Initiating Lithium Therapy and Contraindications
Lithium should generally not be given to patients with significant renal or cardiovascular disease, severe debilitation, dehydration, sodium depletion, or those receiving diuretics, as the FDA states the risk of lithium toxicity is very high in such patients. 1
Absolute Contraindications
The FDA drug label establishes clear contraindications 1:
- Significant renal impairment (particularly GFR < 30 ml/min/1.73 m²) 2, 1
- Significant cardiovascular disease 1
- Severe debilitation or dehydration 1
- Sodium depletion 1
- Concurrent diuretic use 1
If the psychiatric indication is life-threatening and other measures have failed, lithium may be used with extreme caution, daily serum level monitoring, and hospitalization 1.
Mandatory Baseline Laboratory Assessment
Before initiating lithium, the following tests must be obtained 3, 2, 4:
- Complete blood count 3, 4
- Thyroid function tests (TSH, free T4) 3, 2, 4
- Renal function: blood urea nitrogen, creatinine, and GFR 3, 2, 4
- Serum electrolytes including calcium 3, 2, 4
- Urinalysis 3, 2, 4
- Pregnancy test in female adolescents 3
- Baseline ECG (to assess for QT prolongation risk) 4
Initial Dosing Strategy
Standard Adult Dosing
Start with 12-24 mmol (450-900 mg) per day depending on age and body weight 5:
- Age < 40 years: 25-35 mmol (925-1300 mg) daily maintenance 5
- Age 40-60 years: 20-25 mmol (740-925 mg) daily maintenance 5
- Age > 60 years: 15-20 mmol (550-740 mg) daily maintenance 5
Elderly Patients
Start at 150 mg per day due to increased sensitivity to lithium and reduced clearance 3, 2. Target blood levels of 0.2-0.6 mEq/L are generally adequate and usually achieved with 150-300 mg per day 3.
Patients with Renal Impairment
- GFR < 60 ml/min/1.73 m²: Use lower doses with more frequent monitoring 2
- GFR < 30 ml/min/1.73 m²: Reduce dose by 50% 2
Augmentation Therapy
When lithium is used to augment antidepressants, start with 600-900 mg/day and target lower blood levels of 0.2-0.6 mEq/L 3, 6. Some studies suggest even lower doses (300-450 mg/day) may be effective with fewer side effects 7.
Target Therapeutic Levels
Maintain serum concentrations between 0.6-0.8 mmol/L for most patients 5:
- For sustained-release preparations, keep levels at 0.8-1.0 mmol/L due to later peak concentrations 5
- For augmentation therapy, 0.2-0.6 mEq/L may be adequate 3
- Toxicity risk begins at 1.5 mEq/L and serious toxicity occurs at >2.0 mEq/L 2, 1
Monitoring Schedule
Acute Phase
Check serum lithium levels twice per week until levels and clinical condition stabilize 2. Draw levels 12 hours after the last dose for once or twice-daily dosing, or 24 hours after the last dose for once-daily administration 5.
Maintenance Phase
Once stable, monitor every 3-6 months 3, 4:
- Lithium levels 3
- Renal function tests (BUN, creatinine, urinalysis) 3, 4
- Thyroid function tests 3, 4
- Serum calcium (annually) 4
Critical Safety Considerations
Drug Interactions
Avoid concomitant NSAIDs as they increase lithium levels and toxicity risk 2. Diuretics are contraindicated due to increased toxicity risk 1.
Hydration Status
Maintaining adequate hydration is crucial, especially during intercurrent illness 2. Dehydration significantly increases toxicity risk 1.
Early Toxicity Signs
Monitor for tremor, nausea, diarrhea, and polyuria-polydipsia as early signs of toxicity 4. Neurotoxicity can manifest as peripheral neuritis, optic neuritis, anxiety, depression, and psychosis 4.
Duration of Trial
Allow 6-8 weeks at adequate doses before determining efficacy 3. For augmentation therapy, some patients respond within days, but others require 3-6 weeks 6.
Common Pitfalls to Avoid
- Do not initiate lithium without baseline laboratory assessment 3, 2, 4
- Do not use empirical dosing in elderly patients—start at 150 mg/day 3, 2
- Do not combine with diuretics or NSAIDs 2, 1
- Do not assume therapeutic failure before 6-8 weeks at adequate doses 3
- Do not rely solely on periodic monitoring—educate patients about presenting symptoms of adverse effects 3