Warnings on prescription drugs may have caused overreactions

For most of the past twenty years, teen suicide rates have fallen quite consistently. Many credit the introduction of selective serotonin reuptake inhibitors (SSRIs), a commonly-prescribed class of anti-depressants, for this drop.

 

But in 2004, the teen suicide rate jumped by an unprecedented 18 percent. This increase, according to a recent study in the Journal of American Psychiatry, was likely due to a precipitous decline in the prescription of these drugs.

 

The decline was almost certainly due to a 2003 decision by the U.S. Food and Drug Administration to warn the public that SSRIs might actually encourage suicidal thoughts and behavior. Prompted by studies coming out of Britain, the FDA eventually decided to force drug manufacturers to include a black box — its strongest warning — on SSRI packages describing the potential risk.

 

This admonition came despite the fact that, as the FDA itself admitted, "[t]he data do not clearly establish an association between the use of these drugs and increased suicidal thoughts or actions by pediatric patients."

 

In hindsight, however, this well-intentioned precautionary measure likely resulted in avoidable teen deaths. Several studies have now contradicted the initial fear, with one study's author going so far as to say, "I think the FDA has made a very serious mistake. It should lift its black-box warning because all it?s doing is killing kids."

 

But the black-box warning remains.

 

So how did the FDA get it wrong? And why hasn't the agency removed the warning label?

 

The problem lies in the multitude of factors impacting mental health.

 

Because drugs are often a last resort, SSRIs tend to be prescribed to patients who have more severe cases of depression and are correspondingly at higher risk of suicide.

 

SSRIs can take nearly a month to have any effect on depression. Among a given group of teenagers who start treatment, it could reasonably be concluded that any who take their own lives within a few weeks of starting therapy do so because of that therapy.

 

On the other hand, because the drugs can have little or no impact for the first month they're taken, it's equally possible that they did not have enough time to work.

 

Such competing possibilities make it difficult to determine the cause of a negative outcome. Is it the drug, or is it something else? FDA critics often clamor for warnings and recalls at the slightest indication that a drug may pose a risk.

 

But when it comes to teen suicide, researchers at the University of Colorado Health Science Center suggested that the FDA's black-box warning was premature — and could even be lethal.

 

Many other prominent scientists have come to the same conclusion.

 

One study found that suicide risks declined slowly when SSRIs were prescribed, with high risks in the first few months of treatment that diminished gradually and substantially over the course of treatment. Another found that depressed patients using SSRIs were one-third less likely to commit suicide than those who weren't treated with the drugs.Unsurprisingly, it's often easier to blame a drug for a negative outcome than to give credit when a drug works as intended, resulting in a "non-event."

 

Any treatment has risks. Doctors and patients must balance those risks when deciding upon an appropriate treatment. This is precisely why the FDA approval process for pharmaceuticals is so rigorous.

 

Indeed, many think that process is already too burdensome. It takes more than $800 million and 12 years to bring a new drug from the lab to the market. For every 5,000 compounds developed, tested, and submitted by drug companies to the FDA for approval, only five will make it to the human trial phase. Of these five, only one will make it to the market.

 

Given the substantial chance of failure in the approval process, any drug that makes it through the multiple layers of screening should be considered safe unless later scientific studies prove it unsafe.

 

In the case of teen suicide, the "black box" may have satisfied the industry's critics. Yet by scaring away parents and doctors, it's likely that the warning also was responsible for more suicides than it prevented.

 

Doctors and patients, and in this case, parents, need the best information possible to help them make the right decision about whether a drug is appropriate treatment. The history of SSRIs is instructive, particularly as pressure heats up on the FDA to pull drugs at the first sign of any potential danger. But the FDA and its critics should think twice about whether their excess caution may do more harm than good.

 

*************

Grace-Marie Turner is president of the Galen Institute, a non-profit research organization focusing on free-market solutions to health reform. She can be reached at P.O. Box 320010, Alexandria, VA 22320, or at turner@galen.org.

 

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For most of the past twenty years, teen suicide rates have fallen quite consistently. Many credit the introduction of selective serotonin reuptake inhibitors (SSRIs), a commonly-prescribed class of anti-depressants, for this drop.

 

But in 2004, the teen suicide rate jumped by an unprecedented 18 percent. This increase, according to a recent study in the Journal of American Psychiatry, was likely due to a precipitous decline in the prescription of these drugs.

 

The decline was almost certainly due to a 2003 decision by the U.S. Food and Drug Administration to warn the public that SSRIs might actually encourage suicidal thoughts and behavior. Prompted by studies coming out of Britain, the FDA eventually decided to force drug manufacturers to include a black box — its strongest warning — on SSRI packages describing the potential risk.

 

This admonition came despite the fact that, as the FDA itself admitted, "[t]he data do not clearly establish an association between the use of these drugs and increased suicidal thoughts or actions by pediatric patients."

 

In hindsight, however, this well-intentioned precautionary measure likely resulted in avoidable teen deaths. Several studies have now contradicted the initial fear, with one study's author going so far as to say, "I think the FDA has made a very serious mistake. It should lift its black-box warning because all it?s doing is killing kids."

 

But the black-box warning remains.

 

So how did the FDA get it wrong? And why hasn't the agency removed the warning label?

 

The problem lies in the multitude of factors impacting mental health.

 

Because drugs are often a last resort, SSRIs tend to be prescribed to patients who have more severe cases of depression and are correspondingly at higher risk of suicide.

 

SSRIs can take nearly a month to have any effect on depression. Among a given group of teenagers who start treatment, it could reasonably be concluded that any who take their own lives within a few weeks of starting therapy do so because of that therapy.

 

On the other hand, because the drugs can have little or no impact for the first month they're taken, it's equally possible that they did not have enough time to work.

 

Such competing possibilities make it difficult to determine the cause of a negative outcome. Is it the drug, or is it something else? FDA critics often clamor for warnings and recalls at the slightest indication that a drug may pose a risk.

 

But when it comes to teen suicide, researchers at the University of Colorado Health Science Center suggested that the FDA's black-box warning was premature — and could even be lethal.

 

Many other prominent scientists have come to the same conclusion.

 

One study found that suicide risks declined slowly when SSRIs were prescribed, with high risks in the first few months of treatment that diminished gradually and substantially over the course of treatment. Another found that depressed patients using SSRIs were one-third less likely to commit suicide than those who weren't treated with the drugs.Unsurprisingly, it's often easier to blame a drug for a negative outcome than to give credit when a drug works as intended, resulting in a "non-event."

 

Any treatment has risks. Doctors and patients must balance those risks when deciding upon an appropriate treatment. This is precisely why the FDA approval process for pharmaceuticals is so rigorous.

 

Indeed, many think that process is already too burdensome. It takes more than $800 million and 12 years to bring a new drug from the lab to the market. For every 5,000 compounds developed, tested, and submitted by drug companies to the FDA for approval, only five will make it to the human trial phase. Of these five, only one will make it to the market.

 

Given the substantial chance of failure in the approval process, any drug that makes it through the multiple layers of screening should be considered safe unless later scientific studies prove it unsafe.

 

In the case of teen suicide, the "black box" may have satisfied the industry's critics. Yet by scaring away parents and doctors, it's likely that the warning also was responsible for more suicides than it prevented.

 

Doctors and patients, and in this case, parents, need the best information possible to help them make the right decision about whether a drug is appropriate treatment. The history of SSRIs is instructive, particularly as pressure heats up on the FDA to pull drugs at the first sign of any potential danger. But the FDA and its critics should think twice about whether their excess caution may do more harm than good.

 

*************

Grace-Marie Turner is president of the Galen Institute, a non-profit research organization focusing on free-market solutions to health reform. She can be reached at P.O. Box 320010, Alexandria, VA 22320, or at turner@galen.org.

 

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