What is the recommended dosing of bupropion (Bupropion) for a patient with depression, anxiety, and comorbid post-traumatic stress disorder (PTSD)?

Bupropion Dosing for Depression, Anxiety, and Comorbid PTSD

Start bupropion XL at 150 mg once daily in the morning, then increase to 300 mg once daily after 4-7 days if tolerated, which is the standard therapeutic dose for major depressive disorder and appears effective for comorbid anxiety and PTSD based on emerging evidence. 1, 2

Initial Dosing Strategy

For patients with depression, anxiety, and PTSD, initiate bupropion XL 150 mg once daily in the morning, taken with or without food. 1 After 4 days of dosing at 150 mg, increase to the target dose of 300 mg once daily in the morning if the medication is well tolerated 1. This gradual titration minimizes seizure risk while achieving therapeutic drug levels 3.

• The FDA-approved starting dose for major depressive disorder is 150 mg once daily, with escalation to 300 mg after 4 days 1
• For patients on multiple psychotropic medications or those at higher risk for adverse effects, consider starting at 37.5 mg every morning and increasing by 37.5 mg every 3 days as tolerated 3
• The maximum dose is 450 mg per day for the XL formulation, though 300 mg is typically sufficient for most patients with depression 3, 1

Evidence for Use in PTSD and Anxiety

Emerging evidence suggests bupropion may be effective for PTSD, particularly when comorbid with substance use disorders. A recent case series demonstrated that patients with comorbid PTSD and methamphetamine use disorder had PTSD Checklist scores decrease from 77 at baseline to 35 at discharge and 29 post-discharge when treated with bupropion-containing regimens, compared to minimal improvement (51 to 52 to 53) in patients receiving serotonergic agents alone 2. This represents a dramatic 55% reduction in PTSD symptoms with bupropion versus essentially no change with traditional serotonergic therapy 2.

• A pilot controlled trial found bupropion XL (150-300 mg/day) demonstrated comparable anxiolytic efficacy to escitalopram (10-20 mg/day) in generalized anxiety disorder, with both treatments well-tolerated 4
• While serotonergic agents remain first-line for PTSD per traditional guidelines 5, the 2025 case series suggests earlier initiation of bupropion may be beneficial in PTSD patients with comorbid substance use 2
• The presence of comorbid anxiety does not appear to significantly affect bupropion's comparative efficacy based on STAR*D trial analyses 3

Maintenance Dosing and Duration

Continue bupropion at 300 mg once daily for at least 6-8 weeks before assessing adequacy of response. 5, 3 Acute episodes of depression require several months or longer of antidepressant treatment beyond the initial response 1.

• Begin monitoring patient status, therapeutic response, and adverse effects within 1-2 weeks of initiation, as the risk for suicide attempts is greatest during the first 1-2 months of treatment 5, 3
• If no adequate response occurs by 6-8 weeks at therapeutic doses, modify the treatment approach by either increasing the dose (up to 450 mg/day maximum) or adding augmentation therapy 5, 3
• Response rates to antidepressant therapy may be as low as 50%, with 38% of patients not achieving treatment response during 6-12 weeks 3

Critical Safety Screening Before Prescribing

Absolute contraindications that must be ruled out include: 3, 1

• Seizure disorders or any condition predisposing to seizures (brain tumor, stroke, head trauma) - bupropion lowers seizure threshold with approximately 0.1% risk at doses ≤300 mg/day 3, 6
• Current or recent MAOI use (within 14 days) - risk of hypertensive crisis 1
• Eating disorders (bulimia or anorexia nervosa) - increased seizure risk 3
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs - dramatically increases seizure risk 3
• Uncontrolled hypertension - bupropion can elevate blood pressure and heart rate 5, 3

Dose Adjustments for Special Populations

Hepatic impairment: In moderate to severe hepatic impairment (Child-Pugh score 7-15), the maximum dose is 150 mg every other day 1. In mild hepatic impairment (Child-Pugh score 5-6), reduce the dose and/or frequency 1.

Renal impairment: For patients with glomerular filtration rate <90 mL/min, reduce the total daily dose by 50% 3, 1. Bupropion and its metabolites are cleared renally and may accumulate, requiring close monitoring 3.

Older adults: Start with 37.5 mg every morning, then gradually increase by 37.5 mg every 3 days as tolerated, with a maximum dose of 150 mg twice daily (300 mg total daily) 3. Administer the second dose before 3 PM to minimize insomnia risk 3.

Monitoring Parameters

Monitor the following throughout treatment: 3

• Blood pressure and heart rate periodically, especially in the first 12 weeks, as bupropion can cause elevations in both parameters 3
• Neuropsychiatric symptoms including agitation, irritability, unusual behavioral changes, and suicidal ideation, particularly in patients under 24 years old 5, 3
• Seizure risk factors and ensure maximum dose does not exceed 450 mg/day for XL formulation 3, 1

Augmentation Strategies if Inadequate Response

If bupropion monotherapy fails after 6-8 weeks at 300 mg daily, augment with an SSRI or SNRI rather than switching. 3 Adding an SSRI to existing bupropion therapy demonstrates superior efficacy compared to other augmentation strategies, with remission rates of 30.3% when augmenting with bupropion versus other agents, and significantly lower discontinuation rates due to adverse events (12.5% vs 20.6%, P<0.001) 3.

• Augmentation with bupropion is equally effective as switching to another antidepressant but may be preferred to avoid discontinuation symptoms 3
• The combination of bupropion and sertraline addresses depression through complementary mechanisms, with sertraline affecting serotonin and bupropion working via noradrenergic/dopaminergic pathways 3
• The maximum dose must not exceed 450 mg/day to maintain seizure risk at 0.1% 3

Clinical Advantages of Bupropion

Bupropion offers distinct advantages over SSRIs: 5, 3

• Significantly lower rates of sexual dysfunction compared to SSRIs like fluoxetine, sertraline, and paroxetine 5, 3
• Minimal weight gain or even weight loss, unlike many other antidepressants 3, 7
• Lower rates of sedation than SSRIs, making it particularly beneficial for patients with depression characterized by low energy, apathy, or hypersomnia 3
• Dual benefit for smoking cessation in patients who also want to quit smoking, addressing both depression and nicotine dependence simultaneously 3

Discontinuation Protocol

When discontinuing bupropion XL 300 mg once daily, taper to 150 mg once daily for at least several days before complete discontinuation. 1 This gradual reduction minimizes potential withdrawal symptoms, though bupropion has less risk of discontinuation syndrome compared to shorter-acting SSRIs like paroxetine 5, 3.