akathisia

Akathisia is usually classified as a medication-induced movement disorder. It can also be considered a neuropsychiatric concern, however, as it can be experienced purely subjectively without apparent movement abnormalities. Akathisia is generally associated with antipsychotics, but was previously described in Parkinson's disease and other neuropsychiatric disorders. It can also present with the use of non-psychiatric medications, including calcium channel blockers, antibiotics, anti-nausea and anti-vertigo drugs.

Symptoms of akathisia are often described in vague terms, such as feeling nervous, uneasy, tense, twitchy, restless, and unable to relax. Reported symptoms also include insomnia, a sense of discomfort, motor restlessness, marked anxiety, and panic. Symptoms have also been said to resemble symptoms of neuropathic pain similar to fibromyalgia and restless legs syndrome.{{cite book |title=Akathisia and Restless Legs |page=299 |first=Perminder |last=Sachdev |isbn=978-0-521-03148-6 |publisher=Cambridge University Press |year=2006}} When caused by psychiatric drugs, akathisia usually disappears quickly once the medication is reduced or stopped. However, late-onset akathisia, or tardive akathisia, may persist for months or years after the medication is discontinued.{{cite book |title=Diagnostic and statistical manual of mental disorders : DSM-5. |date=2013 |publisher=American Psychiatric Association |isbn=9780890425541 |pages=711–712 |edition=5th}}

When misdiagnosis occurs in antipsychotic-induced akathisia, more antipsychotics may be prescribed, potentially worsening the symptoms.{{cite journal |doi=10.1136/bmj.292.6527.1034 |title=Akathisia—or not sitting |year=1986 |last1=Szabadi |first1=E |journal=BMJ |volume=292 |issue=6527 |pages=1034–5 |pmid=2870759 |pmc=1340104|type= editorial}} If not identified, akathisia symptoms can increase in severity and lead to suicidal thoughts, aggression and violence.

Visible signs of akathisia include repetitive movements, such as crossing and uncrossing the legs and constant shifting from one foot to the other. Other noted signs include rocking back and forth, fidgeting, and pacing. However, not all observable restless motion is akathisia. For example, while mania, agitated depression, and attention deficit hyperactivity disorder may present like akathisia, movements resulting from them feel voluntary, rather than being due to restlessness.{{Cite journal|vauthors= Forcen FE|date=January 2015|url=http://www.mdedge.com/currentpsychiatry/article/89620/somatic-disorders/akathisia-restlessness-primary-condition-or|journal=Current Psychiatry|volume=14 |issue=1|pages=14–18|via=mededge |title= Akathisia: Is restlessness a primary condition or an adverse drug effect?}}

Jack Henry Abbott, who was diagnosed with akathisia, described the sensation in 1981 as: "You ache with restlessness, so you feel you have to walk, to pace. And then as soon as you start pacing, the opposite occurs to you; you must sit and rest. Back and forth, up and down you go … you cannot get relief …"Jack Henry Abbot In the Belly of the Beast (1981/1991). Vintage Books, 35–36. Quoted in Robert Whitaker, Mad in America (2002, {{ISBN|0-7382-0799-3}}), 187.

Medication-induced akathisia is termed acute akathisia and is frequently associated with the use of antipsychotics. Antipsychotics block dopamine receptors, but the pathophysiology is poorly understood. Even so, drugs with successful therapeutic effects in the treatment of medication-induced akathisia have provided additional insight into the involvement of other transmitter systems. These include benzodiazepines, β-adrenergic blockers, and serotonin antagonists. Another major cause of the syndrome is the withdrawal observed in drug-dependent individuals.{{cite journal |last1=Kane |first1=John M. |last2=Fleischhacker |first2=Wolfgang W. |last3=Hansen |first3=Lars |last4=Perlis |first4=Roy |last5=Pikalov a |first5=Andrei |last6=Assunção-Talbott |first6=Sheila |year=2009 |title=Akathisia: An Updated Review Focusing on Second-Generation Antipsychotics |journal=The Journal of Clinical Psychiatry |type=Review |volume=70 |issue=5 |pages=627–43 |doi=10.4088/JCP.08r04210 |pmid=19389331}}

Akathisia involves increased levels of the neurotransmitter norepinephrine, which is associated with mechanisms that regulate aggression, alertness, and arousal.{{cite book | url=https://books.google.com/books?id=AQeQa5AtpXoC | title=Principles and Practice of Geriatric Psychiatry | publisher=Lippincott Williams & Wilkins | access-date=2013-11-23 |author1=Marc E. Agronin |author2=Gabe J. Maletta | chapter=Chapter 14: Pharmacotherapy in the Elderly | chapter-url=https://books.google.com/books?id=AQeQa5AtpXoC&pg=PA215 | year=2006 | edition=illustrated | page=215 | isbn=978-0-7817-4810-0}} It has been correlated with Parkinson's disease and related syndromes, with descriptions of akathisia predating the existence of pharmacologic agents.

Akathisia can be miscoded in side effect reports from antidepressant clinical trials as "agitation, emotional lability, and hyperkinesis (overactivity)"; misdiagnosis of akathisia as simple motor restlessness occurred, but was more properly classed as dyskinesia.{{medical citation needed|date=July 2020}}{{cite journal |last1=Healy |first1=David |last2=Herxheimer |first2=Andrew |last3=Menkes |first3=David B. | year = 2006 | title = Antidepressants and Violence: Problems at the Interface of Medicine and Law | journal = PLOS Medicine | volume = 3 | issue = 9| page = e372 | doi = 10.1371/journal.pmed.0030372 | pmid = 16968128 | pmc=1564177 |type= Review |doi-access=free }}

The presence and severity of akathisia can be measured using the Barnes Akathisia Scale,{{cite journal |doi=10.1192/bjp.154.5.672 |title=A rating scale for drug-induced akathisia |year=1989 |last1=Barnes |first1=T. R. |journal=The British Journal of Psychiatry |volume=154 |issue=5 |pages=672–6 |pmid=2574607|s2cid=9969975 }}{{cite journal |doi=10.1177/0269881103174013 |title=The Barnes Akathisia Rating Scale–Revisited |year=2003 |last1=Barnes |first1=Thomas R. E. |journal=Journal of Psychopharmacology |volume=17 |issue=4 |pages=365–70 |pmid=14870947|s2cid=29435046 }} which assesses both objective and subjective criteria. Precise assessment of akathisia is problematic, as there are various types making it difficult to differentiate from disorders with similar symptoms.

The primary distinguishing features of akathisia in comparison with other syndromes are primarily subjective characteristics, such as the feeling of inner restlessness and tension.{{cite journal |pmid=14646611 |year=2003 |last1=Kim |first1=JH |last2=Byun |first2=HJ |title=Prevalence and characteristics of subjective akathisia, objective akathisia, and mixed akathisia in chronic schizophrenic subjects |volume=26 |issue=6 |pages=312–6 |journal=Clinical Neuropharmacology |doi=10.1097/00002826-200311000-00010|s2cid=23393707 }}{{cite web |last1=Practitioners |first1=The Royal Australian College of General |title=RACGP - Beyond anxiety and agitation: A clinical approach to akathisia |url=https://www.racgp.org.au/afp/2017/may/beyond-anxiety-and-agitation-a-clinical-approach-to-akathisia/ |website=racgp.org.au |access-date=12 August 2020 |language=en}} Akathisia can commonly be mistaken for agitation secondary to psychotic symptoms or mood disorder, antipsychotic dysphoria, restless legs syndrome, anxiety, insomnia, drug withdrawal states, tardive dyskinesia, or other neurological and medical conditions.{{cite journal |doi=10.4088/JCP.08r04210 |title=Akathisia: An Updated Review Focusing on Second-Generation Antipsychotics |year=2009 |last1=Kane |first1=John M. |last2=Fleischhacker |first2=Wolfgang W. |last3=Hansen |first3=Lars |last4=Perlis |first4=Roy |last5=Pikalov a |first5=Andrei |last6=Assunção-Talbott |first6=Sheila |journal=The Journal of Clinical Psychiatry |volume=70 |issue=5 |pages=627–43 |pmid=19389331|type= Review}}

The controversial diagnosis of "pseudoakathisia" is sometimes given.{{cite journal |vauthors=Salem H, Nagpal C, Pigott T, Teixeira AL |title=Revisiting Antipsychotic-induced Akathisia: Current Issues and Prospective Challenges |journal=Curr Neuropharmacol |volume=15 |issue=5 |pages=789–798 |date=2017 |pmid=27928948 |pmc=5771055 |doi=10.2174/1570159X14666161208153644 |type=Review}}

Acute akathisia induced by medication, often antipsychotics, is treated by reducing or discontinuing the medication.{{cite journal |vauthors=Bratti IM, Kane JM, Marder SR |date=November 2007 |title=Chronic restlessness with antipsychotics |journal=Am J Psychiatry |volume=164 |issue=11 |pages=1648–54 |doi=10.1176/appi.ajp.2007.07071150 |pmid=17974927 |s2cid=35725021}} Low doses of the antidepressant mirtazapine may be of help.{{cite journal |vauthors=Poyurovsky M, Weizman A |title=Treatment of Antipsychotic-Induced Akathisia: Role of Serotonin 5-HT2a Receptor Antagonists |journal=Drugs |volume=80 |issue=9 |pages=871–882 |date=June 2020 |pmid=32385739 |doi=10.1007/s40265-020-01312-0 |s2cid=218541032 |type=Review}}{{cite journal |vauthors=Perry LA, Ramson D, Stricklin S |title=Mirtazapine adjunct for people with schizophrenia |journal=Cochrane Database Syst Rev |volume=2018 |pages=CD011943 |date=May 2018 |issue=5 |pmid=29802811 |pmc=6494505 |doi=10.1002/14651858.CD011943.pub2 |type= Review}}

Biperiden, an antipsychotic antidote, commonly used to improve acute extrapyramidal side effects related to antipsychotic drug therapy, is also used to treat akathisia.

Benzodiazepines, such as lorazepam; beta blockers such as propranolol; anticholinergics such as benztropine; and serotonin antagonists such as cyproheptadine may also be of help in treating acute akathisia but are much less effective for treating chronic akathisia. Vitamin B, and iron supplementation if deficient, may be of help.

Although they are sometimes used to treat akathisia, benzodiazepines and antidepressants can actually cause akathisia.

Approximately one out of four individuals treated with first-generation antipsychotics have akathisia. Prevalence rates may be lower for modern treatment as second-generation antipsychotics carry a lower risk of akathisia. In 2015, a French study found an overall prevalence rate of 18.5% in a sample of outpatients with schizophrenia.{{Cite journal |last1=Berna |first1=F. |last2=Misdrahi |first2=D. |last3=Boyer |first3=L. |last4=Aouizerate |first4=B. |last5=Brunel |first5=L. |last6=Capdevielle |first6=D. |last7=Chereau |first7=I. |last8=Danion |first8=J. M. |last9=Dorey |first9=J. M. |last10=Dubertret |first10=C. |last11=Dubreucq |first11=J. |last12=Faget |first12=C. |last13=Gabayet |first13=F. |last14=Lancon |first14=C. |last15=Mallet |first15=J. |date=2015-12-01 |title=Akathisia: prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the FACE-SZ dataset |url=https://www.sciencedirect.com/science/article/pii/S0920996415300402 |journal=Schizophrenia Research |language=en |volume=169 |issue=1 |pages=255–261 |doi=10.1016/j.schres.2015.10.040 |pmid=26589388 |s2cid=26752064 |issn=0920-9964}}

The term was first used by Czech neuropsychiatrist Ladislav Haškovec, who described the phenomenon in a non-medication induced presentation in 1901.{{cite journal|last1=Mohr|first1=P|last2=Volavka|first2=J|title=Ladislav Haskovec and akathisia: 100th anniversary.|journal=The British Journal of Psychiatry|date=December 2002|volume=181|issue=6|page=537|doi=10.1192/bjp.181.6.537-a|pmid=12456534|doi-access=free}}

Reports of medication-induced akathisia from chlorpromazine appeared in 1954.{{Efn|"In 1954, two separate researchers, Professor Hans Steck of Lausanne, and German psychiatrist Hans Joachim Haase provided the first unambiguous descriptions of a syndrome of abnormally reduced and restricted movement that was associated with chlorpromazine. [...] They also described the drug-induced agitation known as akathisia (Hasse, 1954; Steck, 1954)."{{cite book|author=J. Moncrieff|title=The Bitterest Pills: The Troubling Story of Antipsychotic Drugs|url=https://books.google.com/books?id=yTwiAQAAQBAJ|date=15 September 2013|publisher=Springer|isbn=978-1-137-27744-2}} {{rp|40}}|name=|group=}} Later in 1960 there were reports of akathisia in response to phenothiazines (a related drug). Akathisia is classified as an extrapyramidal side effect along with other movement disorders that can be caused by antipsychotics.

In the former Soviet Union, akathisia-inducing drugs were allegedly used as a form of torture. Haloperidol, an antipsychotic medication, was used to induce intense restlessness and Parkinson's-type symptoms in prisoners.*{{cite book|author=Darius Rejali|title=Torture and Democracy|url=https://books.google.com/books?id=-L8GtJY_J00C&pg=PA390|date=8 June 2009|publisher=Princeton University Press|isbn=978-1-4008-3087-9|pages=392–3|ref={{harvid|Rejali|2009}}}}

In 2020 clinical psychologist and professor of psychology Jordan Peterson was diagnosed with akathisia after being treated for insomnia and depression with benzodiazepines that was associated with an autoimmune disorder and was subsequently treated in Russia.[https://nationalpost.com/health/jordan-peterson-benzodiazepines Why was Jordan Peterson placed in a medically induced coma? What we know about benzodiazepines and treatment] Published 11 February 2020 by the National Post[https://www.youtube.com/watch?v=mmk6aESKYWE Mikhaila Peterson's Response to The Times Article (and subsequent articles)]

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