Akathisia


Article Author:
Jason Patel
Filomena Galdikas


Article Editor:
Raman Marwaha


Editors In Chief:
Myron Bodman
Donald Kushner


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
4/4/2019 1:45:47 PM

Introduction

Akathisia is defined as an inability to remain still. It is a neuropsychiatric syndrome that is associated with psychomotor restlessness. The individual with akathisia will generally experience an intense sensation of unease or an inner restlessness that usually involves the lower extremities. This results in a compulsion to move. In most cases the movement is repetitive. The individual may cross, uncross, swing, or shift from one foot to the other. To the observer, this may appear as a persistent fidget.[1][2][3]

Akathisia is a movement disorder that may be associated with the use of antipsychotic medications.  The primary movement disorders from antipsychotic agents are akathisia, acute dystonia, pseudoparkinsonism, and tardive dyskinesia. Akathisia may also rarely occur with antidepressant agents.

Akathisia may appear soon after the antipsychotic has been started or may appear when the dosage is increased.

In recent years, akathisia has also been known to be associated with calcium channel blockers, antiemetics, antivertigo drugs, and sedatives used in anesthesia. Akathisia has also been noted to occur following abuse of cocaine. The condition may be acute or chronic, with symptoms often lasting many months or even years.

Etiology

The exact etiology of akathisia is unknown, but it is thought to be due to antipsychotic agents blocking dopamine type-2 receptors in the brain.  [4]

The general belief is that there is an imbalance between cholinergic/dopaminergic or serotonergic/dopaminergic systems. The organ where this imbalance occurs is most likely the shell of the nucleus accumbens.

Epidemiology

The incidence varies widely from 21% to 75%. The occurrence of akathisia is higher with first-generation, or typical, antipsychotics, particularly, high-potency agents such as haloperidol than with the second-generation, or atypical, antipsychotics.[5]

Pathophysiology

The pathophysiology of akathisia is poorly understood. Extrapyramidal side effects, particularly acute dystonia and pseudoparkinsonism, are thought to be due to an imbalance of dopamine and acetylcholine in the nigrostriatal pathway of the brain induced by antipsychotic agents blockade of dopamine type-2 receptors. Dystonia and pseudoparkinsonism are often managed with concomitant anticholinergic agents such as benztropine. Akathisia is also observed with antipsychotic agents which block dopamine type-2 receptors, and this supports the notion that it is also linked to diminished dopamine transmission in the brain. However, akathisia does not respond as robustly to anticholinergic agents as dystonia and pseudoparkinsonism suggesting an alternative pathophysiologic mechanism.

History and Physical

Patient’s presenting with akathisia typically have recently started an antipsychotic agent, or their dose has been increased. Akathisia usually develops within the first 2 weeks of antipsychotic therapy. There are subjective and objective components to akathisia. Patients will typically describe a feeling of restlessness with a desire to move. Additionally, patients will be objectively seen manifesting that restlessness by pacing, rocking, and shifting position. Patients with akathisia often feel distressed and uncomfortable.

To assess the severity of akathisia, health care professionals may use tools like the Barnes Akathisia Rating Scale (BARS).

Providers should be aware that the inner restlessness often causes extreme anxiety and dysphoria in the individual. In chronic cases, akathisia has also been associated with a high risk of self-harm or suicidal behavior; therefore, the clinician should obtain a history of depression, anxiety, and suicidal ideations.

Evaluation

The Barnes Akathisia Rating Scale may be used to assess patients with akathisia. However, most clinicians will rely on clinical observation. There are no relevant laboratory or radiographic tests involved in the diagnosis of akathisia. [6][7]

Treatment / Management

Antipsychotic-induced akathisia may be managed by reducing the dose of the offending agent or switching to an alternative antipsychotic agent. Beta-blockers such as propranolol and benzodiazepines have historically been used for the treatment of akathisia although the amount of high-quality data supporting their use is limited. Anticholinergic agents such as benztropine may be utilized if concomitant pseudoparkinsonism is present. Mirtazapine may also be utilized for the management of akathisia. Low-dose mirtazapine has been found to be as effective as beta-blockers and may be considered first-line therapy. However, one should use caution with this agent, because there are reports that high doses of mirtazapine may worsen akathisia.[3][8][9]

When using beta-blockers, clinicians should be aware of the risk of bradycardia and hypotension.

Many other agents, including vitamin B6, have been used to treat akathisia, but there are no randomized controlled trials to determine their efficacy.

Differential Diagnosis

Akathisia is often underdiagnosed because its symptoms often mimic or overlap other psychiatric disorders like psychosis, mania, attention deficit hyperactivity disorder (ADHD), or agitated depression. Thus, it is important to obtain a complete medical history and rule out other psychiatric disorders.

Prognosis

Prognosis is good if the condition is recognized and the drug causing it is discontinued. If the condition is left untreated, it has a high morbidity and can even lead to suicidal ideations.

Complications

Akathisia can be disabling and leads to disability if not recognized.

Many people with the condition develop severe anxiety and dysphoria. Reports even exist of suicidal ideations in these patients.

Consultations

Once the diagnosis of akathisia is made, the patient should be referred to a neurologist and a psychiatrist. Making decisions on the medications can be tricky since most patients rely on antipsychotics for their mental health condition.

Deterrence and Patient Education

The drug regimen may have to be altered or the dose of the drug reduced to stop akathisia.

Pearls and Other Issues

Akathisia is defined as an inability to remain still. It is a neuropsychiatric syndrome that is associated with psychomotor restlessness.

The individual with akathisia will generally experience an intense sensation of unease or an inner restlessness that usually involves the lower extremities-this results in a compulsion to move. In most cases the movement is repetitive.

Akathisia is a movement disorder that may be associated with the use of antipsychotic medications. The primary movement disorders from antipsychotic agents are akathisia, acute dystonia, pseudoparkinsonism, and tardive dyskinesia. Akathisia may also rarely occur with antidepressant agents.

It may be difficult to determine whether a patient is experiencing akathisia or anxiety or agitation. Early identification and management are important as akathisia may be associated with treatment nonadherence.

Antipsychotic-induced akathisia may be managed by reducing the dose of the offending agent or switching to an alternative antipsychotic agent.

Beta-blockers such as propranolol and benzodiazepines have historically been used for the treatment of akathisia although the amount of high-quality data supporting their use is limited.

Anticholinergic agents such as benztropine may be utilized if concomitant pseudoparkinsonism is present.

Enhancing Healthcare Team Outcomes

For the most part, akathisia is associated with the use of antipsychotic medications. Once the movement disorder has started, treatment is not always easy. Discontinuation of the drug is not always the solution since these patients rely on the medication for their primary mental health disorder. Mental health nurses, pharmacists, and primary care physicians who encounter akathisia should immediately refer the patient to the psychiatrist for definitive care. Unfortunately, once akathisia has developed it can take months for the disorder to subside. Case reports exist indicating that this movement disorder also increases the risk of suicidality. Hence, all patients with akathisia need to be closely monitored and the family should be educated about the potential for suicide. [10][11] (Level V)


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Akathisia - Questions

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Which of the following best characterizes akathisia?



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A schizophrenic patient has a need to be in constant motion. He rocks while standing or sitting, lifts his feet as if marching, and repeatedly crosses and uncrosses his legs. He has chronically been treated with a medication, which causes dopaminergic receptor blockade. Which of the following is the most likely diagnosis?



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Patients on chronic neuroleptic treatment often develop internal restlessness that is unpleasant and can be relieved somewhat by volitional movement. What is the term for this sensation?



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Which of the following antipsychotic medications is most likely to cause akathisia?



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A 35-year-old male patient began treatment with haloperidol 5mg twice a day by mouth 2 weeks ago. Today he is presenting to his outpatient psychiatrist for a follow-up visit. He is observed to be pacing around the psychiatrist office and unable to sit still. When questioned about his pacing, he states that he just feels like he needs to move. Which of the following movement disorders is he experiencing?



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A male patient began treatment with haloperidol 5 mg PO twice a day 2 weeks ago. Today he is presenting for a follow-up visit. He is observed pacing around the office and is unable to sit still. When questioned about his pacing, he states that he just feels like he needs to move. Which of the following movement disorders is he experiencing?



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Which of the following classes of medications is most commonly associated with akathisia?



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Akathisia is thought to be due to the blockade of which neurotransmitter in the brain by antipsychotic agents?



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Which of the following approaches may be utilized to manage a patient with antipsychotic-induced akathisia?



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During your rotation in neurology, the resident has asked you to examine a patient with akathisia. Which of the following features will be most obvious on the exam?



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A 27-year-old male with schizoaffective disorder, depressive type, presented to the emergency department for a psychotic episode after his medication was discontinued. History was scant given the state of disorganization of the patient. A bottle of fluoxetine with his name on it was found in his pocket. He was admitted to the inpatient unit, treated with aripiprazole for psychosis, lorazepam as needed for agitation, restarted on fluoxetine for depression, and trazodone for sleep. On hospital day 5, the team notes that despite marked improvement in function, he is always pacing the unit. The patient describes an internal state of restlessness that "he just cannot seem to shake off." What is the best treatment?



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A 65-year-old male with a history of depression, diabetes, and lung cancer presents to your office for his mental health follow up. He is currently undergoing chemotherapy for his lung cancer. His depression has been in remission for 1 year now. His medications include fluoxetine, metformin, glipizide, cisplatin, docetaxel, prochlorperazine, and oxycodone. On examination, his legs are frequently moving and he is restless. Upon questioning, he replies "it's been horrible! Ever since I've had cancer, I can't seem to sit still!". What is the most likely cause?



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A 65-year-old man with a long-standing history of schizophrenia, diabetes, hypertension, and COPD presents to your clinic for his mental health follow up. His current medications include haloperidol, metformin, lisinopril, tiotropium, formoterol, and albuterol. His antipsychotic was switched two weeks ago because he could not afford the previous one. He finds the current one effective and affordable, but he believes that he is getting restless over time. In the office, he prefers to stand rather than sit. You consider a medication to treat the side effects - to determine the tolerability which of the following is the most appropriate question?



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A 27-year-old male with schizophrenia, methamphetamine use disorder, and obsessive-compulsive disorder presents to the emergency department for evaluation of suicidal ideation. He was recently discharged after a lengthy inpatient hospitalization where he was started on olanzapine, fluoxetine, and trazodone. He reports his compulsive and psychotic symptoms have improved with the treatment, but he has become increasingly agitated now despite being compliant with his medications, living with a supportive family, and no new stressors in his life. Urine drug screen and complete metabolic panel are unremarkable. Upon interview, he provides a coherent history as he continues to pace around the room and shake his legs. He says, "I have never felt like this before! I am so uncomfortable; I just want to jump off a bridge or shoot myself to end this!". What is the cause of his presentation?



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A 30-year-old male with schizoaffective disorder, bipolar type arrives for his follow-up appointment with his brother. The patient mentions that his symptoms have resolved ever since he started taking risperidone, but while sitting down, he frequently fidgets and moves his legs. When asked if he has been getting up and pacing, his brother remarks that he has been and that he has complained of the discomfort being caused but is withholding information because the patient "wants the appointment over with." Lithium is his only other medication. Upon physical exam, rigidity is noted in the upper extremities at the elbows bilaterally. The provider discusses a number of treatment options, their side effects, and the alternatives with the patient and his brother. Which would be the mechanism of action of the most appropriate medication in this case?



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Akathisia - References

References

Dallocchio C,Matinella A,Arbasino C,Arno' N,Glorioso M,Sciarretta M,Braga M,Tinazzi M, Movement disorders in emergency settings: a prospective study. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2018 Oct 15     [PubMed]
O'Brien H,Kiely F,Barry A,Meaney S, Cross-sectional examination of extrapyramidal side effects in a specialist palliative care inpatient unit. BMJ supportive     [PubMed]
Poyurovsky M,Weizman A, Very Low-Dose Mirtazapine (7.5 mg) in Treatment of Acute Antipsychotic-Associated Akathisia. Journal of clinical psychopharmacology. 2018 Dec     [PubMed]
Hirjak D,Kubera KM,Bienentreu S,Thomann PA,Wolf RC, [Antipsychotic-induced motor symptoms in schizophrenic psychoses-Part 1 : Dystonia, akathisia und parkinsonism]. Der Nervenarzt. 2018 Aug 20     [PubMed]
Inada T, [Drug-Induced Akathisia]. Brain and nerve = Shinkei kenkyu no shinpo. 2017 Dec     [PubMed]
Balint B,Killaspy H,Marston L,Barnes T,Latorre A,Joyce E,Clarke CS,De Micco R,Edwards MJ,Erro R,Foltynie T,Hunter RM,Nolan F,Schrag A,Freemantle N,Foreshaw Y,Green N,Bhatia KP,Martino D, Development and clinimetric assessment of a nurse-administered screening tool for movement disorders in psychosis. BJPsych open. 2018 Sep     [PubMed]
Rodríguez-Blázquez C,Forjaz MJ,Kurtis MM,Balestrino R,Martinez-Martin P, Rating Scales for Movement Disorders With Sleep Disturbances: A Narrative Review. Frontiers in neurology. 2018     [PubMed]
Takeshima M,Ishikawa H,Kikuchi Y,Kanbayashi T,Shimizu T, Successful Management of Clozapine-induced Akathisia with Gabapentin Enacarbil: A Case Report. Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology. 2018 Aug 31     [PubMed]
Shams-Alizadeh N,Bakhshayesh H,Rezaei F,Ghaderi E,Shams-Alizadeh N,Hassanzadeh K, Effect of Vitamin B6 Versus Propranolol on Antipsychotic-Induced Akathisia: A pilot Comparative Double-blind Study. Iranian journal of pharmaceutical research : IJPR. 2018 Winter     [PubMed]
Tachere RO,Modirrousta M, Beyond anxiety and agitation: A clinical approach to akathisia. Australian family physician. 2017     [PubMed]
Rogers ML,Ringer FB,Joiner TE, A meta-analytic review of the association between agitation and suicide attempts. Clinical psychology review. 2016 Aug     [PubMed]

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