The SSRI Debate Rages On
> 12/12/2005 3:12:54 PM

In a sprawling feature in November 28th’s issue of Fortune David Stipp takes a look at the growing backlash surrounding SSRIs like Prozac, Zoloft and Lexapro.  Making references to everything from a 12 year old murderer to the Church of Scientology to akathisia to an unholy union of liberals and conservatives, Stipp’s piece, titled "Trouble in Prozac Nation," gives a state of the union for the entire field of psychopharmacology. 

The jumping off point for Stipp’s analysis is provided by a lawsuit pending against Zoloft producer Pfizer, who made $3.1 billion in sales of their SSRI in 2004 alone.  Kim Witczak, whose husband committed suicide less than two months after his first dose of Zoloft, alleges that not only did the drug induce her husband’s suicide, but that Pfizer failed to provide adequate warning about the drug’s potential side effects.  

This case has drawn the battle lines for both sides of the fight, and the question is clear: are SSRIs really the miracle drug that they were touted to be upon their approval by the FDA in 1988? 

The SSRI phenomenon began almost the minute Prozac appeared. Doctors embraced the drugs because of a virtue that seems increasingly ironic: It's hard to commit suicide by overdosing on SSRIs, so they are deemed safer to give to severely depressed patients than are older, more acutely toxic antidepressants such as the so-called tricyclics. Indeed, the drugs once seemed so benign that some psychiatrists marveled about how they appear to violate the law of "conservation of mood"-a seemingly universal pattern in which drug-induced emotional lifts are always followed by crashes, resulting in no net gain. Such talk made Prozac seem safer than coffee. That paved the way for massive prescribing by general practitioners with no special training in complex mental disorders--in recent years some 70% of SSRI prescriptions have been written by primary-care doctors. (emphasis, mine)

As this paragraph makes clear, it wasn’t long before SSRIs were being prescribed for even borderline “health” problems like shyness.  

For harried doctors faced with lots of patients complaining of depression, anxiety, or compulsions, drugs billed as versatile and safe can seem a godsend. Prescribing SSRIs "has almost become a way that physicians are regulating demands on their time," says University of Pennsylvania psychology professor James Coyne. "What happens a lot in primary care, though, is that people on the drugs don't get adequate follow-up. About half the time they need an adjustment in dose, which they often don't get," increasing the chance of side effects.

While the potential for danger is clear when drugs are prescribed haphazardly or with only minimal screening, many doctors now are questioning the very theoretical foundation on which the drugs’ use is based.  Drug companies like Pfizer tout the effects of SSRI as “restoring a natural balance” of serotonin in the brain.  Of course this sounds great, but an article in the December issue of the journal PLoS Medicine (Public Library of Science) points out that these assumptions about the drugs effects of SSRIs might be just that, assumptions.

This brings us back to the most ghastly villain of them all, marketers.  And there, as Stipp continuously comes back to, is the rub of all rubs.  These drugs make some serious money ($11 billion by last count).  As anyone knows, when you start mixing government regulations, massive sums of money and the well being of over 5% of the American public, you’re talking about a serious powder keg.  Allegations have been flying all over the place and it seems likely that no one will ever really know what the FDA and the producers of these drugs may or may not have known and when they may or may not have known it.

One of the most interesting nuggets, for me as a reader, was buried somewhat inconspicuously in the middle of Stipp’s piece.  The writer spoke with a clinical instructor at Harvard named Joseph Glenmullen, who wrote a book, Prozac Backlash, which highlights many of the frightening side effects of SSRIs.  Glenmullen discusses the cycle of drug “fads” in psychiatry, which he says appear “like clockwork.”  He traces these fads from cocaine in the 19th century to amphetamines in the 30’s to barbiturates and finally tranquillizers like Valium.

Each fad followed the same trajectory. The medicines were first hailed as wonder drugs for major mental illnesses. Then general practitioners began prescribing them not just for major problems but for all sorts of relatively minor maladies. Next, scattered reports of serious side effects appeared. After 20 years or so of use, sellers of the medicines could no longer plausibly deny the problems, leading finally to sharply curtailed prescribing. Given that SSRIs' popularity took off in 1990, Glenmullen predicts that "we're still five to ten years away" from full disenchantment with them.

Stipp does make sure to note that Glenmullen is in a minority, scientifically speaking, but nevertheless, his point is worthy of consideration.  The overriding sense when one walks away from Stipp’s article is that nothing is an absolute.  SSRIs have helped literally millions of people suffering from possibly hundreds of mental health disorders.  But they are clearly not the be all, end all in psychiatry or psychopharmacology.  It is clear that too often these drugs are used as a crutch, when psychoanalysis and more traditional therapy are probably safer, more successful alternatives.  There are over 100 neurotransmitters in the brain, and as Dr. Solomon Snyder recounted in The Archives of General Psychiatry back in 2002, truly understanding them all would require more than a lifetime of study.  SSRIs may not be the miracle drug, but for a lot of people, their benefits have been nothing short of miraculous.  Stipp’s well researched and reported article reminds readers that when dealing with medications of the mind one can never be too careful or aware.


If the David Stipps, David Healeys and other promoters of the SSRI cause suicides concept want me to believe they need to explain how it is that other antidepressants with differing chemistry also have been implicated as have the non chemical vagus nerve stimulator[1] and psychotherapy[2].

It is not even clear that the data used to support the SSRI suicide link is reliable based as it is on meta analysis of studies with varying methodology.


"An FDA watchdog group criticized the agency's recent approval of a new electrical stimulation device for depression Monday. It says that the device has not been proven to work and may increase patients' risk of suicide.

...Twenty-five patients using VNS also attempted suicide in several company studies.


Am J Psychiatry. 2005 Nov;162(11):2173-2175

Emergent Suicidality in a Clinical Psychotherapy Trial for Adolescent Depression.

Bridge JA, Barbe RP, Birmaher B, Kolko DJ, Brent DA. (Abstract:
Posted by: Ian 12/12/2005 10:28:39 AM

Ian,I agree that the Fortune article tells half-truths regarding SSRI's and the manner in which Fortune has cherry picked studies is amazingly self serving. It is a reality that SSRI's are the treatment of choice for depression and help millions of patients annually. It is easy to take pot shots from the ivory tower of intellectualism. That being said understanding that psychotherapy has a vital role in the treatment of depression is a valid point frequently overlooked in the insurance driven health care industry. SSRI's should not be used to the exclusion of credible psychotherapy.Thanks for reading.Bill Hapworth
Posted by: William E. Hapworth M.D. 12/13/2005 7:52:17 AM

I have been on Celaxa for 8 months and I can honestly say it has changed my life. The help it has provided has been impossible to measure. I don't know a thing about pharmacology but I do know this is working for me.
Posted by: anon 7/11/2006 6:02:08 AM

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