Antipsychotics and other common psychoactive medications can cause neuropsychiatric complications such as akathisia – it is an (EPS) extrapyramidal symptom characterized by an uncomfortable sensation of internal restlessness and need to move.
EPS encompass several acute/reversible (akathisia and dystonia) and chronic/irreversible (tardive dyskinesia and focal perioral tremor) side effects of psychoactive medications. They are believed to be caused by a blockade of dopamine receptors (D2) or depletion of dopamine in the basal ganglia. Older ("typical" or "first generation antipsychotics") have a higher propensity for producing EPS because of strong binding to dopamine receptors (D2). Newer ("atypical", or "second-generation antipsychotics") have a lower risk of EPS, in part due to blockage of serotonin receptors. Continued untreated akathisia is a risk factor for developing chronic akathisia.
The incidence of akathisia with strong dopamine blockers such as haloperidol is 30%, and 5% to 15% with drugs with weaker blocking. Elevated risk occurs with higher potency D2 binding, parenteral administration, and rapid dose escalation. Additional drugs known to cause akathisia include: metoclopramide, prochlorperazine, promethazine, tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin norepinephrine reuptake inhibitors.

Treatment
Identifying the causative agent and removing it is the most effective treatment strategy.
1. If the akathisia is causing severe distress to a patient, immediately try to reduce symptoms by administering diphenhydramine or benztropine.
2. Discontinue or lower the dose of the medication or medications thought to be causing the akathisia.
3. If an antipsychotic is needed, rotate to an antipsychotic with a lower risk of EPS.
- Chlorpromazine has a lower risk of EPS compared with other older antipsychotics such as haloperidol, and can be administered IM, IV, PR, or PO.
- Quetiapine has the lowest D2 receptor affinity and is often effective in the elderly at low doses due to a 40% lower drug clearance. It has been found to be the least likely to cause EPS effects of all of the widely available newer antipsychotics.
- Olanzapine has been shown to have slightly less incidence of akathisia compared to risperidone or aripiprazole.
4. If discontinuation or rotation to another antipsychotic is not possible, adjunctive medications can be added to help prevent or reduce the akathisia. This practice is largely empiric, and no treatment has been clearly shown to be superior. Limited controlled trial data support the efficacy of mirtazapine and propranolol.
- Serotonin antagonist: mirtazapine
- Nonselective beta-blocker: propranolol
- Anticholinergics: diphenhydramine, benztropine
- Benzodiazepines: lorazepam, clonazepam
- Adrenergic blocker: clonidine

See reference for more information.

Adapted from Durkin E, Probolus JA, Kayden C. Akathisia. Felton M et al. Palliative Care Network of Wisconsin. Fast facts and concepts #282. Internet. Accessed on December 28, 2019.