The best we can say for antidepressants is they work for some people.

by John McManamy


WE left off with the rather depressing and unavoidable conclusion that antidepressants do not work very well for depression. Critics of psychiatry would have us believe that the fault lies in the medication, which is partly true. The real problem, however, lies in our false assumptions. Suppose - just suppose - that a good deal of what we call clinical depression is not clinical depression at all. And what if not all depressions are the same?

Depression or Bipolar?

Let's start with the obvious, with the unipolar/bipolar distinction. All too often, people with bipolar walk in the door depressed, are misdiagnosed with unipolar depression, and given an antidepressant. If they are lucky (as I was), the antidepressant will quickly flip them into mania, which will put even the dumbest clinician on notice to change both the diagnosis and treatment.

If the patient is unlucky (as many are), the antidepressant may initially make that individual feel better before feeling worse. Then that individual endures the heartbreak and frustration of being tried on one antidepressant after another, years on end. Ten or 11 years later (the time it usually takes to make an accurate bipolar II diagnosis), a smart clinician finally considers the obvious.

There is now widespread agreement that an antidepressant, even with a concomitant mood stabilizer, does nothing (as a general rule) to improve bipolar. Moreover, we know these meds run a high risk of making it worse.

There is also an emerging consensus that this may be the case for many so-called unipolar depressions, as well. These are individuals that Goodwin and Jamison in their second edition to "Manic-Depressive Illness" characterize as "highly recurrent." In other words, there is a cycling nature to the course of their illness, much like bipolar, even if the "ups" fall well short of mania or hypomania. But give these individuals an antidepressant and that may change. In effect, an antidepressant may turn an unsuspecting unipolar into a bipolar.

Obviously, psychiatry needs to light a match to the DSM and start over. Whether one calls highly recurrent depression a new form of depression or a new form of bipolar hardly matters, so long as clinicians are put on notice to think twice before prescribing an antidepressant. But that is not the end of the story.

Depression or Personality Disorder?

In 2006, I had this to report, from a lecture delivered by Joel Paris of the University of Toronto at the 2006 APA:

In true Axis I depression, Dr Paris explained, when patients come out of a depression, they are nice people again. Individuals with personality disorders, by contrast, can come out of a depression and still have problems with life. Unfortunately, clinicians prefer not to want to hear about personality. It means trouble. They would rather throw more meds at the problem.



Dr Paris was talking about borderline personality disorder, which is often misdiagnosed as a mood disorder. With psychiatry at long last showing signs of breaking off its love affair with Pharma (thanks to psychiatric meds losing their patent protection), personality disorders are starting to get a lot more respect.

Depression or Temperament?

Let's take this a step further. Suppose, in some cases, that depression itself could be considered as part of one's baseline temperament? In this context, depression is a natural (and possibly even healthy) part of a person's personality rather than a deviation from from one's normal healthy state.

So What Are We Really Dealing With?

So - imagine a patient walking into a psychiatrist's office manifesting depressive symptoms. Assuming the cause is not physical (such as a thyroid condition) or neurological (such as dementia), we have five (not necessarily mutually exclusive) possibilities, namely:




  1. Classic unipolar depression.
  2. The depressive phase of bipolar disorder, either I or II or cyclothymia.
  3. Something in between, or overlapping with, classic depression and classic bipolar, such as highly recurrent depression.
  4. A personality disorder, such as borderline.
  5. A personality trait or temperament.

Five possibilities. Four chances to get it wrong. Only one chance to get it right. Is it any wonder that doctors get such bad results or that patients undergo so much misery? But even if the clinician spins the wheel correctly, we are talking numerous sub-possibilities within the one possibility that holds out promise. In other words, even more chances to get it wrong.

Chances are your clinician is missing this. He or she is thinking: Looks like depression, must be depression, ergo antidepressant. But we know that antidepressants can make bipolar worse. Likewise, there is good support for the proposition that people with highly recurrent depression need to avoid them, as well. And even a caveman's dumb half-brother knows that there is no med for changing a personality.



Clearly, a good many of you reading this should never have been put on an antidepressant in the first place. A placebo would have worked a lot better and with no side effects. At least you wouldn't be feeling worse. But maybe you're one of the "lucky" ones, with classic depression. An antidepressant for depression is just what the doctor ordered, right? Um, uh, define depression.

A Quick Depression History Lesson

The DSM-II of 1968 viewed depression as both separate from (in the sense of "depressive neurosis") and as part of manic-depression (in the sense of "manic-depressive illness, depressed type") and tied into anxiety (in the form of "involuted melancholia" and as the driving force of "neurosis") as well as embedded into personality (as in "cyclothymic personality disorder characterized by depression").

Moreover, the DSM-II distinguished between depression seen as a result of the mysterious biology of the brain ("endogenous") and depression seen to be caused by a reaction to events ("exogenous").

The DSM-III of 1980 replaced all that with a monolithic view of unipolar depression, separating it out from manic-depression and anxiety and personality and doing away with the endogenous-exogenous distinction. Instead, for the first time, we were treated to the famous and extraordinarily arbitrary nine-item symptom checklist.

In my book, "Living Well with Depression and Bipolar Disorder," I cite a 2004 article by Gordon Parker MD, PhD of the University of New South Wales in support of the proposition that this one-size-fits-all view of depression results in clinical trials that indiscriminately lump all patients together, with no regard to critical distinctions that may spell the difference between success and failure.

We know for instance that an SSRI such as Paxil gets 50 percent of patients with "major depression" 50 percent better over a period of about six weeks. This is good enough for the drug companies, who now have a license to print money, but what about the patients? Who wants a 50 percent chance of success? And who wants to be just 50 percent better?

What do we know about Paxil, anyway? Does it work better on a patient whose depression is marked by sadness? If so, is it possible to target this group of patients? Maybe then we would be seeing 80 percent of these individuals getting 80 percent better.

And try this on for size. Maybe a patient whose main feature is lack of motivation (about which the DSM has nothing to say) would benefit from something else, as would depression brought on by stress (the type of "exogenous" depression axed from the DSM-III). Maybe these drugs don't exist. Maybe Pharma would be encouraged to develop them. As Dr Parker in a 2007 piece concludes:

Depression is a diagnosis that will remain a non-specific "catch all" until common sense brings current confusion to order. As the American journalist Ed Murrow observed in another context: "Anyone who isn't confused doesn't really understand the situation."

Wrapping Up Antidepressants

To tie this in a bow: It's not enough that a clinician accurately diagnoses depression, as the term is at best an umbrella designation, the way "infectious disease" is an umbrella designation. Yes, an antibiotic may be useful against many types of infectious disease, but we cannot make the same claim for an antidepressant for the zillion different things going on inside our brains that we happen to lump together as depression. The best we can say for antidepressants is that they work for some individuals with DSM depression. The catch is we don't know in advance who these people are.

Next article: Antidepressants - The Chemical Imbalance Myth

Previous article: Antidepressants - The Bad News First

Reviewed June 30, 2016


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