In middle‑aged to older adults with chronic dizziness, possibly due to vestibular migraine or anxiety/depression, can flunarizine or duloxetine be used as therapy?

Flunarizine and Duloxetine for Chronic Dizziness

Flunarizine has proven efficacy for vestibular migraine-related dizziness at 10 mg daily, while duloxetine is effective when anxiety or depression coexist with chronic dizziness, particularly in patients who have failed SSRIs. 1, 2

Clinical Decision Algorithm

Step 1: Establish the Underlying Diagnosis

• If vestibular migraine is suspected (episodic vertigo lasting minutes to hours, migraine features, motion sensitivity): Flunarizine is the evidence-based choice 1, 3
• If anxiety/depression predominates with persistent non-vertiginous dizziness: Start with an SSRI (sertraline or escitalopram) as first-line 2
• If both conditions coexist (chronic migraine with depression/anxiety): Consider flunarizine combined with duloxetine 4

Step 2: Flunarizine for Vestibular Migraine

Dosing and efficacy:

• Start at 10 mg once daily at bedtime 1, 3
• Proven efficacy in reducing frequency and severity of vertiginous episodes in migrainous vertigo (significant improvement in vertigo frequency p=0.010 and severity p=0.046 versus control) 3
• Clinical benefit may take 2-3 months to manifest; give an adequate trial before declaring failure 1

Critical safety concerns in middle-aged to older adults:

• Depression and extrapyramidal symptoms occur particularly in elderly persons—this is an absolute contraindication if depression history exists 1, 5
• Common adverse events include sedation, weight gain, and abdominal pain 1
• Screen for depression using validated instruments before initiating flunarizine 2

Common pitfall: Flunarizine is often unavailable in the United States but widely used in countries where available 1

Step 3: Duloxetine for Anxiety/Depression-Related Dizziness

When to use duloxetine:

• Middle-aged to older adults with chronic dizziness and comorbid anxiety or depression who have failed or cannot tolerate SSRIs 2, 6
• Patients with chronic migraine, medication overuse, and depression (64% responder rate in one study) 7
• SNRIs (venlafaxine or duloxetine) are appropriate alternatives if SSRIs are ineffective or not tolerated 2

Dosing strategy:

• Start at 30 mg once daily for 7 days to minimize nausea (the most common side effect) 6
• Increase to 60 mg once daily after the first week (standard therapeutic dose) 6
• Maximum dose 120 mg daily if clinically indicated and 60 mg is tolerated 6
• Elderly or frail patients should use slower escalation with lower initial dose (20 mg) 6

Monitoring requirements:

• Blood pressure and pulse regularly (duloxetine can increase both parameters) 2, 6
• Renal function (requires dosage adjustment in renal insufficiency) 2, 6
• Assess treatment response at 4 and 8 weeks using standardized measures 2

Common side effects: Nausea, dry mouth, headache, constipation, dizziness, fatigue, diaphoresis, insomnia 6

Step 4: Combination Therapy (Flunarizine + Duloxetine)

Evidence for combination:

• One randomized controlled trial showed flunarizine combined with duloxetine in chronic migraine with depression/anxiety significantly reduced inflammatory markers (TNF-α, IL-6, hs-CRP), HAMD scores, and HAMA scores compared to flunarizine with loxoprofen 4
• This combination effectively improves neuroelectrophysiological indices and reduces both depression and anxiety 4

When to consider combination:

• Chronic migraine with significant vestibular symptoms AND comorbid depression/anxiety 4
• Failed monotherapy with either agent alone after 2-3 months 5

Critical contraindications:

• History of depression is an absolute contraindication to flunarizine, making this combination inappropriate if depression preceded treatment 5
• Elderly patients are at increased risk of falls, depression, and extrapyramidal symptoms with this combination 5

Monitoring for additive effects:

• Sedation and weight gain (both drugs cause these) 5
• Depression worsening (flunarizine can cause or worsen depression, particularly in elderly) 1, 5
• Anticholinergic burden (dry mouth, constipation from potential additive effects) 5

What NOT to Use

Avoid vestibular suppressants (benzodiazepines, antihistamines):

• Not routinely recommended for chronic dizziness except short-term management of severe nausea/vomiting 1
• Benzodiazepines significantly increase risk of cognitive impairment, delirium, falls, fractures, and dependence in older adults 1, 2
• Vestibular suppressants may help psychological anxiety secondary to vestibular symptoms but do not treat the underlying condition 1

Avoid fluoxetine in older adults:

• Higher rates of adverse effects, extensive CYP2D6 interactions, very long half-life problematic in elderly 2

Avoid paroxetine in older adults:

• Strong anticholinergic effects, higher adverse event incidence, severe discontinuation syndrome 2

Treatment Duration and Reassessment

• Assess response at 4 weeks and 8 weeks using standardized validated instruments 2
• If symptoms stable or worsening after 8 weeks despite good adherence, adjust regimen by switching medications or adding psychological intervention 2
• For first episode, continue treatment at least 4-12 months after symptom remission 2
• After period of stability, consider tapering or discontinuing treatment 1
• Never discontinue SSRIs/SNRIs abruptly—taper gradually over 10-14 days to avoid discontinuation syndrome (dizziness, paresthesias, anxiety, irritability) 2

Special Considerations for Older Adults

• Start low and go slow: Use doses approximately 50% of standard adult starting doses 2
• Elderly patients have reduced renal function and medication clearance even without overt renal disease 2
• Obtain serum sodium level before starting duloxetine (SSRIs/SNRIs cause hyponatremia in 0.5-12% of older adults, typically within first month) 2
• If patient requires NSAIDs or antiplatelet agents, prescribe gastroprotection (PPI) to mitigate GI bleeding risk with duloxetine 2
• Review all current medications for potential CYP450 interactions before starting duloxetine 2

Cognitive Behavioral Therapy Integration

• CBT has the highest level of evidence for anxiety disorders in all age groups and should be offered alongside or before pharmacotherapy 2
• Most elderly patients prefer psychological treatments over medication when given the choice 2
• Individual therapy sessions are generally preferred over group therapy due to superior clinical effectiveness 2