Can I start lithium 400 mg at night for bipolar affective disorder?

Starting Lithium 400mg Nocte for Bipolar Affective Disorder

Direct Recommendation

Yes, you can start lithium 400mg at night for bipolar affective disorder, but this dose is likely subtherapeutic and will require titration to achieve therapeutic serum levels of 0.8-1.2 mEq/L for acute treatment or 0.6-1.0 mEq/L for maintenance. 1, 2

Evidence-Based Rationale

Lithium is a first-line treatment for bipolar disorder with the strongest evidence base among all mood stabilizers. The American Academy of Child and Adolescent Psychiatry recommends lithium for both acute mania and maintenance therapy, with superior long-term efficacy compared to alternatives. 1 Lithium uniquely reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect independent of its mood-stabilizing properties. 1

Dosing Algorithm for Initiation

Starting Dose Considerations

• For patients weighing ≥30 kg: Begin with 300mg three times daily (900mg/day total), not 400mg once daily. 1
• For patients <30 kg: Start with 300mg twice daily (600mg/day). 1
• Single daily dosing at 400mg is acceptable but represents a conservative starting point that will require upward titration. 3 Single daily administration may reduce long-term renal damage risk and enhance compliance compared to multiple daily doses. 3

Titration Schedule

• Increase by 300mg weekly until therapeutic levels of 0.8-1.2 mEq/L are achieved for acute treatment. 1
• Check lithium level after 5 days at steady-state dosing (typically after each dose adjustment). 1
• Target maintenance levels of 0.6-1.0 mEq/L once stabilized. 1
• Some patients respond at lower concentrations, but therapeutic monitoring guides optimization. 2

Mandatory Baseline Laboratory Assessment

Before starting lithium, obtain: 1, 2

• Complete blood count
• Thyroid function tests (TSH and free T4)
• Urinalysis
• Blood urea nitrogen (BUN) and serum creatinine
• Serum calcium
• Pregnancy test in females of childbearing potential

Ongoing Monitoring Requirements

• Lithium levels: Check after 5 days at each stable dose, then every 3-6 months during maintenance. 1, 2
• Renal function (BUN, creatinine): Every 3-6 months. 1, 2
• Thyroid function (TSH): Every 3-6 months. 1, 2
• Urinalysis: Every 3-6 months. 1, 2

Critical Safety Considerations

Patient and Family Education

• Educate on early signs of lithium toxicity: Fine tremor, nausea, diarrhea. 1
• Seek immediate medical attention if: Coarse tremor, confusion, or ataxia develop. 1
• Medication storage: Secure lithium and remove access to lethal quantities, particularly in patients with suicidal ideation, as lithium overdoses can be fatal. 1
• Hydration and salt intake: Maintain adequate hydration and consistent salt intake, as dehydration and sodium depletion increase lithium toxicity risk. 1

Narrow Therapeutic Window

Lithium should only be initiated where close clinical and laboratory monitoring are available due to its narrow therapeutic index (0.5-1.2 mM serum concentration). 1, 4 The stigma around lithium often relates to adverse effects at therapeutic doses, but proper monitoring minimizes these risks. 4

Expected Timeline for Response

• Initial response: Therapeutic effects become apparent after 1-2 weeks at therapeutic levels. 1
• Full assessment: Requires 6-8 weeks at adequate doses before concluding effectiveness. 1
• Response rates: 38-62% for acute mania. 1

When to Consider Combination Therapy

If inadequate response after 6-8 weeks at therapeutic lithium levels, consider adding: 1, 5

• Atypical antipsychotic (aripiprazole, risperidone, quetiapine) for severe mania or psychotic features
• Valproate for mixed episodes, rapid cycling, or treatment-resistant cases
• Lamotrigine for predominant depressive symptoms (added after stabilization)

Combination therapy with lithium plus another mood stabilizer or atypical antipsychotic is superior to monotherapy for severe presentations and provides effective prevention of both manic and depressive episodes. 5, 6

Maintenance Therapy Duration

• Minimum duration: Continue for at least 12-24 months after mood stabilization. 1, 2
• Long-term considerations: Some patients require lifelong treatment, particularly those with multiple severe episodes or rapid cycling. 1
• Withdrawal risk: Abrupt discontinuation dramatically increases relapse risk, with >90% of noncompliant patients relapsing versus 37.5% of compliant patients. 1 If discontinuation is necessary, taper gradually over 2-4 weeks minimum. 1

Common Pitfalls to Avoid

• Starting at subtherapeutic doses without titration plan: 400mg nocte is likely insufficient; plan for dose escalation based on serum levels. 1
• Inadequate monitoring: Failure to check lithium levels and organ function regularly increases toxicity risk. 1
• Premature discontinuation: Stopping before 12-24 months leads to high relapse rates. 1
• Ignoring psychosocial interventions: Pharmacotherapy should be combined with psychoeducation and cognitive-behavioral therapy for optimal outcomes. 1