The FDA warning on antidepressants revealed as wrong, harmful

In 2004, the FDA assigned a "black box" warning on prescription of antidepressants to patients under 25. This was because of a flurry of anecdotal evidence linking the beginning of treatment with SSRIs to increases in suicide risk and because of placebo vs. drug trials that showed these increases in risk on the beginning of treatment for these age groups.

At the time, there was not enough evidence to release such a warning, but the FDA was under spectacular pressure. Mothers testified before committees about their lost children. Not heard -- or at least not heard sufficiently -- were the mothers of children who benefit from these drugs.

Now a study by the American Journal of Psychiatry has revealed the association suicide risks with antidepressants is spurious.

In a study of more than 100,000 patients treated for depression, suicide attempts declined during the first month of treatment -- whether that treatment consisted of medication, psychotherapy, or both. The findings, published by Group Health researchers in the July American Journal of Psychiatry, show a similar pattern for populations of adolescents and young adults (up to age 24) as for older adults.

The study sheds new light on the "black box" advisory that the U.S. Food and Drug Administration (FDA) placed in 2004 and has revised since then, said Greg Simon, MD, MPH, the Group Health psychiatrist who led the study. The advisory -- which has concerned many patients, families, and care providers -- warns that suicidal behavior may emerge soon after people younger than 25 start treatment with newer antidepressant medications called selective serotonin reuptake inhibitors (SSRIs). It was spurred by randomized placebo-controlled trials showing that starting to take an SSRI can make thoughts of suicide more common among some teens and young adults.

Dr. Simon's study is the first published research to compare the risk of suicide attempts before and after the start of treatment with not only antidepressants but also psychotherapy. It is based on computerized medical and pharmacy records for more than 109,000 patients who started treatment for depression at Group Health from 1996 to 2005.

In the study, suicide attempts were about twice as common among patients up to age 24 as among older adults. However, the time pattern was the same for both age groups, regardless of the type of treatment they received: Suicide attempts were most likely during the month before treatment started, falling by at least 50 percent in the month after treatment began, with steady declines thereafter.

At all time points -- up to three months before and six months after starting treatment -- patients who received their antidepressant prescription from a psychiatrist tended to be most likely to attempt suicide. Those who received it from their primary care doctor were least likely to attempt suicide, with levels in between for those who got individual psychotherapy from a therapist other than a psychiatrist. "That's not because seeing a psychiatrist makes you want to kill yourself," said Dr. Simon. Rather, he suggested, these results reflect the fact that people with severe depression, who tend to be more suicidal, are more likely to be referred to psychiatrists, while those with milder depression stick with their primary doctors.

"Our study indicates that there's nothing specific to antidepressant medications that would either make large populations of people with depression start trying to kill themselves -- or protect them from suicidal thoughts," said Dr. Simon. "Instead, we think that, on average, starting any type of treatment -- medication, psychotherapy, or both -- helps most people of any age have fewer symptoms of depression, including thinking about suicide and attempting it." That said, he likened population-based studies -- both observational studies such as this one and randomized controlled trials of medications -- to "circumstantial evidence" about what happens to individual patients.

Like other psychiatrists, Dr. Simon has seen a few depressed patients start having suicidal thoughts while taking antidepressant medication despite never having thought about suicide before then. He hypothesizes that subgroups of people may be vulnerable to becoming more agitated or suicidal after taking these drugs. "We hope to learn how to identify these people in advance," he said. (Emphasis mine.)

There are a couple of things you need to take away from this study.

1) The association of suicide with younger age groups seeking treatment is not incorrect. It is quite real. Younger patients show a higher risk of suicide.

2) What was wrong is the association of suicide with starting medication exclusively. This study found that all groups -- psychotherapy or drugs -- showed increases in suicide risk. Not only did the study show a decrease in suicide risk for all groups but the effect was regardless of the type of intervention. Therefore, it is not a specific effect of the medication.

3) It is possible and perhaps even likely that individuals at particularly high risk of committing suicide on beginning treatment can be identified. It seems obvious that one of the risk factors is age. However, the fear of suicide is no reason to prevent these individuals from seeking treatment. In fact, this study resoundingly shows -- yet again -- the benefits of seeking treatment over the long-term for all the groups tested.

Now, Dr. Simon seems relatively diplomatic about the meaning of his study. For example, "he likened population-based studies -- both observational studies such as this one and randomized controlled trials of medications -- to "circumstantial evidence" about what happens to individual patients."

I am not interested in being diplomatic. He may be willing to call the science "circumstantial," but frankly circumstantial evidence in the form of anecdote was what got us into this mess in the first place.

And, for those of you who do not believe that listening to circumstantial evidence and anecdote has a cost, I would point you to another study also in the American Journal of Psychiatry.

Libby et al. examined the diagnosis rates of depression in the US before and after the "black box" warning imposed by the FDA. The study contains the following shocking figures.

This figure depicts the diagnosis rates of adolescent depression for boys and girls before and after the FDA advisory in 2004. It also shows the trends of diagnosis from pre-advisory levels. Note the precipitous decline in diagnoses of childhood depression after the advisory:

i-18552778c59e8dfb7fbb76a0c970ef8a-diagnosis.jpg

This figure depicts the percentages of prescriptions filled by SSRIs before and after the advisory with those filled by no medications. Note the increase in individuals with no prescriptions filled at the expense of those receiving antidepressants:

i-0d238d98735d34a8ae2c3245cc5bb803-presciptions.jpg

The authors describe their conclusions from these observations:

These changes may be driven by both providers and consumers. While providers are diagnosing depression less frequently, antidepressant prescriptions are also being filled less frequently. It is possible that part of the reduced rate of diagnosis of depression stems from a new reluctance on the part of families, in the wake of the advisory, to seek treatment or to disclose depressive symptoms. Similarly, providers may be writing prescriptions for antidepressants that families do not fill.

Those who think America's youth overdiagnosed and overmedicated might find these results to be good news. However, the observed rates of diagnoses of depression, 3-5 per 1,000 (that is, 0.3%-0.5%), were lower than the published incidences of child (0.4%-2.5%) and adolescent (0.4%-8.3%) depression. It may be that the previous upward trend reflected improved recognition of depression by the public and practitioners.

A more sobering perspective on these data gives cause for concern. Pharmacoepidemiological studies examining the relationship between trends in sales or prescription fills of SSRIs have consistently shown a relationship between increases in SSRI prescription rates and declines in adolescent suicide rates. On the basis of those studies, one might expect that the adolescent suicide rate would begin increasing in the wake of the FDA advisory after a decade of steady decline. (Emphasis mine. Citations removed.)

To think of the number of young people going undiagnosed, to think about the number of diagnosed who are going untreated, to think of the number of untreated and undiagnosed who are now going to kill themselves for that absence, baffles and shocks me beyond description. This is the suffering caused by government regulation. This is the cost.

And why? What possible justification exists for this policy? Simple: the FDA has chosen a standard for patient risk that substitutes anecdote for evidence and hear-say for reason.

I am not a fan of the FDA. I do not appreciate when a bureaucrat tells me how to do my business or how I can and cannot protect my health. He is not I. He has neither the right nor the incentive nor the ability to make those decisions properly. Unfortunately, we do have an FDA, and I have accepted that the people who run it do have power.

However, if we must have an FDA, let us at least have one that operates according to rational and objective standards of evidence. Let us at least have one that makes the situation better rather than worse.

This is nonsense. That "black box" standard should be repealed today.

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This study found that all groups -- psychotherapy or drugs -- showed increases in suicide risk.

It seems to suggest the opposite (i.e. both groups showed a decrease in suicide risk) as does the paper.

Jake,

Where have you been? You remind me of a friend who said "What Cold War" in 1990 when I said I was certainly relieved that the cold war was finished.

Since you have had your head in a cloud what with drinking & building vegatable catapults, it would all be too complicated to try and explain it in one email.

Obviously you didn't know that the mothers of the dead children at the FDA 2004 Feb. Meeting had no effect whatsoever on the FDA. No, it was the fact that the findings of Dr. Andrew Mosholder, the FDA's own SCIENTIST, were surpressed [and this was revealed at the Meeting!]that forced the FDA to do the Columbia study where they found the increased risk in suicidal behaviors on drugs vs. placebo.

Of course, Thomas Moore had published these findings about clinical trials with SSRIs and suicide in adults [in 1995) which showed more suicides in the drug group than the placebo group. Bet you don't even know who Thomas Moore is and why I bring up his name.

What I can't believe is that you actually fell for this study of Simon's. Myself, I don't believe a word of it. It is all drug money - over 15 billion a year for antidepressants alone. In fact, I have two studies that show SSRIs among youth increased up until November of 2004. How do you explain this?

I can email these studies to you if you email me your address.

Moderator: Rosie: www.ssristories.com

My mistake Vaughan. I misread this:

Suicide attempts were most likely during the month before treatment started, falling by at least 50 percent in the month after treatment began, with steady declines thereafter.

I thought that there was a brief up-tick in suicide risk right after beginning treatment followed by an overall decline.

However, I don't think that changes my point. If anything, it strengthens it.

Jake,

I checked GoStats for my Website and you have not clicked on the Index to SSRI Stories. You need to be extremely curious in order to be a scientist, especially a neuroscientist. Curiosity is a big part of the creative process.

If you had checked my Website, you would have come across an article from Nature, one of the most prestigious Journals for the Biosciences.

Here is a teaser for the article, plus the URL
----------------------------------------------------
Last paragraph reads: "She adds that in some cases it might be better for psychiatrists not to prescribe SSRIs. Data from animals suggest that SSRIs can increase the number of serotonin receptors now linked to suicide. That could be why a small minority of patients are more likely to commit suicide once on this medication, Dracheva speculates."

http://www.nature.com/news/2006/061016/full/061016-1.html

News
[]
Published online: 16 October 2006; | doi:10.1038/news061016-1

Brain changes may suggest suicide risk
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SSRI Moderator: Rosie: www.ssristories.com

Its a shame that you chose not to disclose the physician's financial ties to the Pharmaceutical Industry.

It is important to note that FDA placed a Black Box warning on antidepressants for those under the age of 18 for three reasons.

1)They cause suicide
2)They cause children to act out VIOLENTLY
3)In clinical trials antidepressants failed to demonstrate EFFICACY

FDA and Congress got it right, by placing a Black Box warning.

The increase of suicide could be due to abrupt withdrawl of an antidepressant, or more likely, the 170% increase of prescribing of antipsychotics to children, some as young under 12mos old...Please justify that one...

By Lisa Van Syckel (not verified) on 03 Jul 2007 #permalink

Current Depression Medications: Do The Benefits Outweigh the Harm?

Presently, for the treatment of depression and other what some claim are mental disorders, as they are questionable, selective serotonin reuptake inhibitors are the drugs of choice by most prescribers. Such meds, meds that affect the mind, are called psychotropic medications. SSRIs also include a few meds in this class with the addition of a norepinephrine uptake inhibitor added to the SSRI, and these are referred to SNRI medications. Examples of SNRIs are Cymbalta and Effexor. Some consider these classes of meds a next generation after benzodiazepines, as there are similarities regarding their intake by others, yet the mechanisms of action are clearly different, but not their continued use and popularity by others.

Some Definitions:

Serotonin is a neurotransmitter thought to be associated with mood. The hypothesis was first suggested in the mid 1960s that this neurotransmitter may play a role in moods and emotions in humans. Yet to this day, the serotonin correlation with such behavioral and mental conditions is only theoretical. In fact, the psychiatrists bible, which is the DSM, states that the definite etiology of depression remains a mystery and is unknown. So a chemical imbalance in the brain is not proven to be the cause of mood disorders, it is only suspected with limited scientific evidence. In fact, diagnosing diseases such as depression is based on subjective assessment only, as interpreted by the prescriber, so one could question the accuracy of such diagnoses.

Norepinephrine is a stress hormone, which many believe help those who have such mood disorders as depression. Basically, with the theory that by adding this hormone, the SSRI will be more efficacious for a patient prescribed such a med.

And depression is only one of those mood disorders that may exist, yet possibly the most devastating one. An accurate diagnosis of these mood conditions lack complete accuracy, as they can only be defined conceptually, so the diagnosis is dependent on subjective criteria, such as questionnaires. There is no objective diagnostic testing for depression. Yet the diagnosis of depression in patients has increased quite a bit over the decades. Also, few would argue that depression does not exist in other people. Yet, one may contemplate, actually how many other people are really depressed?

Several decades ago, less than 1 percent of the U.S. populations were thought to have depression. Today, it is believed that about 10 percent of the populations have depression at some time in their lives. Why this great increase in the growth of this condition remains unknown and is subject to speculation. What is known is that the psychiatry specialty is the one specialty most paid to by certain pharmaceutical companies for ultimately and eventual support of their psychotropic meds, as this industry clearly desires market growth of these products. Regardless, SSRIs and SRNIs are the preferred treatment methods if depression or other mood disorders are suspected by a health care provider. Yet these meds discussed clearly are not the only treatments, medicinally or otherwise, for depression and other related disease states.
Over 30 million scripts of these types of meds are written annually, and the franchise is around 20 billion dollars a year, with some of the meds costing over 3 dollars per tablet. There are about ten different SSRI/SRNI meds available, many of which are now generic, yet essentially, they appear to be similar in regards to their efficacy and adverse events. The newest one, a SNRI called Pristiq, was approved in 2008, and is believed to being promoted for treatment for menopause. The first one of these SSRI meds was Prozac, which was available in 1988, and the drug was greatly praised for its ability to transform the lives of those who consumed this medication in the years that followed. Some termed Prozac, the happy pill. In addition, as the years went by and more drugs in this class became available, Prozac was the one of preference for many doctors for children. A favorable book was published specifically regarding this medication soon after it became so popular with others.

Furthermore, these meds have received additional indications besides depression for some really questionable conditions, such as social phobia and premenstrual syndrome. With the latter, I find it hard to believe that a natural female experience can be considered a treatable disease. Social phobia is a personality trait, in my opinion, which has been called shyness or perhaps a term coined by Dr. Carl Jung, which is introversion, so this probably should not be labeled a treatable disease as well. There are other indications for certain behavioral manifestations as well with the different SSRIs or SRNIs. So the market continues to grow with these meds. Yet, it is believed that these meds are effective in only about half of those who take them, so they are not going to be beneficial for those suspected of having certain medical illnesses treated by such meds. The makers of such meds seemed to have created such conditions besides depression for additional utilization of these types of medications, and are active and have been active in forming symbiotic relationships with related disease- specific support groups, such as providing financial support for screenings for the indicated conditions of their meds- screening of children and adolescents in particular, I understand, and as a layperson, I consider such activities dangerous and inappropriate for several reasons.

Danger and concerns by others primarily involves the adverse effects associated with these types of meds, which include suicidal thoughts and actions, violence, including acts of homicide, and aggression, among others, and the makers of such drugs are suspected to have known about these effects and did not share them with the public in a timely and critical manner. While most SSRIs and SNRIs are approved for use in adults only, prescribing these meds to children and adolescents has drawn the most attention and debate with others, such as those in the medical profession as well as citizen watchdog groups. The reasons for this attention are due to the potential off-label use of these meds in this population, yet what may be most shocking is the fact that some of the makers of these meds did not release clinical study information about the risks of suicide as well as the other adverse events related to such populations, including the decreased efficacy of SSRIs in general, which is believed to be less than 10 percent more effective than a placebo. Paxil caught the attention of the government regarding this issue of data suppression some time ago, this hiding such important information- Elliot Spitzer specifically, as I recall.

And there are very serious questions about the use of SSRIs in children and adolescents regarding the effects of these meds on them. For example, do the SSRIs correct or create brain states considered not within normal limits, which in effect could cause harm rather than benefit? Are adolescents really depressed, or just experiencing what was once considered normal teenage angst? Do SSRIs have an effect on the brain development and their identity of such young people? Do adolescents in particular become dangerous or bizarre due to SSRIs interfering with the myelination occurring in their still developing brains? No one seems to know the correct answer to such questions, yet the danger associated with the use of SSRIs does in fact exist. It is observed in some who take such meds, but not all who take these meds. Yet health care providers possibly should be much more aware of these possibilities
Finally, if SSRIs are discontinued, immediately in particular instead of a gradual discontinuation, withdrawals are believed to be quite brutal, and may be a catalyst for suicide in itself, as not only are these meds habit forming, but discontinuing these meds, I understand, leaves the brain in a state of neurochemical instability, as the neurons are recalibrating upon discontinuation of the SSRI that altered the brain of the consumer of this type of med. This occurs to some degree with any psychotropic med, yet the withdrawals can reach a state of danger for the victim in some classes of meds such as SSRIs, it is believed.

SSRIs and SRNIs have been claimed by doctors and patients to be extremely beneficial for the patients well -being regarding the patients mental issues where these types of meds are used, yet the risk factors associated with this class of medications may outweigh any perceived benefit for the patient taking such a drug. Considering the lack of efficacy that has been demonstrated objectively, along with the deadly adverse events with these meds only recently brought to the attention of others, other treatment options should probably be considered, but that is up to the discretion of the prescriber.

I use to care, but now I take a pill for that. --- Author unknown

Dan Abshear