Lithium Treatment for Bipolar Disorder
Lithium is the gold standard medication for bipolar disorder and should be considered first-line therapy for both acute mania and maintenance treatment, with a recommended therapeutic serum level of 0.6-0.8 mmol/L for most patients. 1, 2
Indications and Efficacy
- Lithium is FDA-approved for acute mania and maintenance therapy in bipolar disorder for patients aged 12 years and older 1
- Lithium demonstrates superior efficacy in preventing manic episodes and reducing suicide risk compared to other mood stabilizers 3, 2
- Lithium is more effective than aripiprazole, valproic acid, and quetiapine for improving manic symptoms 2
- For maintenance therapy, serum lithium levels between 0.6-0.8 mmol/L are recommended for most adults, with evidence showing significantly higher relapse rates (2.6 times higher) with lower serum concentrations (0.4-0.6 mmol/L) 3, 4
Dosing Recommendations
Adults:
- Initial dose: 300 mg three times daily (900 mg/day) for patients ≥30 kg 5
- Titration: Increase by 300 mg weekly based on clinical response and tolerability 5
- Target serum level: 0.6-0.8 mmol/L for maintenance therapy 3
- For acute mania, higher serum levels (0.8-1.0 mmol/L) may be more effective but come with increased side effects 4
Children and Adolescents (12-17 years):
- Initial dose: 300 mg twice daily (600 mg/day) for patients <30 kg 5
- Initial dose: 300 mg three times daily (900 mg/day) for patients ≥30 kg 5
- Titration: Increase by 300 mg weekly based on clinical response 5
- Target serum level: Same as adults (0.6-0.8 mmol/L) but may be achieved with lower doses 3
Elderly:
- Start with lower doses and target lower serum levels initially 3
- More frequent monitoring of renal function is recommended 3
Monitoring Requirements
Baseline assessments before starting lithium therapy: 1
- Complete blood count
- Thyroid function tests
- Urinalysis
- Blood urea nitrogen, creatinine, and serum calcium levels
- Pregnancy test in females of childbearing potential
Regular monitoring: 1
- Lithium serum levels: Initially weekly until stable, then every 3-6 months
- Renal function: Every 3-6 months
- Thyroid function: Every 3-6 months
- Urinalysis: Every 3-6 months
Clinical Considerations
- Phase of illness should guide treatment decisions - lithium is most robustly supported for maintenance treatment and acute mania, with more modest evidence for acute bipolar depression 3, 6
- For bipolar depression, lithium may be less effective as monotherapy, and evidence is more limited compared to its use in mania and maintenance 6
- Combination therapy may be necessary for some patients, particularly those with treatment-resistant symptoms or bipolar depression 1
- For patients with rapid cycling or mixed episodes, combination therapy with an atypical antipsychotic may be more effective 1
Common Side Effects and Management
- Common side effects include tremor, diarrhea, urinary frequency, weight gain, and metallic taste 4
- Side effects are dose-related and more common with serum levels above 0.8 mmol/L 4
- Lithium has potential cardiac effects including QT prolongation, T-wave changes, and bradycardia 1
- Long-term use requires monitoring for potential nephrotoxicity 3
Important Precautions
- Avoid unnecessary polypharmacy but recognize that combination therapy is often required 1
- Antidepressants should be used cautiously in bipolar patients as they may trigger manic episodes; always use with a mood stabilizer 1
- Lithium should be used with caution in patients with cardiac disease due to potential arrhythmogenic effects 1
- Maintenance therapy should continue for at least 12-24 months after stabilization, with many patients requiring lifelong treatment 1
- Abrupt discontinuation increases relapse risk; any attempts to discontinue should be done gradually with close monitoring 1
Treatment Duration
- After acute stabilization, maintenance therapy should continue for at least 12-24 months 1
- For patients with multiple episodes, longer-term or indefinite maintenance therapy is often indicated 1, 3
- The WHO recommends maintenance treatment with lithium for at least 2 years after the last episode of bipolar disorder 1