In a 67-year-old patient found with altered mental status and rhabdomyolysis who is taking amitriptyline, baclofen, buprenorphine, Allerga, gabapentin 600 mg four times daily, hydroxyzine (Atarax) 25 mg three times daily, quetiapine (Seroquel) 25 mg daily, and venlafaxine 75 mg twice daily, which medication should be discontinued at discharge?

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Discontinue Amitriptyline, Gabapentin, Hydroxyzine (Atarax), and Quetiapine (Seroquel) at Discharge

In this 67-year-old patient with altered mental status and rhabdomyolysis, you should discontinue amitriptyline, gabapentin, hydroxyzine (Atarax), and quetiapine (Seroquel) at discharge, as these medications are the most likely contributors to both the rhabdomyolysis and altered mental status, and are classified as potentially inappropriate medications in older adults.

Primary Offenders to Discontinue

1. Gabapentin (600 mg QID = 2400 mg/day)

  • Highest priority for discontinuation given the direct causal link to rhabdomyolysis 1
  • Recent 2025 systematic review identified gabapentinoid-induced rhabdomyolysis with median CPK of 3,095 U/L, rapid onset (≤7 days in 52.9%), and renal impairment in 78.9% of cases
  • Risk dramatically amplified by polypharmacy (89.5% of cases had multiple medications) and renal dysfunction 1
  • The dose of 2400 mg/day is substantial and particularly concerning in a 67-year-old who likely has age-related decline in renal function

2. Quetiapine (Seroquel 25 mg daily)

  • Second priority for discontinuation despite low dose
  • Multiple 2025 studies confirm quetiapine-associated rhabdomyolysis can occur even at therapeutic doses 2, 3
  • Quetiapine had the highest proportion (27.75%) of rhabdomyolysis cases in FAERS database analysis, with ROR of 3.81 2
  • Rhabdomyolysis can develop from 2 days to 8 months after initiation, with no clear dose-response relationship 3
  • FDA labeling confirms risk of falls, orthostatic hypotension, and altered mental status in elderly patients 4
  • Beers Criteria 2019 explicitly recommends avoiding or tapering antipsychotics in older adults, particularly for behavioral control, with FDA black box warning for increased mortality risk 5, 6

3. Amitriptyline (Tricyclic Antidepressant)

  • Third priority for discontinuation
  • Beers Criteria 2019 classifies tricyclic antidepressants (TCAs) as potentially inappropriate medications in older adults due to strong anticholinergic properties 5
  • Causes CNS impairment, delirium, slowed comprehension, sedation, and falls 6
  • Recent 2025 case report demonstrates amitriptyline can cause profound altered mental status and cardiac conduction abnormalities in elderly patients 7
  • Contributes significantly to anticholinergic burden when combined with hydroxyzine and quetiapine

4. Hydroxyzine (Atarax 25 mg TID)

  • Fourth priority for discontinuation
  • Beers Criteria 2019 explicitly lists old antihistamines including hydroxyzine as anticholinergic medications to avoid in older adults 5, 6
  • Causes CNS impairment, delirium, sedation, impaired vision, urinary retention, and falls 6
  • At 75 mg/day total dose, this represents substantial anticholinergic burden

Medications to Continue (with caution)

Venlafaxine (75 mg BID)

  • Can continue but monitor closely
  • While SNRIs were added to Beers Criteria 2019 for patients with history of falls/fractures 5, venlafaxine is treating depression and the benefit likely outweighs risk once the more dangerous medications are removed
  • One case report showed complications with quetiapine/venlafaxine combination overdose 8, but this was in context of intentional overdose, not therapeutic dosing
  • Caveat: Do not abruptly discontinue due to risk of withdrawal syndrome

Buprenorphine

  • Continue for opioid use disorder or pain management
  • While opioids carry risks in elderly (sedation, falls, cognitive impairment per Beers Criteria 6), buprenorphine has ceiling effect for respiratory depression
  • Discontinuation would risk opioid withdrawal or inadequate pain control

Baclofen

  • Continue with dose verification
  • Muscle relaxants are on Beers Criteria caution list 6, but abrupt discontinuation of baclofen can cause severe withdrawal including seizures
  • Ensure dose is appropriate for renal function

Allegra (Fexofenadine)

  • Continue - this is a non-sedating antihistamine without significant anticholinergic properties
  • Not included in Beers Criteria concerns about old antihistamines 5

Critical Safety Considerations

Polypharmacy Syndrome: This patient exemplifies dangerous polypharmacy with multiple CNS-active drugs. The 2019 Beers Criteria specifically warns about using three or more CNS-active drugs together, which increases fall risk, cognitive impairment, and drug-drug interactions 5.

Drug-Drug Interaction Alert: The combination of gabapentin with opioids (buprenorphine) increases respiratory depression risk. The combination of multiple anticholinergics (amitriptyline + hydroxyzine + quetiapine) creates additive toxicity 5.

Rhabdomyolysis Monitoring: Even after discontinuation, monitor CPK levels, renal function, and urine myoglobin. Biochemical resolution typically occurs within 14 days 1.

Tapering vs. Abrupt Discontinuation:

  • Gabapentin: Can taper over 1 week or discontinue abruptly given acute rhabdomyolysis
  • Quetiapine: At 25 mg dose, can discontinue without taper
  • Amitriptyline: Taper over 2-4 weeks to avoid cholinergic rebound
  • Hydroxyzine: Can discontinue abruptly

Alternative Management: For the underlying conditions these medications were treating, consider non-pharmacologic interventions first (cognitive behavioral therapy for anxiety/sleep, physical therapy for pain), then safer alternatives if needed (acetaminophen for pain, short-term trazodone for sleep at lower doses) 6.

References

6
Guideline

polypharmacy management in older patients.

Mayo Clinic Proceedings, 2021

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.