What to do if someone is depressed while taking Wellbutrin (bupropion)?

Management of Depression While Taking Wellbutrin (Bupropion)

If a patient is experiencing depression while taking Wellbutrin (bupropion), you should assess for inadequate response to treatment, evaluate medication adherence, check for dose-related issues, screen for emergence of suicidal thoughts, and consider treatment modification if the response has been inadequate for 6-8 weeks. 1

Initial Assessment

When a patient reports depression while on bupropion, conduct a targeted evaluation:

• Duration of current treatment: Determine if the patient has been on bupropion for an adequate trial period (at least 6-8 weeks)
• Dosage adequacy: Check if the patient is on an appropriate therapeutic dose
  • Bupropion dosing typically ranges from 100-400mg daily for SR formulation or up to 300mg daily for XL formulation 1, 2
  • Underdosing is a common reason for inadequate response
• Medication adherence: Assess if the patient is taking the medication as prescribed
• Emergence of suicidality: Screen for suicidal thoughts, agitation, irritability, or unusual changes in behavior 2
• Symptom progression: Determine if depression symptoms are worsening, unchanged, or partially improved

Key Questions to Ask

1. Adherence assessment:

   • "Have you been taking your medication regularly as prescribed?"
   • "Have you missed any doses in the past week?"

2. Response evaluation:

   • "How have your symptoms changed since starting bupropion?"
   • "Are there any symptoms that have improved while others remain problematic?"

3. Side effect screening:

   • "Have you experienced any side effects like insomnia, agitation, headaches, or dry mouth?"
   • "Have you noticed any changes in your appetite or weight?"

4. Suicidality assessment:

   • "Have you had thoughts of harming yourself or that life isn't worth living?"
   • "Have you noticed increased irritability, anxiety, or unusual changes in your behavior?"

5. Comorbidity evaluation:

   • "Have you been using alcohol or other substances that might interact with your medication?"
   • "Are there any significant stressors or life changes that have occurred recently?"

Decision Algorithm

If inadequate response after 6-8 weeks:

The American College of Physicians strongly recommends modifying treatment if the patient does not have an adequate response to pharmacotherapy within 6-8 weeks 1. Options include:

1. Dose adjustment: Consider increasing bupropion dose if below maximum recommended dose (450mg/day) 2

   • Caution: Doses exceeding 450mg/day increase seizure risk 2 and may potentially trigger manic episodes in susceptible individuals 3

2. Medication switch: Consider changing to another second-generation antidepressant

   • SSRIs or SNRIs may be appropriate alternatives based on adverse effect profiles 1
   • Note that bupropion has lower rates of sexual dysfunction compared to many SSRIs 4

3. Augmentation strategy: Consider adding another agent to bupropion

If adequate trial has not been completed:

If the patient has been on bupropion for less than 6-8 weeks, encourage continued treatment with close monitoring, as full response may take time to develop.

Monitoring Recommendations

The American College of Physicians strongly recommends that clinicians assess patient status, therapeutic response, and adverse effects beginning within 1-2 weeks of initiation of therapy 1:

• Schedule follow-up within 1-2 weeks to assess for emergence of suicidality
• Monitor for agitation, irritability, or unusual changes in behavior
• Continue regular monitoring throughout treatment

Special Considerations

• Bipolar disorder: If patient has or develops manic symptoms, bupropion may need to be discontinued, as high doses have been associated with triggering mania 3
• Cardiovascular disease: While bupropion generally has a favorable cardiovascular profile compared to tricyclic antidepressants, monitor blood pressure as it can cause elevations 5
• Seizure risk: Assess for factors that may lower seizure threshold (e.g., history of seizures, head trauma, eating disorders, or concomitant medications) 2

Remember that approximately 38% of patients do not achieve a treatment response during 6-12 weeks of treatment with second-generation antidepressants, and 54% do not achieve remission 1. Treatment modification is often necessary to achieve optimal outcomes.