What is the best treatment option for a 27-year-old female with palpitations, anxiety, and dizziness, who is taking Vyvanse (lisdexamfetamine) and Wellbutrin (bupropion), and has a history of orthostatic hypotension and Raynaud's-like phenomenon, and refuses to stop or decrease the dose of her current medications?

Treatment Recommendation for Palpitations with Orthostatic Hypotension

In this patient with medication-induced PVCs, orthostatic hypotension, and Raynaud's phenomenon who refuses to discontinue Vyvanse or Wellbutrin, midodrine is the preferred initial treatment to address the orthostatic hypotension, while propranolol should be avoided due to the high risk of worsening her orthostatic symptoms and Raynaud's phenomenon. 1

Clinical Context and Problem Analysis

This 27-year-old presents with a complex clinical picture:

• Documented frequent PVCs on EKG during symptomatic episodes, likely exacerbated by the combination of Vyvanse (lisdexamfetamine) and Wellbutrin (bupropion) 2
• Orthostatic hypotension with associated dizziness and lightheadedness that worsens with positional changes 1
• Raynaud's-like phenomenon suggesting underlying autonomic dysfunction 3
• Normal cardiac structure and function (EF 64%, normal echo) ruling out structural heart disease 3

The key issue is that both medications are known to cause tachycardia, palpitations, and can exacerbate ventricular arrhythmias, particularly in combination 2. However, the patient refuses medication adjustment despite strong medical recommendations.

Why Midodrine Over Propranolol

Midodrine Advantages in This Patient:

• Directly treats orthostatic hypotension through alpha-1 adrenergic agonism, increasing peripheral vascular resistance and venous return 1
• Proven efficacy for orthostatic symptoms when nonpharmacologic measures fail 1, 4
• Does not worsen Raynaud's phenomenon through peripheral vasoconstriction mechanisms that differ from cold-induced vasospasm 3
• Will not exacerbate the patient's anxiety, which is already problematic and contributing to her symptoms 5

Propranolol Contraindications in This Patient:

Propranolol is contraindicated or highly problematic in this clinical scenario for multiple reasons:

• Worsens orthostatic hypotension: Beta-blockers are well-documented to cause and exacerbate orthostatic hypotension, particularly in patients with underlying autonomic dysfunction 2, 6
• Exacerbates Raynaud's phenomenon: Beta-blockers, especially non-selective ones like propranolol, worsen peripheral vasospasm and are relatively contraindicated in Raynaud's 2
• May worsen depression and anxiety: Propranolol can precipitate or exacerbate depression and anxiety symptoms, which this patient already experiences 2, 5
• Drug interactions: Propranolol has significant interactions with multiple drug classes and can cause additive hypotensive effects 2

Recommended Treatment Algorithm

Step 1: Nonpharmacologic Interventions (Mandatory First-Line)

Before initiating midodrine, implement these evidence-based strategies 1:

• Increase fluid intake to 2-3 liters daily and salt intake to 6-9 grams (100-150 mmol) per day, unless contraindicated 3, 1
• Compression stockings (thigh-high, 30-40 mmHg) to reduce venous pooling 3
• Patient education on postural changes: Rise slowly from supine to sitting to standing, avoid prolonged standing 1, 4
• Head-up tilt during sleep (10-20 degrees) to reduce nocturnal diuresis and improve morning orthostatic tolerance 1

Step 2: Midodrine Initiation

If nonpharmacologic measures are insufficient after 2-4 weeks 1:

• Starting dose: 2.5-5 mg three times daily (morning, midday, late afternoon) 1, 4
• Timing: Last dose should be at least 4 hours before bedtime to avoid supine hypertension 1
• Titration: Increase by 2.5-5 mg per dose every 3-7 days as tolerated, up to maximum 10 mg three times daily 1
• Monitoring: Check supine and standing blood pressure before each dose increase and regularly thereafter 1

Step 3: Address the Root Cause

Continue strong counseling about medication adjustment 2:

• The combination of Vyvanse and Wellbutrin significantly increases arrhythmia risk and is likely the primary driver of her PVCs 2
• Document repeated discussions about dose reduction or discontinuation in the medical record
• Consider involving psychiatry for medication optimization if patient remains resistant
• Wellbutrin has a relatively favorable cardiovascular profile compared to other antidepressants, with low rates of orthostatic hypotension (unlike tricyclics), but still can cause tachycardia and palpitations 7

Important Caveats and Monitoring

Midodrine-Specific Concerns:

• Supine hypertension is the most common adverse effect; patients must avoid lying down within 4 hours of dosing 1, 4
• Piloerection, pruritus, and paresthesias occur in some patients but are usually mild 1
• Urinary retention can occur, particularly in patients with prostatic hypertrophy (not applicable here) 1

What This Patient Should NOT Receive:

• Beta-blockers (propranolol, atenolol, metoprolol) due to orthostatic hypotension and Raynaud's 2, 6
• Calcium channel blockers (verapamil, diltiazem) which can worsen orthostatic hypotension 3, 6
• Tricyclic antidepressants which cause significant orthostatic hypotension 6

Alternative if Midodrine Fails:

If midodrine is ineffective or not tolerated 1, 4:

• Fludrocortisone 0.1-0.2 mg daily (mineralocorticoid causing sodium/water retention) 3, 1, 4
• Monitor for hypokalemia, edema, and supine hypertension 3
• Pyridostigmine 30-60 mg three times daily (acetylcholinesterase inhibitor) as third-line option 1

Long-Term Management Strategy

The palpitations and PVCs in this patient are benign from a mortality standpoint given normal cardiac structure and function 3. The primary goals are:

1. Symptom relief through treatment of orthostatic hypotension 1
2. Anxiety management which may be amplifying symptom perception 3, 5
3. Continued attempts at medication optimization with psychiatry involvement 2
4. Regular cardiovascular monitoring given the arrhythmogenic medication combination 3

The patient's refusal to adjust psychiatric medications does not eliminate the physician's responsibility to document the increased cardiovascular risk and continue counseling about safer alternatives. 2