In the patient on numerous medications, drug interactions are always a constant concern.  In the scenario below, I lay out some strategies to monitor the bupropion nortriptyline interaction with a brief description of what might happen on account of this drug-drug interaction.

A 58 year old female has refractory depression and is managed by psychiatry.  In addition to the depression she has also had quite a bit of trouble with insomnia. She has been experiencing an increase in depressive symptoms and another agent is looking to be added to her regimen.  She has had partial responses to many of her medications and is reluctant to come off of any of her current psych meds. Her current medication list includes:

• Nortriptyline 100 mg once daily
• Duloxetine 30 mg once daily
• Buspirone 10 mg BID
• Trazodone 100 mg at bedtime for sleep
• Aspirin 81 mg daily
• Lipitor 10 mg once daily
• Ibuprofen 400 mg three times per day

The primary provider adds bupropion extended release 150 mg once daily for 7 days and then increase to 300 mg per day.

In 6 weeks, the patient is followed up with and notes to be feeling very lethargic, with complaints of dry mouth and a report of not being able to “think clearly”.

In this situation, the likelihood of bupropion causing these side effects is low.  These side effects definitely mimic the potential of anticholinergic effects.  Bupropion can impact CYP2D6 which is a primary pathway for nortriptyline to be metabolized.  In layman’s terms, bupropion caused the drug levels of the nortriptyline to increase, leading to the potential adverse effects.

Looking back at this situation, the bupropion nortriptyline interaction should have been recognized prior to prescribing the bupropion.  If it was deemed necessary that the bupropion was essential for the resolution of depression, a lower dose and more cautious approach should have been employed with closer monitoring of the patient.  Another possibility would be to check nortriptyline levels as this is often done anyway in the management of depression.

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