Depressing News About Depression and Antidepressants

 Treating mental illness with drugs is an area that faces major difficulties.  First, mental illness provides few physical manifestations; there are no medical tests that will verify a diagnosis.  Second, it is difficult to hypothesize a treatment when there are no physical clues to begin with.  Third, mental illness has long been a refuge for desperately unhappy people as a convenient way to cry out for help and easily receive it.  Over the years several mental health manifestations have become popular before disappearing from history as others have taken their place.  When was the last time a woman was diagnosed with “hysteria?” These factors make it difficult for researchers who diligently try to find means of lessening human suffering.  But on the other hand, it makes it easier to make money selling treatments and drugs of dubious value. 

The treatment of depression is perhaps the best example of all three factors in play.  The defining of depression as a mental illness leads most conveniently to the notion that it must be caused by some change in brain function.  If one is driven to provide treatment, then the assumption that a chemical imbalance is responsible is convenient; chemical imbalances can be dealt with.  But which chemicals and what is the cause.  With nothing better to go with, try changing the quantities of chemicals that are known to affect brain behavior.  Easy choices included the neurotransmitters serotonin, dopamine, and norepinephrine.  Trying to control the quantity of serotonin active in the brain became the treatment of choice.  Most antidepressant drugs in the marketplace are classified as SSRIs (selective serotonin uptake inhibitors).  Serotonin is produced by the brain as needed and then reabsorbed.  These drugs inhibit this reabsorption to produce an altered, higher level of serotonin.  People suffering from depression tend to feel relief from their symptoms when SSRIs are prescribed.  This has led to relief for many patients and vast profits for pharmaceutical companies.

This happy convergence of interests has recently been called into question by scientists who managed to measure or alter the level of serotonin in subjects’ brains by other means—not an easy thing to do.  The results of these studies were commented upon in The Economist in the note A popular medical explanation for depression is rebuffed.  The researchers’ findings are briefly summarized.

“One looks at levels of serotonin and its breakdown products in blood and spinal-cord fluid, taking these as proxies for the amount in the brain, which it is unsafe to measure directly in living people. Work in this strand, the review concludes, shows no difference between the clinically depressed and the healthy.”

“A…line of research depends on the fact that serotonin is made from tryptophan, a substance the body cannot synthesise, and so must ingest from food. In these experiments participants’ serotonin levels are lowered by depriving them of tryptophan. Dr Moncrieff’s team concluded that lowering serotonin in this way did not produce depression in hundreds of healthy volunteers.”

“Last, the researchers looked at big genetic analyses. These found no differences between genes that regulate the serotonin transporter in those with depression and those without it.”

According to these findings, serotonin has nothing to do with depression.  The article treats this as a startling result.

“If serotonin is not the cause of depression, that raises questions about SSRIs. These do help some new patients, but not others. And they come at a cost. Possible side-effects include loss of libido and inability to reach an orgasm. They can also be hard to stop taking, leaving some who recover from depression dependent on them for life.”

“Already, clinical practice is changing to emphasise dealing with environmental triggers of depression, such as adversity and poor coping skills, rather than deploying drugs. But it would still be good to understand upfront who will benefit from SSRIs and who won’t. Without the serotonin hypothesis, doctors are, in this regard, back to square one.”

That conclusion is incorrect.  This is not the first time that the popular press has been led to conclude that “antidepressants don’t work.”  Doctors and pharmaceutical companies will most likely sell and prescribe SSRIs just as they always have.  They have long known that SSRIs operated mostly—perhaps entirely—by a placebo effect.  The clinical tests providing approval for sale indicate that SSRIs behave only slightly better than an inert placebo pill.  Double blind tests can be manipulated to bias results in the desired direction.  Telling a participant that they might be given a pill that would improve their depression means that they likely will feel better if they think they have received the active pill.  That is the placebo effect.  Since SSRIs produce side effects, this can produce an enhanced placebo effect making the SSRI look even better than it is.  These considerations have led to many confrontations over the efficacy, if any, of SSRIs.  This situation was described in Antidepressant Drugs versus Placebos.

The article is correct in suggesting that there are other ways of approaching depression that need not involve taking dangerous drugs.  In Treating Depression: It’s Free, It’s Healthy, and It Works, the benefits of physical exercise were highlighted.  Apparently, exercise is a better antidepressant than an SSRI, and with only positive side effects.

You can learn a little about a lot of things or you can learn a lot about a very few things. Guess which is the most fun.