|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.
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