New FDA Warning on Antidepressants: What Does It Mean to the Depression Patient?

THE NEW "BLACK BOX WARNING" ON ANTIDEPRESSANTS: WHAT DOES IT MEAN TO ME AS SOMEONE WITH DEPRESSION?

On May 2, 2007 the FDA required a label change for antidepressant medications. This was the second time such a change had been required. The first was in 2004, when the FDA required that a black box warning (the most serious warning) appear on the package insert advising of a possible increase in suicidality in children and teens taking antidepressant drugs. The most recent action increased the age of those included from below 18 years to age 25.

As a clinician, I have already heard from many patients and family members worried about this recent change. Their concern basically is "what does this really mean to me or my loved one? Should we avoid taking the depression medicines, or stop them?" Before answering this concern, let me acquaint you with the background that led to the change.

WHAT IS A BLACK BOX WARNING, ANYWAY?

In the package insert sheets that come with a box of medication (which is usually thrown away by the pharmacist before you get the medicine), there are warnings about the use of the drug being prescribed. The strongest of these warnings is a "black box warning" (called such because of the bold black border around the wording). It is rarely read by patients, but news reports or patient brochures often mention the warnings. The "black box warning" for children and adolescents taking antidepressants can be found here. This FDA mandated wording warned of the possibility of increased suicidality and other symptoms which might be experienced by patients early in treatment with antidepressants. Beside suicidality, the following other symptoms might appear:

• increase in anxiety or panic attacks
• trouble sleeping
• worsening anger-irritability or aggressive behavior
• abnormal increase in activity or talkativeness, or "other unusual changes in behavior."

SO WHAT IS SUICIDALITY?

Suicidal refers to thinking of taking one's life, or actions towards this end. It is not the same as suicide itself. In fact in the 4400 children and adolescents studied in the clinical trials that led to this warning, there was not a single suicide. So, it was rather an expression of suicidal thinking or behaviors, rather than the actual taking of one's life, that was being referred to.

During the trials, in the group of children and adolescents on active antidepressant drug, there was a doubling of suicidality compared to those on placebo (sugar pills). That sounds ominous until one looks at the real numbers-4% on active drug vs. 2% on placebo. Increased to be sure, but not in actuality by a large number. That means in a group of 1000 kids taking the antidepressant drug, the number with suicidality is around 18. In the young adults aged 18-25 studies, it was an additional 5 cases of suicidality. No increase in suicides, but in suicidality. By the way, in adults over 25 there was no increase in suicidalty and in seniors age 65 and above, there was actually a decrease in suicidality.

THE IMPACT OF THE CHILD/ADOLESCENT WARNINGS

Since the warnings were instituted, there has been a marked decrease in the number of kids for whom antidepressants have been prescribed. At the same time, there has been an increase in actual suicides in this age group (8%↑ in ages 10-14, and 12%↑ in ages 15-19). This information does not necessarily demonstrate cause and effect, but is alarming. The job of physicians who treat children and adolescents has become particularly difficult as family members have become more alarmed at the information and news reports of the warnings.

WHAT CAUSES THE INCREASE IN SUICIDALITY?

Experts are not in full agreement about the cause of the increase in suicidality when taking antidepressant medication, but there are several theories, the most prominent being:

• early change in brain chemicals effected by antidepressants
• early side effects caused by antidepressants
• and the use of antidepressants in patients who are really suffering from bipolar depression.

I will talk about all three, but first want to mention that the risk for suicidality is greatest during the first several weeks of treatment, or shortly after an increase in dose.

EARLY INCREASE IN BRAIN CHEMICALS: Most are familiar with the fact that the modern day antidepressants that effect serotonin do so by increasing the amount of the neurotransmitter in the space (synapse) between brain nerves (neurons). Research has shown that initially there may actually be a decrease in the amount of serotonin released to the synapse, and this decrease may last for several days to weeks. One theory of suicidality is that this decrease may lead to suicidal thinking.

EARLY SIDE EFFECTS OF ANTIDEPRESSANTS: Early in treatment, the modern day antidepressants can cause in some: increase in anxiety, worsening of insomnia, agitation, and a feeling of need to move about caused by a feeling of needles and pins in the legs and feet (a symptom known as akathisia). These symptoms are usually temporary and most often are gone within a few days to weeks. They can be treated if they are bothersome, but if not reported or recognized can lead to an increase in suicidality.

OVERLOOKING BIPOLAR DEPRESSION: Most of our readers are now aware of the existence of bipolar disorder, in which patients have one or more episodes of mania or hypomania in addition to symptoms of depression. In some patients it is not the speeded up manic phase that presents, but the depression which shows up initially, and only later can the diagnosis of bipolar disorder be made with accuracy. The "so what" of this confusion between unipolar and bipolar depression is that the use of usual antidepressant medications, although "right on" for the treatment of unipolar depression may cause problems for those with bipolar depression. Some of those with bipolar depression can be "flipped" into a hypomanic or manic episode which can present with agitation, increased movement and thought, and increase in suicidal thinking.

MOST IMPORTANT: Depression is a disease that can tragically result in suicide. In addition, the physical, occupational, and social impact of depression can be huge, as depression affects not only the patient but family, friends and coworkers as well. In addition, new research shows that patients with depression are more likely to suffer and die from a variety of other diseases. Antidepressant medication can reduce both the suffering and the risk of death from suicide, and can decrease the likelihood of death from other medical illnesses as well.

SO WHAT TO DO?

As a patient or "concerned other," I believe it is important to understand the intention of the FDA warnings regarding antidepressants à ¢Ã¢â€š ¬Ã¢â‚¬Å“to alert us to the possibility of suicidality and other symptoms during early usage or dose increases of antidepressant medication. Certainly notify the physician if these symptoms appear, and ask for appropriate help in dealing with them. Remember that the decision to use antidepressants, or any treatment, is ultimately up to the patient or guardian-and that this decision should always be an "informed one" - always weighing the risks of non-treatment against the benefits of the medication or therapy recommended.

by Harry Croft, MD
Medical Director of HealthyPlace.com

Harry Croft, MD is a practicing psychiatrist and medical researcher. He also conducts clinical trials on behalf of American pharmaceutical companies and is Medical Director of HealthyPlace.com.

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