

Ketamine is a sedative first synthesized in 1962; its patents have long elapsed and it costs pennies; it has many uses and is also sold illegally for use as a recreational drug, but in recent years it has been used with remarkable efficacy as a treatment for a variety of disorders, including depression, anxiety, and chronic pain (I have lifelong chronic pain and my specialist has prescribed very low doses of it for me at bedtime).



Recently, the FDA approved Esketamine, a ketamine-like drug in a nasal spray for use as fast-acting relief, but Johnson & Johnson, the company that developed Esketamine, has only done four efficacy studies of mixed results. Esketamine isn't ketamine: it's a mirror-image of the ketamine molecule ("left-handed ketamine," or "S-for-sinister-ketamine"). This mirroring is what let Johnson & Johnson get a patent on a drug that's been around since 1962.





So why is Esketamine — new, largely unstudied and unpromising — approved for use, while ketamine — old, well-studied, and widely used — still off-label for treating depression and pain?

Scott Alexander (previously) has a theory: "I suspect this was a political move based on how embarrassing it was to have everyone know ketamine was a good antidepressant, but not have it officially FDA-approved."





Alexander goes into some detail on Estketamine's background, which is bound up in the (pretty terrible) history of antidepressants, as well as the limitations on administering ketamine infusions (which require patients to be sedated and hallucinating, while under medical supervision, for hours at a stretch, or even many consecutive days).



The FDA, in its approval for esketamine, specified that it could only be delivered at specialty clinics by doctors who are specially trained in ketamine administration, that patients will have to sit at the clinic for at least two hours, and realistically there will have to be a bunch of nurses on site. My boss has already said our (nice, well-funded) clinic isn't going to be able to jump through the necessary hoops; most other outpatient psychiatric clinics will probably say the same. This removes most of the advantages of having it be intranasal, so why are they doing this? They give two reasons. First, they want to make sure no patient can ever bring ketamine home, because they might get addicted to it. Okay, I agree addiction is bad. But patients bring prescriptions of OxyContin and Xanax home every day. Come on, FDA. We already have a system for drugs you're worried someone will get addicted to, it's called the Controlled Substances Act. Ketamine is less addictive than lots of chemicals that are less stringently regulated than it is. This just seems stupid and mean-spirited.



The other reason the drugs have to be given in a specially monitored clinic is because ketamine can have side effects, including hallucinations and dissociative sensations. I agree these are bad, and I urge patients only to take hallucinogens/dissociatives in an appropriate setting, such as a rave. Like, yeah, ketamine can be seriously creepy, but now patients are going to have to drive to some overpriced ketamine clinic a couple of times a week and sit there for two hours per dose just because you think they're too frail to handle a dissociative drug at home?



Ketamine: Now By Prescription [Scott Alexander/Slate Star Codex]