Managing Anxiety in Patients Taking Wellbutrin (Bupropion)
Direct Answer
Bupropion does not increase anxiety in clinical practice and can be safely continued in patients with comorbid anxiety, but if anxiety requires specific treatment, add an SSRI (preferably sertraline or escitalopram) rather than discontinuing bupropion. 1, 2
Evidence Contradicting the Clinical Myth
The longstanding belief that bupropion exacerbates anxiety is not supported by controlled evidence:
A large naturalistic study (N=8,457) using propensity matching found no difference in anxiety outcomes between patients prescribed SSRIs versus bupropion over 12 weeks of treatment. 1
Two randomized controlled trials comparing bupropion SR to sertraline demonstrated that baseline anxiety levels did not predict differential response to either medication, and both agents had comparable anxiolytic effects. 2, 3
In a 4-week placebo-controlled trial, bupropion significantly reduced Hamilton Anxiety Scale scores compared to placebo (P < 0.01), demonstrating direct anxiolytic properties in depressed patients with comorbid anxiety. 4
FDA Safety Warnings About Anxiety
The FDA label for bupropion requires monitoring for emergence or worsening of anxiety, agitation, panic attacks, and irritability, particularly early in treatment or with dose adjustments. 5
This warning applies to all antidepressants due to the black box warning for suicidal ideation in patients under 24 years old. 5
Patients and families should be instructed to report severe, abrupt onset anxiety that was not part of the presenting symptoms, as this may indicate need for medication adjustment. 5
The FDA specifically notes that bupropion "should not be used in agitated patients," but this refers to acute agitation, not generalized anxiety disorder. 6
When to Add Medication for Anxiety
If a patient on bupropion develops clinically significant anxiety requiring pharmacologic intervention:
First-Line: Add an SSRI
Add sertraline as the preferred first choice because:
- It is well-tolerated with minimal effect on metabolism of other medications compared to other SSRIs. 6
- It demonstrated comparable anxiolytic efficacy to bupropion in head-to-head trials for depression with anxiety. 6
- SSRIs are the primary evidence-based pharmacotherapy for all anxiety disorders (generalized anxiety, social anxiety, panic disorder). 6
Escitalopram is an excellent alternative because:
- It has the least effect on CYP450 isoenzymes, minimizing drug interactions with bupropion. 6
- Start at 10 mg daily, maximum 40 mg daily. 6
Avoid paroxetine as first choice due to:
Dosing Considerations When Combining
Titrate the SSRI slowly at 1-2 week intervals for shorter half-life agents (sertraline, escitalopram). 6
Monitor for serotonin syndrome when combining SSRIs and bupropion, though the risk is low with this combination. 6
Allow 6-8 weeks at adequate doses before determining treatment response. 7
Second-Line: SNRIs
SNRIs (venlafaxine or duloxetine) are second-line options with demonstrated efficacy for anxiety disorders, though venlafaxine showed superior anxiolytic effects compared to fluoxetine in some trials. 6
What NOT to Do
Do Not Add Buspirone
- Buspirone takes 2-4 weeks to become effective and is only useful for mild-moderate agitation. 6
- It has a less robust evidence base compared to SSRIs for anxiety disorders. 6
Do Not Add Benzodiazepines for Chronic Management
- Benzodiazepines are not first-line for chronic anxiety treatment and carry risk of dependence with chronic use. 6
- If a patient is already on benzodiazepines and opioids, avoid prescribing opioids and benzodiazepines concurrently whenever possible due to quadrupling of overdose death risk. 8
Do Not Discontinue Bupropion Prematurely
Baseline anxiety levels do not predict differential response between bupropion and SSRIs, so there is no evidence-based reason to discontinue bupropion solely due to anxiety. 2, 3
Bupropion may be particularly beneficial for patients with depression characterized by low energy, apathy, or hypersomnia due to its activating properties. 7
Critical Monitoring Parameters
Early Treatment (First 1-2 Weeks)
Monitor for worsening depression, suicidal ideation, or behavioral changes, particularly in patients under 24 years of age, as the risk for suicide attempts is greatest during the first 1-2 months of treatment. 7
Monitor blood pressure and heart rate periodically, especially in the first 12 weeks, as bupropion can cause elevations in both parameters. 7
Ongoing Assessment
Assess for adequate response within 6-8 weeks before considering treatment modification. 7
If no adequate response occurs by 6-8 weeks at therapeutic doses, modify the treatment approach rather than continuing ineffective therapy. 7
Special Considerations
Seizure Risk Management
Instruct patients to discontinue bupropion if they experience a seizure while on treatment. 5
The excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can increase seizure risk. 5
Maximum dose should not exceed 450 mg per day for XL formulation or 400 mg per day for SR formulation to minimize seizure risk. 7
Contraindications Related to Anxiety Disorders
Bupropion is contraindicated in patients with eating disorders (bulimia or anorexia nervosa) due to increased seizure risk. 7
Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs is an absolute contraindication for bupropion use due to increased seizure risk. 7
Clinical Algorithm Summary
Continue bupropion if patient has comorbid anxiety, as evidence shows no increased anxiety compared to SSRIs. 1, 2
If anxiety requires specific treatment, add sertraline (first choice) or escitalopram (alternative), titrating slowly over 1-2 weeks. 6
Monitor closely in first 1-2 weeks for emergence of severe, abrupt anxiety that was not part of presenting symptoms. 5
Allow 6-8 weeks at therapeutic doses before determining if combination therapy is effective. 7
Avoid benzodiazepines for chronic anxiety management and buspirone as monotherapy augmentation. 6