The Monoamine Hypothesis Revisited

So, I've gotten a couple comments regarding my previous post--The Monoamine Hypothesis.


The first comment was essentially that I actually have good scientific reasons for much of what I said in the post, but that I didn't include any references. And that much of what I said came off as hippy bullshit without strong scientific backing. Indeed, much of what I wrote is unconventional. Some of what I wrote was some of own my conjecture and alluded to questions that I have regarding the topic. (For example, we know hormones affect mood. So why all this emphasis on neurotransmitters?)

Marcia Angell, MD, and former editor of the New England Journal of Medicine wrote a review in the New York Review of Books on a few books that tackle the topic of antidepressants usage in this country. She writes,

When it was found that psychoactive drugs affect neurotransmitter levels in the brain, as evidenced mainly by the levels of their breakdown products in the spinal fluid, the theory arose that the cause of mental illness is an abnormality in the brain’s concentration of these chemicals that is specifically countered by the appropriate drug. For example... because certain antidepressants increase levels of the neurotransmitter serotonin in the brain, it was postulated that depression is caused by too little serotonin. Thus, instead of developing a drug to treat an abnormality, an abnormality was postulated to fit a drug.
That was a great leap in logic, as all three authors point out....

But the main problem with the theory is that after decades of trying to prove it, researchers have still come up empty-handed. All three authors document the failure of scientists to find good evidence in its favor. Neurotransmitter function seems to be normal in people with mental illness before treatment. In Whitaker’s words:

Prior to treatment, patients diagnosed with schizophrenia, depression, and other psychiatric disorders do not suffer from any known “chemical imbalance.” However, once a person is put on a psychiatric medication, which, in one manner or another, throws a wrench into the usual mechanics of a neuronal pathway, his or her brain begins to function…abnormally.

Carlat refers to the chemical imbalance theory as a “myth” (which he calls “convenient” because it destigmatizes mental illness), and Kirsch, whose book focuses on depression, sums up this way: “It now seems beyond question that the traditional account of depression as a chemical imbalance in the brain is simply wrong.” Why the theory persists despite the lack of evidence is a subject I’ll come to...

So, that more or less sums up what in my previous blog post was factual. I would recommend to anyone interested in this topic that they read the remainder of the review--it is quite fascinating. Or the books that she reviews--I've read both Unhinged and Anatomy of an Epidemic.

The second comment (posted to the comments section of my previous post) asked what my biases towards antidepressants are. 

Yes. I am biased against antidepressants. I'm hesitant to take medications in general, but more specifically, I don't know anyone who's taken them who speaks highly of them. Some of the people I know who have taken them say that they work and some say they don't. But even those who say that they do work complain of various side effects--sexual dysfunction, feeling emotionally numb, and unwanted personality changes.  I don't know anyone who has killed themselves on them, either though.

That said, I have tried to approach this question several times with an open mind. There have been a few instances over the past few months where I have felt shitty enough that I hoped that there existed some sort of medication that would ameliorate problems with relatively few side effects. When I look into the data on them, though, I am never particularly impressed. I consistently find that they are not particularly effective, we know very little about their long-term use (but what we do know doesn't look good), and they cause problematic side-effects. There is one medication that does seem to be comparatively effective for OCD--clomipramine (anafranil). Clomipramine is a first generation antidepressant--a tricyclic not an SSRI. I would consider taking it shortish-term, but it's side effects are particularly nasty. There's no way I would be prescribed it even if I asked for it for this reason.

There are a number of long-term concerns I would have with taking SSRIs. First of all, let's say that they are effective short-term (which is questionable--they beat a placebo in only about 50% of the studies done on them; unfortunately it is this 50% that is published). I still am not sure I would want to take them. SSRIs do induce mania in a significant number of cases (I'll have to look up the percentage). A few of my relatives have bipolar, so this is something that concerns me. If on the other hand they helped me, what would happen when I decided to go off of them? SSRIs cause "discontinuation syndrome"--a euphemism for withdrawal--which could cause me to experience a relapse worse than what I am experiencing now. So, then, I would be confronted with the choice of whether or not to remain on them long-term. Well, there are a few concerns with remaining on them long-term. They stop working as well the longer you take them, so that might lead to an increased dosage or a relapse (back to square one). Also, they've been linked to cognitive decline (memory loss) with long-term use.

I should note that most of what I read about efficacy of SSRIs--both short- and long-term--relates to depression. Since it is somewhere around 10 to 20 times more common than OCD, it is much more studied.