Ketamine’s effect bolsters a new theory of mental illness

A few words about new theories. All new theories that can garner such enthusiasm for their presentation are invariably bolstered by something. No-one writes magazine articles about ambiguous signals from an exciting new theory. If the evidence presented is not in some way definitive, then it should be viewed as a precondition for the propagation of the theory, not evidence in favour of it. Few of us are expert judges of neurological theories, and we are not able to tell if there is anything substantial beyond the feeling that we experience that something valuable has been learned.

I know that the effects of Ketamine in treating serious episodic depression are very exciting. I feel that I understand enough to suggest that neuroplasticity is not an especially 'new' theory, or a 'theory' by itself. The neuroplastic response is real, well documented, and undisputed. What is a theory, and had not been established as fact, the last time I discussed it with someone, is that idea that the neuroplastic response is the central intermediary between the physical effect of the drug and the clinical effect of the drug. It occurs, but it had not been established that it is causal.

The central suggestion regarding the 'vaccine' effect seemed to be buried a bit in the article (unless I missed something in skimming), but it is the actual new information, which is interesting and heartening. Soldiers coming to a forward operating medical station with severe burns were treated with Ketamine rather than another anaesthetic because of its relative safety. They subsequently developed PTSD half as often as all soldiers and civilians treated for less or equally severe burns with other anaesthetics.

On the basis of the theory that PTSD and depression emerge an erosion of neurosynaptic connections, the leap is made from there to the idea that Ketamine might perhaps serve as a true 'vaccine' when people were going into high-stress situations. From my relatively uneducated perspective, this seems a bit irresponsible in two separate ways.

Firstly, the evidence is that the soldiers were 'vaccinated' against psychological disturbances associated with extreme trauma... after the initial extreme trauma had occurred. There is evidence from studies with mice that a Ketamine treatment changes their response to stressors in a way that seems both dramatic and positive. Ketamine is a common recreational drug. If we should be excited about the prospect of this response being replicated in humans, then why is there not already ample evidence that this response is replicated in humans?

Secondly, there is absolutely no reason that we should conclude that the effect of the Ketamine on the burn victims has anything to do with neuroplastic response. Ketamine is an anesthetic. It limits pain, which is traumatic. Anesthetics operate in different ways. Ketamine seems to inhibit the transmission of pain signals in the spinal cord. This prevents them from reaching the limbic system. Other forms of anesthesia may not. Ketamine is, infamously, an amnesic and a dissociative. Stress disorders require memory formation. Ketamine prevents memory formation. Other forms of anesthesia may not. And so on. In the context of the surfeit of plausible explanations for this effect, to suggest that the effect is particular evidence supporting a theory that PTSD is cured by neuroplastic regeneration of synaptic connections is not particularly responsible. It might not be terrible journalism, but it is definitely bad science, and almost certainly not something that was presented as science to the journalist.

I can tell you that my condition eventually responded dramatically to medication, and that I would not be able to live the life I live now if it were not for that medication; furthermore, that because of the medication and my experience during the years I have been on it, I can look forwards to continuing to reduce my dependence on that medication.

Depression is indeed a normal response to ongoing helplessness and despair. I probably share your experience of depression in this regard, because the 'depression' that I had been treated for for years was suddenly completely irrelevant the moment my brain finally responded to medication.

However, there are several things that this account leaves out. You can't scoff and say that depression is just an normal response any more than people can scoff and say the reason you don't want to take a shower is because you're lazy. For one, as you know, depression can be very self-perpetuating. People come to believe things that keep them depressed, ruminating on their depressed state over and over again. People always see verification and never contradiction of their worldview, even though the entire world has somehow failed to just lay down and die over the course of many thousands of years, which is what it would do if that understanding of reality was valid. And people very definitely do encounter depression that does not have a proximate external cause to justify the response; many of those Afghanis, for instance, will suffer from the bleakest of depressions for many years after the wars in Afghanistan are ended. All of these things constitute a medical condition. If you don't like the word "illness" because of how it makes you feel, I can sympathize. But that doesn't invalidate the fact that depression is something that frequently does become a genuine medical problem and frequently does require a solution beyond the reach of the person suffering from it.