Antidepressants for Depression: Nassir Ghaemi Weighs In

Patient Expert

We all think we know what depression is. Think again. Do we? If we have no idea what the illness is, then how can we possibly treat it? This, in essence, is the question Nassir Ghaemi and his co-authors asked in an article in the Feb 20013 Acta Psychiatrica Scandanavia.

Dr Ghaemi is a professor at Tufts University and one of the leading authorities on mood disorders. I first met him at a psychiatric conference in Philadelphia back in 2002, and we have stayed in touch ever since. This includes a glowing blurb he wrote for my 2006 book, "Living Well with Depression and Bipolar Disorder."

In my book, I mention the blockbuster mentality of the pharmaceutical industry, which regards all depressions as the same. "If shoe manufacturers had this one-size-fits-all mentality," I wrote, "they would be out of business. Some people obviously do well on an antidepressant. Others do not, but we have no way of knowing in advance which ones and why."

What got me thinking this way was a 2004 article by Gordon Parker of the University of New South Wales. After my book came out, in 2007 Dr Parker wrote:

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."

Dr Ghaemi begins his piece by noting that, historically, depression fell into three categories:

1. Manic-depression. This included both recurrent unipolar depression and bipolar. What was relevant was the course of the illness, not the presence of depression or mania per se. What clinicians looked for were repeated severe mood episodes alternating with normal or less severe episodes.

2. Melancholia. This meant a severe depressive mood characterized by marked psychomotor retardation, anhedonia, and lack of change in mood.

3. Neurotic depression, characterized by a lot of anxiety.

The modern DSM, which debuted in 1980, changed all that. According to Dr Ghaemi:

The concept of depression has been widened to include all kinds of depressive symptoms including: chronic mild to moderate depression, anxiety, agitated depression, and highly reactive and labile mood presentations.

So now we have this mysterious and amorphous entity called depression. The catch, Dr Ghaemi says in so many words, is that antidepressants weren't built to treat something this vague.

In support, Dr Ghaemi cites some well-publicized meta-analyses (including Kirsch et al) showing that in clinical trials the antidepressant fares little better than the placebo. Dr Ghaemi notes that a breakdown in the data suggests that antidepressants seem to work best on those with severe depression, at least in the short term.

In Dr Ghaemi's view, severe depression implies a biological illness rather than a mere reaction to whatever life happens to throw our way. It's more complicated than that, but perhaps it is safe to say that antidepressants are not meant to treat our perfectly "normal" responses to personal loss and grief and other misfortunes, however much our condition may resemble depression.

In the long term, the evidence for antidepressants is totally underwhelming. Dr Ghaemi cites the NIMH-sponsored STAR*D trials of the mid-2000s. The trials involved 3000 patients started on the antidepressant Celexa. Those who did not optimally respond were switched to another antidepressant (or a meds combo). In turn, those who did not respond were given other treatment options, and so on.

Short-term response rates were fairly encouraging, in the 60-to-70 percent range. But over one year, things fell apart, with 40-to-50 percent of the responders relapsing into a new major depression by one year. This meant that after one year, only one in three stayed well on their antidepressant (30 percent), half the number previously thought.

A parallel series of NIMH trials - STEP-BD - tested antidepressants (in conjunction with a mood stabilizer) on bipolar patients. The antidepressants were found to be the equivalent of a placebo.

According to   Dr Ghaemi:

Thus, antidepressants are less effective in major depressive disorder than previously believed according to our best recent data, especially in the long term, and they are ostensibly ineffective in bipolar depression.

He goes on to say:

The traditional analogy of antidepressant usage for depression to insulin usage to diabetes may be wrong-headed: Depression is not a single disease entity even if polyfactorial and chronic like diabetes, and antidepressants do not have marked long-term benefits as insulin does in diabetes.

Rather ...

Antidepressants should be analogized to antibiotics, with their marked acute benefit for severe episodes, but lack of benefit when continued long term. Furthermore, they are completely ineffective for some kinds of depression, as in bipolar illness.

Dr Ghaemi is quick to point out that the problem may have more to do with our overly broad conception of depression than with the antidepressant. This brings us back full circle - if we don't know what we're treating, how can we treat it?

Questions, questions ...

Please note: This article is not to be construed as medical advice. Do not interpret this article as a reason to go off your antidepressant, if you are on one. On the other hand, feel free to ask your doctor hard questions, which is essential in making informed decisions.

There may be a valid reason for you to remain on your antidepressant. Any decision to go off your med should be made with you and your doctor. This involves a tapered wean over several weeks with your doctor's guidance.

See also on HealthCentral:

Antidepressants for Depression - The Evidence

Antidepressants for the Short Term

Antidepressants Over the Medium and Long Term