Should a patient with stabilized mood on lithium (lithium carbonate) 450 mg at night and 300 mg in the morning, and receiving Abilify (Aripiprazole) Maintena injections, continue their current regimen with an adjustment to 960 mg Abilify Maintena every two months?

Continuation of Current Lithium and Aripiprazole Regimen with Dose Adjustment

Continue the current lithium regimen of 450 mg at night and 300 mg in the morning (750 mg total daily), and adjust Abilify Maintena to 400 mg every month rather than 960 mg every two months, as this aligns with FDA-approved dosing and evidence-based maintenance therapy for bipolar disorder. 1, 2

Critical Issue with Proposed Abilify Maintena Dosing

The proposed 960 mg dose every two months is not an FDA-approved dosing schedule for Abilify Maintena and lacks evidence-based support. 1

• Standard Abilify Maintena dosing for maintenance therapy is 400 mg intramuscularly once monthly, which provides consistent therapeutic plasma levels and superior relapse prevention compared to extended dosing intervals. 1, 3
• Extended dosing intervals (every two months) create significant fluctuations in plasma aripiprazole concentrations, potentially leading to breakthrough symptoms and increased relapse risk during the latter half of the dosing interval. 1
• The combination of aripiprazole with lithium demonstrates superior efficacy for both acute mania control and long-term maintenance compared to monotherapy, but requires consistent therapeutic levels of both agents. 1, 3

Evidence Supporting Current Lithium Dosing

The current lithium regimen of 750 mg daily (450 mg at night + 300 mg in the morning) is appropriate for maintenance therapy, targeting serum levels of 0.6-1.2 mEq/L. 1, 2

• Once-daily dosing of lithium (all 750 mg at night) would be equally effective and may improve tolerability, reducing urinary frequency and potentially enhancing compliance while maintaining equivalent antimanic efficacy. 4, 5
• Single daily dosing produces similar therapeutic outcomes to divided dosing but with 30-50% lower peak plasma concentrations using sustained-release formulations, potentially reducing adverse effects without compromising efficacy. 6, 5
• Patients receiving twice-daily lithium experienced significantly higher urinary frequency (p=0.008 at Day 21, p=0.035 at Day 42) and required higher total daily doses compared to once-daily administration. 4

Optimal Maintenance Strategy

Combination therapy with lithium plus aripiprazole should continue for at least 12-24 months after achieving mood stability, with some patients requiring indefinite treatment. 1, 7

• Withdrawal of maintenance lithium therapy dramatically increases relapse risk, especially within 6 months following discontinuation, with >90% of noncompliant adolescents relapsing versus 37.5% of compliant patients. 1, 7
• The median time to relapse after switching from combination therapy to monotherapy is approximately 3 months, highlighting the importance of maintaining both agents during the maintenance phase. 7
• Lithium possesses unique anti-suicidal properties, reducing suicide attempts 8.6-fold and completed suicides 9-fold independent of mood-stabilizing effects, making it particularly valuable for long-term maintenance. 1, 8

Required Monitoring Parameters

Lithium levels, renal function, and thyroid function must be monitored every 3-6 months during maintenance therapy. 1, 9, 2

• Draw lithium levels 8-12 hours after the previous dose (ideally 12 hours post-dose for twice-daily dosing, or 24 hours post-dose if converting to once-daily). 2, 6
• Target maintenance lithium levels of 0.6-1.2 mEq/L, though some patients respond adequately at 0.6-0.8 mEq/L. 1, 2, 6
• For Abilify Maintena, monitor BMI monthly for 3 months then quarterly, and assess blood pressure, fasting glucose, and lipids at 3 months then annually. 1

Recommended Dosing Algorithm

1. Continue lithium 750 mg daily (either as 450 mg at night + 300 mg in the morning, or consider consolidating to 750 mg once daily at bedtime using sustained-release formulation to reduce urinary frequency). 2, 4, 5

2. Administer Abilify Maintena 400 mg intramuscularly once monthly rather than 960 mg every two months, ensuring consistent therapeutic plasma levels throughout the maintenance phase. 1, 3

3. Verify lithium levels are within 0.6-1.2 mEq/L range within 2 weeks of any dosing schedule change, then every 3-6 months during stable maintenance. 1, 2

4. Monitor renal function (BUN, creatinine) and thyroid function (TSH) every 3-6 months, as lithium requires ongoing surveillance for potential nephrotoxicity and thyroid dysfunction. 1, 9

Common Pitfalls to Avoid

• Never extend Abilify Maintena dosing intervals beyond monthly administration without clear evidence of therapeutic plasma levels, as this increases breakthrough symptom risk and relapse rates. 1
• Avoid abrupt lithium discontinuation, as this precipitates rebound mania in >90% of patients; any future discontinuation must occur gradually over 2-4 weeks minimum. 1, 7
• Do not rely solely on serum lithium levels—accurate patient evaluation requires both clinical assessment and laboratory monitoring, as some patients exhibit toxicity at therapeutic levels while others respond at lower concentrations. 2, 6
• Inadequate duration of maintenance therapy leads to high relapse rates; continue combination therapy for minimum 12-24 months after stabilization, with many patients requiring lifelong treatment. 1, 7