Should I order Ativan (lorazepam) as needed for a patient with ESRD on HD and a history of myoclonic jerking, currently on Depakote (valproate)?

Ativan PRN is NOT Recommended for This Patient with ESRD on HD and Myoclonic Jerking

Do not order Ativan (lorazepam) PRN for this patient—instead, optimize his Depakote dosing and consider adding levetiracetam or clonazepam for breakthrough myoclonus, as benzodiazepines carry significant risks in ESRD patients including oversedation, falls, respiratory depression, and paradoxical agitation. 1

Critical Safety Concerns with Lorazepam in ESRD

Renal Impairment Considerations

• Lorazepam requires careful dose adjustment in renal impairment, and elderly or debilitated patients (which includes dialysis patients) are more susceptible to sedative effects 1
• The FDA label explicitly states that initial dosage should not exceed 2 mg in elderly or debilitated patients, and these patients should be monitored frequently with careful dose titration 1
• Lorazepam may worsen hepatic encephalopathy, which can occur in uremic patients, making it particularly problematic in ESRD 1

Fall Risk—A Major Concern

• This patient just fell out of his chair and hit his head—adding a benzodiazepine would substantially increase his fall risk 2
• The American Geriatrics Society specifically identifies elderly patients, those with renal impairment, and patients on multiple medications as high-risk populations for falls when prescribed benzodiazepines 2
• Lorazepam causes sedation, unsteadiness, dizziness, and orthostatic hypotension—all of which increase fall risk in a patient already experiencing myoclonic jerking 1

Additional Adverse Effects

• Paradoxical reactions (agitation, anxiety) are more likely in elderly patients and could worsen the clinical picture 1
• Risk of respiratory depression, oversedation, and confusion, particularly problematic in dialysis patients 1
• Drug interactions with valproate: concurrent administration increases lorazepam plasma concentrations and reduces clearance, requiring approximately 50% dose reduction 1

Appropriate Management of Myoclonus in ESRD

Optimize Current Antiepileptic Therapy

• Depakote 500 mg once daily is likely subtherapeutic for controlling myoclonus 3
• Valproate is first-line therapy for myoclonic seizures and has proven efficacy 4, 5, 6, 7
• Consider checking valproate levels and increasing the dose before adding other agents 3

Evidence-Based Alternatives for Breakthrough Myoclonus

Levetiracetam is the preferred first-line addition:

• Levetiracetam is suggested as first-line treatment for cortical myoclonus and is effective for various myoclonic syndromes 4
• It can be used as adjunctive therapy in refractory cases 3
• Levetiracetam requires renal dose adjustment in ESRD but is generally well-tolerated 3

Clonazepam as a second-line option:

• Clonazepam has antimyoclonic properties and is commonly used for myoclonus treatment 3, 4, 7
• It was effective in combination therapy for severe action myoclonus in multiple studies 7
• However, it still carries benzodiazepine-related risks (sedation, falls, respiratory depression) and should be used cautiously 3

Propofol for acute severe myoclonus:

• Propofol is effective to suppress post-anoxic myoclonus in acute settings 3
• This would require ICU-level monitoring and is not appropriate for PRN outpatient use 3

Specific Considerations for ESRD Patients

• In adults with RLS and ESRD, gabapentin is suggested over no treatment, though this is for RLS rather than myoclonus 3
• Avoid medications that accumulate in renal failure or have active metabolites that could worsen encephalopathy 1
• Phenytoin is often ineffective for myoclonus and should be avoided 3

Clinical Algorithm for This Patient

Immediate Steps:

1. Check valproate level and assess for therapeutic range
2. Increase Depakote dose if level is subtherapeutic (typical doses for myoclonus are higher than 500 mg daily) 3
3. Evaluate for metabolic triggers: electrolyte imbalances (particularly calcium, magnesium), uremia, medication toxicity 3, 8
4. Review all medications for pro-myoclonic agents (metoclopramide, certain antibiotics) 8

If Myoclonus Persists Despite Optimized Valproate:

1. Add levetiracetam with renal dose adjustment (typically start 250-500 mg after dialysis) 3, 4
2. Consider clonazepam only if levetiracetam fails, starting at very low doses (0.25-0.5 mg) given fall risk 4, 7
3. Implement fall precautions: home safety assessment, physical therapy evaluation, assistive devices 2

Monitor Closely:

• Reassess neurological status after any medication changes
• Monitor for adverse effects: sedation, confusion, worsening falls 2, 1
• Consider neurology consultation if myoclonus remains refractory to optimized therapy 3

Key Pitfalls to Avoid

• Do not use lorazepam PRN without addressing the underlying inadequate seizure control 1
• Do not ignore the drug interaction between lorazepam and valproate, which requires 50% dose reduction of lorazepam 1
• Do not prescribe benzodiazepines to patients who have just fallen without implementing comprehensive fall prevention strategies 2
• Do not use phenytoin for myoclonus—it is often ineffective 3
• Do not forget renal dose adjustments for all medications in ESRD patients 3, 1