Starting Dose for Lithium in Adult Bipolar Disorder
For an adult patient with bipolar disorder and normal renal function, initiate lithium carbonate at 900 mg daily (divided into 2-3 doses), targeting a serum level of 0.8-1.2 mEq/L for acute mania treatment, with dose adjustments based on serum levels drawn 12 hours post-dose after 5-7 days. 1, 2
Evidence-Based Dosing Algorithm
Initial Dosing by Age
- Adults <40 years: Start with 900-1300 mg daily (25-35 mmol), typically 300 mg three times daily 2
- Adults 40-60 years: Start with 740-925 mg daily (20-25 mmol) 2
- Adults >60 years: Start with 550-740 mg daily (15-20 mmol) due to age-related decline in renal clearance 2
Target Serum Levels by Clinical Phase
- Acute mania: 0.8-1.2 mEq/L, with individual patients potentially responding at lower concentrations 1, 3
- Maintenance therapy: 0.6-0.8 mEq/L (or 0.8-1.0 mEq/L for standard dosing to minimize relapse risk) 4, 5
- Elderly patients or augmentation: 0.2-0.6 mEq/L may be adequate with 150-300 mg daily 6
Dosing Schedule Considerations
Once-daily evening dosing is equally effective as divided dosing and may improve compliance while potentially reducing long-term renal toxicity. 7, 2
- Standard-release formulations reach peak plasma concentration at 1-2 hours 2
- Sustained-release formulations peak at 4-5 hours and reduce peak concentrations by 30-50% 2
- For sustained-release preparations, target the upper therapeutic range (0.8-1.0 mEq/L) rather than 0.6-0.8 mEq/L 2
Monitoring Protocol
Baseline Assessment (Before First Dose)
- Complete blood count, thyroid function tests (TSH, free T4), urinalysis, BUN, creatinine, serum calcium, and pregnancy test in females 1, 6
- Baseline ECG if cardiac risk factors present 1
Therapeutic Drug Monitoring
- First level: Draw 12 hours post-dose after 5-7 days at steady state 1, 2
- Ongoing monitoring: Lithium levels, renal function (creatinine), and thyroid function every 3-6 months 1, 6, 4
- For once-daily dosing, the 24-hour trough serves as the control value 2
Dose-Response Relationship
Higher serum levels (0.8-1.0 mEq/L) are significantly more effective than lower levels (0.4-0.6 mEq/L) for preventing relapse, with a 2.6-fold higher relapse risk at lower concentrations. 5
- Response rates for acute mania: 38-62% at therapeutic levels 1
- Relapse rate with standard range (0.8-1.0 mEq/L): 13% 5
- Relapse rate with low range (0.4-0.6 mEq/L): 38% 5
Critical Safety Considerations
Narrow Therapeutic Index
- Lithium has an elimination half-life of 18-36 hours, requiring 5-7 days to reach steady state 2
- Brain lithium concentrations are approximately 50% of serum levels, occasionally reaching 75-80% 2
- Lithium clearance decreases with aging, necessitating lower doses in elderly patients 2
Patient Education on Toxicity Signs
- Early toxicity: Fine tremor, nausea, diarrhea, urinary frequency 1, 5
- Severe toxicity: Coarse tremor, confusion, ataxia—requires immediate medical attention 1
- Secure medication storage is essential, particularly in suicidal patients, as lithium overdoses can be lethal 1
Common Pitfalls to Avoid
- Underdosing: Starting with doses that achieve only 0.4-0.6 mEq/L increases relapse risk 2.6-fold compared to 0.8-1.0 mEq/L 5
- Inadequate trial duration: Lithium requires 6-8 weeks at therapeutic levels before concluding ineffectiveness 1
- Abrupt discontinuation: Taper over 2-4 weeks minimum, as >90% of patients who stop abruptly experience relapse 1
- Ignoring drug interactions: NSAIDs, ACE inhibitors, and thiazide diuretics increase lithium levels and toxicity risk 8
- Delayed monitoring: Failure to check levels after 5-7 days risks both toxicity and subtherapeutic dosing 2
Special Populations
Pregnancy
- Lithium clearance increases 30-50% during the last trimester due to increased glomerular filtration rate, requiring dose adjustments 2
- Lithium passes freely into breast milk 2