In an adult with major depressive disorder and mild‑to‑moderate anxiety, does bupropion treat (cure) anxiety or at least not worsen it?

Bupropion Does Not Worsen Anxiety in Major Depressive Disorder with Mild-to-Moderate Anxiety

The American Academy of Family Physicians recommends bupropion as an appropriate choice for anxiety when it occurs as part of a depressive syndrome, particularly in patients with depression and comorbid mild-to-moderate anxiety who also have prominent apathy, fatigue, or low energy. 1

Evidence Supporting Bupropion's Safety in Comorbid Anxiety

Baseline anxiety levels do not predict differential response between bupropion and SSRIs, and do not serve as a basis for avoiding bupropion in depressed patients with anxiety. 2 In a pooled analysis of 692 patients with major depressive disorder, pretreatment anxiety levels were not related to antidepressant response to either bupropion SR or sertraline, nor did they differentiate between responders to the two medications 2.

Bupropion demonstrates comparable anxiolytic efficacy to serotonergic antidepressants in patients with depression and mild-to-moderate anxiety. 3 Clinical trials show bupropion significantly reduces anxiety symptoms in depressed patients, with efficacy comparable to SSRIs and SNRIs for mild to moderate anxiety 3. In a 4-week placebo-controlled trial, bupropion (300-600 mg/day) was significantly more effective than placebo on the Hamilton Anxiety Scale (P < 0.01) in treating accompanying anxiety in depressed inpatients 4.

When to Avoid Bupropion

The American Academy of Family Physicians states that bupropion should generally be avoided as a first-line option for primary anxiety disorders and is specifically contraindicated in patients with agitated depression or prominent anxiety symptoms. 1 This distinction is critical: bupropion is appropriate for anxiety as part of depression but not for primary anxiety disorders 1.

For individuals whose primary diagnosis is an anxiety disorder without comorbid depression, initiate an SSRI or SNRI instead of bupropion. 1

Practical Implementation Strategy

Patient Selection Algorithm:

• Depression with mild-to-moderate anxiety + apathy/fatigue/low energy → Bupropion is appropriate 1
• Depression with severe/prominent anxiety or agitation → Avoid bupropion; choose SSRI 1
• Primary anxiety disorder without depression → Avoid bupropion; choose SSRI 1

Dosing to Minimize Anxiogenic Effects:

• Administer the second daily dose before 3 PM to minimize insomnia, which can exacerbate anxiety 1
• Start at lower doses and titrate gradually while monitoring for emergence of agitation, irritability, or unusual behavioral changes 1

Monitoring Timeline:

• Assess patient status within 1-2 weeks of initiation, monitoring specifically for emergence of agitation, irritability, anxiety, or unusual behavioral changes 1
• Evaluate response after 6-8 weeks; if inadequate, modify treatment rather than continuing ineffective therapy 1

Comparative Advantages

Bupropion has lower rates of sexual adverse events compared to SSRIs, which may improve quality of life in patients with comorbid depression and anxiety. 1 This is particularly relevant given that sexual dysfunction affects adherence and long-term outcomes 1.

Bupropion is particularly effective for symptoms of apathy and lack of energy in depression through its beneficial effect on dopamine levels. 1 This makes it especially suitable for patients whose depression presents with prominent fatigue and low motivation alongside anxiety 1.

Critical Safety Considerations

Bupropion should be avoided in patients with conditions predisposing to seizures, including anorexia or bulimia nervosa, or abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs. 1 The seizure risk is approximately 0.1% among those receiving bupropion for any indication 5.

Blood pressure monitoring is required, especially at treatment initiation, as bupropion can exacerbate uncontrolled hypertension. 1

Common Pitfalls to Avoid

The most common clinical error is assuming that bupropion's "activating" properties automatically worsen anxiety in all contexts 1. While bupropion can increase anxiety in susceptible patients—particularly those with primary anxiety disorders or severe agitation 6—this does not apply to patients with depression and mild-to-moderate comorbid anxiety 3, 2.

The stimulating properties of bupropion can provoke anxiety particularly at higher doses, so a cautious approach with lower initial doses and gradual titration is recommended. 3