What pharmacological solutions can safely improve mental fog, severe fatigue, photosensitivity, and dizziness/chronic headaches in a patient with this complex medical profile?

Pharmacological Management of Mental Fog, Severe Fatigue, Photosensitivity, and Chronic Headaches

Given your complex polypharmacy regimen (8 medications) and multiple comorbidities, the safest approach is to first optimize your existing migraine therapy with ubrogepant by adding an NSAID during acute attacks, while avoiding any new medications that could worsen your already significant medication burden and risk of drug-drug interactions. 1

Immediate Optimization of Current Therapy

Acute Headache Management

• Add an NSAID to your existing ubrogepant during migraine attacks, as combination therapy is more effective than monotherapy and should be initiated as early as possible after headache onset 1, 2
• Consider ibuprofen 800mg or naproxen sodium 550mg taken with ubrogepant at the first sign of headache 1, 3
• Strictly limit NSAID use to fewer than 15 days per month and ubrogepant to fewer than 10 days per month to prevent medication overuse headache, which could be contributing to your chronic daily symptoms 1

Critical Medication Overuse Assessment

• You are at extremely high risk for medication overuse headache given your headache frequency, migraine diagnosis, anxiety/depression history, and current use of multiple medications 1
• If you are using ubrogepant or any analgesics more than twice weekly, this may be perpetuating rather than relieving your symptoms 1
• A headache diary tracking frequency, severity, and medication use is essential to identify if medication overuse is contributing to your chronic symptoms 1, 3

Preventive Therapy Considerations

First-Line Preventive Options

• Topiramate 25-100mg daily is the most appropriate preventive option for your situation, as it addresses migraine prevention while potentially promoting weight loss (beneficial given your bariatric surgery history and use of Wegovy/orlistat) 1, 3
• However, topiramate can cause cognitive inefficiency, paresthesia, and fatigue as adverse effects, which could worsen your mental fog 1

Alternative Preventive Options

• Candesartan 16mg daily or telmisartan 80mg daily are strongly recommended for episodic migraine prevention and would not add cognitive side effects 1
• These angiotensin receptor blockers have cardiovascular benefits and minimal interaction with your current medications 1

CGRP Antagonists for Prevention

• Erenumab, fremanezumab, or galcanezumab (monthly injections) are strongly recommended for both episodic and chronic migraine prevention 1
• These have minimal drug interactions and would not contribute to polypharmacy burden since they are monthly injections rather than daily pills 1
• They do not cause cognitive side effects or worsen fatigue 1

Critical Safety Concerns with Your Current Regimen

Polypharmacy Risk

• Your current 8-medication regimen creates substantial complexity that increases risk of medication errors, drug interactions, and adverse effects 4
• The combination of venlafaxine, bupropion, lamotrigine, and prazosin requires careful monitoring for interactions 4
• Adding any new daily medication should be approached with extreme caution given your already complex regimen 4, 5

Wegovy (Semaglutide) Side Effects

• Wegovy commonly causes fatigue, dizziness, and dysgeusia (altered taste), which may be contributing to your mental fog and fatigue symptoms 6
• Gastrointestinal side effects occur in 36.4% of patients on the 1mg dose, which could worsen overall symptom burden 6
• Consider whether your severe fatigue worsened after starting or escalating Wegovy dose 6

Venlafaxine Considerations

• Venlafaxine can cause nausea, palpitations, and has limited evidence for migraine prevention 1
• There is insufficient evidence to recommend venlafaxine specifically for headache prevention 1

What NOT to Do

Medications to Strictly Avoid

• Never use opioids or butalbital-containing compounds for your headaches, as these cause medication overuse headache, dependency, and worsen long-term outcomes 1, 7
• Avoid adding gabapentin for migraine prevention, as it is recommended against for episodic migraine 1
• Do not add additional daily oral medications without first attempting to optimize or streamline your current regimen 4

Addressing Photosensitivity and Sleep Apnea

Sleep Apnea Optimization

• Untreated or undertreated sleep apnea is likely a major contributor to your mental fog, fatigue, and headaches 1
• Ensure your sleep apnea is adequately treated with CPAP compliance, as this alone may significantly improve cognitive symptoms and headache frequency 1
• Poor sleep is a well-established migraine trigger and contributor to chronic daily headache 1, 2

Photosensitivity Management

• Photosensitivity is a common migraine symptom but has no specific pharmacological treatment 1
• Non-pharmacological approaches include wearing FL-41 tinted glasses and avoiding bright/flickering lights 1

Lifestyle Modifications (Non-Negotiable)

• Maintain strict sleep hygiene with consistent sleep-wake times to address both sleep apnea and migraine triggers 1, 2
• Stay well-hydrated and maintain regular meal schedules 1, 2
• Engage in regular moderate-intensity aerobic exercise 40 minutes three times weekly, which is as effective as topiramate for migraine prevention 3
• Implement stress management through relaxation techniques or mindfulness practices 1, 2

Recommended Action Plan

1. Track all medication use and headache patterns for 2-4 weeks using a daily diary before making any changes 1, 3
2. If using ubrogepant or any pain medication more than twice weekly, implement a medication holiday under physician supervision to rule out medication overuse headache 1
3. Add combination therapy (ubrogepant + NSAID) for acute attacks, strictly limiting use to fewer than 10 days per month 1, 2
4. Consider starting candesartan 16mg daily or a CGRP antagonist injection for prevention rather than adding another daily oral medication 1
5. Evaluate whether Wegovy is contributing to fatigue and dizziness, and discuss with your prescriber whether dose adjustment is appropriate 6
6. Ensure optimal CPAP compliance for sleep apnea treatment 1

When to Seek Specialist Consultation

• Consult a headache specialist or neurologist if symptoms persist despite optimization of current therapy, as your complex presentation may benefit from specialized management 1
• Consider clinical pharmacologist consultation to review your entire medication regimen for potential interactions, redundancies, or medications contributing to your symptoms 5