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Non-participants (antidepressants)

dr jason cafer MD's book on antidepressants low r
Bubbles and boxes - medications with minimal pharmacokinetic interactions - visual mnemonic for psychiatry by Dr Jason Cafer MD

We will display medications “in a bubble” or “in a box” if they are not expected to serve as clinically significant substrates, inducers or inhibitors. There is a hole at the top of the boxes to suggest some degree of vulnerability to relevant kinetic interactions, but not to an extent prescribers need to routinely worry about. In general, medications that are renally cleared have  relatively few drug–drug interactions because their metabolism does not rely on CYP enzymes. 

Non-participants visual mnemonic by Dr Jason Cafer MD for pharmacokinetic drug interactions - zulresso brexanolone sunosi solriamfetol l-methylfoate deplin periactin cyproheptadine skelaxin metaxalone

For a substrate metabolized through multiple pathways, serum levels are not significantly affected by inHibition of a single CYP. For instance, over half of prescription drugs are 3A4 substrates, but will not be depicted as fish (page 16) if they are multi-CYP substrates. Multi-CYP substrates are depicted in a box (not a bubble) because interactions do occur but are unlikely to matter much.


A multi-CYP substrate is more likely to be victimized by an inDucer than by an inHibitor. It is worthwhile to run an interaction check on a patient’s medication list if they are taking a “shredder” inDucer (see below), even for the boxed medications. 


A bubble/box certifies the medication is:

  • No more than a weak CYP inhibitor or inducer, and...

  • Either a multi-CYP substrate or a substrate not metabolized by any CYP


A bubble does not imply that a medication does not participate in dynamic interactions, because almost all drugs do. Acamprosate (Campral) and N-acetylcysteine (NAC) are rare exceptions, depicted in a double bubble. 


Cafer's Psychopharmacology: Visualize to Memorize 270 Medication Mascots contains over 270 monographs of medications with mascots designed to help you pair trade names with generic names, and to remember kinetic interactions. 

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