What is the recommended dose of Latuda (lurasidone) for bipolar disorder?

Latuda Dosing for Bipolar Disorder

For bipolar I depression, start Latuda (lurasidone) at 20 mg once daily taken with food (at least 350 calories), with a maximum dose of 120 mg/day as monotherapy or adjunctive to lithium or valproate. 1

Adult Dosing Algorithm

Starting Dose and Titration

• Begin at 20 mg once daily - no initial titration required 1
• The effective dose range is 20-120 mg/day for both monotherapy and adjunctive therapy 1
• In monotherapy trials, higher doses (80-120 mg/day) did not provide additional efficacy compared to lower doses (20-60 mg/day), so consider staying in the 20-60 mg range unless inadequate response 1

Critical Administration Requirement

• Must be taken with food containing at least 350 calories - this increases absorption 2-fold (AUC) and peak levels 3-fold (Cmax) 1
• Failure to take with adequate food substantially reduces drug exposure and efficacy 1

Pediatric Dosing (Ages 10-17)

• Start at 20 mg once daily as monotherapy 1
• May increase after one week based on clinical response 1
• Effective range: 20-80 mg/day (maximum 80 mg/day) 1
• Most pediatric patients (67%) in trials received 20-40 mg daily at study end 1
• Note: Lurasidone is NOT approved for mania in any age group 1

Dose Adjustments for Special Populations

Renal Impairment

• Moderate impairment (CrCl 30-50 mL/min): Start 20 mg/day, maximum 80 mg/day 1
• Severe impairment (CrCl <30 mL/min): Start 20 mg/day, maximum 80 mg/day 1

Hepatic Impairment

• Moderate (Child-Pugh 7-9): Start 20 mg/day, maximum 80 mg/day 1
• Severe (Child-Pugh 10-15): Start 20 mg/day, maximum 40 mg/day 1

Drug Interactions

• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir): CONTRAINDICATED - do not use together 1
• Moderate CYP3A4 inhibitors (diltiazem, erythromycin, fluconazole): Reduce lurasidone dose to half the original level; if starting fresh, begin at 20 mg with maximum 80 mg/day 1

Clinical Context and Evidence Quality

Efficacy Data

• Lurasidone demonstrated statistically and clinically significant reduction in depressive symptoms with NNT of 5-7 for response (≥50% MADRS reduction) 2, 3
• Treatment effects were small to medium, but consistent across monotherapy and adjunctive trials 2
• The American Academy of Child and Adolescent Psychiatry recognizes lurasidone as a rational first-line choice, particularly for patients with previous positive response 4

Safety Profile Advantages

• Minimal metabolic effects: No clinically meaningful weight gain, glucose, or lipid changes compared to placebo 5, 6, 2
• NNH for ≥7% weight gain was 29-5550 (extremely favorable) 3
• This contrasts sharply with other approved bipolar depression treatments like olanzapine-fluoxetine combination (single-digit NNH for weight gain) 3

Common Adverse Effects

• Most frequent: akathisia, extrapyramidal symptoms, somnolence, and nausea 1, 5, 2
• NNH for these effects ranged from 11 (nausea) to 130 (somnolence) 3
• Dopamine-related effects (parkinsonism, elevated prolactin) are rare and mild 6

Critical Pitfalls to Avoid

• Taking without adequate food - this is the most common error that leads to treatment failure due to inadequate absorption 1
• Premature dose escalation - lower doses (20-60 mg) are often as effective as higher doses 1
• Combining with strong CYP3A4 inhibitors - this is contraindicated and can lead to dangerous drug levels 1
• Using for acute mania - lurasidone is NOT approved or effective for manic episodes 1
• Discontinuing maintenance therapy prematurely - continue for at least 12-24 months after stabilization 4

Duration of Treatment

• Effectiveness beyond 6 weeks has not been established in controlled trials 1
• However, maintenance therapy typically continues 12-24 months minimum, with some patients requiring lifelong treatment 4
• Periodically re-evaluate long-term necessity for individual patients 1