|Common sign of akathisia|
|Symptoms||Feelings of restlessness, inability to stay still, uneasy|
|Complications||Violence or suicidal thoughts|
|Duration||Short- or long-term|
|Causes||Antipsychotics, selective serotonin reuptake inhibitors, metoclopramide, reserpine, Parkinson’s disease, untreated schizophrenia|
|Diagnostic method||Based on symptoms|
|Differential diagnosis||Anxiety, tic disorders, tardive dyskinesia, dystonia, medication-induced parkinsonism, restless leg syndrome|
|Treatment||Reduce or switch antipsychotics, correct iron deficiency|
|Medication||Diphenhydramine, trazodone, benzodiazepines, benztropine, mirtazapine, beta blockers|
Akathisia is a movement disorder characterized by a feeling of inner restlessness accompanied by mental distress and an inability to stay still. Usually, the legs are most prominently affected. Those affected may fidget, rock back and forth, or pace, while some may just have an uneasy feeling in their body. The most severe cases may result in aggression, violence or suicidal thoughts.
Antipsychotics, particularly the first generation antipsychotics, are a leading cause. Other causes may include selective serotonin reuptake inhibitors, metoclopramide, reserpine, Parkinson’s disease, and untreated schizophrenia. It may also occur upon stopping antipsychotics. The underlying mechanism is believed to involve dopamine. Diagnosis is based on the symptoms. It differs from restless leg syndrome in that akathisia is not associated with sleeping.
Treatment may include switching to an antipsychotic with a lower risk of the condition. The antidepressant mirtazapine has demonstrated benefit, and there is tentative evidence of benefit for diphenhydramine, trazodone, benzatropine and beta blockers. Vitamin B6 or correcting iron deficiency may also be useful. Around half of people on antipsychotics develop the condition. The term was first used by Czech neuropsychiatrist Ladislav Haškovec, who described the phenomenon in 1901. It is from Greek a-, meaning "not", and καθίζειν kathízein, meaning "to sit", or in other words an "inability to sit".
Signs and symptoms
Symptoms of akathisia may vary from a mild sense of disquiet or anxiety to a sense of terror.[medical citation needed] People typically pace for hours because the pressure on the knees reduces the discomfort somewhat; once their knees and legs become fatigued and they are unable to continue pacing, they sit or lie down, although this does not relieve the akathisia. When misdiagnosis occurs in antipsychotic-induced akathisia, more antipsychotic may be prescribed, potentially worsening the symptoms. The most severe cases of akathisia have been linked to aggression, violence or suicidal ideation. However, some reviews have noted that a link to suicide may be confounded by the pre-existing psychiatric conditions being treated.[medical citation needed] Those with akathisia-linked suicidal ideation have tended to be younger and already more depressed or suicidal.[medical citation needed]
Individuals describe symptoms of neuropathic pain akin to fibromyalgia and restless legs syndrome (RLS). Although these side effects usually disappear quickly and remarkably when the medication is reduced or stopped, tardive akathisia which has a late onset, may go on long after the medication is discontinued, for months and sometimes years. Akathisia has been described as tension, insomnia, a sense of discomfort, motor restlessness, and marked anxiety and panic.
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 …“ 
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.
|Antipsychotics||Haloperidol, amisulpride, risperidone, aripiprazole, lurasidone, ziprasidone|
|SSRIs||Fluoxetine, paroxetine, citalopram, sertraline|
|Antidepressants||Venlafaxine, tricyclics, trazodone, and mirtazapine|
|Antiemetics||Metoclopramide, prochlorperazine, and promethazine|
|Drug withdrawal||Antipsychotic withdrawal|
|Serotonin syndrome||Harmful combinations of psychotropic drugs|
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. 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. 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 RLS, a form of akathisia focused in the legs,[medical citation needed] 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.
Akathisia involves increased levels of the neurotransmitter norepinephrine, which is associated with mechanisms that regulate aggression, alertness, and arousal. It has been correlated with Parkinson's disease and related syndromes, and descriptions of akathisia predate 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]
The presence and severity of akathisia can be measured using the Barnes Akathisia Scale, which assesses both objective and subjective criteria. Precise assessment of akathisia is problematic, as there are various types it is difficult to differentiate from a 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. Akathisia can commonly be mistaken for agitation secondary to psychotic symptoms or mood disorder, antipsychotic dysphoria, restless legs syndrome (RLS), anxiety, insomnia, drug withdrawal states, tardive dyskinesia, or other neurological and medical conditions.
The controversial diagnosis of "pseudoakathisia" is sometimes given.
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. Descriptions of akathisia predate the association with antipsychotics, having been earlier identified in Parkinson’s disease and other neuropsychiatric disorders. Generally associated with the use of antipsychotics, it also presents with the use of non-psychiatric medications, including calcium channel blockers, antibiotics, anti-nausea and anti-vertigo drugs.
Acute akathisia induced by medication, often antipsychotics, is treated by reducing or discontinuing the medication. Low doses of the antidepressant mirtazapine may be of help. 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.
As of 2007, published epidemiological data for akathisia was mostly limited to studies before the availability of second-generation antipsychotics. Prevalence rates may be lower for modern treatment as second-generation antipsychotics carry a lower risk of akathisia.
Approximately one out of four individuals treated with first-generation antipsychotics have akathisia.
Reports of medication-induced akathisia from phenothiazines first appeared in 1960, in a published description of three individuals with restlessness. Akathisia was later classified as an extrapyramidal side effect along with other movement disorders that can be caused by antipsychotics.
- 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.
- 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.
- Kaufman, David Myland; Milstein, Mark J. (2012). Kaufman's Clinical Neurology for Psychiatrists E-Book. Elsevier Health Sciences. p. 429. ISBN 978-1455740048.
- 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.
- 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.
- 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.
- 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.
- Encyclopedia of Movement Disorders. Academic Press. 2010. p. 17. ISBN 9780123741059.
- Szabadi, E (1986). "Akathisia—or not sitting". BMJ (editorial). 292 (6527): 1034–5. doi:10.1136/bmj.292.6527.1034. PMC 1340104. PMID 2870759.
- Sachdev, Perminder (2006). Akathisia and Restless Legs. Cambridge University Press. p. 299. ISBN 978-0-521-03148-6.
- Diagnostic and statistical manual of mental disorders : DSM-5 (5th ed.). American Psychiatric Association. 2013. pp. 711–712. ISBN 9780890425541.
- 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.
- 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.
- Forcen FE (January 2015). "Akathisia: Is restlessness a primary condition or an adverse drug effect?". Current Psychiatry. 14 (1): 14–18 – via mededge.
- Diaz, Jaime (1996). How Drugs Influence Behavior. Englewood Cliffs: Prentice Hall.[page needed]
- 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.
- 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.
- "Remeron (Mirtazapine) Drug Information". RxList. Retrieved 28 March 2016.
- 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.
- 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.
- 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.
- 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.
- Barnes, Thomas R. E. (2003). "The Barnes Akathisia Rating Scale–Revisited". Journal of Psychopharmacology. 17 (4): 365–70. doi:10.1177/0269881103174013. PMID 14870947.
- 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.
- 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.
- Perry LA, Ramson D, Stricklin S (May 2018). "Mirtazapine adjunct for people with schizophrenia". Cochrane Database Syst Rev (Review). 5: CD011943. doi:10.1002/14651858.CD011943.pub2. PMC 6494505. PMID 29802811.
- 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.