In a patient with vertigo and anxiety, is buspirone preferred over brexpiprazole (Rexulti) as first‑line therapy, and what are the recommended dosing and monitoring guidelines?

Buspirone is Preferred Over Rexulti for Anxiety in Patients with Vertigo

For a patient with vertigo and anxiety, buspirone is strongly preferred over brexpiprazole (Rexulti) as first-line therapy. This recommendation is based on the critical safety concern that Rexulti can cause or worsen vertigo and dizziness, while buspirone has established efficacy for anxiety without vestibular suppression effects.

Key Safety Concern with Rexulti

The FDA label for Rexulti explicitly lists discontinuation syndrome with SSRIs (which Rexulti is used adjunctively with) includes vertigo, dizziness, and imbalance 1. Additionally, common side effects of Rexulti itself include dizziness 2. Using Rexulti in a patient already experiencing vertigo would likely exacerbate their vestibular symptoms and complicate both diagnosis and management of the underlying vertigo.

Why Buspirone is the Better Choice

Evidence for Efficacy

• Recent 2025 multicenter study demonstrated buspirone effectively reduced anxiety (HAMA scores decreased from 25.2 to 15.4 over 12 weeks, p<0.001) in patients with depression and anxiety, with only 3.7% adverse event rate 3
• Proven efficacy in generalized anxiety disorder with coexisting depressive symptoms, showing significant improvement over placebo (p<0.03 for anxiety, p<0.05 for depression) 4
• Well-tolerated in elderly patients with multiple comorbidities receiving concomitant medications 5

Safety Profile Compatible with Vertigo

• Does not cause vestibular suppression, unlike benzodiazepines which are contraindicated in vertigo management 6
• Most common side effects are nausea, dizziness (typically mild and transient), somnolence, and sweating 4
• Safe for long-term use up to one year with no withdrawal syndrome upon discontinuation 7

Recommended Dosing Protocol for Buspirone

Starting dose: 5 mg twice daily (10 mg/day total)

Titration schedule:

• Increase by 5 mg/day every 2-3 days as tolerated
• Target therapeutic range: 15-30 mg/day divided into 2-3 doses
• Maximum dose: 45 mg/day (rarely needed) 4

Typical effective dose: 15-20 mg/day in most patients 7

Important Timing Consideration

Buspirone has a 1-2 week lag time before anxiolytic effects become apparent 8. Counsel patients about this delay to maintain compliance and avoid premature discontinuation.

Why Rexulti is Inappropriate Here

Rexulti is FDA-approved only as adjunctive therapy for major depressive disorder (not primary anxiety) in patients who have failed adequate trials of antidepressants 2. The indication requires:

• Documented inadequate response to 1-3 prior antidepressant courses
• 8 weeks of prospective antidepressant treatment failure 2

Rexulti dosing (for reference only, not recommended here):

• Starting: 0.5-1 mg daily
• Target: 2 mg daily for MDD
• Maximum: 3 mg daily for MDD 2

However, this is not appropriate for your patient because:

1. Vertigo is a known side effect/complication
2. It requires concurrent SSRI/SNRI use (which themselves can cause dizziness/vertigo) 1
3. No evidence for primary anxiety disorder treatment
4. Significantly more expensive and complex than buspirone

Monitoring Guidelines for Buspirone

Initial phase (first 4 weeks):

• Weekly assessment of anxiety symptoms using standardized scales (HAM-A if available)
• Monitor for side effects, particularly GI symptoms and dizziness
• Assess vertigo symptoms to ensure no worsening
• Confirm medication adherence given delayed onset of action

Maintenance phase:

• Monthly visits for first 3 months
• Then every 3 months once stable
• Reassess need for continued therapy every 6-12 months 7

Red flags requiring immediate evaluation:

• Worsening vertigo (though buspirone should not cause this)
• New-onset severe dizziness distinct from pre-existing vertigo
• Suicidal ideation (though buspirone has low risk)

Clinical Pitfalls to Avoid

1. Do not use benzodiazepines for anxiety in vertigo patients - guidelines explicitly recommend against vestibular suppressants in BPPV and other vestibular disorders 6

2. Do not expect immediate results - the 1-2 week lag time is normal; premature dose escalation or discontinuation is common error

3. Do not combine with MAOIs - absolute contraindication (though rare in practice)

4. Address the underlying vertigo - ensure proper evaluation and treatment (e.g., canalith repositioning procedures for BPPV) rather than just treating secondary anxiety 6

5. Consider that anxiety may improve once vertigo is successfully treated, potentially allowing buspirone discontinuation

The evidence strongly supports buspirone as the appropriate first-line anxiolytic in this clinical scenario, with Rexulti being contraindicated due to its potential to worsen vertigo symptoms and lack of indication for primary anxiety disorders.