What causes akathisia?

From the Guidelines

Akathisia is primarily caused by antipsychotic medications, such as haloperidol, risperidone, and aripiprazole, as well as certain antidepressants like SSRIs and SNRIs, which can lead to dopamine blockade in the basal ganglia and create an imbalance between dopaminergic and cholinergic systems 1. The condition can develop within hours or days of starting a medication, increasing the dose, or occasionally when discontinuing a drug. Other potential causes include Parkinson's disease, certain antiemetics like metoclopramide, and rarely calcium channel blockers. Some key points to consider about akathisia include:

• Risk factors include higher medication doses, previous akathisia episodes, iron deficiency, and dehydration 1.
• The American Psychiatric Association recommends that patients who have akathisia associated with antipsychotic therapy be treated with options such as lowering the dosage of the antipsychotic medication, switching to another antipsychotic medication, adding a benzodiazepine medication, or adding a beta-adrenergic blocking agent 1.
• If you experience restlessness, an inability to sit still, or a compelling need to move while taking these medications, consult your healthcare provider immediately as dose adjustment, medication change, or addition of beta-blockers like propranolol or benzodiazepines may be necessary to manage symptoms 1. Some medications that can cause akathisia include:
• Antipsychotics like haloperidol, risperidone, and aripiprazole
• Antidepressants like SSRIs and SNRIs
• Antiemetics like metoclopramide
• Calcium channel blockers (rarely) It is essential to note that the treatment of akathisia should prioritize the reduction of morbidity, mortality, and improvement of quality of life, and healthcare providers should consider the latest evidence-based guidelines when managing patients with this condition 1.

From the Research

Akathisia Causes

• Akathisia is a common and distressing neuropsychiatric syndrome associated with antipsychotic medication, characterised by subjective and objective psychomotor restlessness 2.
• It is attributed to an imbalance between dopaminergic and noradrenergic neurotransmission in the basal ganglia 3.
• Akathisia can be caused by various medications, including:
  • Antipsychotic drugs, particularly first-generation antipsychotics (FGAs) and some second-generation antipsychotics (SGAs) 2, 3, 4.
  • Selective serotonin reuptake inhibitors (SSRIs) 3.
  • Serotonin norepinephrine reuptake inhibitors (SNRIs) 3.
  • Stimulants 3.
  • Mirtazapine 3.
  • Tetrabenazine 3.
• The exact pathophysiology of akathisia is still unknown, but numerous risk factors have been described, including the use of certain medications and individual patient characteristics 5.

Risk Factors

• The use of antipsychotic medications, particularly FGAs and some SGAs, is a major risk factor for akathisia 2, 3, 4.
• Other risk factors include:
  • Individual patient characteristics, such as a history of extrapyramidal symptoms or motor disabilities 3, 5.
  • The dose and duration of antipsychotic treatment 2, 5.
  • The use of multiple antipsychotic medications (polypharmacy) 2.

Newly Approved Antipsychotics

• Newly approved antipsychotics (NAPs), such as asenapine, lurasidone, iloperidone, cariprazine, and brexpiprazole, can also cause akathisia 4.
• The incidence of akathisia with NAPs varies, with iloperidone showing the most benign akathisia profile and cariprazine showing the least benign profile 4.