Akathisia

Akathisia
Specialty	Neurology

Typical symptoms of akathisia (note that the patient is forced to eat while standing instead of sitting).

Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless (hence the word's origin in Ancient Greek: from καθίζειν - kathízein - "to sit" with a privative a as prefix expressing negation or absence; literally meaning inability to sit). It can be a side effect of medications, or it can, to a lesser extent, be caused by Parkinson's disease and related syndromes, and likely other neurological diseases. However, this may be due more to the drugs used in treatment such as sinemet (l-dopa) and less with the Parkinson's disease itself. Another major cause is withdrawal from almost any physical addiction, for example, in benzodiazepine withdrawal syndrome. It was discovered that akathisia involves increased levels of the neurotransmitter norepinephrine, which is associated with mechanisms that regulate aggression, alertness, and arousal. Though no further research has been done as of yet, it may also be involved with disrupted NMDA channels in the brain, which have both synergistic and regulatory effects on norepinephrine.

Description

Akathisia may range in intensity from a sense of disquiet or anxiety, to severe 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. The anticholinergic procyclidine reduces neuroleptic-induced akathisia to a certain degree, in addition to preventing and sometimes eliminating the muscle stiffness that can occur alongside akathisia. Some doctors report an anti-anxiety drug such as clonazepam helps to reduce the anxiety which occurs along with the akathisia.. When misdiagnosis occurs in antipsychotic neuroleptic-induced akathisia, more antipsychotic neuroleptics may be prescribed, potentially worsening the symptoms. 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. 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—unlike the related tardive dyskinesia, which can be permanent.

The presence and severity of akathisia can be measured using the Barnes Akathisia Scale.

The term was coined before the introduction of antipsychotics by the Czech neuropsychiatrist Ladislav Haskovec (1866–1944) who described the phenomenon in 1901. Reports of akathisic states can be found in the medical literature before the advent of neuroleptics. 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. Interestingly, in some people the opposite response to SSRIs occurs, in the form of emotional blunting; but sufficient clinical research has not yet been made in this area.

Jack Henry Abbot (1981), a convicted murderer and author, described the effects of akathisia produced by antipsychotic drugs when given without the necessary medication for side effects (e.g. procyclidine) as may occur in prison and even sometimes hospitals:

These drugs, in this family, do not calm or sedate the nerves. They attack. They attack 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. For hours every day this will occur. 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. The pain grinds into your fiber ... 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 in pain you cannot locate, in such wretched anxiety you are overwhelmed, because you cannot get relief even in breathing.

— 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.

Patients who suffer from neuroleptic-induced akathisia often react by refusing treatment. At the extreme end, patients who have been treated with neuroleptic antipsychotics for psychotic episodes or prochlorperazine for nausea may rarely run away from hospitals or emergency rooms due to the terror of this sensation.

Causes

Akathisia is most often seen as a side effect of antipsychotic medications, but has other causes as well:

• Antipsychotics such as haloperidol (Haldol), droperidol, pimozide, trifluoperazine, amisulpride, risperidone, aripiprazole (Abilify), ziprasidone and asenapine (Saphris). Less common in sedating antipsychotics such as zuclopenthixol (Cisordinol) or chlorpromazine where anticholinergic and antihistaminergic effects counteract akathisia to a degree.
• SSRIs, such as fluoxetine (Prozac). It has also been documented with the use of paroxetine (Paxil). Akathisia has been studied as the mechanism by which SSRI-induced suicidality occurs.
• Other antidepressants, such as venlafaxine (Effexor), the tricyclics and trazodone (Desyrel).
• Certain anti-emetic drugs, particularly the dopamine blockers, such as metoclopramide (Reglan), prochlorperazine (Compazine), and promethazine.
• Antihistamines, such as cyproheptadine or diphenhydramine.
• Opioid withdrawal.
• Barbiturates withdrawal.
• Cocaine withdrawal (Mostly in heavy and long-term users).
• Amphetamines and any stimulant (including coffee, tea, tobacco, etc.).
• Benzodiazepine, and alcohol withdrawal.
• GHB- gamma hydroxy butyric acid.
• Chondromalacia patellae, resulting in discomfort when knees are bent.
• Serotonin syndrome.

The 2006 UK study by Healy, Herxheimer, and Menkes 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. Healy, et al., further show links between antidepressant-induced akathisia and violence, including suicide, as akathisia can "exacerbate psychopathology." The study goes on to state that there is extensive clinical evidence correlating akathisia with SSRI use, showing that approximately ten times as many patients on SSRIs as those on placebos showed symptoms severe enough to drop out of a trial (5.0% compared to 0.5%).

Treatment

Akathisia can be reduced by withdrawing or decreasing the dose of the causative agent, or by administering other drugs, though the latter proves many times to be counter-productive unless the person administering and managing the drugs has an extensive knowledge of neurobiology and pharmacokinetics. The first-line treatment of akathisia is usually propranolol. Benzodiazepines such as clonazepam are also effective to a certain degree. Benztropine, procyclidine and trihexyphenidyl can also be used.

One study showed that vitamin B₆ is effective for the treatment of neuroleptic-induced akathisia.

N-acetyl cysteine also showed a positive effect on akathisia in an RCT.

See also

• Restless legs syndrome