What is akathisia

Akathisia is defined as an inability to remain still. Akathisia is a subjective disorder characterized by feeling of inner restlessness and the urge to move, to be in constant motion resulting in an inability to sit still and a compulsion to move; as well as objective components (rocking while standing or sitting, lifting feet as if marching on the spot and crossing and uncrossing the legs while sitting). The individual with akathisia will generally experience an intense sensation of unease or an inner restlessness that usually involves the lower extremities ¹. This results in a compulsion to move. In most cases the movement is repetitive. The individual may cross, uncross, swing, or shift from one foot to the other. To the observer, this may appear as a persistent fidget ². Akathisia is a frequent and common side effect of treatment with antipsychotic (neuroleptic) drugs. Antipsychotic-induced akathisia can be classified according to the time of onset in the course of antipsychotic treatment (acute, tardive akathisia, withdrawal and chronic akathisia). The primary movement disorders from antipsychotic agents are akathisia, acute dystonia, pseudoparkinsonism, and tardive dyskinesia. Akathisia may also rarely occur with antidepressant agents ¹.

In recent years, akathisia has also been known to be associated with calcium channel blockers, antiemetics, antivertigo drugs, and sedatives used in anesthesia ¹. Akathisia has also been noted to occur following abuse of cocaine. Akathisia may be acute or chronic, with symptoms often lasting many months or even years.

Reported prevalence rates of akathisia vary widely between 21% to 75% ¹. Numerous risk factors for acute akathisia have been described and the exact pathophysiology of akathisia is still unknown. Since akathisia is a drug-induced adverse effect, optimal management involves its prevention rather than treatment. Akathisia may appear soon after the antipsychotic has been started or may appear when the dosage is increased. Standardized titration and the use of novel antipsychotics are successful measures of prevention. Based on the available literature, propranolol or other lipophilic beta-blockers seem to be the most consistently effective treatment for acute akathisia. There is nothing in the literature to guide a clinician when treatment with beta-blockers fails. Addition of benzodiazepines would appear to be a sensible next choice, especially if subjective distress persists. If all of these drugs are unsuccessful, amantadine or clonidine can be tried. Other agents that have been investigated include ritanserin, piracetam, valproic acid (sodium valproate) and tricyclic antidepressants. Evidence on the treatment of tardive akathisia is unsatisfactory.

Akathisia causes

The exact cause of akathisia is unknown, but it is thought to be due to antipsychotic agents blocking dopamine type-2 receptors in the brain ³. The occurrence of akathisia is higher with first-generation, or typical, antipsychotics, particularly, high-potency agents such as haloperidol than with the second-generation, or atypical, antipsychotics ⁴.

The general belief is that there is an imbalance between cholinergic/dopaminergic or serotonergic/dopaminergic systems. The organ where this imbalance occurs is most likely the shell of the nucleus accumbens ¹.

The pathophysiology of akathisia is poorly understood. Extrapyramidal side effects, particularly acute dystonia and pseudoparkinsonism, are thought to be due to an imbalance of dopamine and acetylcholine in the nigrostriatal pathway of the brain induced by antipsychotic agents blockade of dopamine type-2 receptors ¹. Dystonia and pseudoparkinsonism are often managed with concomitant anticholinergic agents such as benztropine. Akathisia is also observed with antipsychotic agents which block dopamine type-2 receptors, and this supports the notion that it is also linked to diminished dopamine transmission in the brain ¹. However, akathisia does not respond as robustly to anticholinergic agents as dystonia and pseudoparkinsonism suggesting an alternative pathophysiologic mechanism ¹.

Akathisia symptoms

Patient’s presenting with akathisia typically have recently started an antipsychotic agent, or their dose has been increased. Akathisia usually develops within the first 2 weeks of antipsychotic therapy. There are subjective and objective components to akathisia. Patients will typically describe a feeling of restlessness with a desire to move. In most cases the movement is repetitive. Additionally, patients will be objectively seen manifesting that restlessness by pacing, rocking, and shifting position. Patients with akathisia often feel distressed and uncomfortable. The inner restlessness often causes extreme anxiety and dysphoria in the individual. In chronic cases, akathisia has also been associated with a high risk of self-harm or suicidal behavior; therefore, the clinician should obtain a history of depression, anxiety, and suicidal ideations.

Akathisia complications

Akathisia can be disabling and leads to disability if not recognized.

Many people with the condition develop severe anxiety and dysphoria. Reports even exist of suicidal ideations in these patients.

Akathisia diagnosis

Once the diagnosis of akathisia is made, the patient should be referred to a neurologist and a psychiatrist. Making decisions on the medications can be tricky since most patients rely on antipsychotics for their mental health condition.

To assess the severity of akathisia, health care professionals may use tools like the Barnes Akathisia Rating Scale (BARS). However, most clinicians will rely on clinical observation. There are no relevant laboratory or radiographic tests involved in the diagnosis of akathisia ⁵.

Akathisia is often underdiagnosed because its symptoms often mimic or overlap other psychiatric disorders like psychosis, mania, attention deficit hyperactivity disorder (ADHD), or agitated depression. Thus, it is important to obtain a complete medical history and rule out other psychiatric disorders.

Akathisia treatment

Antipsychotic-induced akathisia may be managed by reducing the dose of the offending agent or switching to an alternative antipsychotic agent. Beta-blockers such as propranolol and benzodiazepines have historically been used for the treatment of akathisia although the amount of high-quality data supporting their use is limited ¹. Anticholinergic agents such as benztropine may be utilized if concomitant pseudoparkinsonism is present. Mirtazapine may also be utilized for the management of akathisia. Low-dose mirtazapine has been found to be as effective as beta-blockers and may be considered first-line therapy. However, one should use caution with this agent, because there are reports that high doses of mirtazapine may worsen akathisia ⁶.

When using beta-blockers, clinicians should be aware of the risk of bradycardia and hypotension.

Many other agents, including vitamin B6, have been used to treat akathisia, but there are no randomized controlled trials to determine their efficacy.

Akathisia prognosis

Akathisia prognosis is good if the condition is recognized and the drug causing it is discontinued. If the condition is left untreated, it has a high morbidity and can even lead to suicidal ideations.

1. Patel J, Galdikas FJ, Marwaha R. Akathisia. [Updated 2018 Nov 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519543[↩][↩][↩][↩][↩][↩][↩][↩][↩]
2. Dallocchio C, Matinella A, Arbasino C, Arno’ N, Glorioso M, Sciarretta M, Braga M, Tinazzi M. Movement disorders in emergency settings: a prospective study. Neurol. Sci. 2019 Jan;40(1):133-138.[↩]
3. Hirjak D, Kubera KM, Bienentreu S, Thomann PA, Wolf RC. [Antipsychotic-induced motor symptoms in schizophrenic psychoses-Part 1 : Dystonia, akathisia und parkinsonism]. Nervenarzt. 2019 Jan;90(1):1-11[↩]
4. Inada T. [Drug-Induced Akathisia]. Brain Nerve. 2017 Dec;69(12):1417-1424.[↩]
5. Balint B, Killaspy H, Marston L, Barnes T, Latorre A, Joyce E, Clarke CS, De Micco R, Edwards MJ, Erro R, Foltynie T, Hunter RM, Nolan F, Schrag A, Freemantle N, Foreshaw Y, Green N, Bhatia KP, Martino D. Development and clinimetric assessment of a nurse-administered screening tool for movement disorders in psychosis. BJPsych Open. 2018 Sep;4(5):404-410[↩]
6. Poyurovsky M, Weizman A. Very Low-Dose Mirtazapine (7.5 mg) in Treatment of Acute Antipsychotic-Associated Akathisia. J Clin Psychopharmacol. 2018 Dec;38(6):609-611.[↩]