010 Jul;24(7):1031-5. [PubMed]47.Christodoulou C, Kalaitzi C. Antipsychotic drug-induced acute laryngeal dystonia: two case reports and a mini review. J Psychopharmacol. 2005 May;19(3):307-11. [PubMed]48.Cavanaugh JJ, Finlayson RE. Rhabdomyolysis due to acute dystonic reaction to antipsychotic drugs. J Clin Psychiatry. 1984 Aug;45(8):356-7. [PubMed]49.Termsarasab P, Frucht SJ. Dystonic storm: a practical clinical and video review. J Clin Mov Disord. 2017;4:10. [PMC free article] [PubMed]50.Cho HJ, Hallett M. Non-Invasive Brain Stimulation for Treatment of Focal Hand Dystonia: Update and Future Direction. J Mov Disord. 2016 May;9(2):55-62. [PMC free article] [PubMed]51.Novick D, Haro JM, Bertsch J, Haddad PM. Incidence of extrapyramidal symptoms and tardive dyskinesia in schizophrenia: thirty-six-month results from the European schizophrenia outpatient health outcomes study. J Clin Psychopharmacol. 2010 Oct;30(5):531-40. [PubMed]52.Levinson DF, Simpson GM. Neuroleptic-induced extrapyramidal symptoms with fever. Heterogeneity of the 'neuroleptic malignant syndrome'. Arch Gen Psychiatry. 1986 Sep;43(9):839-48. [PubMed]53.Ogino S, Miyamoto S, Miyake N, Yamaguchi N. Benefits and limits of anticholinergic use in schizophrenia: focusing on its effect on cognitive function. Psychiatry Clin Neurosci. 2014 Jan;68(1):37-49. [PubMed]54.Abouzaid S, Tian H, Zhou H, Kahler KH, Harris M, Kim E. Economic burden associated with extrapyramidal symptoms in a medicaid population with schizophrenia. Community Ment Health J. 2014 Jan;50(1):51-8. [PMC free article] [PubMed]