Is Latuda (lurasidone) indicated for bipolar disorder?

Is Latuda Indicated for Bipolar Disorder?

Yes, Latuda (lurasidone) is FDA-approved specifically for bipolar I disorder, but only for the treatment of depressive episodes (bipolar depression), not for mania. 1

FDA-Approved Indications

Lurasidone is indicated for:

• Monotherapy treatment of major depressive episodes associated with bipolar I disorder in adults and pediatric patients (10 to 17 years) 1
• Adjunctive treatment with lithium or valproate for major depressive episodes associated with bipolar I disorder in adults 1

Critical Limitation: Not Approved for Mania

The efficacy of lurasidone in the treatment of mania associated with bipolar disorder has not been established. 1 This is a crucial distinction—if your patient presents with acute mania or mixed episodes, lurasidone is not an appropriate choice. For acute mania, first-line options include lithium, valproate, or other atypical antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone). 2

Dosing and Administration

Adults with Bipolar Depression

• Starting dose: 20 mg once daily (no initial titration required) 1
• Effective dose range: 20-120 mg/day as monotherapy or adjunctive therapy 1
• Maximum dose: 120 mg/day 1
• Must be taken with food (at least 350 calories) to ensure adequate absorption—administration with food increases AUC approximately 2-fold and Cmax approximately 3-fold 1

Pediatric Patients (10-17 years) with Bipolar Depression

• Starting dose: 20 mg once daily as monotherapy 1
• Effective dose range: 20-80 mg/day 1
• Maximum dose: 80 mg/day 1
• In clinical studies, most pediatric patients (67%) received 20 mg or 40 mg once daily 1

Clinical Efficacy Evidence

Lurasidone demonstrates robust efficacy for bipolar depression:

• Number needed to treat (NNT) for response: 5 for monotherapy (both dose ranges) and 7 for adjunctive therapy 3
• NNT for remission: 6-7 across all treatment groups 3
• Treatment effect sizes: 0.51 for monotherapy, 0.34 for adjunctive therapy compared to placebo 4
• Reduced Montgomery-Åsberg Depression Rating Scale (MADRS) total scores by >50% from baseline 5

Safety and Tolerability Profile

Common Adverse Events

The most frequently occurring adverse events (incidence ≥5% and at least twice the rate for placebo) include:

• Akathisia (NNH ranging from 11-130 depending on dose and formulation) 6, 3
• Extrapyramidal symptoms 5, 6
• Somnolence 5, 6, 3
• Nausea (NNH as low as 11 for higher doses) 3

Favorable Metabolic Profile

Lurasidone has a notably favorable metabolic profile compared to other atypical antipsychotics approved for bipolar depression:

• NNH for ≥7% weight gain: 29-5550 (extremely high, indicating minimal risk) 3
• No clinically meaningful mean weight or metabolic changes compared to placebo 3, 7
• Minimal elevations in weight, glucose, and lipids even in 6-month continuation studies 7
• This represents a significant advantage over olanzapine-fluoxetine combination and quetiapine, which have single-digit NNHs for weight gain and sedation 3

Discontinuation Rates

• NNH for discontinuation due to adverse events: 642 for lower doses (20-60 mg/day), indicating excellent tolerability 3
• Dopamine-related side effects (Parkinsonism, elevated prolactin) are rare and mild 7

Clinical Context and Positioning

When to Use Lurasidone

Lurasidone is a rational first-line choice for:

• Patients with bipolar I depression who have metabolic concerns (obesity, diabetes, dyslipidemia) 3, 7
• Patients who previously responded well to lurasidone 2
• Pediatric patients (10-17 years) with bipolar I depression where metabolic safety is paramount 1
• Patients requiring adjunctive therapy to lithium or valproate for inadequate response to mood stabilizer monotherapy 1, 5

Comparison to Other Approved Bipolar Depression Treatments

Prior to lurasidone's approval, only quetiapine and olanzapine-fluoxetine combination were FDA-approved for bipolar depression. 6 Lurasidone offers comparable efficacy (all have single-digit NNTs) but substantially better tolerability, with likelihood to be helped or harmed (LHH) ratios substantially >1, compared to LHH <1 or ~1 for quetiapine and olanzapine-fluoxetine. 3

Important Clinical Caveats

Duration of Treatment

• The effectiveness of lurasidone for longer than 6 weeks has not been established in controlled studies 1
• Physicians using lurasidone for extended periods should periodically re-evaluate long-term usefulness 1
• Based on general bipolar disorder guidelines, maintenance therapy should continue for at least 12-24 months after stabilization 2

Dose Adjustments

• Renal impairment: Starting dose 20 mg/day, maximum 80 mg/day for moderate (CrCl 30-50 mL/min) or severe (CrCl <30 mL/min) renal impairment 1
• CYP450 interactions: Dose adjustment needed with moderate CYP450 inhibitors or inducers 6

Black Box Warnings

• Increased mortality in elderly patients with dementia-related psychosis (lurasidone is not approved for this indication) 1
• Suicidal thoughts and behaviors: Antidepressants, including lurasidone for bipolar depression, increase risk in pediatric and young adults—close monitoring required 1

Common Pitfalls to Avoid

• Using lurasidone for acute mania—it has no established efficacy for this indication 1
• Administering without food—this dramatically reduces absorption and efficacy 1
• Combining with antidepressant monotherapy—antidepressants should never be used alone in bipolar disorder due to risk of mood destabilization 2, 8
• Failing to monitor for akathisia, particularly in the first weeks of treatment 5, 6