What treatment approach is recommended for a patient on Wellbutrin (bupropion) with severe anxiety, nightly panic attacks, and concerns for Attention Deficit Hyperactivity Disorder (ADHD)?

Management of Severe Anxiety and Panic Attacks in a Patient on Wellbutrin with ADHD Concerns

Immediate Priority: Address the Severe Anxiety and Nightly Panic Attacks

Bupropion is inherently activating and can exacerbate anxiety or agitation, making it a problematic choice for patients with severe anxiety and panic attacks—you should discontinue or taper the Wellbutrin and initiate an SSRI as first-line treatment for the panic disorder and severe anxiety. 1

Why Wellbutrin Must Be Reconsidered

• Bupropion is explicitly noted to cause headache, insomnia, and anxiety as side effects, which directly contradicts the needs of a patient experiencing nightly panic attacks and severe anxiety 1
• The activating properties of bupropion can worsen anxiety symptoms, particularly in patients with comorbid anxiety disorders 1
• Critical pitfall to avoid: The American Academy of Child and Adolescent Psychiatry warns against assuming a single antidepressant like bupropion will effectively treat both ADHD and anxiety/panic, as no single antidepressant is proven for this dual purpose 1

First-Line Treatment for Panic Disorder and Severe Anxiety

• SSRIs (fluoxetine or sertraline) are the treatment of choice for anxiety disorders and panic disorder, with the highest level of evidence supporting their use 2, 3
• SSRIs should be continued for 6 to 12 months after remission of anxiety symptoms 3
• Cognitive behavioral therapy combined with an SSRI shows superior outcomes compared to either alone for anxiety disorders, with improvements in global function, response rates, and remission rates 2

Monitoring During SSRI Initiation

• SSRIs can take 3-4 weeks to reach full therapeutic effect 2
• Monitor for initial anxiety or agitation as an adverse effect during the first few weeks 2
• Systematically assess for suicidal ideation, clinical worsening, and unusual behavioral changes, especially during the first few months or at dose changes 2

---

Second Priority: Address ADHD After Anxiety Stabilization

Once the panic attacks and severe anxiety are controlled with an SSRI (typically after 4-6 weeks), initiate a stimulant medication trial as first-line treatment for ADHD, as stimulants have 70-80% response rates and work within days. 1, 2

Why Stimulants Should Be First-Line for ADHD

• Stimulants (methylphenidate or amphetamines) are the gold standard first-line treatment for ADHD in adults, with the largest effect sizes and most robust evidence from over 161 randomized controlled trials 1
• Outdated concern debunked: Early concerns about stimulants worsening anxiety have been disproven—the MTA study showed that ADHD patients with comorbid anxiety actually have better treatment responses to stimulants than those without anxiety 2
• Stimulants work rapidly (within days), allowing quick assessment of ADHD symptom response 1, 2

Specific Stimulant Recommendations

• Start with long-acting methylphenidate (18-54 mg daily) or lisdexamfetamine (20-70 mg daily) to provide all-day coverage and minimize rebound symptoms 1, 2
• Prefer extended-release formulations for once-daily dosing, which improves medication adherence 1, 2
• Titrate systematically to optimal effect rather than using strict mg/kg calculations, as more than 70% of patients respond optimally when proper titration protocols are followed 1

Monitoring Requirements with Stimulants

• Monitor blood pressure and pulse at baseline and regularly during treatment 1
• Track appetite, sleep disturbances, and weight changes as common adverse effects 1
• Avoid stimulants in patients with uncontrolled hypertension or symptomatic cardiovascular disease 1

---

Alternative Approach: If Stimulants Are Not Tolerated or Contraindicated

If the patient cannot tolerate stimulants or has contraindications, atomoxetine (60-100 mg daily) is the only FDA-approved non-stimulant for adult ADHD and has evidence supporting its use in ADHD with comorbid anxiety. 1, 2

Atomoxetine Considerations

• Atomoxetine provides "around-the-clock" effects without rebound and is an uncontrolled substance with lower abuse potential 1, 2
• Requires 2-4 weeks to achieve full therapeutic effect, unlike stimulants which work within days 1
• Black box warning: Monitor for suicidality, clinical worsening, and unusual behavioral changes, particularly when combined with SSRIs 1
• SSRIs can elevate serum atomoxetine levels through CYP2D6 inhibition, requiring dose adjustment 1

Adjunctive Options for Persistent Symptoms

• If anxiety remains problematic despite adequate SSRI dosing and ADHD treatment, add cognitive behavioral therapy to the medication regimen 2
• Alpha-2 agonists (guanfacine 1-4 mg daily or clonidine) can be used as adjunctive therapy, particularly if sleep disturbances are present 1, 2

---

What NOT to Do: Critical Pitfalls

• Do not continue bupropion as monotherapy for a patient with severe anxiety and panic attacks, as its activating properties directly worsen these symptoms 1
• Do not assume anxiety is a contraindication to stimulants—this outdated belief deprives patients of the most effective ADHD treatment 2
• Do not prescribe benzodiazepines for chronic anxiety management in ADHD patients, as they may reduce self-control and have disinhibiting effects 1
• Do not use MAO inhibitors concurrently with stimulants or bupropion due to risk of hypertensive crisis 1
• Do not treat only one condition (either ADHD or anxiety)—both require simultaneous management for optimal outcomes 2

---

Treatment Algorithm Summary

1. Week 0-1: Taper and discontinue bupropion; initiate SSRI (sertraline 50-200 mg or fluoxetine 20-80 mg daily) 2, 3
2. Week 4-6: Once panic attacks and severe anxiety are controlled, add a long-acting stimulant (methylphenidate 18-54 mg or lisdexamfetamine 20-70 mg daily) 1, 2
3. Week 8-10: If ADHD symptoms improve but anxiety persists, optimize SSRI dosing and add CBT 2
4. Week 12+: If response is insufficient, consider switching stimulant class or adding atomoxetine/alpha-2 agonist as adjunctive therapy 1, 2