ADHD & Depression: Psychotropic Drug-Drug Interactions

25 year old male with history of ADHD and extensive substance abuse is stabilized on Atomoxetine 80 mg/day for ADHD.
On further evaluation he meets criteria for major depressive disorder and agreed for a trial of antidepressant. He is not using illicit substances for 2 years now.
Which of the following antidepressant will be your preferred choice?

This question is more directed toward drug-drug interactions and the role of Cytochrome P450:

Atomoxetine is metabolized by CYP2D6, so we should avoid medications inhibiting CYP2D6.

CYP2D6 inhibitors are classified into following three categories:

(A) Strong inhibitors: one that causes a > 5-fold increase in the plasma AUC values or more than 80% decrease in clearance.

  • Bupropion,
  • Fluoxetine and
  • Paroxetine

(B) Moderate inhibitors: one that causes a > 2-fold increase in the plasma AUC values or 50-80% decrease in clearance.

  • Sertraline,
  • Duloxetine

(C) Weak inhibitors: one that causes a > 1.25-fold but < 2-fold increase in the plasma AUC values or 20-50% decrease in clearance.

  • Cimetidine,
  • Amidoarone.

Based on this information, Sertraline is the best option available

Interaction Between Atomoxetine and Bupropion:

An open-label, non-randomized, two-period, sequential clinical trial was conducted (reference 3). They found:

  • the effect of bupropion on CYP2D6 activity was responsible for an increased systemic exposure to atomoxetine (5.1-fold) and also for a decreased exposure to its main metabolite 4-hydroxyatomoxetine-O-glucuronide (1.5-fold)
References:
  • Drug Interactions Flockhart Table ™ (Table)
  • Atomoxetine package insert. (PDF)
  • J Pharm Pharm Sci. 2016 Apr-Jun;19(2):198-207. (PubMed PMID: 27518170)
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READ THE FOLLOWING COURSE CHAPTERS FOR MORE DETAILS:

Psychotropic Medications: Drug-Drug Interactions

(1) Medications affecting Clozapine levels: 

(AVAILABLE FOR A FREE PREVIEW)

(2) Interactions with Warfarin: (I) Antidepressants: 

(3) Interactions with Warfarin: (II) Antipsychotics:

(4) Antidepressants and Cardiac Medications:

(5) Lamotrigine and Oral Contraceptive Pills:

(6) Lamotrigine and Other Anticonvulsants (Carbamazepine, Phenytoin, Phenobarbital, Pyrimidine or Valproate):

(7) Tamoxifen and Psychotropic Medications:

(8) Medical Cannabis and Psychotropic Interactions:

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