|Common symptom-expression of akathisia|
|Symptoms||Restlessness, inability to stay still, uneasy|
|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, Tourette syndrome, tardive dyskinesia, dystonia, parkinsonism, restless leg syndrome|
|Treatment||Switching antipsychotics, correcting iron deficiency|
|Medication||Diphenhydramine, trazodone, benztropine, mirtazapine, beta blockers|
Akathisia is a movement disorder characterized by a feeling of inner restlessness and inability to stay still. Usually the legs are most prominently affected. People may fidget, rock back and forth, or pace. Others may just feel uneasy. Complications include suicide.
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 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. Medications with tentative evidence of benefit include diphenhydramine, trazodone, benztropine, mirtazapine, 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 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. 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 neuroleptic-induced akathisia, more antipsychotic may be prescribed, potentially worsening the symptoms. Neuro-psychologist Dennis Staker had drug-induced akathisia for two days. His description of his experience was this: "It was the worst feeling I have ever had in my entire life. I wouldn't wish it on my worst enemy." Many patients describe symptoms of neuropathic pain akin to fibromyalgia and restless legs syndrome. 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]." 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.
...[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 addition, 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.
Akathisia is frequently associated with the use of dopamine receptor antagonist antipsychotic drugs. 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. 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, 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.
It has been correlated with Parkinson's disease and related syndromes. It is unclear, however, whether this is due more to Parkinson's or the drugs used to treat it, such as carbidopa/levodopa (levocarb).
Antidepressants can also induce the appearance of akathisia, due to increased serotonin signalling within the central nervous system. This also explains why serotonin antagonists are often a very effective treatment. 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)". The study further points out that misdiagnosis of akathisia as simple motor restlessness occurs, but that this is more properly classed as dyskinesia.
The table below summarizes factors that can induce akathisia, grouped by type, with examples or brief explanations for each:
|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|
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 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. 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.
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".
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. Taylor et al. found success in lowering the dose of antipsychotic medication as an initial response to drug-induced akathisia, which should be done gradually, if possible. To minimize the risk of akathisia from antipsychotics, the clinician is advised to be conservative when increasing dosages.
Additional pharmacologic interventions found to have antiakathisia effects (especially for neuroleptic-induced akathisia) include β-adrenergic antagonists (e.g., propranolol), benzodiazepines (e.g., lorazepam), anticholinergics (e.g., benztropine), and serotonin antagonists (e.g., cyproheptadine) as an alternative.
Published epidemiological data for akathisia are mostly limited to treatment periods preceding the arrival of second-generation antipsychotics. Sachdev (1995) 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%. In all likelihood, rates of prevalence are lower for current treatment as second-generation antipsychotics carry a lower risk of akathisia.
- Forcen, FE; Matsoukas, K; Alici, Y (February 2016). "Antipsychotic-induced akathisia in delirium: A systematic review". Palliative & Supportive Care. 14 (1): 77–84. doi:10.1017/S1478951515000784. PMC 5516628. PMID 26087817.
- Lohr, JB; Eidt, CA; Abdulrazzaq Alfaraj, A; Soliman, MA (December 2015). "The clinical challenges of akathisia". CNS Spectrums. 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 1455740047.
- 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. 17 (5): 823–32. doi:10.1017/S1461145713001417. PMID 24286228.
- 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. 13 (5): 681–91. doi:10.2174/1570159x13666150115220221. PMC 4761637. PMID 26467415.
- Encyclopedia of Movement Disorders. Academic Press. 2010. p. 17. ISBN 9780123741059.
- 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.
- Kompoliti, Katie; Verhagen-Metman, Leo, eds. (2010). Encyclopedia of Movement Disorders. Oxford: Academic Press. p. 17. ISBN 9780123741059.
- Szabadi, E (1986). "Akathisia—or not sitting". BMJ. 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.
- 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. doi:10.1016/j.jocn.2013.03.021. PMID 23953640.
- 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.
- Espi Forcen, Fernando (January 2015). "MD, PhD". Current Psychiatry. 14 (1): 14–18 – via mededge.
- 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. doi:10.4088/JCP.08r04210. PMID 19389331.
- Kaye, Neil S. (2003). "Psychic akathisia". Journal of Clinical Psychopharmacology. 23 (2): 206, discussion 206–7. doi:10.1097/00004714-200304000-00015. PMID 12640224.
- Tack, E.; De Cuypere, G.; Jannes, C.; Remouchamps, A. (1988). "Levodopa addiction". Acta Psychiatrica Scandinavica. 78 (3): 356–60. doi:10.1111/j.1600-0447.1988.tb06347.x. PMID 2973725.
- Stahl, SM; Lonnen, AJ (2011). "The Mechanism of Drug-induced Akathsia". CNS Spectrums. PMID 21406165.
- Lane, RM (1998). "SSRI-induced extrapyramidal side-effects and akathisia: Implications for treatment". Journal of Psychopharmacology. 12 (2): 192–214. doi:10.1177/026988119801200212. PMID 9694033.
- 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. doi:10.1331/JAPhA.2009.08083. PMID 19289334.
- Leo, RJ (1996). "Movement disorders associated with the serotonin selective reuptake inhibitors". The Journal of Clinical Psychiatry. 57 (10): 449–54. doi:10.4088/JCP.v57n1002. PMID 8909330.
- 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.
- 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.
- 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. ISSN 0271-0749. PMID 7962686.
- "Remeron (Mirtazapine) Drug Information". RxList. Retrieved 28 March 2016.
- 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.
- Akagi, H.; Kumar, TM (2002). "Lesson of the week: Akathisia: Overlooked at a cost". BMJ. 324 (7352): 1506–7. doi:10.1136/bmj.324.7352.1506. PMC 1123446. PMID 12077042.
- 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.
- 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. doi:10.1080/13668250802065190. PMID 18569404.
- Bratti, I. M.; Kane, J. M.; Marder, S. R. (2007). "Chronic Restlessness with Antipsychotics". American Journal of Psychiatry. 164 (11): 1648–54. doi:10.1176/appi.ajp.2007.07071150. PMID 17974927.
- 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. doi:10.4088/JCP.v65n1118. PMID 15554771.
- Sachdev P (1995). Akathisia and Restless Legs. New York: Cambridge University Press.[page needed]