The two most exciting developments in psychopharmacology in the 21st century so far have been ketamine for depression and MDMA for PTSD.
Unlike other antidepressants, which work intermittently over a space of weeks, ketamine can cause near-instant remission of depression with a single infusion – which lasts a week or two and can be repeated if needed. Ketamine use may be successful in 50-70% of patients who have failed treatment with conventional antidepressants. Ketamine treatment has some issues right now, but the race is on to create an oral non-hallucinogenic version which could be the next big blockbuster drug and revolutionize depression treatment.
MDMA (“Ecstasy”) is undergoing FDA Phase 3 clinical trials as a treatment for PTSD. Preliminary research has been small and underpowered, but suggests response rates up to 80% and effect sizes greater than 1 in this otherwise-hard-to-treat condition. None of this is on really firm footing – that’ll have to wait for the Phase 3. But signs are looking very good.
I say these are the two most exciting developments mostly because no other developments have been exciting. In terms of normal psychiatric drugs, the best that the 21st century has given us has probably been pimavanserin and aripiprazole, modest updates to the standard atypical antipsychotic model. These drugs are probably a bit better than existing ones for the people who need them (especially pimavenserin for psychosis in Parkinson’s) but they don’t revolutionize the treatment of any condition and nobody ever claimed that they did. And most drugs aren’t even at this level – they’re new members of well-worn classes with slightly different side effect profiles. The landscape was so quiet that ketamine came in like a bolt from the blue, and MDMA is set to do the same in a couple of years when the trial results come out.
(if I’m wrong, and history decides these two drugs weren’t the biggest developments, the most likely failure mode is that psilocybin turned out to be more important than MDMA)
There’s a morality tale to be told here about how the War on Drugs choked off vital research on some of the most powerful psychiatric compounds and cost us fifty years in exploring these effects and treating patients. I agree with this morality tale as far as it goes, but I also think there’s another, broader morality tale beneath it.
Suppose that neither ketamine nor MDMA were illegal drugs. Ketamine was just used as an anaesthetic. MDMA was just used as a chemical intermediate in producing haemostatic drugs, its original purpose. Now the story is that, fifty years later, we learn that this anaesthetic and this haemostatic turn out to have incredibly powerful psychiatric effects. What’s our narrative now?
For me it’s about the weird inability of intentional psychopharmaceutical research to discover anything as good as things random druggies use to get high.
For decades, pharmaceutical companies have been coming out with relatively lackluster mental health offerings – aripiprazole, pimavanserin, and all the rest. And when asked why, they answer that mental health is hard, the brain is the most complicated organ in the known universe, we shouldn’t expect there to be great cures with few side effects for psychiatric diseases, and if there were we certainly shouldn’t expect them to be easy to find.