A Clinical Approach to Akathisia

Background

When patients suddenly become restless and cannot sit or remain still, especially in general medical settings, anxiety is often the main differential diagnosis on every doctor’s mind. However, one should always consider the possibility of the very subjective distressing condition called ’akathisia’ .

Aim

The aim of this article is to discuss a clinical approach to the management of akathisia, based on the presentation of a patient admitted to a general medicine ward.

Basics

Akathisia , a subjective and highly distressing feeling of restlessness, has been found to be caused by a wide range of medications used in general medical settings, such as azithromycin, antiemetics, and antipsychotics. Despite its high incidence and association with increased suicidal thoughts, it often goes unnoticed. This work highlights the need for its early recognition, provides diagnostic guidance and an approach to its management.

Akathisia is a ’subjective sensation of motor restlessness manifested by a pressing need to be in constant movement’ .

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), describes acute drug-induced akathisia as:

Subjective complaints of restlessness, often accompanied by observed excessive movements (e.g., restless leg movements, rocking from foot to foot, pacing, inability to sit or stand still), developing within a few hours. weeks after starting or increasing the dose of a medication (such as a neuroleptic) or after reducing the dose of a medication used to treat extrapyramidal symptoms .

Patients with akathisia often describe feeling very tense and uncomfortable, and unable to sit still. Swaying, pacing, weight shifting while standing, and inability to remain seated are frequently observed clinically.

The need for all clinicians to be competent to rapidly identify and manage akathisia cannot be overemphasized. As highlighted in Table 1, this is particularly important because akathisia can be caused by medications from several categories, including antiemetics (e.g., metoclopramide), antidepressants (e.g., selective serotonin receptor inhibitors such as paroxetine), reserpine, alpha methyldopa, buspirone, diltiazem, cinnarizine and antipsychotics (including those in the second generation class).

Recently, akathisia caused by azithromycin (a commonly used antibiotic) and pregabalin (commonly used for peripheral neuropathy and postherpetic neuralgia) was reported. It is worth emphasizing that akathisia is a very distressing condition that is known to increase the risk of impulsive behavior and suicidal ideation.

Although there is no clear data on the prevalence of akathisia in general medical settings, a recent large study among a community sample of patients with schizophrenia taking various psychotropic medications found a prevalence of around 15% to 35%. Unfortunately, akathisia often goes unnoticed. This is due, in part, to the lack of well-defined criteria for its diagnosis, as well as many other mimetic conditions such as agitation and anxiety related to mood or psychotic disorders, restless legs syndrome, substance-related conditions (eg, withdrawal states) and movement disorders.

Through this document, we aim to raise awareness of akathisia, which is often not considered by doctors when patients become ’anxious’ or ’agitated’ . We discuss its clinical management based on the presentation of a patient admitted to the medical ward to illustrate the need for urgent recognition and treatment.

Case

Ms D, aged 27, was admitted to a medical ward with a history of persistent abdominal pain, nausea and vomiting for approximately three months. Her past medical history was significant for type 1 diabetes mellitus (with several complications including retinopathy, neuropathy, and gastroparesis). She also had high blood pressure and end-stage renal failure. Prior to admission, she was taking citalopram 20 mg daily for depression (this was stopped earlier during this admission due to gastrointestinal issues). Mrs. D’s other usual medications included insulin, zopiclone, furosemide, ondansetron, amitriptyline, amlodipine, prochlorperazine, domperidone, rabeprazole, scopolamine, erythropoietin, and pregabalin.

Given the greater difficulty in controlling nausea, despite making medication adjustments, he was started on regular oral haloperidol 1 mg every four hours, in addition to an order of oral or intramuscular haloperidol 1 mg every eight hours. An urgent psychiatric consultation was requested five days after starting haloperidol because he was ’...showing a lot of anxiety and suicidal ideation...’.

When seen by the psychiatric team, Ms. D indicated that she felt restless and could not help moving her legs. She reported that her symptoms were "miserable" and "very distressing . " She had no history of similar symptoms and she denied alcohol or other substance use. Objectively, she appeared restless and had obvious motor restlessness in her extremities when she was sitting and lying down. Mrs. D could not sit still in one place without moving. She did not have tremors or other parkinsonian signs. She confirmed that she had a low mood and reported thoughts of suicide in the context of the uncontrollable restlessness she was experiencing. The physicians determined that Ms. D had acute akathisia due to her clinical characteristics (subjective report and objective findings) and the fact that she had recently started haloperidol. Her haloperidol was tapered over three days, and doctors simultaneously converted her lorazepam to a regular dose of longer-acting clonazepam. She was provided with continuous and daily monitoring in the medical ward. By the third day, there was no observable restlessness and she reported that she was ’back to myself’ .

Discussion

Akathisia is a ’subjective sensation of motor restlessness manifested by a pressing need to be in constant movement’. Making a diagnosis of akathisia is often challenging due to the lack of specific, well-defined criteria. Furthermore, as described in this article, akathisia may not be a single ’clear’ entity , and patients with akathisia often present in different ways. Therefore, clinicians should seriously consider akathisia and review the patient’s medications whenever anxiety or agitation arises as a possible side effect.

The criteria for drug-induced akathisia initially proposed by Sachdev for research purposes are highly applicable in the clinical setting. These include the essential criterion of taking a suspected medication, in addition to subjective reporting and objective findings. Subjectively, there could be one or more of the following:

• Sensation of restlessness or inner tension or discomfort, with special reference to the lower limbs.
   
• An urgent need to constantly move the legs and sometimes other parts of the body (e.g. arms, trunk).
   
• Difficulty or inability to maintain a posture for several minutes.

A key point worth emphasizing is that clinicians should observe patients in at least two positions , preferably sitting and standing in one place. Objectively, Sachdev suggests that features highly suggestive of akathisia include one or more of the following:

While sitting :

- Semi-intentional or purposeless movements in the leg, foot, hand, arm and/or trunk.

- Tendency to repeatedly change body position in the chair and inability to remain seated for several minutes, with a tendency to get up and walk or pace.

While standing in one place :

- Semi-intentional or purposeless movements in the leg, foot, hand, arm and/or trunk.

- A tendency to shift weight from one foot to the other or walk in the same place.

- Inability to stand in a place with a tendency to walk or move.

The clinical application of these criteria will help distinguish akathisia from other conditions such as anxiety, restless legs syndrome, agitation due to other causes, and states of drug withdrawal or intoxication. It is important to clarify that although the above symptoms and signs are practically bilateral , their severity may be asymmetric and none of them are pathognomonic, although rocking from one foot to the other while standing is considered (in the context of taking a suspicious medication) as very characteristic.

Although its exact pathophysiology remains unclear, akathisia is currently attributed to a reduction in dopaminergic activity in the mesocortical pathway that projects from the ventral tegmental area to the limbic system and prefrontal cortex. This results in the suppression of the usual inhibitory effects on motor function , leading to unwanted involuntary movements. This view is supported by animal studies. However, an indirect mechanism has also been postulated ; That is, an increase in serotonin and norepinephrine may contribute to akathisia by indirectly reducing dopaminergic activity in the ventral tegmental area.

As a first step in the pharmacological management of akathisia, it is recommended to reduce the dose of the offending medication. Switching to an alternative agent should also be considered. Among adjuvant medications, evidence favors propranolol (40–80 mg po twice daily) and low-dose mirtazapine (15 mg po daily), with mianserin (15 mg po daily) and cyproheptadine (8–16 mg daily) alternatives based on less evidence.

Benzodiazepines (eg, clonazepam 0.5–1 mg po twice daily) can be used alone or in combination with propranolol . Anticholinergic medications (eg, benztropine, 2 mg po twice daily) are often helpful when other extrapyramidal features are present. Other options include clonidine (0.2 to 0.8 mg/day), amantadine (100 mg PO three times daily), and diphenhydramine (50 mg PO daily). 20–24

Considering the incidence of akathisia, its association with several commonly used medications, its severely distressing nature, and the associated increased risk of impulsive behavior and suicidal ideation, it is very important that clinicians recognize it and offer appropriate treatment to patients with readiness.

In addition to obtaining written informed consent from the patient directly, the authors sought and obtained approval (Ethics Reference Number: HS20267 (H2016:410)) from the Health Research Ethics Board of the University of Manitoba, Canada.