Can a patient with impaired renal function (kidney disease) experience withdrawal symptoms when stopping or reducing lithium treatment?

Lithium Withdrawal Symptoms in Patients with Impaired Renal Function

Yes, patients can experience withdrawal symptoms when stopping lithium, but the primary concern in patients with kidney disease is not withdrawal—it is the risk of continued renal deterioration versus psychiatric relapse, requiring careful risk-benefit analysis before any discontinuation decision.

Understanding Lithium and Kidney Disease

Lithium causes progressive renal impairment in a substantial proportion of patients, with chronic kidney disease (CKD) developing at an incidence of 0.012 cases per exposed patient-year 1. The duration of lithium therapy is the most important risk factor for both polyuria and chronic kidney disease 2. In patients treated with lithium for over 15 years, approximately 34.4% develop eGFR <60 mL/min/1.73 m² (CKD stage 3), compared to only 13.1% in controls 3.

Critical Decision Point: When to Stop Lithium

KDIGO guidelines recommend considering dose reduction or discontinuation of lithium in patients with eGFR <15 mL/min/1.73 m² when there are uremic symptoms, uncontrolled hyperkalemia despite medical treatment, or symptomatic hypotension 4. However, this decision must weigh psychiatric stability against renal risk.

Key Factors Determining Renal Outcomes After Lithium Discontinuation:

• Patients with relatively preserved renal function (eGFR >30-45 mL/min/1.73 m²) show either no progression or improvement after lithium discontinuation 2
• Patients with more advanced renal damage (eGFR <30 mL/min/1.73 m²) frequently show continued deterioration even after lithium is stopped 2
• The average decline in eGFR is 1.8 mL/min/year in patients who develop CKD stage 3 1

Monitoring Requirements During Lithium Therapy

KDIGO guidelines mandate that all patients taking lithium should have their GFR, electrolytes, and drug levels regularly monitored 4. If eGFR falls rapidly or drops below 60 mL/min/1.73 m², consultation with a nephrologist is recommended 2.

Acute Illness Management: Temporary Discontinuation

KDIGO recommends temporary discontinuation of lithium in patients with GFR <60 mL/min/1.73 m² (CKD stages G3a-G5) who have serious intercurrent illness that increases the risk of acute kidney injury 4. This includes situations with:

• Volume depletion or dehydration
• Concurrent use of NSAIDs, ACE inhibitors, or ARBs
• Serious infections or febrile illness
• Procedures requiring contrast agents

Withdrawal Symptoms: What to Expect

While the provided guidelines do not specifically detail lithium withdrawal symptoms, general medical knowledge indicates that abrupt lithium discontinuation can precipitate:

• Psychiatric relapse (most significant concern—bipolar disorder recurrence)
• Rebound mood instability
• Potential for manic or depressive episodes

The risk of psychiatric relapse must be weighed against continued renal deterioration when making discontinuation decisions 2.

Practical Management Algorithm

For patients with eGFR 30-60 mL/min/1.73 m²:

• Continue lithium with close monitoring (every 3-6 months)
• Optimize lithium levels to lower therapeutic range
• Address modifiable risk factors (hypertension, diabetes, nephrotoxic drugs)
• Ensure adequate hydration 5

For patients with eGFR 15-30 mL/min/1.73 m²:

• Consult nephrology immediately 2
• Consider dose reduction rather than complete discontinuation
• Evaluate for uremic symptoms, hyperkalemia, and hypotension 4
• Prepare psychiatric transition plan if discontinuation necessary

For patients with eGFR <15 mL/min/1.73 m²:

• Strongly consider discontinuation, especially if uremic symptoms, uncontrolled hyperkalemia, or symptomatic hypotension are present 4
• Coordinate with psychiatry for alternative mood stabilizer
• Recognize that renal function may continue to decline even after stopping 2

Critical Pitfalls to Avoid

• Do not abruptly stop lithium without psychiatric consultation and transition plan—the risk of severe psychiatric relapse may outweigh renal concerns in stable patients 2
• Do not assume stopping lithium will reverse advanced CKD—patients with eGFR <30 mL/min/1.73 m² often show continued deterioration despite discontinuation 2
• Do not forget that lithium toxicity risk increases dramatically with dehydration—patients with polyuria are at particular risk and require extra caution during physical illness 5
• Do not continue lithium during acute illness without temporary discontinuation—serious intercurrent illness in patients with eGFR <60 mL/min/1.73 m² requires stopping lithium to prevent acute kidney injury 4