Akathisia

Akathisia is a movement disorder of inner restlessness and an urge to move, with observable restless behaviours such as shifting weight, pacing and crossing and uncrossing the legs. It is a common, distressing adverse effect of dopamine blocking drugs and is linked with agitation, non-adherence and suicide.

It affects about 20 to 30% of people taking antipsychotics, and rates are higher with high potency first generation drugs and aripiprazole and similar partial agonists. It also occurs with metoclopramide, prochlorperazine and antidepressants.

Types. Acute (within days to weeks of starting or increasing a drug), tardive (after months to years of exposure) and withdrawal (after dose reduction).

Causes. Antipsychotics, metoclopramide, prochlorperazine, selective serotonin reuptake inhibitors, tetrabenazine, calcium channel blockers and lithium.

Pathophysiology.

Reduced dopaminergic transmission in mesocortical and mesolimbic circuits, with altered serotonergic, noradrenergic and cholinergic input, causes inner restlessness.

The exact mechanism is not settled.

• Subjective inner restlessness and a compulsion to move, with distress and inability to sit still.
• Observed rocking from foot to foot when standing, shifting when sitting, pacing, and crossing the legs.
• Irritability, anxiety, insomnia, dysphoria and, in severe cases, aggression or suicidal thinking.
• Symptoms worse in the afternoon and evening, and with caffeine or stress.

Red flags.

• Suicidal thoughts, aggression or violent behaviour.
• Worsening psychosis or agitation mistaken for relapse and treated with more antipsychotic.
• Fever and rigidity (neuroleptic malignant syndrome).

• Clinical diagnosis from the symptom of restlessness, the movements and the link with a causative drug.
• Validated rating scale for severity at baseline and after each change.
• Exclude restless legs syndrome, anxiety, agitation from psychosis relapse, mania, stimulant use and withdrawal syndromes, thyroid disease and iron deficiency.
• Check ferritin, thyroid function, electrolytes and a drug history including caffeine, nicotine and recreational drugs.

Differential diagnosis. Psychotic agitation, anxiety disorders, mania, restless legs syndrome, tardive dyskinesia, withdrawal states, hyperthyroidism and delirium.

• Identify the cause and reduce the dose of the causative drug, slow the titration, or switch to an agent with a lower risk, with the psychiatric team.
• Propranolol: 10 mg orally twice daily, increased every 2 to 3 days to a usual 40 to 80 mg daily in 2 to 3 divided doses. Maximum 120 mg daily. Monitor heart rate and blood pressure. Avoid in asthma, bradycardia, heart block, hypotension and peripheral vascular disease; reduce dose in hepatic impairment; use caution in pregnancy.
• Mirtazapine 15 mg orally once at night. Maximum 15 mg daily for this use (antidepressant doses reach 45 mg). Review at 1 week and stop after 2 to 4 weeks if there is no benefit. Monitor sedation, weight gain, neutropenia symptoms (sore throat, fever) and suicidal thoughts. Avoid with monoamine oxidase inhibitors; halve the dose in severe hepatic and renal impairment (creatinine clearance under 40 mL/min); use caution in pregnancy.
• Clonazepam as a short bridge: 0.5 mg orally twice daily for up to 2 weeks. Maximum 2 mg daily for this use. Monitor sedation, falls and dependence. Avoid in severe respiratory disease, sleep apnoea and severe hepatic impairment; use lower doses in older adults; withdraw slowly.
• Benztropine and other anticholinergics have a weaker effect and are used if parkinsonism coexists.
• Avoid increasing the antipsychotic dose without considering akathisia as the cause.
• Reduce caffeine and correct iron deficiency.

Monitoring. Review within 1 week of any change, then at 2 to 4 weeks; reassess restlessness and mood at each visit.

Referral and escalation. Psychiatry for drug changes; urgent review for suicidal thoughts or aggression.

Special groups. Older adults: use lower doses and watch for falls and sedation. Pregnancy: choose with psychiatric and obstetric advice.