In a 66‑year‑old man with stage 3 chronic kidney disease who is taking pregabalin for anxiety, what alternative treatments can be used when the pregabalin dose is reduced?

Alternative Treatments When Reducing Pregabalin in Stage 3 CKD

When pregabalin is reduced in a patient with stage 3 CKD taking it for anxiety, cognitive behavioral therapy (CBT) should be the primary replacement, with SSRIs or SNRIs as pharmacological alternatives if needed, while gabapentin can serve as a bridging agent during the taper but requires similar renal dose adjustment.

Critical Context: Pregabalin Dose Adjustment in Stage 3 CKD

Before discussing alternatives, your patient's pregabalin dose likely needs adjustment rather than complete cessation, as pregabalin is eliminated 98% unchanged by the kidneys 1, 2. In stage 3 CKD (eGFR 30-59 mL/min), dose reduction of 25-50% is typically required 1.

Tapering Protocol for Pregabalin Reduction

• Reduce by 25-50 mg every 1-2 weeks over a minimum of 6-8 weeks to avoid withdrawal symptoms including seizures 3, 4
• Never abruptly discontinue pregabalin, as this can precipitate seizures even in patients without epilepsy, particularly in those with renal impairment 4
• For elderly patients with stage 3 CKD, extend the taper to 12-16 weeks minimum due to increased vulnerability 3, 5

Primary Non-Pharmacological Alternative

Cognitive Behavioral Therapy (CBT) should be initiated before or during the pregabalin taper, as it provides durable anxiety reduction without medication-related risks in CKD patients. This is the safest long-term approach for anxiety management in patients with renal impairment.

Pharmacological Alternatives for Anxiety

First-Line: SSRIs/SNRIs

Selective serotonin reuptake inhibitors (SSRIs) are the preferred pharmacological alternative for anxiety in CKD patients:

• Sertraline or citalopram are preferred as they have minimal renal clearance and no active metabolites requiring dose adjustment in stage 3 CKD
• Start at half the usual dose and titrate slowly over 4-6 weeks
• These agents do not require the same degree of renal dose adjustment as pregabalin

Bridging Option: Gabapentin

Gabapentin can serve as a temporary bridge during pregabalin taper if anxiety symptoms worsen, though it has similar renal considerations:

• In stage 3 CKD (CrCl 30-59 mL/min), start gabapentin at 100-200 mg/day with maximum 400-1400 mg/day divided twice daily 6
• Reduce total daily dose by at least 50% from standard dosing 6
• Start with 100 mg at bedtime for 3-7 days, then increase by 100-300 mg every 3-7 days as tolerated 6
• Calculate creatinine clearance using Cockcroft-Gault equation rather than relying on serum creatinine alone, especially in elderly patients 6

Critical Monitoring During Gabapentin Use

• Monitor for dose-dependent adverse effects including altered mental status, confusion, myoclonus, dizziness, and falls 6
• Common prescribing error: failing to calculate CrCl accurately in elderly patients with reduced muscle mass, leading to toxicity 6

Medications to Avoid

Do NOT use benzodiazepines as a replacement, as they:

• Increase fall risk significantly in elderly patients
• Have prolonged half-lives in renal impairment
• Carry high dependence potential
• Interact synergistically with any residual pregabalin during taper 3

Monitoring During Transition

Withdrawal Symptom Surveillance

Monitor for pregabalin withdrawal symptoms during dose reduction 3, 5:

• Headache, nausea, dizziness
• Anxiety rebound or worsening
• Insomnia
• Seizures (rare but serious) 4

Renal Function Monitoring

• Check serum creatinine and eGFR every 2-4 weeks during medication transitions 7
• If eGFR declines further during taper, slow the reduction schedule and adjust any replacement medication doses accordingly 6

Fall Risk Assessment

• Elderly patients require close monitoring for dizziness, confusion, and balance disturbances during dose changes 5
• Assess fall risk at each visit during the transition period 6

Common Pitfalls to Avoid

1. Abrupt discontinuation: This can precipitate seizures even without epilepsy history, particularly in renal impairment 4
2. Inadequate taper duration: Minimum 6-8 weeks required; rushing increases withdrawal risk 3
3. Failing to calculate CrCl: Serum creatinine alone underestimates renal impairment in elderly patients 6
4. Starting replacement therapy too late: Begin CBT or SSRI before completing pregabalin taper to prevent anxiety gap
5. Using fixed percentage reductions: This results in progressively smaller absolute reductions that may be too slow initially 3

Special Consideration: If Acute Kidney Injury Develops

If your patient develops acute kidney injury (AKI) on chronic stage 3 CKD:

• Do not abruptly stop pregabalin even with worsening renal function 4
• Reduce dose proportionally to new eGFR but maintain some dose to prevent withdrawal
• Pregabalin-induced myoclonus can occur even with therapeutic drug levels in AKI, representing a threshold phenomenon rather than pure accumulation 8