Today's Antidepressants: Some Sad Facts

Not all that effective.

Posted Nov 14, 2009

There are a lot of sad facts about today's antidepressants.  The list is a long one.  I'm going to put down what I reckon are the saddest of the sad facts; others are welcome to add their own.

I want to emphasize the word "facts."  In this post I report the findings of scientific research.  Findings aren't opinions, they are findings.  They may not jibe with your personal experience, but that alone is not invalidating.

I should also emphasize, for the sake of maximum clarity, the word "today's."  I'm talking about newer antidepressants, mainly those SSRIs that so dominate the marketplace.  I am not talking about tricyclics or MAOIs.

One last thing.  By publishing this post I am not aiming to convince you that your antidepressants do not work for you.  Maybe they do.  I'm also not telling you to stop taking your antidepressants.  That decision is between you and your prescriber.  What I am trying to draw attention to is the glaring disparity between the allure of SSRIs and their actuality.  For this disparity we have Eli Lilly, Pfizer, and others to thank, as well as their young, cute, briefcase-full-of-free-samples-toting drug rep minions.

Sad Fact #1.  Today's antidepressants are not all that effective.  A wonderful study, well worth reading in its entirety, used the Freedom of Information act to access the actual datasets from original FDA protocols on which the efficacy of a host of SSRI-type antidepressants was based (including Prozac, Paxil, Zoloft, Effexor, and Celexa).  The main finding?  An overall 82% placebo duplication rate.  82% of the total drug effect was matched by placebo, a chemically inert substance.  The news is even worse for particular medications.  Prozac's duplication rate was 89%--a morbidly ironic fact given the absurd fanfare greeting Prozac's arrival in the marketplace back in the late 80s.

Sad Fact #2.  The same study found no dosage related effects of the medicines on mood.  Whether people were on a higher or a lower dose of the drug under review made no difference when it came to feeling less depressed.  20 milligrams was no more helpful than, say, 40 milligrams.  This seems especially important since most prescribers appear to assume the opposite. 

Sad Fact #3.  Antidepressants are not more effective as a function of initial severity of depression.  This finding comes from a different study you can read here.  It's a little complicated.  What the researchers found was this:  the relation between initial severity and antidepressants is not attributable to the increasing efficacy of the drugs but to the decreasing efficacy of placebo.  Placebo efficacy drops steadily off as severity increases; drug efficacy plateaus and drops off too, but not as steadily as does placebo.  So it's not the case that antidepressants are more effective for more severe depressions; it's just that placebos are less effective.

Sad Fact #4.  This is in some ways the opposite of Sad Fact #3.  In the FDA trials, Prozac's efficacy in treating mild depression was assessed.  It did not outperform placebo.

Sad Fact #5.  We do not know why antidepressants work (when they do).  As even Peter Kramer reports in "Listening to Prozac," the so-called biogenic-amine model of mood is at best "incomplete" and at worst "false."  Maybe depression has something to do with serotonin, or with norepinephrine, but what, exactly, is hard to say for sure.  It is one thing to know the effect a drug has on brain chemistry; it's quite a different thing to know a drug's mechanism-of-action.  If you look up SSRI-type drugs in a Physician's Desk Reference, mechanism-of-action is listed as "unknown."  Here's one reason why:  antidepressants affect amine activity almost immediately, but they do not lift mood (when they do) until about 2 to 4 weeks later.  What is happening in the brain during those 2 to 4 weeks?  Lots of theories on that; no answers.  And though theories have this insidious way of becoming received wisdom, they are not facts; they go beyond facts, by definition.  They tell a story about facts.

I'll leave it there for now.  More sad facts to come...