Akathisia
Other namesAcathisia
Common sign of akathisia
SpecialtyNeurology, psychiatry
SymptomsFeelings of restlessness, inability to stay still, uneasy[1]
ComplicationsViolence or suicidal thoughts[2]
DurationShort- or long-term[2]
CausesAntipsychotics, selective serotonin reuptake inhibitors, metoclopramide, reserpine[2]
Diagnostic methodBased on symptoms[2]
Differential diagnosisAnxiety, tic disorders, tardive dyskinesia, dystonia, medication-induced parkinsonism, restless leg syndrome[2][3]
TreatmentReduce or switch antipsychotics, correct iron deficiency[2]
MedicationDiphenhydramine, trazodone, benzodiazepines, benztropine, mirtazapine, beta blockers[4][2]
FrequencyRelatively common[4]

Akathisia (IPA: /æ.kə.ˈθɪ.si.ə/) is a movement disorder[5] characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still.[6][4] Usually, the legs are most prominently affected.[2] Those affected may fidget, rock back and forth, or pace,[7] while some may just have an uneasy feeling in their body.[2] The most severe cases may result in aggression, violence, and/or suicidal thoughts.[2] 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.[8]

Antipsychotic medication, particularly the first generation antipsychotics, are a leading cause.[4][7] Other agents commonly responsible for this side-effect may also include selective serotonin reuptake inhibitors, metoclopramide, and reserpine, though any medication listing agitation as a side effect may trigger it.[2][9] It may also occur upon stopping antipsychotics.[2] The underlying mechanism is believed to involve dopamine.[2] Diagnosis is based on the symptoms.[2] It differs from restless leg syndrome in that akathisia is not associated with sleeping. However, despite a lack of historical association between restless leg syndrome and akathisia, this does not guarantee that the two conditions do not share symptoms in individual cases.[2]

Treatment may include switching to an antipsychotic with a lower risk of the condition, if the akathisia was caused by an antipsychotic.[2] The antidepressant mirtazapine has demonstrated benefit,[5] as well as diphenhydramine, trazodone, benzatropine, cyproheptadine, and beta blockers, particularly propranolol.[2][4][10]

The term was first used by Czech neuropsychiatrist Ladislav Haškovec, who described the phenomenon in 1901 long before the discovery of antipsychotics, with drug-induced akathisia first being described in 1960.[1] It is from Greek a-, meaning "not", and καθίζειν kathízein, meaning "to sit", or in other words an "inability to sit".[2]

Classification

Akathisia is usually grouped as a medication-induced movement disorder but is also seen to be a neuropsychiatric concern as it can be experienced purely subjectively with no apparent movement abnormalities.[2] Akathisia is generally associated with antipsychotics but it was already described in Parkinson's disease, and other neuropsychiatric disorders.[5] It also presents with the use of non-psychiatric medications, including calcium channel blockers, antibiotics, anti-nausea and anti-vertigo drugs.[5]

Signs and symptoms

Symptoms of akathisia are often described in vague terms such as feeling nervous, uneasy, tense, twitchy, restless, and an inability to relax.[1] Reported symptoms also include insomnia, a sense of discomfort, motor restlessness, marked anxiety, and panic.[11] Symptoms have also been said to resemble symptoms of neuropathic pain that are similar to fibromyalgia and restless legs syndrome.[12] When due to psychiatric drugs, the symptoms are side effects that usually disappear quickly and remarkably when the medication is reduced or stopped. However, tardive akathisia which has a late onset, may go on long after the medication is discontinued, for months and sometimes years.[13]

When misdiagnosis occurs in antipsychotic-induced akathisia, more antipsychotic may be prescribed, potentially worsening the symptoms.[7][14] If symptoms are not recognised and identified akathisia can increase in severity and lead to suicidal thoughts, aggression and violence.[1][2]

Visible signs of akathisia include repetitive movements such as crossing and uncrossing the legs, and constant shifting from one foot to the other.[1] Other noted signs are rocking back and forth, fidgeting and pacing.[7] However, not all observable restless motion is akathisia. For example, mania, agitated depression, and attention deficit hyperactivity disorder may look like akathisia, but the movements feel voluntary and not due to restlessness.[15]

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 …"[16]

Causes

Medication-induced

Medication related causes of akathisia
CategoryExamples
Antipsychotics[17]Haloperidol, amisulpride, risperidone, aripiprazole, lurasidone, ziprasidone
SSRIs[18]Fluoxetine,[18] paroxetine,[11] citalopram, sertraline[19]
AntidepressantsVenlafaxine, tricyclics, trazodone, and mirtazapine[20]
AntiemeticsMetoclopramide, prochlorperazine, and promethazine
Drug withdrawalAntipsychotic withdrawal[2]
Serotonin syndrome[21]Harmful combinations of psychotropic drugs

Medication-induced akathisia is termed acute akathisia and is frequently associated with the use of antipsychotics.[13] Antipsychotics block dopamine receptors, but the pathophysiology is poorly understood. Additionally, 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.[22] Another major cause of the syndrome is the withdrawal observed in drug-dependent individuals. Since dopamine deficiency (or disruptions in dopamine signalling) appears to play an important role in the development of Restless Legs Syndrome (RLS), a form of akathisia focused in the legs, the sudden withdrawal or rapidly decreased dosage of drugs which increase dopamine signalling may create similar deficits of the chemical which mimic dopamine antagonism and thus can precipitate RLS. This is why sudden cessation of opioids, cocaine, serotonergics, and other euphoria-inducing substances commonly produce RLS as a side-effect.[22]

Akathisia involves increased levels of the neurotransmitter norepinephrine, which is associated with mechanisms that regulate aggression, alertness, and arousal.[23] It has been correlated with Parkinson's disease and related syndromes, and descriptions of akathisia predate the existence of pharmacologic agents.[5]

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.[11]

Diagnosis

The presence and severity of akathisia can be measured using the Barnes Akathisia Scale,[24][25] which assesses both objective and subjective criteria.[24] Precise assessment of akathisia is problematic, as there are various types making it difficult to differentiate from disorders with similar symptoms.[5]

The primary distinguishing features of akathisia in comparison with other syndromes are primarily subjective characteristics, such as the feeling of inner restlessness and tension.[26][27] 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.[22]

The controversial diagnosis of "pseudoakathisia" is sometimes given.[1]

Treatment

Acute akathisia induced by medication,[13] often antipsychotics, is treated by reducing or discontinuing the medication.[2][28] Low doses of the antidepressant mirtazapine may be of help.[5][29] 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.[28] Vitamin B, and iron supplementation if deficient, may be of help.[2][4] Although they are sometimes used to treat akathisia, benzodiazepines and antidepressants can actually cause akathisia.

Epidemiology

Approximately one out of four individuals treated with first-generation antipsychotics have akathisia.[5] Prevalence rates may be lower for modern treatment as second-generation antipsychotics carry a lower risk of akathisia.[28] In 2015, a French study found an overall prevalence rate of 18.5% in a sample of outpatients with schizophrenia.[30]

History

The term was first used by Czech neuropsychiatrist Ladislav Haškovec, who described the phenomenon in a non-medication induced presentation in 1901.[31][1]

Reports of medication-induced akathisia from chlorpromazine appeared in 1954.[lower-alpha 1] Later in 1960 there were reports of akathisia in response to phenothiazines (a related drug).[1] Akathisia is classified as an extrapyramidal side effect along with other movement disorders that can be caused by antipsychotics.[1]

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.[33]

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.[34][35][36]

See also

Notes

  1. ↑ "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)."[32] : 40 

References

  1. 1 2 3 4 5 6 7 8 9 Salem H, Nagpal C, Pigott T, Teixeira AL (2017). "Revisiting Antipsychotic-induced Akathisia: Current Issues and Prospective Challenges". Curr Neuropharmacol (Review). 15 (5): 789–798. doi:10.2174/1570159X14666161208153644. PMC 5771055. PMID 27928948.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Lohr, JB; Eidt, CA; Abdulrazzaq Alfaraj, A; Soliman, MA (December 2015). "The clinical challenges of akathisia". CNS Spectrums (Review). 20 (Suppl 1): 1–14, quiz 15–6. doi:10.1017/S1092852915000838. PMID 26683525. S2CID 4253429.
  3. ↑ Kaufman, David Myland; Milstein, Mark J. (2012). Kaufman's Clinical Neurology for Psychiatrists E-Book. Elsevier Health Sciences. p. 429. ISBN 978-1455740048.
  4. 1 2 3 4 5 6 Laoutidis, ZG; Luckhaus, C (May 2014). "5-HT2A receptor antagonists for the treatment of neuroleptic-induced akathisia: a systematic review and meta-analysis". The International Journal of Neuropsychopharmacology (Review). 17 (5): 823–32. doi:10.1017/S1461145713001417. PMID 24286228.
  5. 1 2 3 4 5 6 7 8 Poyurovsky M, Weizman A (June 2020). "Treatment of Antipsychotic-Induced Akathisia: Role of Serotonin 5-HT2a Receptor Antagonists". Drugs (Review). 80 (9): 871–882. doi:10.1007/s40265-020-01312-0. PMID 32385739. S2CID 218541032.
  6. ↑ Forcen, FE; Matsoukas, K; Alici, Y (February 2016). "Antipsychotic-induced akathisia in delirium: A systematic review". Palliative & Supportive Care (Review). 14 (1): 77–84. doi:10.1017/S1478951515000784. PMC 5516628. PMID 26087817.
  7. 1 2 3 4 Thomas, JE; Caballero, J; Harrington, CA (2015). "The Incidence of Akathisia in the Treatment of Schizophrenia with Aripiprazole, Asenapine and Lurasidone: A Meta-Analysis". Current Neuropharmacology (Review). 13 (5): 681–91. doi:10.2174/1570159x13666150115220221. PMC 4761637. PMID 26467415.
  8. ↑ Stubbs, J. H.; Hutchins, D. A.; Mountjoy, C. Q. (2000). "Relationship of akathisia to aggressive and self-injurious behaviour: A prevalence study in a UK tertiary referral centre". International Journal of Psychiatry in Clinical Practice. 4 (4): 319–325. doi:10.1080/13651500050517894. ISSN 1365-1501. PMID 24926584. S2CID 26486432.
  9. ↑ "MISSD - The Medication-Induced Suicide Prevention and Education Foundation in Memory of Stewart Dolin - Akathisia Support". missd.co. Retrieved 26 August 2022.
  10. ↑ Fischel, T.; Hermesh, H.; Aizenberg, D.; Zemishlany, Z.; Munitz, H.; Benjamini, Y.; Weizman, A. (December 2001). "Cyproheptadine versus propranolol for the treatment of acute neuroleptic-induced akathisia: a comparative double-blind study". Journal of Clinical Psychopharmacology. 21 (6): 612–615. doi:10.1097/00004714-200112000-00013. ISSN 0271-0749. PMID 11763011. S2CID 22663143.
  11. 1 2 3 Healy, David; Herxheimer, Andrew; Menkes, David B. (2006). "Antidepressants and Violence: Problems at the Interface of Medicine and Law". PLOS Medicine (Review). 3 (9): e372. doi:10.1371/journal.pmed.0030372. PMC 1564177. PMID 16968128.
  12. ↑ Sachdev, Perminder (2006). Akathisia and Restless Legs. Cambridge University Press. p. 299. ISBN 978-0-521-03148-6.
  13. 1 2 3 Diagnostic and statistical manual of mental disorders : DSM-5 (5th ed.). American Psychiatric Association. 2013. pp. 711–712. ISBN 9780890425541.
  14. ↑ Szabadi, E (1986). "Akathisia—or not sitting". BMJ (editorial). 292 (6527): 1034–5. doi:10.1136/bmj.292.6527.1034. PMC 1340104. PMID 2870759.
  15. ↑ Forcen FE (January 2015). "Akathisia: Is restlessness a primary condition or an adverse drug effect?". Current Psychiatry. 14 (1): 14–18 – via mededge.
  16. ↑ 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.
  17. ↑ Diaz, Jaime (1996). How Drugs Influence Behavior. Englewood Cliffs: Prentice Hall.
  18. 1 2 Hansen, Lars (2003). "Fluoxetine Dose-Increment Related Akathisia in Depression: Implications for Clinical Care, Recognition and Management of Selective Serotonin Reuptake Inhibitor-Induced Akathisia". Journal of Psychopharmacology. 17 (4): 451–2. doi:10.1177/0269881103174003. PMID 14870959. S2CID 40974047.
  19. ↑ Altshuler, L. L.; Pierre, J. M.; Wirshing, W. C.; Ames, D. (August 1994). "Sertraline and akathisia". Journal of Clinical Psychopharmacology. 14 (4): 278–279. doi:10.1097/00004714-199408000-00010. ISSN 0271-0749. PMID 7962686.
  20. ↑ "Remeron (Mirtazapine) Drug Information". RxList. Retrieved 28 March 2016.
  21. ↑ Dunkley, E.J.C.; Isbister, G.K.; Sibbritt, D.; Dawson, A.H.; Whyte, I.M. (18 August 2003). "The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity". QJM. 96 (9): 635–642. doi:10.1093/qjmed/hcg109. PMID 12925718.
  22. 1 2 3 Kane, John M.; Fleischhacker, Wolfgang W.; Hansen, Lars; Perlis, Roy; Pikalov a, Andrei; Assunção-Talbott, Sheila (2009). "Akathisia: An Updated Review Focusing on Second-Generation Antipsychotics". The Journal of Clinical Psychiatry (Review). 70 (5): 627–43. doi:10.4088/JCP.08r04210. PMID 19389331.
  23. ↑ Marc E. Agronin; Gabe J. Maletta (2006). "Chapter 14: Pharmacotherapy in the Elderly". Principles and Practice of Geriatric Psychiatry (illustrated ed.). Lippincott Williams & Wilkins. p. 215. ISBN 978-0-7817-4810-0. Retrieved 23 November 2013.
  24. 1 2 Barnes, T. R. (1989). "A rating scale for drug-induced akathisia". The British Journal of Psychiatry. 154 (5): 672–6. doi:10.1192/bjp.154.5.672. PMID 2574607. S2CID 9969975.
  25. ↑ Barnes, Thomas R. E. (2003). "The Barnes Akathisia Rating Scale–Revisited". Journal of Psychopharmacology. 17 (4): 365–70. doi:10.1177/0269881103174013. PMID 14870947. S2CID 29435046.
  26. ↑ Kim, JH; Byun, HJ (2003). "Prevalence and characteristics of subjective akathisia, objective akathisia, and mixed akathisia in chronic schizophrenic subjects". Clinical Neuropharmacology. 26 (6): 312–6. doi:10.1097/00002826-200311000-00010. PMID 14646611. S2CID 23393707.
  27. ↑ Practitioners, The Royal Australian College of General. "RACGP - Beyond anxiety and agitation: A clinical approach to akathisia". racgp.org.au. Retrieved 12 August 2020.
  28. 1 2 3 Bratti IM, Kane JM, Marder SR (November 2007). "Chronic restlessness with antipsychotics". Am J Psychiatry. 164 (11): 1648–54. doi:10.1176/appi.ajp.2007.07071150. PMID 17974927. S2CID 35725021.
  29. ↑ Perry LA, Ramson D, Stricklin S (May 2018). "Mirtazapine adjunct for people with schizophrenia". Cochrane Database Syst Rev (Review). 2018 (5): CD011943. doi:10.1002/14651858.CD011943.pub2. PMC 6494505. PMID 29802811.
  30. ↑ Berna, F.; Misdrahi, D.; Boyer, L.; Aouizerate, B.; Brunel, L.; Capdevielle, D.; Chereau, I.; Danion, J. M.; Dorey, J. M.; Dubertret, C.; Dubreucq, J.; Faget, C.; Gabayet, F.; Lancon, C.; Mallet, J. (1 December 2015). "Akathisia: prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the FACE-SZ dataset". Schizophrenia Research. 169 (1): 255–261. doi:10.1016/j.schres.2015.10.040. ISSN 0920-9964. PMID 26589388. S2CID 26752064.
  31. ↑ Mohr, P; Volavka, J (December 2002). "Ladislav Haskovec and akathisia: 100th anniversary". The British Journal of Psychiatry. 181 (6): 537. doi:10.1192/bjp.181.6.537-a. PMID 12456534.
  32. ↑ J. Moncrieff (15 September 2013). The Bitterest Pills: The Troubling Story of Antipsychotic Drugs. Springer. ISBN 978-1-137-27744-2.
  33. ↑
  34. ↑ 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
  35. ↑ Jordan Peterson says he was suicidal, addicted to benzos
  36. ↑ Mikhaila Peterson's Response to The Times Article (and subsequent articles)
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