Is lithium and lurasidone (Latuda) a suitable treatment regimen or should an alternative antipsychotic such as quetiapine (Seroquel) or olanzapine (Zyprexa) be considered?

Lithium and Lurasidone: An Evidence-Based Combination for Bipolar Disorder

The combination of lithium and lurasidone is an excellent, evidence-based treatment regimen that is specifically FDA-approved and guideline-supported for bipolar depression. 1

Why This Combination is Optimal

Lurasidone is FDA-approved specifically as adjunctive therapy with lithium (or valproate) for bipolar depression, making your current regimen directly supported by regulatory approval and clinical trial data. 1 In the pivotal adjunctive therapy trial, lurasidone 20-120 mg/day combined with lithium or valproate demonstrated statistically significant superiority over lithium/valproate alone, with a placebo-subtracted difference of -3.6 points on the MADRS scale. 1

• The Number Needed to Treat (NNT) for response with adjunctive lurasidone is 7, meaning for every 7 patients treated with this combination, one additional patient will respond compared to lithium alone. 2
• The Number Needed to Treat for remission is also 7, demonstrating consistent therapeutic benefit. 2
• Lithium provides superior long-term prophylaxis for preventing both manic and depressive episodes, making it the ideal mood stabilizer foundation. 3

Tolerability Advantages Over Alternatives

Lurasidone has a substantially more favorable metabolic and tolerability profile compared to quetiapine or olanzapine, the other antipsychotics commonly used in bipolar depression. 2, 4

Metabolic Profile Comparison:

• Lurasidone NNH for ≥7% weight gain is 42 (adjunctive therapy), compared to quetiapine's NNH of 16 and olanzapine-fluoxetine combination's NNH of 6. 2, 4
• Lurasidone causes minimal to no metabolic changes in weight, glucose, and lipids over 6-month continuation periods. 5, 6
• No significant cardiovascular or electrocardiogram abnormalities have been observed with lurasidone. 6, 7

Side Effect Profile:

• The most common adverse effects with lurasidone are nausea, akathisia, and somnolence, with NNH values ranging from 11 to 130 (higher NNH means less likely to cause harm). 2
• Quetiapine has single-digit NNH values for somnolence (NNH=3) and dry mouth (NNH=4), meaning these side effects are much more likely. 4
• The Likelihood to be Helped or Harmed (LHH) ratio is substantially more favorable (>>1) with lurasidone compared to quetiapine or olanzapine-fluoxetine combination (LHH<1 or ~1). 2, 4

Why Not Switch to Quetiapine or Olanzapine

Quetiapine and olanzapine-fluoxetine combination have comparable efficacy (NNT 4-7 for response) but significantly worse tolerability profiles. 4

• Olanzapine causes substantial weight gain with an NNH of only 6 for ≥7% weight gain, and also causes diarrhea (NNH=9). 4
• Quetiapine causes marked sedation (NNH=3) and dry mouth (NNH=4), which can significantly impair quality of life. 4
• Both alternatives carry higher metabolic risks including diabetes and dyslipidemia compared to lurasidone. 2, 7

Critical Monitoring and Administration Requirements

Lurasidone must be taken with food (at least 350 calories) to ensure maximal absorption, as food increases bioavailability significantly. 8, 6

For Lithium:

• Monitor lithium levels, renal function, thyroid function, and urinalysis every 3-6 months. 3
• Baseline assessment should include CBC, thyroid function tests, urinalysis, BUN, creatinine, and serum calcium. 3

For Lurasidone:

• Monitor BMI monthly for 3 months, then quarterly. 3
• Monitor blood pressure, fasting glucose, and lipids at 3 months, then yearly. 3
• Dose adjustment is required with moderate CYP450 inhibitors/inducers and in renal disease. 6

Maintenance Therapy Considerations

Continue this regimen for at least 12-24 months after achieving stability, as premature discontinuation leads to relapse rates exceeding 90% in noncompliant patients. 3

• Lithium withdrawal is associated with dramatically increased relapse risk within 6 months. 3
• Some patients will require lifelong treatment when benefits outweigh risks. 3

Common Pitfalls to Avoid

• Do not discontinue lurasidone prematurely if the patient is stable and tolerating the medication well, as this combination has proven efficacy. 3
• Do not add antidepressant monotherapy without maintaining the mood stabilizer, as this risks mood destabilization. 3
• Do not ignore the food requirement for lurasidone, as absorption is significantly reduced without adequate caloric intake. 8, 6
• Do not fail to monitor metabolic parameters, even though lurasidone has a favorable profile, baseline and periodic monitoring remains essential. 3

Your current regimen of lithium plus lurasidone is evidence-based, FDA-approved, and offers superior tolerability compared to alternatives—there is no compelling reason to switch unless the patient experiences inadequate response or intolerable side effects.