In an adult with ADHD, generalized anxiety disorder, and major depressive disorder taking bupropion (Wellbutrin) 300 mg daily, lisdexamfetamine (Vyvanse) 30 mg daily, and sertraline (Zoloft) 100 mg daily, who reports frequent crying after a recent increase in bupropion dose, what is the most appropriate next step in management?

Management of Persistent Crying Despite Optimized ADHD Treatment

Optimize the sertraline dose to 150–200 mg daily before making any other medication changes, because the patient's frequent crying indicates inadequately treated depression or anxiety despite the recent bupropion increase. 1

Understanding the Current Medication Regimen

Your patient is on a rational three-medication regimen targeting distinct neurobiological systems:

• Vyvanse 30 mg addresses ADHD through dopaminergic mechanisms and is working effectively for attention symptoms 1
• Bupropion 300 mg provides norepinephrine-dopamine reuptake inhibition for both ADHD augmentation and depression 2, 3
• Sertraline 100 mg targets serotonergic pathways for depression and generalized anxiety disorder 1

The fact that she reports Vyvanse is working but continues to cry frequently indicates the mood/anxiety component is undertreated, not the ADHD component. 1

Why Increasing Bupropion Was Likely Insufficient

• Bupropion has activating properties that can exacerbate anxiety or agitation, making it potentially problematic when anxiety symptoms are prominent 1
• The American Academy of Child and Adolescent Psychiatry explicitly warns that bupropion can cause headache, insomnia, and anxiety as side effects 1
• No single antidepressant is proven to effectively treat both ADHD and depression; bupropion is positioned as a second-line agent for ADHD compared to stimulants 1, 2
• While bupropion augmentation of SSRIs shows lower discontinuation rates than buspirone augmentation, the primary mood stabilization should come from optimizing the SSRI 1

Primary Recommendation: Optimize Sertraline First

Increase sertraline from 100 mg to 150 mg daily immediately, then reassess after 2 weeks; if crying persists, titrate to 200 mg daily. 1

Rationale for SSRI Optimization

• SSRIs remain the treatment of choice for depression and generalized anxiety disorder and are weight-neutral with long-term use 1
• The therapeutic range for sertraline extends to 200 mg daily, and your patient is currently at a mid-range dose 1
• If ADHD symptoms improve but mood symptoms persist, adding or optimizing an SSRI is the evidence-based approach rather than further stimulant or bupropion adjustment 1
• The combination of stimulant plus SSRI is well-established, safe, and lacks significant pharmacokinetic interactions 1

Monitoring During Sertraline Titration

• Screen for suicidality at every visit, particularly during SSRI dose changes 1
• Assess for akathisia (inner restlessness), which can present as agitation or crying and may require dose reduction 1
• Monitor for activation syndrome in the first 2–4 weeks, though this is more common with bupropion than SSRIs 1

Secondary Consideration: Reassess Bupropion's Role

If anxiety or crying worsens after the bupropion increase to 300 mg, consider reducing bupropion back to the previous dose or discontinuing it entirely while maintaining the stimulant and optimized SSRI. 1

Why Bupropion May Be Counterproductive

• Bupropion is inherently activating and can exacerbate anxiety or agitation, particularly in patients with prominent generalized anxiety disorder 1
• The patient's frequent crying may represent anxiety manifestation or emotional dysregulation that bupropion's activating properties are worsening 1
• Monitor closely for worsening hyperactivity, insomnia, anxiety, and agitation during the first 2–4 weeks when using bupropion, and be especially cautious in patients with comorbid anxiety disorders 1

When Bupropion Remains Appropriate

• If the patient has comorbid smoking cessation goals, bupropion provides dual benefit 2
• If weight gain from antidepressants is a concern, bupropion is the only antidepressant that promotes weight loss 1
• If there is history of substance abuse, bupropion is an uncontrolled substance with no abuse potential 2, 4

Algorithm for Next Steps

Week 1–2: Immediate Action

1. Increase sertraline to 150 mg daily 1
2. Continue Vyvanse 30 mg (it's working for ADHD) 1
3. Maintain bupropion 300 mg temporarily to assess sertraline response 1
4. Screen for suicidality at this visit 1

Week 2–4: Reassessment

• If crying improves by ≥50%: continue current regimen and monitor 1
• If crying persists or worsens:
  • Increase sertraline to 175–200 mg daily 1
  • Consider reducing bupropion to 150 mg or discontinuing if anxiety is prominent 1

Week 6–8: Final Optimization

• If mood symptoms are still inadequate despite sertraline 200 mg:
  • Refer to psychiatry for consideration of alternative antidepressants or augmentation strategies 1
  • Consider whether bipolar spectrum disorder has been adequately ruled out, as antidepressants can worsen mood cycling 1

Critical Monitoring Parameters

• Blood pressure and pulse at each visit (all three medications can affect cardiovascular parameters) 1, 2
• Sleep quality and appetite (stimulants and bupropion both suppress appetite and disrupt sleep) 1, 2
• Suicidality screening at every visit using systematic inquiry 1
• Functional improvement across work, social, and personal domains 1

Common Pitfalls to Avoid

• Do not assume bupropion will treat both ADHD and depression adequately; it is a second-line ADHD agent with activating properties that may worsen anxiety 1, 2
• Do not increase Vyvanse dose when the problem is mood-related, not attention-related; the patient explicitly states Vyvanse is working 1
• Do not add benzodiazepines for anxiety in this population, as they may reduce self-control and have disinhibiting effects 1
• Do not switch SSRIs (e.g., from sertraline to another SSRI) without first optimizing the current SSRI dose, as the STAR*D trial showed no difference in response rates between SSRI switches 1

Integration of Psychotherapy

Strongly recommend cognitive behavioral therapy (CBT) specifically developed for ADHD, which is the most extensively studied psychotherapy and shows increased effectiveness when combined with medication for treating ADHD with comorbid depression. 1

• Mindfulness-Based Cognitive Therapy (MBCT) helps profoundly with emotion regulation, executive function, and quality of life 1
• Psychotherapy should complement, not replace, optimized pharmacotherapy 1

When to Refer to Psychiatry

• Severe mood symptoms with suicidal ideation, psychosis, or marked neurovegetative signs 1
• Treatment-resistant cases after optimizing all three medications 1
• Suspicion of bipolar spectrum disorder, especially if mood symptoms worsen with antidepressant increases 1
• Multiple medication failures or complex polypharmacy requiring specialized management 1