How to manage akathisia in a patient with parkinsonism who is on levodopa (L-Dopa) carbidopa, ropinirole (Dopamine agonist), and trihexyphenidyl (Anticholinergic)?

Management of Akathisia in Parkinson's Disease Patients on Levodopa-Carbidopa, Ropinirole, and Trihexyphenidyl

First, reduce or discontinue the dopamine agonist (ropinirole) as it is the most likely culprit for akathisia in this medication regimen, then add propranolol or low-dose mirtazapine for symptomatic relief while avoiding additional anticholinergics. 1

Distinguish Akathisia from Other Movement Disorders

Akathisia presents as severe restlessness with purposeless pacing or physical agitation, often accompanied by dysphoria and subjective inner tension that is temporarily relieved by movement. 2, 1 This is critically different from:

• Myoclonus: Involuntary jerking movements, not restlessness 3
• Dyskinesia: Choreic or athetoid movements without the subjective restlessness component 4
• Restless legs syndrome: Symptoms worse at rest and in evening, relieved by leg movement specifically 2
• Psychotic agitation: Lacks the motor-driven quality and physical relief from movement 2

Identify the Causative Agent

In your patient's regimen, ropinirole (dopamine agonist) is the most probable cause of akathisia, as dopamine agonists can induce akathisia even when they produce no other extrapyramidal symptoms. 1 While levodopa-carbidopa can occasionally cause akathisia, it is less common than with dopamine agonists. 5 Trihexyphenidyl (anticholinergic) is not typically associated with akathisia and should not be increased, as anticholinergics are ineffective for akathisia treatment. 2

Stepwise Management Algorithm

Step 1: Medication Adjustment (Primary Strategy)

• Reduce or discontinue ropinirole as the first intervention, as akathisia commonly resolves upon withdrawal of the causative dopaminergic agent. 5, 1
• If motor symptoms worsen after ropinirole reduction, optimize levodopa-carbidopa timing and dosing rather than increasing ropinirole back. 6, 7
• Do not increase trihexyphenidyl or add other anticholinergics (benztropine), as these are not effective for akathisia and should be avoided in elderly patients with parkinsonism. 2

Step 2: Pharmacological Symptomatic Treatment

If akathisia persists after medication adjustment, add one of the following evidence-based treatments:

• Propranolol: Most thoroughly studied agent for akathisia, typically started at low doses (10-20 mg twice daily) and titrated as needed. 2, 1
• Low-dose mirtazapine: Well-studied alternative, particularly useful if the patient has comorbid depression or insomnia. 1
• Benzodiazepines (lorazepam, oxazepam): Can provide relief but carry risks of tolerance, cognitive impairment, and paradoxical agitation in approximately 10% of elderly patients. 2, 1
• Gabapentin or pregabalin: Voltage-gated calcium channel blockers may be effective, particularly if benzodiazepines are contraindicated. 1

Step 3: Optimize Levodopa Absorption

While addressing akathisia, ensure levodopa-carbidopa efficacy is maximized:

• Take levodopa at least 30 minutes before meals to avoid protein competition for absorption. 6, 7
• Separate from iron and calcium supplements by at least 2 hours to prevent absorption interference. 6, 7
• Consider protein redistribution (low-protein breakfast/lunch, normal protein at dinner) if motor fluctuations are present. 6, 7

Critical Pitfalls to Avoid

• Do not misinterpret akathisia as worsening psychosis or anxiety and increase antipsychotic or anxiolytic medications without addressing the underlying drug-induced cause. 2
• Do not add anticholinergic agents (benztropine, additional trihexyphenidyl) as they are ineffective for akathisia and increase anticholinergic burden in elderly patients. 2
• Do not assume all movement disorders in Parkinson's patients are disease-related—maintain high suspicion for drug-induced akathisia, especially with dopamine agonists. 1
• Avoid abrupt discontinuation of all antiparkinsonian medications, as this can worsen motor function; taper ropinirole while maintaining levodopa-carbidopa. 5

Management of Resistant Cases

If akathisia persists despite the above interventions (chronic or tardive akathisia):

• Rotation between different pharmacological strategies (propranolol → mirtazapine → gabapentinoids → benzodiazepines) may be necessary, as chronic akathisia can prove resistant to single-agent therapy. 1
• Consider complete discontinuation of the dopamine agonist if not already done, as tardive akathisia may persist after withdrawal but has better chance of resolution than with continued exposure. 1
• Opioids have been reported effective in resistant cases but should be reserved for severe, refractory akathisia due to addiction potential. 1

Monitoring and Follow-up

• Reassess akathisia severity within 72 hours of medication adjustment, as resolution can occur rapidly after discontinuation of the causative agent. 5
• Monitor for worsening parkinsonian motor symptoms after ropinirole reduction and adjust levodopa-carbidopa accordingly. 8
• Evaluate for orthostatic hypotension if propranolol is initiated, particularly in elderly patients already at risk from dopaminergic medications. 2