Can a patient with type 2 diabetes (HbA1c 6%) who is taking metformin, dapagliflozin, insulin glargine, rosuvastatin, aspirin 81 mg, and ergocalciferol (vitamin D) start bupropion (Wellbutrin) and what initial and target dosing should be?

Can This Patient Start Bupropion (Wellbutrin)?

Yes, this patient with well-controlled type 2 diabetes (HbA1c 6%) can safely start bupropion, with no absolute contraindications present in her current medication regimen.

Safety Assessment with Current Medications

Bupropion is compatible with this patient's diabetes regimen. The combination of metformin, dapagliflozin (Farxiga), insulin glargine (Lantus), rosuvastatin, aspirin, and vitamin D presents no direct drug interactions that would preclude bupropion use 1. Importantly, bupropion does not significantly affect glucose metabolism or insulin sensitivity 2.

Key Safety Considerations

• Seizure risk is the primary concern with bupropion, occurring at therapeutic doses in approximately 0.1-0.4% of patients, with risk increasing at doses above 450 mg/day 3.
• Screen for seizure risk factors before initiating: history of seizures, eating disorders (bulimia/anorexia), alcohol withdrawal, benzodiazepine withdrawal, head trauma, or CNS tumors 1, 3.
• Hypoglycemia risk requires monitoring when bupropion is combined with insulin and sulfonylureas, though this patient is not on a sulfonylurea 1.

Recommended Dosing Protocol

Initial Dosing (Bupropion SR - Twice Daily)

Start with bupropion SR 150 mg once daily in the morning for 3-4 days, then increase to 150 mg twice daily (total 300 mg/day) if tolerated 2. This gradual titration minimizes side effects, particularly nausea and insomnia.

Alternative: Bupropion XL (Once Daily)

If once-daily dosing is preferred, start bupropion XL 150 mg once daily in the morning, then increase to 300 mg once daily after 3-4 days 2. The XL formulation offers improved adherence with equivalent efficacy.

Target Maintenance Dose

• Standard therapeutic dose: 300 mg/day (either 150 mg SR twice daily or 300 mg XL once daily) 2
• Maximum dose: 450 mg/day (either 200 mg SR twice daily + 50 mg SR once daily, or 450 mg XL once daily), though seizure risk increases above 400 mg/day 1, 3
• Most patients achieve therapeutic benefit at 300 mg/day without requiring dose escalation 2

Critical Monitoring Requirements

Glucose Monitoring

Intensify glucose monitoring during the first 2-4 weeks of bupropion therapy, checking fasting and pre-meal glucose levels daily 1. While bupropion does not directly affect glucose metabolism, appetite suppression may alter carbohydrate intake, potentially affecting insulin requirements.

Hypoglycemia Vigilance

This patient is at modest hypoglycemia risk due to insulin glargine use, though her current HbA1c of 6% suggests well-titrated therapy 1. Watch for:

• Increased hypoglycemic episodes (glucose <70 mg/dL)
• Changes in appetite or meal patterns
• Need for insulin dose adjustment if weight loss occurs

Blood Pressure Monitoring

Check blood pressure at baseline and periodically, as bupropion can cause modest increases (5-10 mmHg) in some patients 1, 2.

Common Pitfalls to Avoid

• Do not exceed 450 mg/day total dose, as seizure risk increases substantially 3
• Do not use bupropion in patients with eating disorders (bulimia, anorexia), as seizure risk is markedly elevated 1, 3
• Do not combine with MAO inhibitors or use within 14 days of MAOI discontinuation 1
• Do not abruptly discontinue if patient reaches 450 mg/day dose; taper over at least 1 week 1
• Do not ignore new-onset seizures; bupropion was the third leading cause of drug-related new-onset seizures in one emergency department study, accounting for 1.4% of all new-onset seizures 3

Expected Benefits and Side Effects

Therapeutic Benefits

Bupropion typically requires 4-6 weeks for full antidepressant effect, though some patients notice improvement within 1-2 weeks 2. It offers advantages over SSRIs including:

• Less sexual dysfunction compared to SSRIs like escitalopram 2
• Less somnolence than tricyclic antidepressants 2
• Potential for modest weight loss (1-2 kg), which may benefit diabetes management 1

Common Side Effects

• Nausea, headache, and insomnia are most common, typically resolving within 1-2 weeks 1, 2
• Dry mouth and constipation occur in 10-20% of patients 1
• Anxiety or agitation may occur, particularly at higher doses 1

Special Considerations for This Patient

This patient's excellent glycemic control (HbA1c 6%) provides a safety buffer for initiating bupropion 1. Her stable diabetes regimen—metformin, dapagliflozin, and insulin glargine—is well-established and unlikely to require adjustment solely due to bupropion initiation 4, 5.

Continue all current diabetes medications unchanged unless glucose patterns shift significantly 1. The combination of metformin and dapagliflozin provides complementary glucose-lowering mechanisms with cardiovascular benefits that should be maintained 4, 5.