Adding Rexulti to Wellbutrin in a Patient with Vertigo
Yes, Rexulti (brexpiprazole) can be safely added to Wellbutrin (bupropion) in a patient with vertigo, but the vertigo itself requires proper evaluation and management first, as neither medication is indicated for treating vertigo.
Key Safety Considerations
Drug-Drug Interaction Profile
The combination of brexpiprazole and bupropion has no documented contraindications or significant drug interactions 1. In vitro studies demonstrate that brexpiprazole exhibits only weak inhibitory effects on cytochrome P450 enzymes and is unlikely to cause clinically relevant drug interactions 2. Bupropion primarily affects CYP2B6 and CYP2D6 3, while brexpiprazole is metabolized by CYP2D6 and CYP3A4 4. There are no published case reports of adverse effects when these agents are combined 5.
Vertigo Management Takes Priority
Vestibular suppressant medications are NOT recommended for treating vertigo, particularly benign paroxysmal positional vertigo (BPPV), which is the most common cause of episodic vertigo 6, 7, 6, 8. The guidelines explicitly state that medications like antihistamines and benzodiazepines should not be routinely used for vertigo treatment, as they:
- Provide no definitive benefit for BPPV
- Interfere with central vestibular compensation
- Decrease diagnostic sensitivity during Dix-Hallpike maneuvers
- May cause adverse effects without therapeutic benefit 7, 8
Important clinical pitfall: One case series documented that bupropion itself can cause falling backward and parkinsonian symptoms in elderly patients, which could be confused with or exacerbate vertigo 9. This is thought to be mediated through dopaminergic effects in the basal ganglia.
Clinical Algorithm for This Patient
Step 1: Evaluate the Vertigo
- Perform Dix-Hallpike testing to differentiate BPPV from central causes
- If positive for BPPV: Treat with canalith repositioning procedures (Epley maneuver), NOT medications 7, 8
- If negative or atypical: Consider neuroimaging to rule out central causes (stroke, tumor, demyelinating disease) 10
- Reassess within 1 month to confirm symptom resolution 6, 8
Step 2: Address the Psychiatric Indication
If brexpiprazole is being considered for:
- Major depressive disorder adjunctive therapy: Brexpiprazole 2-3 mg/day has demonstrated efficacy when added to antidepressants, with significant MADRS score improvements 11
- Schizophrenia: Brexpiprazole is FDA-approved for this indication 1
- Agitation in Alzheimer's disease: Brexpiprazole 2 mg shows optimal benefit 12, 13, 14
Step 3: Monitor for Additive Side Effects
Both medications can cause:
- Dizziness: Common with brexpiprazole (listed as frequent adverse effect) 1
- Orthostatic hypotension: Brexpiprazole can cause decreased blood pressure when changing positions 1
- Falls risk: Brexpiprazole may cause sleepiness, dizziness, and orthostatic hypotension leading to falls 1
The combination may theoretically increase dizziness and fall risk, particularly in elderly patients. Close monitoring is essential, especially during the first 2-4 weeks of treatment.
Practical Prescribing Recommendations
If proceeding with the combination:
- Start brexpiprazole at 0.5-1 mg daily and titrate slowly
- Target dose is typically 2 mg daily for most indications 12, 11
- Educate patient about orthostatic precautions (rise slowly from sitting/lying)
- Schedule follow-up within 2 weeks to assess tolerability
- Monitor for increased dizziness, falls, or worsening balance
- Consider dose adjustment if patient has renal/hepatic impairment or takes CYP2D6/3A4 inhibitors 1, 4
Critical Caveat
Do not use either medication to treat the vertigo itself. If the patient's vertigo is BPPV, the appropriate treatment is canalith repositioning maneuvers, not pharmacotherapy 7, 8. Vestibular rehabilitation may be offered for persistent symptoms or balance impairment after successful repositioning 7, 8.