What is the maximum recommended daily dose of lithium extended‑release (Lithium XR)?

Maximum Recommended Daily Dose of Lithium Extended-Release

The maximum recommended daily dose of lithium extended-release is 1800 mg per day (equivalent to approximately 48.6 mmol of lithium), though most patients achieve therapeutic serum concentrations at lower doses of 900-1500 mg daily. 1

Standard Dosing Guidelines

Acute Treatment Phase

• For acute mania, target serum lithium levels of 0.8-1.2 mEq/L are typically required, which usually necessitates total daily doses of 900-1800 mg depending on age, renal function, and individual pharmacokinetics 2, 1
• The initial recommended dose is typically 450-900 mg per day (12-24 mmol), depending on age and body weight 1

Maintenance Therapy Dosing by Age

The usual maintenance daily doses vary significantly by age due to declining renal clearance 1:

• Patients <40 years: 925-1300 mg daily (25-35 mmol)
• Patients 40-60 years: 740-925 mg daily (20-25 mmol)
• Patients >60 years: 550-740 mg daily (15-20 mmol)

Between ages 40-95 years, the total daily dose required to achieve a given serum concentration decreases threefold (e.g., 500 mg vs. 1500 mg to achieve 1.0 mmol/L), with this trend continuing into the ninth and tenth decades of life 3

Extended-Release Formulation Considerations

Pharmacokinetic Differences

• Extended-release formulations reach peak plasma concentrations at 4-5 hours (versus 1-2 hours for immediate-release), resulting in 30-50% reductions in peak plasma concentrations without major changes in total drug exposure 1
• With sustained-release preparations, serum concentrations should be maintained in the upper therapeutic range (0.8-1.0 mmol/L) rather than 0.6-0.8 mmol/L recommended for standard formulations 1

Dosing Frequency

• Once-daily dosing with extended-release formulations is well-established and recommended by expert panels, typically administered as a single evening dose 1, 4, 5
• Once-daily dosing produces similar efficacy to divided doses but may reduce renal adverse effects (particularly urinary frequency) and improve compliance 4, 5

Critical Dose Adjustments

Renal Impairment

• For patients with eGFR <60 mL/min/1.73 m², consider lower doses and more frequent monitoring 6
• Reduce dose by 50% in patients with eGFR <30 mL/min/1.73 m² 6
• Renal insufficiency is considered a relative contraindication to lithium use, especially if sodium restriction is required 1

Elderly Patients

• For elderly patients, start with very low doses of 150-300 mg daily due to increased sensitivity and reduced clearance 2, 6
• Greater age is independently associated with lower lithium dose requirements to achieve target serum concentrations 3

Therapeutic Monitoring Requirements

Target Serum Concentrations

• Maintenance therapy: 0.6-1.0 mEq/L (some sources recommend 0.8-1.2 mEq/L) 1, 7
• Acute mania: 0.8-1.2 mEq/L 2
• Augmentation strategies or elderly patients: 0.2-0.6 mEq/L may be adequate 2, 6

Serum lithium levels of 0.8-1.0 mmol/L are significantly more effective than 0.4-0.6 mmol/L for preventing relapse (relapse rate 13% vs. 38%), though higher levels are associated with increased side effects 7

Monitoring Schedule

• During acute treatment, check serum lithium twice weekly until levels and clinical condition stabilize 2, 6
• During maintenance, monitor lithium levels every 3-6 months, along with renal function (BUN, creatinine), thyroid function (TSH), and urinalysis 2, 6
• Draw serum concentrations 12 hours after the last dose for twice-daily regimens, or 24 hours after dose for once-daily administration 1

Common Pitfalls to Avoid

• Never exceed 1800 mg daily without compelling clinical justification and intensive monitoring, as toxicity risk increases substantially above this threshold 1
• Avoid concomitant NSAIDs, as they can increase lithium levels and toxicity risk 2, 6
• Never load lithium rapidly or increase doses more frequently than every 5-7 days, as steady-state requires 7-8 days to achieve 2
• Do not assume elderly patients require the same doses as younger adults—threefold dose reductions may be necessary 3
• Maintain adequate hydration (2.5-3 L daily, plus 0.5-1 L extra during heat exposure) to prevent toxicity 6

Safety Considerations

Lithium toxicity is closely related to serum concentrations and can occur at doses close to therapeutic levels, with toxicity risk beginning at 1.5 mEq/L and serious toxicity at >2.0 mEq/L 6

For patients with suicidal ideation, prescribe limited quantities (7-14 day supplies) with third-party supervision, as lithium overdoses can be lethal 8