This week, MIA featured a news item regarding a recent “proof of concept” study conducted at Washington University of St. Louis that investigated whether nitrous oxide, commonly known as laughing gas, was effective in reducing symptoms of depression. In a press release, one of the investigators, notably the anesthesiologist on the team, was quoted as saying,“It’s kind of surprising that no one ever thought about using a drug that makes people laugh as a treatment for patients whose main symptom is that they’re so very sad.”
Surprising indeed. I think one needs to be in the rabbit hole of modern psychiatry to understand why a drug like this would be overlooked as a treatment for depression. I would argue that it is a reflection of what Joanna Moncrieff has called the disease-centered approach to understanding these drugs. We have the conceit that the drugs we prescribe rather than being generic euphoriants or tranquilizers target specific disease states. The narrative of modern psychiatry includes the notion that these states – or disorders – are ones that psychiatrists are adept at identifying. It would have been damaging to the basic premise of modern psychiatry – bolstered by the neo-Kreplinians at Washington University – to admit we were just giving out psychoactive drugs, i.e., substances that would impact most everyone in similar ways. If I were to inhale nitrous oxide, my mood would undoubtedly be elevated. I never tried it during its heyday when I was in college, but I knew many others who did and I did not need a rating scale to know they were – at least for a time – a pretty happy bunch.
There has recently been an interest in the use of ketamine, known as special K, to treat depression. This is another drug that has a dramatic effect on most everyone who uses it. It is used by anesthesiologists and not just for those who are depressed. If you scan the ads in publications aimed towards psychiatry, you will find many ads for stimulants. These drugs, along with the benzodiazepines (Ativan, Valium, etc.), are not disease specific drugs. They may be particularly helpful for those who struggle in certain ways, but they effect us all in similar ways. I do not need to be suffering from any kind of disorder to be sedated by a benzodiazepine.
I remember wondering why we did not give stimulants to depressed patients. As a resident, I was told they were ineffective. It was suggested that they might be helpful for older patients who had low energy but I would have been criticized as a psychiatrist if, thirty years ago, I had prescribed them to a depressed patient. But then the notion was heavily promulgated that children with Attention Deficit Hyperactivity Disorder (ADHD) did not grow out of their problems. We were told that in fact many adults missed out on getting properly diagnosed and were in need of treatment. And the flood gates of stimulant prescribing opened. I see people who have many reasons to be inattentive – on multiple drugs for their other diagnosed conditions, using substances, living in highly stressful environments. I know that it is considered legitimate practice – if they provide the correct history – to diagnoses them with ADHD. As psychiatrists we do not tell patients that there are drugs that – at least in the short run – can increase focus. We say that we have determined that they have an illness and we can give them a drug to treat this. Since ADHD is accepted as a life long problem, when we follow this particular narrative, we create a life long customer for the stimulant industry. I do not think it is a coincidence that this interest in adult ADHD began to arise as most antidepressants were going off patent and their efficacy was being questioned. Although the stimulants have been around for a long time and are available in inexpensive generic forms, what is being promoted now are drugs that resist tampering. These drugs are addictive and often abused. So the market now is for drugs that doctors can prescribe but will be resistant to a problem we know is endemic – misuse, diversion, and abuse. It is interesting that stimulants are now coming back into fashion for the treatment of depression.
While it is not controversial to talk about the general effects of benzodiazepines and stimulants, the group of drugs classified as anti-depressants are thought to be specifically effective for those who are depressed. This idea is worth examining further. Before fluoxetine (Prozac) was marketed, the research focus in psychopharmacology was on determining which individuals would respond to anti-depressants. I was taught in the 1980’s that those individuals who had neuro-vegetative symptoms such as poor sleep with early morning awakening, thoughts of guilt, motoric slowing or agitation, were the ones who should be prescribed anti-depressant drugs. The older antidepressants had many noxious side effects. People – doctors and patients – avoided them. Fluoxetine was considered much safer and better tolerated. So physicians started to prescribe it more broadly, encouraged by the enormous hype surrounding this drug. And what did we find? Many people, not just those who fit the more narrowly defined “melancholic depression” reported improvement. Books were written about their broad effects. But never was the notion widely entertained that these drugs had general effects that most people would experience, the idea was that the drugs worked on people with an ever proliferating set of diagnoses: social phobia, dysthymic disorder, personality disorders, etc.
Why is this a problem? Isn’t it a good thing that these drugs have broader uses? Isn’t it a good thing to reduce suffering among a larger group of people?
Here is the rub. This is what we still do not know about drugs: What are the long term side effects? How hard is it to stop them? How do we deal with the corrupting influence of the profit driven forces so powerful in medicine? Most of these drugs are still studied over weeks and then prescribed for years. With drugs like stimulants, ketamine and nitrous oxide, I have a particular worry because these drugs are known to cause psychosis. Colleagues of mine have told me that they do not see people who become psychotic on stimulants. If they don’t, they are not looking. I am not comfortable assuming when an 18 year old develops psychotic symptoms after several years of treatment with an antidepressant that these two things are not related or that the psychosis was inevitable because the person had a diathesis to Bipolar Disorder. Stimulants are used to create animal models of psychosis because we have known for decades that stimulants can cause a person to become psychotic.
I think these newer drugs have a huge potential for harm. This is due in the short run to the potential for abuse and diversion. But I remain equally worried about long-term consequences. Psychiatry has not begun to reckon with the unanswered questions concerning drugs we have been prescribing for decades. It is reckless to promulgate use of what appear to be even more dangerous drugs before we address these critical questions.