Bupropion finds its real family

When it comes to anti-depressants, there’s SSRIs, tricyclics, MAOIs, and… bupropion*.  I always wondered why it was that every other anti-depressant** came in a variety of forms, but there was only one bupropion.

Bupropion is metabolized into several different compounds in your body, the most important being hydroxybupropion, which is a norepinephrine-selective reuptake inhibitor***, meaning it causes the neurotransmitter norepiniephrine  to hang around longer so your nerves experience more of it.  “Selective” means it doesn’t affect all receptors equally, but is otherwise spectacularly uninformative.  Bupropion itself and several lesser metabolites also increase dopamine availability, but it’s not clear if that happens to any measurable degree in humans in the doses we take.  So we assume the effects on norepinephrine is the major reason bupropion works, but no one really has idea what it is going on in the brain so we can’t be sure.

Turns out there is another NSRI available, and it is actually quite well marketed. Just not for depression.  Atomoxetine is better known as Strattera, one of very few non-stimulant treatments for ADHD.  Its effects are not identical to bupropion, but they’re pretty similar, and there are studies showing atomoxetine is useful for treating depression.  Why then does no one market atomoexetine as an antidepressant, or bupropion as an anti-ADHD treatment (even though it’s shown promise)?  I don’t want to jump to the worst possible explanation, but the FDA requires new trials for every usage of a drug, and crazymeds.us is not wrong when it notes there is more money in treating ADHD and competing with very heavily controlled drugs that work very differently than there is in treating depression and competing with many off-patent drugs, one of which works in a very similar way.  And now that’s its been approved for something, any doctor who wants can still prescribe it for depression.  Meanwhile bupropion went off patent before ADHD was really a thing, so no one has any incentive to pay for additional testing now.

There are a number of other NRIs and NSRIs, few of which made it to the US.  But I hope bupropion takes comfort in knowing it does have a family, even if they spell their name differently.

*Brand name Wellbutrin when marketed as an anti-depressant, Zyban when marketed as an anti-smoking aid.

**Until you get to the really weird stuff they use for treatment-resistant depression.  Every atypical antipsychotic is its own little snowflake.

***The more common name for these is selective norepinephrine reuptake inhibitor, but that has the same acronym as serotonin norepinephrine reuptake inhibitor, a different kind of drug, so I use NSRI to avoid confusion.