What alternative treatment options are suitable for a patient with ADHD, depressive symptoms, opioid use disorder, and urinary difficulties, who is currently on Atomoxetine (Strattera) 80mg and Suboxone (Buprenorphine/Naloxone), with a history of nicotine and marijuana use, and no seizure history, without prescribing stimulants?

Discontinue Atomoxetine and Initiate Bupropion for ADHD and Depressive Symptoms

Discontinue atomoxetine immediately and initiate bupropion SR 100-150 mg daily (or XL 150 mg daily), titrating to 150 mg twice daily (SR) or 300 mg daily (XL) over 2-4 weeks, as this addresses both ADHD symptoms, depressive symptoms, and eliminates the urinary difficulties caused by atomoxetine's noradrenergic effects. 1

Rationale for Discontinuing Atomoxetine

Atomoxetine is directly causing the urinary retention symptoms through its norepinephrine reuptake inhibition, which increases urethral sphincter tone. 2 The FDA labeling specifically lists urinary retention and difficulties with micturition as known adverse effects in adults. 3 Given that the patient reports no improvement in ADHD symptoms after adequate trial, there is no therapeutic benefit to offset these bothersome urinary side effects. 2

• Atomoxetine requires 6-12 weeks to achieve full therapeutic effect, and if symptoms haven't improved by now at 80 mg (near the maximum dose of 100 mg), further dose escalation is unlikely to help. 4
• The patient's urinary symptoms (straining, hesitancy) are classic anticholinergic/noradrenergic effects that will resolve upon discontinuation. 3

Why Bupropion is the Optimal Choice

Bupropion addresses multiple clinical needs simultaneously while avoiding stimulants in this patient with opioid use disorder:

• ADHD efficacy: Bupropion has demonstrated efficacy for ADHD as a second-line agent, though with smaller effect sizes than stimulants (standardized mean difference of -0.50 compared to placebo). 1
• Depression management: Bupropion is FDA-approved for depression and will address the patient's reported depressive symptoms with reduced energy. 1
• Substance use considerations: Bupropion is specifically recommended as a first-line option when treating adults with ADHD and substance abuse history, as it has no abuse potential and is not a controlled substance. 5, 1
• Smoking cessation benefit: Given the patient's nicotine vaping, bupropion may provide additional benefit for nicotine dependence. 1
• No urinary effects: Unlike atomoxetine, bupropion does not cause urinary retention. 1

Specific Dosing Protocol

Start bupropion SR 100-150 mg once daily in the morning for the first week:

• After 1 week, increase to 150 mg twice daily (morning and early afternoon) if tolerated. 1
• Alternatively, use bupropion XL 150 mg daily, increasing to 300 mg daily after 1 week. 1
• Maximum dose is 450 mg per day (do not exceed this due to seizure risk). 1
• The patient has no seizure history, which is favorable, but monitor for factors that lower seizure threshold. 1

Critical Monitoring Parameters

Monitor closely during the first 2-4 weeks for:

• Worsening anxiety, agitation, or insomnia: Bupropion is inherently activating and can exacerbate these symptoms. 1
• Suicidality: Both atomoxetine and bupropion carry warnings about suicidal ideation, particularly important given the patient's depressive symptoms. 2
• Blood pressure and pulse: Though less pronounced than with stimulants, monitor cardiovascular parameters. 1
• Substance use relapse: Schedule monthly follow-up visits and consider urine drug screening to ensure compliance and detect any return to substance use. 1
• Resolution of urinary symptoms: These should improve within days to weeks of stopping atomoxetine. 3

Why Stimulants Remain Contraindicated

Your decision to withhold stimulants in this patient with active opioid use disorder (on Suboxone) is clinically appropriate:

• Guidelines recommend exercising caution when prescribing stimulants to patients with comorbid substance abuse disorders. 1, 6
• Long-acting stimulant formulations with lower abuse potential (like lisdexamfetamine or OROS methylphenidate) could theoretically be considered, but only after substance use stabilization and with careful monitoring. 6
• The patient's continued marijuana use and nicotine vaping indicate ongoing polysubstance use, making stimulant therapy particularly risky. 6
• Atomoxetine and bupropion are specifically recommended as first-line options in patients with substance use history. 4, 5

Addressing Comorbid Depression

If depressive symptoms persist after 4-6 weeks on bupropion at therapeutic doses, consider adding an SSRI:

• SSRIs remain the treatment of choice for depression and can be safely combined with bupropion. 1
• There are no significant pharmacokinetic interactions between bupropion and SSRIs. 1
• However, give bupropion an adequate trial first (4-6 weeks at therapeutic dose) before adding another agent. 1

Multimodal Treatment Approach

Pharmacotherapy must be combined with psychosocial interventions:

• Continue behavioral therapy and addiction treatment for opioid use disorder. 4, 5
• Consider cognitive-behavioral therapy for both ADHD and depression. 1
• Address lifestyle factors: regular sleep schedule, stress management, and exercise can enhance medication effectiveness. 1
• Provide psychoeducation about medication adherence and realistic expectations for symptom improvement. 1

Common Pitfalls to Avoid

• Do not assume bupropion alone will fully treat both ADHD and depression: No single antidepressant is proven for this dual purpose, and bupropion is a second-line agent for ADHD compared to stimulants. 1
• Do not use MAO inhibitors concurrently: There is a risk of hypertensive crisis with bupropion. At least 14 days should elapse between discontinuation of an MAOI and initiation of bupropion. 1
• Do not exceed 450 mg/day of bupropion: This increases seizure risk significantly. 1
• Do not discontinue Suboxone: Continue opioid use disorder treatment as the foundation of this patient's care. 5

Expected Timeline

• Urinary symptoms: Should improve within 3-7 days of stopping atomoxetine. 3
• ADHD symptoms: Bupropion works more rapidly than atomoxetine but still requires 2-4 weeks for full effect. 1
• Depressive symptoms: Expect 4-6 weeks for antidepressant effects to manifest fully. 1
• Follow-up schedule: See patient in 1-2 weeks initially, then monthly until symptoms stabilize. 1, 6