Akathisia

Akathisia (Template:IPAc-en Template:Respell) is a movement disorder<ref name="Poyurovsky2020" /> characterized by a subjective feeling of inner restlessness accompanied by mental distress and/or an inability to sit still.<ref name="For2016">Template:Cite journal</ref><ref name="La2014">Template:Cite journal</ref> Usually, the legs are most prominently affected.<ref name="Lo2015">Template:Cite journal</ref> Those affected may fidget, rock back and forth, or pace,<ref name="Tho2015">Template:Cite journal</ref> while some may just have an uneasy feeling in their bodies.<ref name="Lo2015" /> The most severe cases may result in poor adherence to medications, exacerbation of psychiatric symptoms, and, because of this, aggression, violence, and/or suicidal thoughts.<ref name="Lo2015" /> Akathisia is also associated with threatening behaviour and physical aggression in mentally disordered patients.<ref>Template:Cite journal</ref> However, the attempts to find potential links between akathisia and emerging suicidal or homicidal behaviour were not systematic and were mostly based on a limited number of case reports and small case series.<ref name=":0">Template:Cite journal</ref> Apart from these few low-quality studies, there is another more recent and better quality study (a systematic review from 2021)<ref name=":0" /> that concludes akathisia cannot be reliably linked to the presence of suicidal behavior in patients treated with antipsychotic medication.<ref name=":0" />

Antipsychotic medication, particularly the first generation antipsychotics, are a leading cause.<ref name="La2014" /><ref name="Tho2015" /> 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.<ref name="Lo2015" /><ref>Template:Cite web</ref> It may also occur upon stopping antipsychotics.<ref name="Lo2015" /> The underlying mechanism is believed to involve dopamine.<ref name="Lo2015" /> When antidepressants are the cause, there is no agreement on the distinction between activation syndrome and akathisia.<ref name=":1">Template:Cite journal</ref> Akathisia is often included as a component of activation syndrome.<ref name=":1" /> However, the two phenomena are not the same since the former, namely antipsychotic-induced akathisia, suggests a known neuroreceptor mechanism (e.g., dopamine-receptor blockade).<ref name=":1" /> Diagnosis is based on the symptoms.<ref name="Lo2015" /> 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.<ref name="Lo2015" />

If akathisia is caused by an antipsychotic, treatment may include switching to an antipsychotic with a lower risk of the condition.<ref name=Lo2015/> The antidepressant mirtazapine, although paradoxically associated with the development of akathisia in some individuals, has demonstrated benefit,<ref name= Poyurovsky2020/> as have diphenhydramine, trazodone, benzatropine, cyproheptadine, and beta blockers, particularly propranolol.<ref name=Lo2015/><ref name=La2014/><ref>Template:Cite journal</ref>

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.<ref name= Salem2017/> It is from Greek a-, meaning "not", and Template:Lang kathízein, meaning "to sit", or in other words an "inability to sit".<ref name=Lo2015/>

Classification

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.<ref name=Lo2015/> Akathisia is generally associated with antipsychotics, but was previously described in Parkinson's disease and other neuropsychiatric disorders.<ref name= Poyurovsky2020/> It can also present with the use of non-psychiatric medications, including calcium channel blockers, antibiotics, anti-nausea and anti-vertigo drugs.<ref name= Poyurovsky2020/>

Signs and symptoms

Symptoms of akathisia are often described in vague terms, such as feeling nervous, uneasy, tense, twitchy, restless, and unable to relax.<ref name=Salem2017/> Reported symptoms also include insomnia, a sense of discomfort, motor restlessness, marked anxiety, and panic.<ref name= Healy2006/> Symptoms have also been said to resemble symptoms of neuropathic pain similar to fibromyalgia and restless legs syndrome.<ref name= CUP>Template:Cite book</ref> 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.<ref name="DSM5">Template:Cite book</ref>

When misdiagnosis occurs in antipsychotic-induced akathisia, more antipsychotics may be prescribed, potentially worsening the symptoms.<ref name=Tho2015/><ref name="szabadi">Template:Cite journal</ref> If not identified, akathisia symptoms can increase in severity and lead to suicidal thoughts, aggression and violence.<ref name=Salem2017/><ref name="Lo2015" />

Visible signs of akathisia include repetitive movements, such as crossing and uncrossing the legs and constant shifting from one foot to the other.<ref name=Salem2017/> Other noted signs include rocking back and forth, fidgeting, and pacing.<ref name=Tho2015/> 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.<ref name=Forcen2015>Template:Cite journal</ref>

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 …"<ref>Jack Henry Abbot In the Belly of the Beast (1981/1991). Vintage Books, 35–36. Quoted in Robert Whitaker, Mad in America (2002, Template:ISBN), 187.</ref>

Causes

Medication-induced

Medication related causes of akathisia

Category	Examples
Antipsychotics<ref>Template:Cite bookTemplate:Page needed</ref>	Haloperidol, amisulpride, risperidone, aripiprazole, lurasidone, ziprasidone
SSRIs<ref name="Hansen">Template:Cite journal</ref>	Fluoxetine,<ref name="Hansen" /> paroxetine,<ref name=Healy2006 /> citalopram, sertraline<ref>Template:Cite journal</ref>
Antidepressants	Venlafaxine, tricyclics, trazodone, mirtazapine,<ref>Template:Cite web</ref> and brexpiprazole
Antiemetics	Metoclopramide, prochlorperazine, droperidol
Drug withdrawal	Antipsychotic withdrawal<ref name=Lo2015/>
Serotonin syndrome<ref>Template:Cite journal</ref>	Harmful combinations of psychotropic drugs

Medication-induced akathisia is termed acute akathisia and is frequently associated with the use of antipsychotics.<ref name="DSM5"/> 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.<ref name="JM Kane2">Template:Cite journal</ref>

Akathisia involves increased levels of the neurotransmitter norepinephrine, which is associated with mechanisms that regulate aggression, alertness, and arousal.<ref>Template:Cite book</ref> It has been correlated with Parkinson's disease and related syndromes, with descriptions of akathisia predating the existence of pharmacologic agents.<ref name= Poyurovsky2020/>

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.Template:Medical citation needed<ref name=Healy2006>Template:Cite journal</ref>

Diagnosis

The presence and severity of akathisia can be measured using the Barnes Akathisia Scale,<ref name="BARS">Template:Cite journal</ref><ref>Template:Cite journal</ref> which assesses both objective and subjective criteria.<ref name="BARS" /> Precise assessment of akathisia is problematic, as there are various types making it difficult to differentiate from disorders with similar symptoms.<ref name=Poyurovsky2020/>

The primary distinguishing features of akathisia in comparison with other syndromes are primarily subjective characteristics, such as the feeling of inner restlessness and tension.<ref>Template:Cite journal</ref><ref name="racgp">Template:Cite web</ref> 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.<ref name="JM Kane">Template:Cite journal</ref>

The controversial diagnosis of "pseudoakathisia" is sometimes given.<ref name= Salem2017>Template:Cite journal</ref>

Treatment

Acute akathisia induced by medication,<ref name="DSM5"/> often antipsychotics, is treated by reducing or discontinuing the medication.<ref name=Lo2015/><ref name="Bratti">Template:Cite journal</ref> Low doses of the antidepressant mirtazapine may be of help.<ref name= Poyurovsky2020 >Template:Cite journal</ref><ref name= Perry2018>Template:Cite journal</ref> 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.<ref name="Bratti"/> Vitamin B, and iron supplementation if deficient, may be of help.<ref name=Lo2015/><ref name=La2014/> Although they are sometimes used to treat akathisia, benzodiazepines and antidepressants can actually cause akathisia.<ref name="La2014" />

Epidemiology

Approximately one out of four individuals treated with first-generation antipsychotics develop akathisia.<ref name="Poyurovsky2020" /> Prevalence rates may be lower for modern treatment as second-generation antipsychotics carry a lower risk of akathisia.<ref name="Bratti" /> In 2015, a French study found an overall prevalence rate of 18.5% in a sample of outpatients with schizophrenia.<ref>Template:Cite journal</ref>

History

The term was first used by Czech neuropsychiatrist Ladislav Haškovec, who described the phenomenon in a non-medication induced presentation in 1901.<ref>Template:Cite journal</ref><ref name= Salem2017/>

Reports of medication-induced akathisia from chlorpromazine appeared in 1954.Template:Efn Later in 1960 there were reports of akathisia in response to phenothiazines (a related drug).<ref name="Salem2017" /> Akathisia is classified as an extrapyramidal side effect along with other movement disorders that can be caused by antipsychotics.<ref name= Salem2017/>

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.<ref>*Template:Cite book</ref>

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.<ref>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</ref><ref>Mikhaila Peterson's Response to The Times Article (and subsequent articles)</ref>

See also

• Stimming