What can cause akathisia (involuntary movement disorder) in adults, besides psychotropic medications, especially in those with a history of neurological or endocrine disorders, such as Parkinson's disease or hyperthyroidism?

Non-Psychotropic Causes of Akathisia

Akathisia can be caused by several non-psychotropic medications and medical conditions, most notably SSRIs (particularly fluoxetine), antiemetics, calcium channel blockers, and paradoxically by benzodiazepines in patients with traumatic brain injury.

Medication-Induced Akathisia (Non-Psychotropic)

Antidepressants

• SSRIs are a well-documented cause of akathisia, with fluoxetine being particularly associated with this side effect 1
• SSRI-induced akathisia carries a critical risk: it is associated with increased suicidality, requiring systematic inquiry about suicidal ideation before and after treatment initiation 1
• Clinicians must be especially alert to suicidality if SSRI treatment coincides with akathisia onset 1

Other Psychoactive Medications

• Various other psychoactive medications beyond traditional antipsychotics can cause akathisia 2
• Tricyclic antidepressants have been implicated in akathisia development 2

Non-Psychotropic Medications

• Antiemetics (particularly dopamine antagonists like metoclopramide and prochlorperazine) are common culprits 2
• Calcium channel blockers can induce akathisia 2
• Occasional other non-psychotropic agents have been reported to cause akathisia 2

Paradoxical Benzodiazepine-Induced Akathisia

• Benzodiazepines (clonazepam, clorazepate, lorazepam) can paradoxically cause akathisia in specific patient populations 3
• This atypical presentation occurs particularly in patients with traumatic brain injury and seizure disorders 3
• The mechanism differs from neuroleptic-induced akathisia and may involve serotonergic systems or the forced normalization phenomenon 3
• This represents a subtype of benzodiazepine-induced disinhibition 3

Medical Conditions Associated with Akathisia

Neurological Disorders

• Parkinson's disease can present with akathisia-like restlessness 4
• Huntington's disease may manifest with movement disorders including akathisia 4
• Traumatic brain injury increases susceptibility to medication-induced akathisia 3
• Seizure disorders appear to be a risk factor for atypical benzodiazepine-induced akathisia 3

Endocrine Disorders

• Hyperthyroidism and thyroid storm can present with restlessness mimicking akathisia 4
• Pheochromocytoma may cause similar symptoms of inner restlessness and agitation 4
• Hypopituitarism and other pituitary disorders can present with behavioral changes including restlessness 4

Metabolic Disturbances

• Hypoglycemia and hyperglycemia can cause agitation and restlessness 4
• Uremia may present with restlessness and movement abnormalities 4
• Hyperammonemia can cause behavioral changes including motor restlessness 4

Critical Diagnostic Considerations

Distinguishing Akathisia from Other Conditions

• Akathisia is characterized by subjective inner restlessness and motor restlessness, NOT constant pain 5
• If constant pain is present, consider alternative diagnoses such as musculoskeletal pain or dystonia (painful spastic muscle contractions that can coexist with akathisia as a separate extrapyramidal symptom) 5
• Akathisia is frequently misinterpreted as psychotic agitation or anxiety, leading to inappropriate medication increases 1

Iron Deficiency

• Iron status may play a pivotal role in the pathophysiology and development of acute akathisia through possible interaction with the D2 receptor 2
• While the practical clinical significance remains unclear, iron deficiency should be considered in the differential diagnosis 2

Clinical Pitfalls to Avoid

• Do not assume all restlessness in patients on antipsychotics is psychiatric worsening—systematically evaluate for akathisia using standardized scales like the Barnes Akathisia Rating Scale 5
• In patients with traumatic brain injury or seizure disorders, be aware that benzodiazepines may paradoxically worsen rather than improve restlessness 3
• When evaluating patients on SSRIs with new-onset restlessness, immediately assess for suicidal ideation given the established link between SSRI-induced akathisia and suicidality 1
• Consider medication review for all non-psychotropic agents, particularly antiemetics and calcium channel blockers, in patients presenting with unexplained restlessness 2