What should be prescribed for anxiety in a patient with stabilized bipolar disorder on lithium and lurasidone (Latuda)?

Treatment of Anxiety in Stabilized Bipolar Disorder on Lithium and Lurasidone

For a patient with stabilized bipolar disorder on lithium and lurasidone, add lamotrigine as the first-line anxiolytic agent, as it provides mood stabilization with particular efficacy for preventing depressive episodes while addressing comorbid anxiety without risking mood destabilization. 1, 2

Primary Recommendation: Lamotrigine

Lamotrigine is the optimal choice because it serves dual purposes—maintaining mood stability while providing anxiolytic effects—and is specifically recommended by the American Academy of Child and Adolescent Psychiatry for maintenance therapy in bipolar disorder, particularly when depressive symptoms or anxiety predominate. 1, 2

Key advantages of lamotrigine in this context:

• Does not cause sedation or significant weight gain, addressing common tolerability concerns with other mood stabilizers 1
• Particularly effective for preventing depressive episodes, which often co-occur with anxiety in bipolar disorder 2
• Can be safely combined with lithium and lurasidone without significant drug interactions 1
• Provides anxiolytic effects through mood stabilization rather than requiring separate anxiety-specific medications 3

Critical titration requirements:

• Must be titrated slowly to minimize risk of Stevens-Johnson syndrome—start at 25mg daily for 2 weeks, then 50mg daily for 2 weeks, then increase by 50mg every 1-2 weeks to target dose of 200mg daily 1
• If lamotrigine is discontinued for more than 5 days, restart with the full titration schedule rather than resuming the previous dose 1

Alternative Approaches if Lamotrigine is Contraindicated or Ineffective

Second-line: Gabapentin or Pregabalin

Anticonvulsants used as mood stabilizers, particularly pregabalin or gabapentin, may provide anxiolytic effects without risking mood destabilization. 1

• Gabapentin: Start 300mg at bedtime, titrate to 900-1800mg daily in divided doses 4
• Pregabalin: Start 75mg twice daily, titrate to 150-300mg twice daily 4
• Both require dose reduction in renal insufficiency and can cause dose-dependent dizziness and sedation 4

Third-line: Cautious SSRI Use

If anxiety remains severe despite mood stabilizer optimization, an SSRI may be added, but ONLY in combination with adequate mood stabilization (lithium plus lurasidone already provides this). 3

• Fluoxetine is preferred as it has FDA approval in combination with olanzapine for bipolar depression 3
• SSRIs carry significant risks in bipolar disorder: mood destabilization, mania induction, rapid cycling, behavioral activation, and suicidal thinking (particularly in younger patients) 1
• Monitor closely for signs of mood destabilization including increased energy, decreased sleep need, impulsivity, or irritability 1

What to Avoid

Benzodiazepines should be reserved for acute, short-term use only:

• May be used PRN for severe acute anxiety (lorazepam 0.25-0.5mg, maximum 2mg daily, not more than 2-3 times weekly) 1
• Carry risks of tolerance, dependence, paradoxical agitation (10% of patients), and four-fold increased overdose risk when combined with other CNS depressants 1
• Abrupt withdrawal can cause seizures, delirium, and rarely death—if discontinuation is needed, taper by 25% every 1-2 weeks 1
• Cognitive behavioral therapy increases tapering success rates and should be offered if benzodiazepine discontinuation is attempted 1

Antidepressant monotherapy is absolutely contraindicated:

• The American Academy of Child and Adolescent Psychiatry explicitly recommends against antidepressant monotherapy due to risk of mood destabilization, mania induction, and rapid cycling 1
• Your patient is already on adequate mood stabilization (lithium + lurasidone), so if an antidepressant is added for anxiety, the mood stabilizer coverage is sufficient 3

Monitoring Requirements

For lamotrigine addition:

• Educate patient about rash recognition—any rash requires immediate discontinuation and evaluation 1
• Monitor for mood symptoms at 2-week intervals during titration 1
• Assess anxiety symptoms using standardized measures at 4 and 8 weeks 1

Maintain existing monitoring for lithium and lurasidone:

• Lithium levels, renal and thyroid function every 3-6 months 1
• BMI monthly for 3 months then quarterly; blood pressure, fasting glucose, and lipids at 3 months then yearly for lurasidone 1

Psychosocial Interventions

Cognitive behavioral therapy should be offered as an adjunctive non-pharmacological approach for anxiety management, as it has strong evidence for both anxiety and depression components of bipolar disorder and may reduce the need for additional medications. 1, 3

Clinical Algorithm Summary

1. First: Add lamotrigine with slow titration (25mg→50mg→100mg→200mg over 6-8 weeks) 1, 2
2. If lamotrigine contraindicated or ineffective after 8 weeks: Add gabapentin or pregabalin 1
3. If anxiety remains severe despite above: Consider adding SSRI (fluoxetine preferred) with close monitoring for mood destabilization 3
4. Reserve benzodiazepines for acute, PRN use only (lorazepam 0.25-0.5mg, maximum 2-3 times weekly) 1
5. Integrate CBT throughout to address anxiety symptoms and potentially reduce medication burden 1, 3

The current regimen of lithium and lurasidone provides excellent mood stabilization and has demonstrated long-term safety and efficacy in bipolar depression, with lurasidone showing minimal metabolic effects and maintained improvement over 2 years of treatment. 5, 6, 7, 8, 9