A female adult patient with well‑controlled anxiety on sertraline and ADHD treated with bupropion extended‑release (Wellbutrin) 300 mg daily reports no improvement in ADHD symptoms; what is the next step in management?

Next Step: Switch from Bupropion to a Stimulant Medication

The next approach is to discontinue bupropion and initiate a stimulant medication trial, as stimulants are the gold-standard first-line treatment for ADHD with 70-80% response rates and the largest effect sizes, while bupropion is explicitly a second-line agent with smaller effect sizes. 1

Why Bupropion Failed and Why Stimulants Are Superior

• Bupropion has medium-range effect sizes of approximately 0.7 compared to stimulants, and is positioned as a second-line agent to be considered only when two or more stimulants have failed or caused intolerable side effects 1
• Stimulants work within days, allowing rapid assessment of ADHD symptom response, whereas bupropion requires weeks to months for full effect 1, 2
• The evidence base for stimulants includes over 161 randomized controlled trials, whereas bupropion has limited data and low-quality evidence 1, 3
• Approximately 70-80% of adults with ADHD respond to stimulants when properly titrated, making them far more likely to succeed than continuing with bupropion 1

Specific Stimulant Recommendations

Start with either:

• Methylphenidate extended-release (e.g., Concerta): Start 18 mg once daily in the morning, titrate by 18 mg weekly up to 54-72 mg daily maximum 1
• Lisdexamfetamine (Vyvanse): Start 20-30 mg once daily in the morning, titrate by 10-20 mg weekly up to 70 mg daily maximum 1
• Mixed amphetamine salts XR (Adderall XR): Start 10 mg once daily in the morning, titrate by 5 mg weekly up to 40-50 mg daily 1

Why Not Optimize Bupropion First

• The patient has already been on 300 mg of bupropion XL (the maximum recommended dose is 450 mg daily, but 300 mg is a robust therapeutic dose) with no improvement in ADHD symptoms 4
• Increasing bupropion further would delay effective treatment and expose the patient to higher seizure risk without strong evidence of benefit 1
• The systematic review found that even when bupropion works, it has smaller effect sizes than stimulants 3, 5

Managing the Transition

Discontinuation of bupropion:

• Taper bupropion over 1-2 weeks to minimize discontinuation effects, though abrupt discontinuation is generally tolerated 1
• Allow at least 2-3 days washout before starting a stimulant to clearly attribute any response or side effects to the new medication 1

Initiation of stimulant:

• Begin with a long-acting formulation to provide all-day coverage and improve adherence 1
• Titrate weekly using standardized ADHD rating scales to assess response 1
• Monitor blood pressure and pulse at baseline and each visit 1
• Assess sleep quality and appetite changes at each visit 1

Maintaining Sertraline for Anxiety

• Continue sertraline unchanged since her anxiety is well-controlled 1
• There are no significant pharmacokinetic interactions between stimulants and SSRIs, making this combination safe and well-established 1
• Stimulants may actually improve anxiety symptoms indirectly by reducing ADHD-related functional impairment 1, 2
• If anxiety worsens after starting a stimulant, this is uncommon but can be managed by dose adjustment or switching to a different stimulant class 1, 2

Trial Both Stimulant Classes if Needed

• Approximately 40% of patients respond to both methylphenidate and amphetamine classes, while another 40% respond to only one class 1
• If the first stimulant class fails after adequate titration (6-8 weeks at therapeutic doses), switch to the other class before considering non-stimulants 1
• Only after failing two different stimulant classes should you consider returning to bupropion or trying atomoxetine 1

Common Pitfalls to Avoid

• Do not assume bupropion will eventually work with more time or higher doses when there has been no improvement at 300 mg—this delays effective treatment 1
• Do not add a stimulant to bupropion as combination therapy, since there is no evidence supporting this approach and it complicates attribution of effects and side effects 1, 2
• Do not avoid stimulants due to anxiety concerns—the MTA study showed that ADHD patients with comorbid anxiety actually have better treatment responses to stimulants than those without anxiety 1, 2
• Do not use strict mg/kg dosing—systematic titration to optimal effect is more important, with 70% of patients responding optimally when proper titration protocols are followed 1

Monitoring During Stimulant Trial

• Obtain weekly ADHD symptom ratings during dose adjustment using standardized scales 1
• Check blood pressure and pulse at each titration visit 1
• Monitor for common side effects: appetite suppression, insomnia, headache 1
• Assess functional improvement across work, home, and social settings 1
• If ADHD symptoms improve but anxiety worsens (unlikely), consider dose reduction or switching stimulant class before discontinuing 1, 2