by Michael D. Anestis, M.S.
Given our recent articles on the various psychosocial and pharmacological treatments for depression (see here and here), I thought it would be a worthwhile venture to open a conversation on the link between antidepressant use and suicidality. To do this, I would like to summarize a recent article published in Professional Psychology: Research and Practice by David Rudd, Liliana Cordero, and Craig Bryan (author of the April 2009 PBB featured article). In this article, the authors sought to clarify the actual meaning of the black box warning on antidepressants and to provide some preliminary data on shifts in suicide rates since the black box first appeared.
The Food and Drug Administration (FDA) first issued the black box warning for antidepressants in 2004, declaring that children and adolescents utilizing antidepressants were at an increased risk for "suicidal thinking and behaviors." In 2007, the warning was expanded to include young adults up to the age of 24. Quite understandably, this raised significant concern amongst clinicians, researchers, and the general public. The idea of a popular treatment for the most common mental illness contributing to suicidality in children and adults is horrifying. That being said, the vast majority of who have heard about this warning - whether they are professionals or nonprofessionals in need of help - do not accurately understand what the black box actually tells us.
Before getting any further into this topic, I want to call your attention to a link provided in the article by Rudd, Cordero, and Bryan (2009). Click on this link to read the complete FDA warning label and a supplemental medication guide for health care providers, patients, and family members.
Now that you have access to the warning label itself, let's discuss what it actually tells us. Based on a sample of 4,400 pediatric patients, the FDA felt compelled to warn about clinical worsening, particular with respect to the first months of an antidepressant drug prescription. Additionally, the FDA suggested that, during this initial phase of treatment, clients should have more frequent contact with practitioners and suicide risk should be assessed regularly. What the warning does not do, however, is mention an increased risk for death by suicide. Why not? Because there was not a single death by suicide in the entire pediatric sample. There was a statistically significant increase in suicidality - defined by the FDA in their study as thoughts of suicide and suicidal behaviors (e.g., failed attempts) - but there was no actual death by suicide. As we have covered repeatedly in our articles on Joiner's (2005) interpersonal-psychological theory of suicidal behavior, there is a very real distinction between thoughts of suicide and suicide attempts and, additionally, there is a big difference between serious and non-serious attempts. All of these thoughts and behaviors are troubling, but they are not all the same thing.
To clarify this point further, the FDA data indicated that, for individuals under the age of 18 who were prescribed antidepressants, there was an additional 14 cases of suicidality per 100,000 people relative to individuals prescribed a placebo. For individuals between the ages of 18 and 24 who were prescribed antidepressants, there was an increase of 5 cases of suicidality per 100,000 people relative to individuals prescribed a placebo. These are meaningful numbers, but remember, suicidality in this study did not involve death by suicide. The suicidality rate in the antidepressant group was 4%, meaning 176 individuals exhibited suicidality. By comparison, there was a suicidality rate of 2% in the placebo group, meaning 88 individuals exhibited suicidality. A difference of 2% is not trivial, but it does indicate that results from 88 individuals (the difference between the two groups) resulted in a warning for all antidepressants.
Importantly, although there were deaths by suicide in the adult sample, there was no statistically significant difference in rates of suicidality between those on antidepressants and those taking a placebo pill for individuals between the ages of 25 and 64. Additionally, for individuals over the age of 65 - the demographic with the highest global rate of death by suicide - there was a significant decrease in suicidality for individuals taking antidepressants (6 fewer cases per 100,000 people).
When the FDA issued this warning, it was not their intention to imply that children and adolescents were dying by suicide as a result of using antidepressants. Similarly, they did not want to discourage practitioners from prescribing antidepressants to these or any other age groups. They simply wanted to call attention to a trend indicating deterioration during early months of therapy and to encourage increased contact between clients and practitioners during this period so as to facilitate regular risk assessments. The impact of the warning, however, has not mirrored the FDA's intentions.
Several studies have reported a substantial drop in the rates of antidepressant prescriptions. In fact, Lineberry et al (2007) reported a 20% decrease in antidepressant prescriptions to children and adolescents. Some might argue that this is fine, as it might mean that alternative paths towards health are being taken. This, however, simply is not the case. Libby and colleagues (2007) reported that there has been a significant drop in the number of children and adolescents being diagnosed with depression. After the 2004 warning, depression diagnoses in this age group decreased by nearly 70%. This does not mean fewer people meet criteria for depression, but rather that fewer people are actually being given the diagnosis. Additionally, despite the decrease in antidepressant prescriptions, there has been no increase in the rate of individuals utilizing psychotherapy. In other words, clinicians have responded to the black box warning by becoming less willing to diagnose depression and the general public has become less willing to seek help. As such, we are not seeing anything resembling an increase in effective care.
Perhaps the most notable change since the institution of the black box warning on antidepressants has been an increased rate of suicide amongst the targets of the warning. In the Netherlands, the youth suicide rate increased by 49% following the introduction of the warning label (Gibbons et al., 2007). In the United States, there was an 18% increase in suicide rates for children, adolescents, and young adults (Bridge, Greenhouse, Weldon, Campo, & Kelleher, 2008). In Canada, the child and adolescent suicide rate increased from 4 per 100,000 to 15 per 100,000 after the warning was issued. This is not to say that the FDA is responsible for the increases, but rather that the warning has actually had the opposite of its intended effect, in large part because most individuals do not actually understand what it is saying.
The confusion regarding the black box warning also appears to be impacting adult populations. Rudd, Cordero, and Bryan (2009) noted that several studies have found a decrease in antidepressant prescriptions for adults, despite the fact that the FDA study showed no relationship between suicidality and antidepressants for adults between the ages of 25 and 64 and a decreased suicidality rate for adults over the age of 65 who were prescribed antidepressants. In other words, because of the findings for children and adolescents, clinicians appear to be less willing to prescribe helpful medication for adults and adults seem less willing to seek out effective care (Valuck et al., 2007). Again, this would be less troubling if adults were increasingly seeking effective psychosocial care; however, there has been no such increase in psychotherapy usage. This particular finding should be taken with a grain of salt, however, given that other studies have shown a massive increase in overall antidepressant usage.
Unfortunately, the black box warning has also failed to cause the desired increase in client contact, as fewer than 5% of patients meet the FDA suggestions for contact with practitioners, a rate that is identical to pre-warning levels. Additionally, Cordero, Rudd, Bryan, and Corso (2008) found that, in a sample of prescribing practitioners, 91% misunderstood the black box warning and the vast majority believed that the data indicated an increased risk for death by suicide.
All of these findings taken together seem to indicate that, despite the best of intentions, the FDA's black box warning has not been helpful. Many individuals mistakenly believe that antidepressants result in an increased risk of death by suicide, fewer clinicians are diagnosing individuals with depression, and fewer depressed individuals are seeking help. Additionally, rather than decreasing, suicide rates in the target populations appear to have increased. Ideally, greater clarity will be found through enhanced education, with practitioners and the general public choosing to read about the actual findings and researchers making a stronger effort to effectively publicize accurate information.
If you would like to learn more about this or other mental health topics, we encourage you to consult our online store.
Mike Anestis is a doctoral candidate in the clinical psychology department at Florida State University.
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