What treatment plan is recommended for a patient experiencing increased migraines, anxiety, and insomnia, with a complex medication regimen including Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide), Cetirizine (hydroxyzine), Zetia (ezetimibe), Vitamin D, Vascepa (icosapent ethyl), Vilazadone, bupropion XR, and Qulipta (atogepant)?

Comprehensive Treatment Plan for Complex Migraine, Anxiety, and Insomnia

Immediate Priority: Address Medication Overuse Headache Risk

You must immediately assess and likely reduce the frequency of acute migraine medications (elitriptan, alprazolam, zolpidem) to prevent medication overuse headache, which is likely contributing to the worsening migraine pattern. 1

• Limit all acute migraine medications to fewer than 10-15 days per month to minimize medication overuse headache risk, with medications containing barbiturates, caffeine, or opioids carrying the highest risk (though your patient is not on these specific agents, the principle applies to all acute treatments). 1
• The increasing frequency of alprazolam and zolpidem use, combined with worsening migraines, strongly suggests medication overuse headache as a contributing factor. 1
• Document headache frequency using a headache diary to objectively track medication use patterns. 1

Migraine Prevention: Add or Optimize Prophylactic Therapy

Given that Qulipta 60 mg daily is already prescribed but migraines are worsening, you need to either optimize this therapy or add a complementary preventive agent. 2, 3

First-Line Preventive Options to Consider:

• Propranolol, metoprolol, or timolol are first-line beta-blockers with established efficacy for migraine prevention, though you must assess for contraindications given potential interactions with the patient's complex regimen. 4, 5, 3
• Topiramate or divalproex are first-line options with strong evidence, though topiramate may help with weight management (atogepant in Qulipta is associated with modest weight loss). 5, 3, 6
• OnabotulinumtoxinA (Botox) injections every 12 weeks should be strongly considered if the patient meets criteria for chronic migraine (≥15 headache days per month), as this has FDA approval and guideline support specifically for chronic migraine. 2

Antidepressant Optimization:

• Consider switching from vilazodone to venlafaxine (SNRI) or adding amitriptyline or nortriptyline at bedtime, as these have superior evidence for migraine prevention compared to SSRIs and may simultaneously address anxiety and insomnia. 5, 3, 7
• Venlafaxine is a second-choice migraine preventive with evidence for efficacy and may be particularly effective given comorbid depression/anxiety. 5, 7
• Amitriptyline has the best evidence for migraine prevention among antidepressants, and its sedating effect would be beneficial for comorbid insomnia. 7
• Nortriptyline is an alternative if amitriptyline is not tolerated. 7

Critical caveat: The patient is already on bupropion XR 300 mg and vilazadone 40 mg; adding another antidepressant requires careful monitoring for serotonin syndrome risk, though this is lower with tricyclics than with multiple serotonergic agents. 8

Anxiety Management: Transition from Benzodiazepines

You must develop a plan to taper and discontinue alprazolam due to dependence risk, rebound anxiety, and potential contribution to medication overuse headache. 1

Recommended Approach:

• Optimize the SNRI strategy by either increasing vilazodone (if not at maximum dose) or switching to venlafaxine, which has dual benefits for anxiety and migraine prevention. 5, 7
• Consider adding buspirone as a non-benzodiazepine anxiolytic that does not carry dependence risk or contribute to medication overuse headache. 1
• Implement a slow alprazolam taper (reduce by 0.125 mg every 1-2 weeks) while simultaneously optimizing other anxiety treatments to prevent withdrawal. 7

Insomnia Management: Non-Benzodiazepine Approaches

Transition away from zolpidem to prevent tolerance, dependence, and medication overuse headache contribution. 1

Recommended Strategy:

• Amitriptyline or nortriptyline at bedtime (10-25 mg initially, titrating up) serves triple duty: migraine prevention, anxiety management, and sleep improvement. 7
• Trazodone 50-100 mg at bedtime is an alternative non-benzodiazepine option for insomnia without migraine-triggering properties. 7
• Address suspected sleep apnea immediately with formal sleep study referral, as untreated sleep apnea is a known migraine trigger and may be contributing to weekend hypersomnia. 4

Corticosteroid Considerations

Minimize corticosteroid use for status migrainosus, as chronic or frequent corticosteroid courses can worsen anxiety and contribute to medication overuse patterns. 1

• Work to establish better acute and preventive migraine control to reduce the need for corticosteroid rescue therapy. 4
• When corticosteroids are necessary, use the shortest effective course. 4

Drug Interaction and HIV Considerations

Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) has minimal drug interactions, but you must verify compatibility with any new medications added. 9

• Biktarvy is generally well-tolerated and does not require significant dose adjustments with most psychiatric medications. 9
• Monitor renal function if adding NSAIDs for migraine prevention (naproxen), though Biktarvy can be used with creatinine clearance ≥30 mL/min. 9

Lifestyle and Trigger Management Algorithm

Despite logistical difficulties, you must emphasize specific, achievable lifestyle modifications that directly impact migraine, anxiety, and sleep. 4

Specific Actionable Steps:

• Limit alcohol to zero given the patient's recognition that it triggers sleep apnea and morning migraines. 4
• Discontinue THC gummies as they are not providing acceptable benefit-to-side-effect ratio. 4
• Establish consistent sleep-wake times even on weekends to prevent the 14-17 hour weekend hypersomnia pattern, which likely represents sleep debt and circadian disruption. 4
• Refer for formal sleep study to diagnose and treat suspected sleep apnea, which is a critical migraine trigger. 4

Monitoring and Follow-Up

Schedule follow-up in 2-4 weeks to assess response to medication changes and monitor for adverse effects. 2, 1

• Use a headache diary to track migraine frequency, acute medication use, and identify patterns. 1
• Monitor for serotonin syndrome symptoms if adding or switching antidepressants. 8
• Assess for benzodiazepine withdrawal symptoms during alprazolam taper. 7
• Document weight changes, as atogepant (Qulipta) is associated with modest weight loss. 6

Addressing Psychosocial Stressors

While medication optimization is critical, the patient's work stress, relative's disability, social isolation, and financial strain are significant migraine and anxiety triggers that require parallel intervention. 4

• Refer for cognitive behavioral therapy (CBT), which has good evidence for migraine prevention and anxiety management. 3
• Consider referral to social work for assistance with disability benefits navigation and community resource connection. 4
• Explore workplace accommodations under ADA if migraine frequency meets disability criteria. 4