What is the most appropriate medication for a 50-year-old man with major depressive disorder (MDD), hypertension, diabetes, obesity (body mass index (BMI) of 32), and a history of smoking one pack of nicotine cigarettes per day, who previously experienced increased blood pressure while taking venlafaxine (Effexor) (venlafaxine)?

Selecting an Antidepressant for a Patient with MDD, Hypertension, Diabetes, and Obesity

Bupropion extended release 150 mg every morning is the most appropriate medication for this patient with MDD, hypertension, diabetes, obesity, and smoking history who previously experienced increased blood pressure with venlafaxine.

Rationale for Medication Selection

Why Bupropion is the Best Choice:

1. Cardiovascular Safety Profile:

   • This patient has hypertension and previously experienced increased blood pressure with venlafaxine (an SNRI). SNRIs like venlafaxine are known to potentially increase blood pressure 1.
   • Bupropion does not significantly affect blood pressure compared to SNRIs and is not listed among antidepressants with significant hypertensive effects in the ACC/AHA hypertension guidelines 1.

2. Metabolic Considerations:

   • The patient has diabetes and obesity (BMI 32). Bupropion is weight-neutral or may promote modest weight loss, making it advantageous for patients with obesity and diabetes 1.
   • Mirtazapine is associated with weight gain and potential metabolic effects that could worsen diabetes control.

3. Smoking Cessation Benefits:

   • The patient smokes 1 pack per day. Bupropion is FDA-approved for smoking cessation in addition to depression treatment 2.
   • Studies show bupropion can help with smoking cessation while also treating depression 1.

4. Efficacy for Depression:

   • Bupropion is an effective antidepressant with efficacy comparable to other antidepressants for major depressive disorder 3.

Why Other Options Are Less Appropriate:

1. Venlafaxine (Restart):

   • Previously caused increased blood pressure in this patient with existing hypertension.
   • SNRIs like venlafaxine are specifically mentioned in hypertension guidelines as medications that may cause elevated blood pressure 1.
   • Restarting a medication with a known adverse effect in this patient would be inappropriate.

2. Mirtazapine:

   • Associated with significant weight gain and potential metabolic effects that could worsen obesity and diabetes 1.
   • Sedating effects may not be desirable for daytime functioning.

3. Amitriptyline:

   • Tricyclic antidepressants (TCAs) like amitriptyline have significant cardiovascular side effects including potential to worsen hypertension 1.
   • TCAs can cause orthostatic hypotension, arrhythmias, and are contraindicated in patients with cardiovascular disease.
   • Can cause weight gain, which would be problematic for this patient with obesity and diabetes.

Implementation Plan

1. Starting Dose:

   • Begin with bupropion extended release 150 mg once daily in the morning.
   • After 1 week, assess for tolerability before considering dose increases.

2. Monitoring:

   • Check blood pressure within 1-2 weeks of starting therapy.
   • Monitor for changes in blood glucose levels and weight.
   • Assess smoking habits and provide additional smoking cessation support.

3. Dose Adjustments:

   • If needed and tolerated, dose can be increased to 300 mg daily (as 150 mg twice daily) after 1-2 weeks.
   • Maximum dose should not exceed 400 mg daily.

4. Special Considerations:

   • Bupropion lowers seizure threshold, but this is dose-dependent and uncommon at recommended doses.
   • Morning dosing is preferred to minimize risk of insomnia.
   • Pharmacokinetics of bupropion are not significantly altered in smokers versus non-smokers, so no dose adjustment is needed based on smoking status 2.

Additional Management Recommendations

1. Hypertension Management:

   • Continue current antihypertensive therapy with close monitoring.
   • Target blood pressure <130/80 mmHg for patients with diabetes 1.
   • Consider ACE inhibitors or ARBs as preferred agents for patients with diabetes and hypertension 1.

2. Diabetes Management:

   • Continue current diabetes medications with regular monitoring.
   • Target HbA1c <7% individualized to patient characteristics 1.

3. Lifestyle Modifications:

   • Smoking cessation counseling to complement bupropion therapy.
   • Dietary counseling for weight management and diabetes control.
   • Regular physical activity appropriate to patient's condition.

By selecting bupropion, we address the patient's depression while avoiding medication-induced hypertension, potentially helping with weight management, and supporting smoking cessation efforts.