Quiz: Non-Stimulant Medications

Will, Age 16

Will is referred by his outpatient substance use counselor after completing a 28-day residential program for cannabis and nicotine use disorder. He was diagnosed with ADHD-Combined type at age 8 and stopped taking methylphenidate at 13, around the time cannabis use escalated. His counselor reports that untreated ADHD is derailing aftercare: he forgets appointments, cannot sustain attention in group therapy, and is falling behind in a credit-recovery program required by his probation. His mother asks to restart "his methylphenidate." Pharmacogenomic testing from residential treatment shows CYP2D6 intermediate metabolizer status.

Q1. Which medication is most appropriate first-line?

Q2. Given Will's CYP2D6 intermediate metabolizer status, which dosing modification is most appropriate when starting atomoxetine?

Q3. At a 3-week follow-up, Will's mother reports no improvement and his counselor agrees. She asks about trying a different medication. Which of the following is the most appropriate response?

Q4. At 6 months, Will is stable on atomoxetine with moderate improvement. His substance use counselor reports 5 months of sustained recovery. His mother again asks about restarting methylphenidate for "better results." Which of the following is most accurate?

Renata, Age 30

Renata presents with newly diagnosed ADHD, Predominantly Inattentive, and comorbid generalized anxiety disorder (GAD) treated with fluoxetine 20 mg for the past year. She has no substance use history. Her psychiatrist explains that she would like to start a non-stimulant ADHD medication. Renata asks why she is not being offered a stimulant like her coworker takes.

Q5. Which of the following best supports choosing atomoxetine over a stimulant for Renata?

Q6. Her psychiatrist plans to start atomoxetine at the standard target dose of 80 mg/day. Given that Renata is taking fluoxetine 20 mg, which of the following is the most important consideration?

Q7. At 8 weeks on reduced-dose atomoxetine, Renata reports moderate improvement in focus but says "my coworker's medication worked in a day." She asks whether she will ever reach full benefit. Which of the following is the most accurate expectation?

Q8. Renata's psychiatrist considers adding a stimulant for residual symptoms. Given her fluoxetine, which stimulant class pairing is pharmacokinetically safer?

Layla, Age 9

Layla has been on optimized OROS methylphenidate 36 mg, approximately 1 mg/kg) for 14 months. Her core inattention is well-controlled during school, and her grades have improved from D's to B's. However, her parents describe severe end-of-day rebound irritability starting at 5 PM with explosive tantrums, and she cannot fall asleep before 10:30 PM despite consistent sleep hygiene. Increasing the dose to 54 mg worsened both the rebound and the insomnia. Melatonin 3 mg helped modestly with sleep onset but did nothing for the irritability. She also has a comorbid tic disorder (motor tics, mild-moderate severity).

Q9. Which of the following is the most appropriate next step?

Q10. Guanfacine XR 1 mg at bedtime is started. At 3 weeks, her teacher reports Layla is drowsy during afternoon lessons and occasionally falls asleep. BP is 90/56, HR 64. Which of the following is the most appropriate management?

Q11. Which of the following is the most important counseling point for Layla's family?

Q12. At a follow-up visit, Layla's father reports her motor tics have decreased noticeably since starting guanfacine. He asks if this is expected. Which of the following is most accurate?

Q13. Three months later, the family goes on vacation and Layla runs out of guanfacine for two days. Her mother calls reporting severe headache, irritability, and pounding heart. What is the most appropriate response?

Devon, Age 34

Devon is referred with a note reading "treatment-resistant ADHD, has failed everything." He was diagnosed at 28. He trialed methylphenidate ER (up to 54 mg), lisdexamfetamine (up to 50 mg, discontinued for severe anxiety), and was started on viloxazine ER 400 mg six weeks ago. He reports the viloxazine "helps a little with focus" but has developed severe insomnia (sleep onset after 1 AM), jitteriness, and intermittent tremors. He drinks 4-5 cups of coffee daily (approximately 500-600 mg caffeine) and has a nightly energy drink. He has never had a formal anxiety evaluation despite the lisdexamfetamine-associated anxiety.

Q14. Before concluding the viloxazine has failed, which of the following should be investigated first?

Q15. Devon's treatment history shows three medication trials, each discontinued for different reasons. Before escalating pharmacotherapy, which step in the treatment-resistant algorithm should be prioritized?

Q16. After reducing caffeine and diagnosing comorbid GAD (treated with sertraline), Devon's viloxazine-related side effects resolve and his ADHD improves. However, residual impulsivity and disorganization persist. His clinician is ready for pharmacological augmentation. Which agent has the strongest evidence as a first augmentation?

Q17. Devon asks about the strength of evidence for viloxazine compared to atomoxetine. Which of the following is most accurate?

Q18. Devon mentions he read online that viloxazine is "basically a faster atomoxetine." What is the key mechanistic difference?

Rosa, Age 32

Rosa has been stable on atomoxetine 80 mg for ADHD, Predominantly Inattentive, for two years. She discovers she is 6 weeks pregnant. She and her husband have been planning this pregnancy. She asks whether to continue, switch, or stop her medication.

Q19. Which of the following is the most appropriate initial approach?

Q20. Rosa decides to discontinue atomoxetine during pregnancy with a plan to resume postpartum. She plans to breastfeed. Which of the following is the most important consideration for postpartum medication selection?

Harris, Age 44

Harris has ADHD and comorbid major depressive disorder (MDD). He also has a history of bulimia nervosa in remission for 3 years. His PCP noted that bupropion could treat both conditions and asks your opinion before prescribing.

Q21. Which of the following is the most important safety concern?

Q22. Given that bupropion is contraindicated, which of the following treatment approaches is most appropriate for Harris's dual diagnosis?

Q23. Harris is started on methylphenidate ER and sertraline. At 6 weeks, his depression is improving but his ADHD response is partial on methylphenidate ER 36 mg. Which of the following is the most appropriate next step?

Kai, Age 28

Kai is a 28-year-old man with newly diagnosed ADHD, Predominantly Inattentive. He has no substance use history. His psychiatrist is reviewing the non-stimulant medication options with him and discussing their pharmacological properties to guide shared decision-making.

Q24. Atomoxetine blocks the norepinephrine transporter (NET). In the prefrontal cortex, NET clears both norepinephrine and a second neurotransmitter. Which neurotransmitter?

Q25. A patient who is a CYP2D6 poor metabolizer has an atomoxetine half-life approximately how long?

Q26. Which property distinguishes guanfacine from clonidine as an alpha-2 agonist?

Q27. Kai's psychiatrist considers viloxazine. Which enzyme does viloxazine strongly inhibit, creating a clinically significant interaction with caffeine?

Q28. Kai is started on guanfacine XR 1 mg at bedtime with good initial response. Two months later, his primary care provider prescribes rifampin for latent tuberculosis. What is the most likely pharmacokinetic consequence for his guanfacine therapy?

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