Children and antidepressants: Sorting through the warnings

Antidepressant medications now have strong warnings about their link to suicidal behavior in children. The warnings don't prohibit the use of antidepressants in children but caution that doctors and parents must carefully weigh the benefits and risks of using these medications.

You may be wondering how medications meant to help children could possibly harm them. Your first reaction may be to have your child immediately stop taking his or her medication. But suddenly stopping treatment could leave youngsters with depression even worse off.

Before you panic, get the facts about the new warnings. Find out why the warnings were issued, who's at risk, what signs of trouble to watch out for, and what other treatment options are available so you can make an informed decision about your child's health.

Why do antidepressants need warnings that they are linked to suicidal behavior in children and adolescents?

Federal authorities say that an extensive analysis of clinical trials shows that antidepressants may increase the risk of suicidal thinking or behavior in children, particularly in the early months of treatment of depression or other psychiatric illnesses.

The Food and Drug Administration (FDA) commissioned researchers to analyze a total of 24 clinical trials involving more than 4,400 children who were taking antidepressants for various psychiatric illnesses, including depression and anxiety disorders, such as obsessive-compulsive disorder (OCD). According to the FDA, the analysis showed that children taking antidepressants had about a 4 percent chance of developing suicidal thoughts or behavior, compared to only 2 percent in children taking a placebo. None of the children in any of the studies committed suicide.

Still, the FDA considers the findings so disturbing that in October 2004 it issued a public health advisory and began requiring manufacturers of antidepressants to label them with strong warnings about the link to suicide in children.

Specifically which antidepressants must have the warnings about suicide?

The warning labels apply to the entire broad category of antidepressant medications. Although the FDA analysis examined only nine drugs, the agency's concern was great enough to extend the warning to all antidepressants.

If your child is now taking any of these antidepressants, should he or she stop?

This decision should be made on a case-by-case basis with guidance from your child's doctor. For children whose depression is improving with medication and who don't experience suicidal thinking, the benefits of taking the medication may outweigh the risk of staying on a medication linked to suicide in a small percentage of children.

Suddenly stopping medication can leave depressed youngsters without appropriate treatment for their depression or other psychiatric illness. Untreated, depression can have a devastating impact on children. It can erode their family life, affect their social skills and disrupt their academic performance. Children with depression are more likely to have other health problems and to engage in risky behavior, such as promiscuity, smoking, and drug and alcohol abuse. They're also more likely to attempt suicide. In fact, suicide is the third leading cause of death among children ages 10 to 19.

In any case, neither children nor adults should stop taking antidepressants suddenly because of the risk of withdrawal-like symptoms, such as nausea, headache, dizziness, lethargy and flu-like symptoms. Your child's doctor can help your child taper off medication to minimize withdrawal.

If you were considering antidepressant treatment for your child, should you now rule it out as an option?

Not necessarily, but careful monitoring will be crucial.

First, a psychiatrist, pediatrician or family doctor should thoroughly evaluate your child, including performing a physical exam and a psychiatric assessment. The psychiatric assessment should include a detailed review of any potential risk factors for suicide or self-harmful behavior. It should also include screening for bipolar disorder, including a family history of that disorder or other psychiatric illnesses.

What are the signs that your child may be at risk of suicidal behavior while taking an antidepressant?

The highest risk of suicidal thinking and behavior occurs during the first few months of treatment or when a medication dosage is increased or decreased. Caregivers should closely observe children on a daily basis during these transition periods and talk to the child's doctor about any concerns. Don't stop antidepressant treatment without the guidance of your child's doctor.

Possible signs that depression may be worsening include:

• Agitation
• Irritability
• Anxiety or panic attacks
• Insomnia or other sleeping problems
• Hostility
• Impulsivity
• Inability to remain still
• Mania or hypomania, such as extreme elation, racing thoughts or rapid talking
• Increasing sadness
• Mood swings
• Unexplained declines in academic performance
• Decreasing ability to have fun or experience pleasure
• Pulling away from relationships
• Spending more time alone

According to the FDA, it's not known if the higher risk of suicidal behavior extends past those early months of treatment, so remain observant for worrisome changes throughout treatment.

Are certain children more at risk than others while taking antidepressants?

Certain factors may raise the risk of suicide attempt for some children, whether or not they're taking antidepressants. Among them:

• Having a psychiatric illness, such as depression, bipolar disorder or anxiety
• Previous suicide attempts
• History of substance abuse
• Biological relatives with depression or suicidal behavior
• History of sexual or physical abuse
• Exposure to violence
• Social stress and isolation
• Access to a means of suicide, such as guns

Your child's doctor should assess your child for these risks during a thorough evaluation before treatment even begins because these factors can help dictate which course of treatment is best.

How can medication meant to help treat depression and other illnesses possibly cause suicidal behavior in children?

Researchers speculate about a variety of potential reasons.

In some cases, children may have undiagnosed bipolar disorder. Treating them with antidepressants could cause an episode of mania that leads to risky, impulsive behavior that could include self-harm.

Antidepressants may also trigger anxiety, agitation, hostility, restlessness and impulsivity, which could be linked to worsening depression or the emergence of suicidal impulses.

Another common theory is that children — and adults — may attempt suicide when they seem to be getting better with treatment because that's when they finally have the energy to act on deep-seated feelings of hopelessness, sadness or worthlessness.

Why is this an issue now? Haven't children taken antidepressants for many years?

Doctors began regularly prescribing antidepressants to children with depression, anxiety disorders and other psychiatric illnesses more than a decade ago, with the development of a type of antidepressant called selective serotonin reuptake inhibitors (SSRIs), even though the drugs weren't extensively safety-tested in children and weren't officially approved for use in children.

It wasn't until early 2003 that the FDA formally approved the first antidepressant for use in children with depression — the SSRI fluoxetine (Prozac). But red flags went up when the manufacturer of another SSRI, paroxetine (Paxil), sought official FDA approval for its use in children with depression. The FDA denied that application and contended that initial reports from clinical trials suggested that children who took paroxetine had a higher risk of suicidal thoughts and actions than those who took a placebo. Those findings triggered broader concerns among parents, federal officials and some doctors about the safety of all antidepressants in children.

Also in 2003, the United Kingdom banned the use of all SSRIs in children with depression, except for fluoxetine — the only drug, regulators said, whose benefits outweighed its risks. The other SSRIs, they said, posed increased risks of such problems as self-harm, suicidal thoughts and agitation. Those warnings added to concerns in the United States, eventually prompting the FDA to launch its investigation.

If only fluoxetine (Prozac) is approved for use in children, how can other antidepressants be prescribed for children?

The FDA normally approves a drug for a particular condition in a particular population, such as depression in adults. However, the agency doesn't regulate the practice of medicine. That means doctors can use their judgment to prescribe the medication for other conditions or other populations — a practice known as off-label use. Off-label use is a common practice for scores of medications, and it's what allows doctors to legally prescribe antidepressants for children even if they haven't been specifically approved for children.

Among the dozens of antidepressants on the U.S. market, fluoxetine is the only one the FDA has actually approved to treat depression in children. That approval was based on results of clinical trials demonstrating the drug's safety and benefits. Fluoxetine is also FDA approved to treat OCD in children, as are the antidepressants sertraline (Zoloft), fluvoxamine and clomipramine (Anafranil).

Clinical trials of other antidepressants in children with depression, OCD or other disorders have failed to prove that they're significantly more beneficial than a placebo, and so they haven't been approved for pediatric use.

Why do some doctors and researchers think the FDA warnings about antidepressants are overly cautious?

Over the years, results from various clinical trials that test antidepressants in children have been mixed. Some studies have found that antidepressants don't increase the risk of suicide. Others have found that a small increase in risk is offset by big benefits — a reduction in the symptoms of depression or anxiety disorders.

In addition, some doctors are troubled by the nature of the FDA analysis that led to the warnings and believe that the evidence linking suicidal behavior to antidepressants is weak.

The American Psychiatric Association, for instance, says it was "premature" to issue warnings based on short-term clinical trials that studied children for up to only four months. Further, because the FDA analysis pooled data from a variety of studies done in different ways and on children with different conditions, some critics contend that there were too many variables that could have influenced the results. In addition, researchers didn't run blood tests on children in the studies to make sure they were actually taking their antidepressant medication.

Some also note that childhood suicide rates have declined in recent years in conjunction with the rise in the use of antidepressants. But whether the decline can be attributed directly to the use of antidepressants hasn't been proved.

Finally, depression itself carries a strong risk of suicide, and some critics contend it's not clear if the antidepressants caused suicidal behavior or if the depression itself did. The FDA, however, stands by its findings.

What are the alternatives to treatment with an antidepressant?

First, keep in mind that the FDA warnings don't prohibit the use of antidepressants in children, nor are they meant to frighten people away from treating children with antidepressants entirely — although that might be the unintended effect.

But if you're simply not comfortable with antidepressants because of the warnings or if they're deemed inappropriate for your child, counseling is another option. However, some studies indicate that counseling alone may not be sufficient to effectively treat depression, especially more severe forms.