Akathisia

Etiology

The exact etiology of akathisia is unknown, but it is thought to be due to antipsychotic agents blocking dopamine type-2 receptors in the brain. [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.

Epidemiology

The incidence varies widely. 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.[5]

Pathophysiology

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. 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. However, akathisia does not generally respond to anticholinergic agents, suggesting an alternative pathophysiologic mechanism.

History and Physical

Patients 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. Additionally, patients will be objectively seen manifesting that restlessness by pacing, rocking, and shifting position. Patients with akathisia often feel distressed and uncomfortable.

To assess the severity of akathisia, health care professionals may use tools like the Barnes Akathisia Rating Scale (BARS).

Providers should be aware that 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.

Evaluation

The Barnes Akathisia Rating Scale may be used to assess patients with akathisia. However, most clinicians will rely on clinical observation. There are no relevant laboratory or radiographic tests involved in the diagnosis of akathisia. [6][7]

Treatment / Management

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. 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.[3][8][9](B2)

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.

Differential Diagnosis

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.

Prognosis

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

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.