Can a patient switch from a Selective Serotonin Reuptake Inhibitor (SSRI) to Wellbutrin (bupropion) after a new diagnosis of Attention Deficit Hyperactivity Disorder (ADHD)?

Switching from SSRI to Wellbutrin for Newly Diagnosed ADHD

Yes, you can switch from an SSRI to bupropion (Wellbutrin) for a patient with newly diagnosed ADHD, but this is not the optimal approach—stimulants remain first-line for ADHD treatment and should be prioritized unless contraindicated. 1

Why Stimulants Should Be Considered First

• Stimulants (methylphenidate or amphetamines) are the gold standard first-line treatment for ADHD in adults, with a 70-80% response rate and the strongest effect sizes for reducing core ADHD symptoms. 2, 1

• The American Academy of Child and Adolescent Psychiatry recommends starting with stimulant medication as first-line treatment for adults with ADHD, with methylphenidate 5-20 mg three times daily or dextroamphetamine 5 mg three times daily to 20 mg twice daily (or equivalent long-acting formulations). 1, 3

• Stimulants work rapidly (within days), allowing quick assessment of treatment response, whereas bupropion requires weeks to reach full efficacy. 1, 3

When Bupropion Is an Appropriate Alternative

Bupropion should be considered as a second-line agent for ADHD in specific clinical contexts:

• History of substance use disorder where stimulant diversion or misuse is a concern 1

• Severe anxiety or pre-existing sleep disorders that might be exacerbated by stimulants 1

• Comorbid depression requiring treatment, particularly if the patient has failed or cannot tolerate SSRIs 3, 4

• Failure to respond to or intolerance of stimulant medications 4, 5

Evidence for Bupropion in ADHD

• Low-quality evidence from randomized controlled trials shows that bupropion decreases ADHD symptom severity (standardized mean difference -0.50) and increases the proportion of patients achieving clinical improvement (RR 1.50). 4

• Bupropion demonstrated efficacy comparable to methylphenidate in head-to-head trials, though a large multicenter study found smaller effect sizes for bupropion compared to methylphenidate. 5

• The typical dosing is bupropion SR 100-150 mg twice daily or XL 150-300 mg daily, with a maximum of 450 mg per day. 3

Critical Considerations for the Switch

If the patient has comorbid depression and ADHD:

• The American Academy of Child and Adolescent Psychiatry explicitly warns against assuming a single antidepressant will effectively treat both ADHD and depression—no single antidepressant is proven for this dual purpose. 3

• The optimal approach is to start with a stimulant for ADHD; if depressive symptoms persist despite ADHD improvement, add an SSRI to the stimulant regimen rather than switching. 3

• Switching from an SSRI to another antidepressant (including bupropion) showed no difference in response or remission rates in the STAR*D trial. 2

Algorithm for Decision-Making

Step 1: Assess for stimulant contraindications

• Active substance use disorder with high diversion risk
• Uncontrolled severe anxiety or panic disorder
• Significant cardiovascular disease
• Active psychosis or mania

Step 2: If no contraindications exist

• Start with stimulant monotherapy (methylphenidate or amphetamine extended-release formulation) 1
• Monitor for 2-4 weeks to assess ADHD and mood symptom response 1

Step 3: If stimulants are contraindicated or the patient refuses them

• Switch from SSRI to bupropion SR/XL, starting at 150 mg daily and titrating to 300-450 mg daily 3, 4
• Monitor closely for worsening anxiety, insomnia, and agitation during the first 2-4 weeks 3

Step 4: If both ADHD and depression require treatment

• Prioritize stimulant for ADHD first 3
• If depression persists after ADHD improvement, continue stimulant and optimize SSRI dose (e.g., escitalopram 10-20 mg daily) 1, 3
• Alternatively, consider augmenting citalopram with bupropion, which showed lower discontinuation rates due to adverse events compared to buspirone augmentation 2

Common Pitfalls to Avoid

• Do not assume bupropion alone will adequately treat both ADHD and depression—it is a second-line agent for ADHD with smaller effect sizes than stimulants. 3, 5

• Bupropion is inherently activating and can exacerbate anxiety, agitation, or hyperactivity, making it problematic for patients with prominent anxiety or hyperactive symptoms. 3

• Be especially cautious in patients with seizure risk, as bupropion lowers the seizure threshold, particularly at doses above 450 mg daily. 3

• Monitor for headache, insomnia, and anxiety as common side effects of bupropion. 3

Safety Profile

• The tolerability of bupropion is similar to placebo, with no significant difference in withdrawal rates due to adverse events. 4

• There are no significant pharmacokinetic interactions between bupropion and stimulants if combination therapy is later considered. 3

• Never use MAO inhibitors concurrently with bupropion due to risk of hypertensive crisis. 3