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Title: Akathisia  
Author: World Heritage Encyclopedia
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Subject: Antipsychotic, Metoclopramide, Neuroleptic malignant syndrome, Clonazepam, Tremor
Collection: Articles Containing Video Clips, Symptoms and Signs: Nervous System, Syndromes
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Common symptom-expression of akathisia
Classification and external resources
Specialty Neurology
ICD-10 G21.1
ICD-9-CM 781.0, 333.99
DiseasesDB 32479
eMedicine neuro/362 emerg/338
MeSH D011595

Akathisia, or acathisia (from Greek καθίζειν kathízein – "to sit", a- indicating negation or absence, lit. "inability to sit") is a movement disorder characterized by a feeling of inner restlessness and a compelling need to be in constant motion, as well as by actions such as rocking while standing or sitting, lifting the feet as if marching on the spot, and crossing and uncrossing the legs while sitting. People with akathisia are unable to sit or keep still, complain of restlessness, fidget, rock from foot to foot, and pace.[1]

The term was coined by the Czech neuropsychiatrist Ladislav Haskovec (1866–1944), who described the phenomenon in 1901.[2][3]

Antipsychotics (also known as neuroleptics), particularly the first generation antipsychotics, may cause akathisia. Other known causes include side effects of certain medications, and nearly any physical dependence-inducing drug during drug withdrawal.[4] It is also associated with Parkinson's disease and related syndromes.[5]


  • Signs and symptoms 1
  • Causes 2
    • Pathophysiological 2.1
    • Drug-induced 2.2
  • Diagnosis 3
    • Classification 3.1
  • Treatment 4
  • Epidemiology 5
  • References 6

Signs and symptoms

Akathisia may range in intensity from a sense of disquiet or anxiety, to excruciating discomfort, particularly in the knees. Patients 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. At high doses or with potent drugs such as haloperidol (Haldol) or chlorpromazine (Thorazine/Largactil), the feeling can last all day from awakening to sleep. When misdiagnosis occurs in antipsychotic neuroleptic-induced akathisia, more antipsychotic neuroleptics may be prescribed, potentially worsening the symptoms.[5] High-functioning patients have described the feeling as a sense of inner tension and torment or chemical torture. Many patients describe symptoms of neuropathic pain akin to fibromyalgia and restless legs syndrome.[6] In Han et al. (2013), the authors describe restless legs syndrome's relation to akathisia, "Some researchers regard RLS as a 'focal akathisia' [in the legs]."[7] Although these side effects disappear quickly and remarkably when the medication is stopped, tardive, or late-persisting akathisia may go on long after the offending drug is discontinued, sometimes for a period of years. Healy, et al. (2006), described the following regarding akathisia: tension, insomnia, a sense of discomfort, motor restlessness, and marked anxiety and panic. Increased labile affect can result, such as weepiness.[8]

Severe akathisia can become a very harrowing experience. Jack Henry Abbot (1981) describes the sensation:[9]

...[It comes] from so deep inside you, you cannot locate the source of the pain … The muscles of your jawbone go berserk, so that you bite the inside of your mouth and your jaw locks and the pain throbs. … Your spinal column stiffens so that you can hardly move your head or your neck and sometimes your back bends like a bow and you cannot stand up. … 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 …

In a psychiatric setting, patients who suffer from neuroleptic-induced akathisia often react by refusing treatment.[10]



Han et al. (2013)[7] reported that upon examination of three patients who experienced abrupt onset of restlessness characteristic of akathisia and RLS, magnetic resonance imaging of the brain revealed pontine infarction (lack of blood to the pons area of the brain). Han et al. wrote, "The features of our three patients suggest that RLS and akathisia may have a common pathophysiological mechanism related to the pontine region of the brain."[7]


Akathisia is frequently associated with the use of dopamine receptor antagonist antipsychotic drugs.[11] Understanding is still limited on the pathophysiology of akathisia, but it is seen to be associated with medications which block dopaminergic transmission in the brain. 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.[11] Another major cause of the syndrome is the withdrawal observed in dependent individuals.[4]

It has been correlated with Parkinson's disease and related syndromes.[5] It is unclear, however, whether this is due more to Parkinson's or the drugs used to treat it, such as carbidopa/levodopa (levocarb).[12]

Antidepressants can also induce the appearance of akathisia.[13][14][15][16] The 2006 UK study by Healy et al. observed that akathisia is often miscoded in antidepressant clinical trials as "agitation, emotional lability, and hyperkinesis (overactivity)".[17] The study further points out that misdiagnosis of akathisia as simple motor restlessness occurs, but that this is more properly classed as dyskinesia.

It was discovered that akathisia involves increased levels of the neurotransmitter norepinephrine, which is associated with mechanisms that regulate aggression, alertness, and arousal.[18]

The table below summarizes factors that can induce akathisia, grouped by type, with examples or brief explanations for each:

Category Examples
Antipsychotics[19] Haloperidol (Haldol), droperidol, pimozide, trifluoperazine, amisulpride, risperidone, aripiprazole (Abilify), lurasidone (Latuda), ziprasidone (Geodon), and asenapine (Saphris)
SSRIs[20] Fluoxetine (Prozac),[20] paroxetine (Paxil),[17] citalopram (Celexa)
Antidepressants Venlafaxine (Effexor), tricyclics, and trazodone (Desyrel)
Antiemetics Metoclopramide (Reglan), prochlorperazine (Compazine), and promethazine
Antihistamines Cyproheptadine (Periactin) or diphenhydramine (Benadryl) — this is more commonly seen at very high doses
Drug withdrawal Opioid withdrawal, barbiturates withdrawal, cocaine withdrawal, and benzodiazepine withdrawal
Serotonin syndrome Harmful combinations of psychotropic drugs


The presence and severity of akathisia can be measured using the Barnes Akathisia Scale,[21][22] which assesses both objective and subjective criteria.[21] Precise assessment of akathisia is problematic, as it is difficult to differentiate from a multitude of disorders with similar symptoms. In a study of movement disorders induced by neuroleptics, akathisia was found in only 26% of patients originally diagnosed with akathisia.[10] The primary distinguishing features of akathisia in comparison with other syndromes are primarily subjective characteristics, such as the feeling of inner restlessness.[23] 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.[11]

Additionally, the controversial diagnosis of "pseudoakathisia" is given, as noted by Mark J. Garcia. In his article discussing akathisia among adults with severe and profound intellectual disability, he describes pseudoakathisia as "comprising all the symptoms of abnormal movements seen with akathisia, but without a sense of restlessness".[24]



Akathisia is sometimes reversible once the causative agent has been identified and discontinued, but in some cases may become permanent.[25] Case reports and small randomized studies suggest benzodiazepines, propranolol, and anticholinergics may help treat acute akathisia, but are much less effective in treating chronic akathisia.[26] Taylor et al. found success in lowering the dose of antipsychotic medication as an initial response to drug-induced akathisia,[24] which should be done gradually, if possible.[26] To minimize the risk of akathisia from antipsychotics, the clinician is advised to be conservative when increasing dosages.[24]

If the patient is experiencing akathisia due to opioid withdrawal, and continuing use of opioids is not viable, drugs typically prescribed for acute idiopathic akathisia can be effective. GABA analogues pregabalin and gabapentin, as well as drugs approved for treating RLS, may also be effective in certain cases.

One study showed vitamin B6 to be effective for the treatment of neuroleptic-induced akathisia.[27]

N-acetylcysteine also showed a positive effect on akathisia in a randomized control trial.[28]

Additional pharmacologic interventions found to have antiakathisia effects (especially for neuroleptic-induced akathisia) include ß-adrenergic antagonists (e.g., propranolol), benzodiazepines (e.g., lorazepam), anticholinergics (e.g., benztropine), and serotonin antagonists (e.g., cyproheptadine) as an alternative.[11]

Trihexyphenidyl has also been prescribed to treat akathisia.


Published epidemiological data for akathisia are mostly limited to treatment periods preceding the arrival of second-generation antipsychotics.[26] Sachdev (1995)[29] reported an incidence rate of acute akathisia of 31% for 100 patients treated for 2 weeks with antipsychotic medications. Sachdev (1995) reported a prevalence range from 0.1% to 41%.[29] In all likelihood, rates of prevalence are lower for current treatment as second-generation antipsychotics carry a lower risk of akathisia.[26]


  1. ^ "Definition of Akathisia".  
  2. ^ Brune, M. (2002). "Ladislav Haskovec and 100 Years of Akathisia". American Journal of Psychiatry 159 (5): 727.  
  3. ^ Mohr, P. (2002). "Ladislav Haskovec and akathisia: 100th anniversary". The British Journal of Psychiatry 181 (6): 537–a.  
  4. ^ a b Kaye, Neil S. (2003). "Psychic akathisia". Journal of Clinical Psychopharmacology 23 (2): 206; discussion 206–7.  
  5. ^ a b c Szabadi, E (1986). "Akathisia—or not sitting". BMJ 292 (6527): 1034–5.  
  6. ^ Sachdev, Perminder (2006). Akathisia and Restless Legs. Cambridge University Press. p. 299.  
  7. ^ a b c Han, Su-Hyun; Park, Kwang-Yeol; Youn, Young Chul; Shin, Hae-Won (2013). "Restless legs syndrome and akathisia as manifestations of acute pontine infarction". Journal of Clinical Neuroscience 21 (2): 354–5.  
  8. ^ Healy, David; Herxheimer, Andrew; Menkes, David B. (2006). "Antidepressants and Violence: Problems at the Interface of Medicine and Law". PLoS Medicine 3 (9): e372. doi:10.1371/journal.pmed.0030372. PMC 1564177. PMID 16968128.
  9. ^ 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.
  10. ^ a b Akagi, H.; Kumar, TM (2002). "Lesson of the week: Akathisia: Overlooked at a cost". BMJ 324 (7352): 1506–7.  
  11. ^ a b c d e f g h i 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 70 (5): 627–43.  
  12. ^ Tack, E.; De Cuypere, G.; Jannes, C.; Remouchamps, A. (1988). "Levodopa addiction". Acta Psychiatrica Scandinavica 78 (3): 356–60.  
  13. ^ Stahl, SM; Lonnen, AJ (2011). "The Mechanism of Drug-induced Akathsia". CNS spectrums.  
  14. ^ Lane, RM (1998). "SSRI-induced extrapyramidal side-effects and akathisia: Implications for treatment". Journal of psychopharmacology 12 (2): 192–214.  
  15. ^ Makela, Eugene H.; Makela, EH (2009). "Selective serotonin reuptake inhibitor-induced akathisia". Journal of the American Pharmacists Association 49 (2): e28–36; quiz e37–8.  
  16. ^ Leo, RJ (1996). "Movement disorders associated with the serotonin selective reuptake inhibitors". The Journal of clinical psychiatry 57 (10): 449–54.  
  17. ^ a b Healy, David; Herxheimer, Andrew; Menkes, David B. (2006). "Antidepressants and Violence: Problems at the Interface of Medicine and Law". PLoS Medicine 3 (9): e372.  
  18. ^ 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.  
  19. ^ Diaz, Jaime (1996). How Drugs Influence Behavior. Englewood Cliffs: Prentice Hall. 
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  22. ^ Barnes, Thomas R. E. (2003). "The Barnes Akathisia Rating Scale–Revisited". Journal of Psychopharmacology 17 (4): 365–70.  
  23. ^ 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.  
  24. ^ a b c Garcia, Mark J.; Matson, Johnny L. (2008). "Akathisia in adults with severe and profound intellectual disability: A psychometric study of the MEDS and ARMS". Journal of Intellectual and Developmental Disability 33 (2): 171–6.  
  25. ^ Munetz, MR; Cornes, CL (December 1983). "Distinguishing akathisia and tardive dyskinesia: a review of the literature.". Journal of Clinical Psychopharmacology 3 (6): 343–50.  
  26. ^ a b c d Bratti, I. M.; Kane, J. M.; Marder, S. R. (2007). "Chronic Restlessness with Antipsychotics". American Journal of Psychiatry 164 (11): 1648–54.  
  27. ^ Lerner, Vladimir; Bergman, Joseph; Statsenko, Nikolay; Miodownik, Chanoch (2004). "Vitamin B6 Treatment in Acute Neuroleptic-Induced Akathisia". The Journal of Clinical Psychiatry 65 (11): 1550–4.  
  28. ^ Berk, Michael; Copolov, David; Dean, Olivia; Lu, Kristy; Jeavons, Sue; Schapkaitz, Ian; Anderson-Hunt, Murray; Judd, Fiona; Katz, Fiona; Katz, Paul; Ording-Jespersen, Sean; Little, John; Conus, Philippe; Cuenod, Michel; Do, Kim Q.; Bush, Ashley I. (2008). "N-Acetyl Cysteine as a Glutathione Precursor for Schizophrenia—A Double-Blind, Randomized, Placebo-Controlled Trial". Biological Psychiatry 64 (5): 361–8.  
  29. ^ a b Sachdev P (1995). Akathisia and Restless Legs. New York: Cambridge University Press. 
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