Should I increase lurasidone (Lurasidone) dose in a patient with bipolar disorder treated with lithium and 20mg of lurasidone (Lurasidone) who has unremitting anxiety?

Should You Increase Lurasidone in This Patient?

No, do not increase lurasidone for unremitting anxiety in this bipolar patient—anxiety in bipolar disorder requires addressing the underlying mood instability first, and lurasidone is not indicated for anxiety treatment. 1, 2

Why Increasing Lurasidone is Not the Right Approach

Lurasidone's Approved Indications

• Lurasidone is FDA-approved specifically for bipolar I depression as monotherapy or adjunctive therapy with lithium or valproate, with an effective dose range of 20-120 mg/day 2
• The FDA label explicitly states that lurasidone's efficacy in treating mania associated with bipolar disorder has not been established 2
• There is no evidence or FDA approval for lurasidone in treating anxiety symptoms in bipolar disorder 2, 3

The Dose-Response Evidence

• In the pivotal monotherapy trial for bipolar depression, the higher dose range (80-120 mg/day) did not provide additional efficacy compared to the lower dose range (20-60 mg/day) 2
• This means that simply increasing the dose is unlikely to address symptoms that lurasidone doesn't target in the first place 2

What You Should Do Instead

Step 1: Optimize Mood Stabilization First

• The American Academy of Child and Adolescent Psychiatry recommends prioritizing mood stabilization before addressing comorbid anxiety, as treating depressive symptoms often improves anxiety symptoms concurrently 1
• Verify that lithium levels are therapeutic (0.8-1.2 mEq/L for acute treatment) with monitoring every 3-6 months including thyroid and renal function 1
• Ensure the patient has had an adequate trial duration—at least 6-8 weeks at therapeutic doses before concluding a medication is ineffective 1

Step 2: Address Anxiety Through Appropriate Interventions

• Cognitive-behavioral therapy should be considered as the primary non-pharmacological intervention for comorbid anxiety symptoms in bipolar disorder 1, 4
• If pharmacological intervention is necessary for anxiety, consider low-dose PRN benzodiazepines (lorazepam 0.25-0.5mg) with clear instructions regarding maximum daily dosage (not exceeding 2mg) and frequency limitations (not more than 2-3 times weekly) 1
• Buspirone 5mg twice daily (maximum 20mg three times daily) may be useful for mild to moderate anxiety, though it takes 2-4 weeks to become effective 4

Step 3: Consider Alternative Mood Stabilizer Augmentation

• If mood symptoms remain inadequately controlled after optimizing lithium, consider adding or switching to valproate, which showed higher response rates (53%) compared to lithium (38%) in some studies of bipolar patients 1
• Combination therapy with lithium plus an atypical antipsychotic is recommended for severe presentations, though lurasidone specifically has not demonstrated efficacy in relapse prevention when added to mood stabilizers 1, 5

Critical Pitfalls to Avoid

Do Not Use Antidepressants for Anxiety

• Antidepressant monotherapy or inappropriate combination in bipolar disorder carries significant risk of mood destabilization, mania induction, and rapid cycling 1
• SSRIs cause dose-related behavioral activation and can induce mania or hypomania in bipolar patients, with effects appearing later in treatment 1
• All SSRIs carry a boxed warning for suicidal thinking and behavior through age 24 1

Recognize Anxiety as a Mood Symptom

• Unremitting anxiety in a bipolar patient on treatment often signals inadequate mood stabilization rather than a separate anxiety disorder requiring additional medication 1
• The American Academy of Child and Adolescent Psychiatry explicitly states that when both depression and anxiety are present in bipolar disorder, prioritize treatment of depressive symptoms first 1

Monitor for Treatment-Emergent Issues

• Verify medication adherence before making any changes—more than 90% of adolescents who were noncompliant with lithium treatment relapsed 1
• Assess for substance use, as this commonly complicates bipolar treatment and can manifest as anxiety 1
• Rule out medical causes of anxiety (thyroid dysfunction, which lithium can cause) through appropriate laboratory monitoring 1

The Bottom Line Algorithm

1. Verify lithium is at therapeutic levels and patient is adherent 1
2. Initiate or intensify CBT for anxiety symptoms 1, 4
3. If acute anxiety relief is needed, use PRN low-dose benzodiazepines sparingly 1
4. If mood symptoms remain inadequately controlled after 6-8 weeks, consider augmenting lithium with valproate or switching mood stabilizers—not increasing lurasidone 1
5. Schedule close follow-up within 1-2 weeks to reassess symptoms and verify adherence 1