Readers may remember that a few weeks ago I became involved in an online debate with the very eminent and scholarly psychiatrist Ronald Pies, MD. That exchange was initiated by a post I wrote concerning a paper on the chemical imbalance theory that Jeffrey Lacasse, PhD, and Jonathan Leo, PhD, had published in the Behavior Therapist in October 2015. In that paper, Drs. Lacasse and Leo had drawn attention to certain aspects of Dr. Pies’ work, but they had also focused some attention on Daniel Carlat, MD, psychiatrist, and author of Unhinged: The Trouble with Psychiatry – A Doctor’s Revelations about a Profession in Crisis.
The subsequent issue of the Behavior Therapist contained replies from Dr. Pies and Dr. Carlat, together with a counter-response from Drs. Lacasse and Leo.
There was nothing new in Dr. Pies’ letter, so I won’t dwell on that here, but Dr. Carlat’s letter warrants, I think, some discussion.
As mentioned above, Dr. Carlat is the author of Unhinged (2010). This is an interesting work: a kind of “confessions of a reformed psychiatrist” book. I read it when it came out, and was impressed by Dr. Carlat’s candor and courage. I wrote a review on the work on October 30, 2010, and have quoted from it on a number of occasions in the subsequent years. I had formed the opinion that Dr. Carlat was a psychiatrist who had recognized the hoax, and was doing what he could to expose it.
CARLAT’S INTERVIEW ON NPR
In July 2010, Dr. Carlat gave an interview on NPR concerning his book, and it was on comments that he had made in that interview that Drs. Lacasse and Leo had focused in their original article. Drs. Lacasse and Leo provided three quotes from the interview. Here’s the full passage from which they quoted. (The interview was conducted by Dave Davies):
“DAVIES: How much do we know about how psychological medications actually work?
Dr. CARLAT: Well, we know both a lot and very little, and the way in which we know a lot is that through clinical trial studies, in which patients are randomly assigned to a medication versus a placebo sugar pill, we know how effective these medications are, in other words how much of an advantage medication has over a placebo.
And that varies from medication to medication. It tends to be a very minimal advantage for antidepressants when treating depression. It tends to be a higher advantage when treating schizophrenia.
But on the other hand, what we don’t know is we don’t know how the medications actually work in the brain. So whereas it’s not uncommon – and I still do this, actually, when patients ask me about these medications, I’ll often say something like, well, the way Zoloft works is it increases the levels of serotonin in your brain, in your synapses, the neurons, and presumably the reason you’re depressed or anxious is that you have some sort of a deficiency.
And I say that not because I really believe it, because I know that the evidence isn’t really there for us to understand the mechanism. I think I say that because patients want to know something, and they want to know that we as physicians have some basic understanding of what we’re doing when we’re prescribing medications.
And they certainly don’t want to hear that a psychiatrist essentially has no idea how these medications work.
DAVIES: But that’s pretty close to the truth?
Dr. CARLAT: Unfortunately, it is close to the truth. We’re in a paradoxical situation, I think, where, you know, we prescribe medications that do work, according to the trials, and yet as opposed to essentially all other branches of medicine, we don’t understand the pathophysiology of what generates mental illness, and we don’t understand exactly how our medications work.
DAVIES: And it can be reassuring if you’re prescribing a medication to tell someone, well, there’s really a biological origin of your difficulty here, and we can treat it with – by treating the biology.
Dr. CARLAT: Right, which is exactly why I still tell patients that at times. But I think, you know, one thing that has happened is that because there’s been such a vacuum in our knowledge about mechanism, the drug companies have been happy to sort of fill that vacuum with their own version of knowledge so that usually, if you see a commercial for Zoloft on TV, you’ll be hearing the line about serotonin deficiencies and chemical imbalances, even though we don’t really have the data to back it up.
It becomes a very useful marketing line for drug companies, and then it becomes a reasonable thing for us to say to patients to give them more confidence in the treatment that they’re getting from us. But it may not be true.
DAVIES: Right. Well, I certainly want to talk a lot more about what drug companies do to market their products, but, you know, help us understand the distinction between the kind of scientific knowledge we have about the brain and its reaction to psychological medications, as opposed to, you know, treatments for cardiac disorders or vascular disease.
Dr. CARLAT: Sure. And – so for example, I’ll take the example of a medication like Zoloft, which is in the class of SSRI, which is specific serotonin reuptake inhibitor.
And as the name implies, what we think these medications do is they prevent the neurons of the brain from sort of vacuuming up the excess chemicals and neurotransmitters that the neurons generate so that if the depression or anxiety disorder is due to a deficiency of a chemical, a reuptake inhibitor would act by pumping out or allowing the neuron to pump out more neurotransmitter, thereby famously balancing the chemicals.
And the problem is that we don’t have any direct evidence that depression or anxiety or any psychiatric disorder is actually due to a deficiency in serotonin because it’s very hard to actually measure serotonin from a living brain.
And any efforts that have been made to measure serotonin indirectly, such as measuring it in the spinal fluid or doing postmortem studies, have been inconclusive. They have not shown conclusively that there is either too little or too much serotonin in the fluids. So that’s where we are with psychiatry.
And then your other question was: How does that differ from some of the other medical fields? Well, for example, in cardiology we have a good understanding of how the heart pumps, what electrical signals generate activity in the heart.
And due to that understanding, we can then target specific cardiac medications to treat problems like heart failure or heart attacks, again based on a pretty well-worked-out knowledge of the pathophysiology – not perfect, but pretty well worked out.
DAVIES: Whereas – to draw an analogy to psychiatry, it might be like saying, well, if nitroglycerin eases your chest pains, then we conclude that your heart problem is a deficiency of nitroglycerin.
Dr. CARLAT: Exactly, or if we find that opiate medications treat pain in general, we might conclude that pain is a opiate or narcotic-deficiency illness, whereas in fact we know that pain is not an opiate-deficiency illness. It’s a symptom that can be caused by many, many different pathologies throughout the body.”
THE CRITIQUE FROM DRS. LACASSE AND LEO
Drs. Lacasse and Leo challenged some of the statements Dr. Carlat made in this interview, and pointed out:
“So Carlat is aware of the clinical trials, which essentially refute the serotonin theory, yet still tells patients that they have a serotonin imbalance.”
“The simple alternative would be to tell patients the truth—that the pathophysiology of depression is unknown and that we have no idea how SSRIs work.”
In the NPR interview, it is clear – or at least is seems clear to me – that Dr. Carlat admitted that he routinely deceives his clients on these issues, and in that regard, the assessment and suggestion put forward by Drs. Lacasse and Leo seem correct and appropriate.
But in his response in the Winter issue of the Behavior Therapist, Dr. Carlat denies any deception on his part. Here’s a quote from his letter:
“In one section of the article, they accuse me of making deceptive statements to my patients about how antidepressants work. I deny this accusation. In talking to patients I simplify neurobiological concepts, using a shorthand to describe, in a simplistic way, some common theories of mental illness. I do this to enhance the placebo effect—which accounts for a significant portion of the overall effectiveness of antidepressants. Two of the most crucial components of the placebo effect are fostering positive expectations of success and reinforcing the medical ritual of pill-taking (Kaptchuk et al., 2010; Leuchter, 2014). In order to augment my patients’ response to antidepressants, I will say something like, ‘This is a very effective medication, you should take this pill every morning, and you will begin to feel better within a couple of weeks.’ If a patient asks me how the medication works, I will respond with, ‘We’re not completely sure, but it has something to do with increasing levels of neurotransmitters like serotonin or norepinephrine—basically, these pills rebalance certain chemicals in the brain.’
There is nothing deceptive about such statements. While we don’t understand exactly what serotonin’s role is, we have some educated hypotheses. A recent review of serotonin and depression identifies 14 known serotonin receptor subtypes. When antidepressants bind to these receptors, a variety of chemical processes unfold, affecting levels of dopamine, norepinephrine, acetylcholine, cortisol—and yes, serotonin. While it isn’t clear exactly how these chemical cascades alleviate depression or anxiety, it is clear that effective antidepressants exert their actions via shifts in the brain’s biochemical milieu—and that serotonin is one of the central players in the drama (Kohler et al., 2015).
The authors, unfortunately, do not seem to be interested in scientific evidence. In their role as the serotonin thought police, they brook no uncertainty: the serotonin theory is discredited, full stop.”
COUNTER-RESPONSE FROM DRS. LACASSE AND LEO
In their response, Drs. Lacasse and Leo pointed out very clearly that in the NPR interview, Dr. Carlat had admitted that he deceived his clients:
“…we don’t believe we’re alone in thinking it’s objectionable to tell patients something you don’t believe yourself.”
Drs. Lacasse and Leo also cited a passage in Dr. Carlat’s book Unhinged where he made similar admissions. They then concluded their response to Dr. Carlat with a paragraph that ought to be carved in stone and displayed prominently in every psychiatric training center in the world:
“We don’t think scientific truth is so flexible, and disagree with shaping it for purposes convenient to the prescriber (e.g., to get patients to take medication, or to reassure the patient of the prescriber’s expert knowledge). Dr. Carlat also writes that he boosts the placebo effect by telling patients that SSRIs are ‘a very effective medication’ (Carlat, 2015; this issue, p. 262). Fournier et al. (2010) demonstrated a Number-Needed-to-Treat (NNT) of 11 for severely depressed patients. In other words, when prescribing to 11 severely depressed patients, a prescriber would expect 1 to have an impressive short-term response as compared to placebo. Given the existence of such data, we question the accuracy of claiming that antidepressants are ‘very effective’ (see also Weitz et al., 2015).”
And to which I would add the following observations”
1. It is clear that, at least in Dr. Carlat’s practice, the chemical imbalance hoax is still alive and well.
2. Deceiving clients “to enhance the placebo effect” betrays an extraordinary level of condescension, and a fundamental misunderstanding of how best to help people who are experiencing problems of thinking, feeling, and/or behaving.
3. In the absence of evidence of efficacy, “fostering positive expectations of success” is a sham, essentially similar to the kind of hype used by traveling snake-oil peddlers in the late 1800’s.
4. “Reinforcing the medical ritual of pill-taking” is a euphemism for drug-pushing.
5. The notion that antidepressants “rebalance certain chemicals in the brain” is a hoax. It is just as likely – in fact, arguably more likely – that these drugs disrupt the normal chemical functions in the brain. Cocaine is a serotonin reuptake inhibitor (SRI), but I have never heard claims that it rebalances brain chemicals. In fact, in most contexts, such a claim would be considered ridiculous.
6. Dr. Carlat’s characterization of Drs. Lacasse and Leo as “the serotonin thought police” is just one more example of entrenched psychiatry’s marginalization of its critics. They can’t gainsay our arguments, so they resort to personal attacks. In addition, there is an enormous irony in a psychiatrist using the epithet “thought police” to express censure, when it is psychiatry itself that routinely incarcerates and forcibly drugs and shocks people on the grounds that their thoughts and speech don’t conform to psychiatry’s standards of normality.