What causes akathisia in young individuals?

From the Guidelines

Akathisia in young individuals is primarily caused by antipsychotic medications, with first-generation antipsychotics like haloperidol and second-generation medications such as risperidone, aripiprazole, and olanzapine being common culprits, as noted in a study published in Pediatrics in 2016 1. The condition is characterized by a subjective feeling of restlessness, which generally occurs within the first few days of antipsychotic medication therapy. Key factors that contribute to the development of akathisia in young people include:

• First exposure to antipsychotic medications
• Rapid dose escalation
• Possibly genetic predisposition
• Use of certain medications such as SSRIs, antiemetics, calcium channel blockers, and certain antibiotics The mechanism involves dopamine blockade in the basal ganglia, creating an imbalance between dopaminergic and cholinergic systems, as discussed in the context of antipsychotic-induced extrapyramidal syndromes 1. Management of akathisia typically involves:
• Dose reduction or medication change
• Temporary use of beta-blockers, such as propranolol 10-40mg three times daily
• Anticholinergics, such as benztropine 0.5-2mg twice daily
• Benzodiazepines Early recognition is crucial, as akathisia can be mistaken for worsening psychiatric symptoms, potentially leading to inappropriate dose increases that worsen the condition. It is essential to consider the potential risks and benefits of antipsychotic medications in young individuals, particularly the risk of QT prolongation and cardiac events, as highlighted in the study 1.

From the FDA Drug Label

Akathisia includes akathisia and restlessness. Motor restlessness (akathisia) may consist of feelings of anxiety, agitation, jitteriness, and insomnia, as well as inability to sit still, pacing, and foot tapping. The causes of akathisia in the young are not explicitly stated in the provided drug labels. However, it is mentioned that akathisia may occur in patients receiving the recommended prescribed dosage of metoclopramide or risperidone.

• Risperidone label mentions that akathisia is one of the most common adverse reactions in clinical trials, but it does not specify the causes.
• Metoclopramide label describes akathisia as motor restlessness, which may consist of feelings of anxiety, agitation, jitteriness, and insomnia, but it does not provide information on the causes in the young. 2 3

From the Research

Akathisia Causes in the Young

• Akathisia is a common and distressing adverse effect of treatment with antipsychotic (neuroleptic) drugs, characterized by subjective and objective psychomotor restlessness 4.
• The exact pathophysiology of akathisia is still unknown, but it has been attributed to an imbalance between dopaminergic and noradrenergic neurotransmission in the basal ganglia 5.
• Akathisia can be caused by various medications, including:
  • Antipsychotic drugs, such as first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) 4, 6.
  • Selective serotonin reuptake inhibitors (SSRIs) 5.
  • Serotonin norepinephrine reuptake inhibitors (SNRIs) 5.
  • Stimulants 5.
  • Mirtazapine 5.
  • Tetrabenazine 5.
• Risk factors for akathisia include:
  • Antipsychotic dose and potency 4, 7.
  • Antipsychotic polypharmacy 7.
  • Switching antipsychotic medication 7.
  • Patient characteristics, such as diagnosis and race 6.

Management of Akathisia

• The treatment of antipsychotic-induced akathisia should be personalized, with consideration of antipsychotic dose reduction, cessation of antipsychotic polypharmacy, and switching to an antipsychotic with a perceived lower liability for akathisia 7.
• Adjuvant medications, such as:
  • Beta-blockers (e.g., propranolol) 4, 7, 8, 5.
  • Anticholinergics 7, 5.
  • 5HT2A antagonists (e.g., mirtazapine) 8, 5.
  • Benzodiazepines 4, 7, 5.
  • Vitamin B6 7.
  • Gabapentinoids (e.g., gabapentin, pregabalin) 5.
• Rotation between different pharmacological management strategies may be optimal in resistant cases 5.