What are the common side effects of lithium therapy and how are they managed?

Common Side Effects of Lithium Therapy and Their Management

Lithium therapy is associated with numerous side effects affecting multiple organ systems, requiring regular monitoring of serum lithium levels, renal function, thyroid function, and calcium levels to prevent toxicity and ensure safe treatment.

Common Side Effects

Immediate/Short-term Side Effects

1. Neurological effects

   • Tremor (affects approximately 50% of patients) 1, 2
   • Management: Dose timing adjustment, maintaining lowest effective serum level, beta-blockers for persistent tremor

2. Gastrointestinal effects

   • Nausea and diarrhea (affects about 20% of patients) 1, 2
   • Management: Taking with food, divided dosing, extended-release formulations

3. Fluid/electrolyte disturbances

   • Polyuria and polydipsia (excessive thirst affects up to 67% of patients) 1, 2, 3
   • Can present as nephrogenic diabetes insipidus
   • Management: Adequate hydration, lower dosing, amiloride in severe cases

4. Weight gain

   • More common than with placebo but less than with olanzapine 4
   • Management: Dietary counseling, regular exercise, monitoring BMI

Long-term Side Effects

1. Renal effects

   • Reduced urinary concentrating ability (15% reduction on average) 4
   • Reduced glomerular filtration rate (average 6.22 mL/min reduction) 4
   • Risk of end-stage renal failure is low (0.5%) but requires monitoring 4
   • Management: Regular monitoring of renal function, maintaining lowest effective dose

2. Thyroid effects

   • Hypothyroidism (5.78 times higher risk than placebo) 4
   • Increased TSH levels (average 4.00 iU/mL increase) 4
   • Management: Regular thyroid function tests, thyroid replacement therapy when indicated

3. Parathyroid/calcium effects

   • Increased blood calcium (+0.09 mmol/L) 4
   • Increased parathyroid hormone (+7.32 pg/mL) 4
   • Management: Regular calcium monitoring, treatment of hyperparathyroidism if necessary

4. Cognitive effects

   • Memory and concentration difficulties
   • Management: Cognitive remediation, dose adjustment, consider alternative mood stabilizers if severe

Monitoring Protocol

Based on guidelines 5, the following monitoring schedule is recommended:

1. Baseline assessment before starting lithium:

   • Complete blood count
   • Thyroid function tests
   • Renal function (BUN, creatinine, GFR)
   • Urinalysis
   • Serum calcium
   • Pregnancy test in females of childbearing age

2. Regular monitoring:

   • Lithium levels: Every 3-6 months once stable
   • Renal function: Every 3-6 months
   • Thyroid function: Every 3-6 months
   • Calcium levels: Periodically due to risk of hyperparathyroidism
   • Weight and BMI: Regularly during treatment

Toxicity Management

Lithium has a narrow therapeutic window, with toxic levels close to therapeutic levels 3. Signs of toxicity include:

1. Early signs:

   • Nausea, diarrhea, blurred vision
   • Coarse tremor, muscle weakness
   • Drowsiness, slurred speech

2. Severe toxicity:

   • Confusion, seizures
   • Cardiac arrhythmias
   • Coma

3. Management of toxicity:

   • Discontinue lithium immediately
   • Supportive care
   • Correction of fluid and electrolyte imbalances
   • Hemodialysis in severe cases

Special Considerations

1. Pregnancy:

   • Potential risk for fetal harm, especially Ebstein's anomaly 3
   • Consider risks vs. benefits before withdrawing lithium during pregnancy
   • Close monitoring if continued during pregnancy

2. Elderly patients:

   • More susceptible to neurotoxicity at higher lithium doses 5
   • Lower doses typically required (150-300 mg/day)
   • Target blood levels of 0.2-0.6 mEq/L may be adequate 5

3. Drug interactions:

   • NSAIDs, ACE inhibitors, diuretics can increase lithium levels
   • Monitor lithium levels more frequently when starting or stopping these medications

Pitfalls to Avoid

1. Dehydration: Can rapidly lead to lithium toxicity; patients must maintain adequate fluid intake, especially during illness, exercise, or hot weather

2. Abrupt discontinuation: Can lead to relapse of bipolar disorder; lithium should be tapered gradually when discontinuing

3. Inadequate monitoring: Regular blood tests are essential for safe lithium use

4. Failure to recognize early toxicity signs: Patients and families should be educated about early warning signs requiring immediate medical attention

By carefully monitoring for these side effects and implementing appropriate management strategies, lithium can be used safely and effectively for long-term treatment of bipolar disorder and other mood disorders.