The Impact of the Black Box Warning

The Impact of the Black Box Warning

In 2004, the FDA issued a black box warning regarding the use of SSRIs (selective serotonin reuptake inhibitors) in children and adolescents suffering from depression and/or anxiety. The impact of this public warning was impressive. Pediatricians and family practice doctors began to refer more young patients suffering from relatively straightforward cases of anxiety and/or depression to an already small pool of psychiatrists for additional evaluation and pharmacotherapy. Additionally, the news media encouraged public fear regarding these medications. In fact, prescriptions written for SSRIs decreased by approximately 18-20% by 2007, just three years after the FDA’s warning was issued. During the same period of time, an increase in the actual suicide rate among children and adolescents (up to the age of 19) rose approximately 18%- the first increase in suicide in over a decade.

So, what data behooved the FDA to issue such a weighty warning? According to Steven P. Cuffe, M.D., “the data showed a small increase in suicidal thought and behaviors, from 2% in the placebo groups to 4% in the medication groups, when data from all trials for all indications were combined. There were no completed suicides in any of the studies conducted on antidepressant medications. The FDA issued the warning despite evidence that increasing prescriptions for SSRI antidepressant medications was clearly correlated with decreasing rates of actual suicide, and the use of antidepressant medications was not associated with suicide in any prior studies.”1 The actions of the FDA in this case are very troubling. In general, we live in a very alarmist society. Most of us are afraid of the impact of medications, vaccines, etc – it takes very little to convince us of the alternatives to allopathic medicinal approaches. Unless, of course, we are the patient suffering with a debilitating illness. But in pediatrics, it is generally the parent that is discussing treatment with me. Even in the case of my adolescent patients, often times, the parent has an idea of whether the patient should be treated medicinally before I even walk into the room, regardless of the condition. It is natural for us, both parents and physicians, to have our opinions regarding treatments. But, doctors, pharmacists, and medical supervising bodies are not at liberty to recommend or repudiate treatment based on personal bias. We have to look at the data- not just the research abstract but the actual data.

Along this vein, in 2006, The New England Journal of Medicine, a highly respected medical journal, published an article purporting a link between late SSRI exposure (> 20 weeks’ gestation) and PPHN (persistent pulmonary hypertension of the newborn). Obstetricians and pediatricians began recommending that pregnant women stop their SSRI medications in the later half of pregnancy secondary to the conclusions of this study, despite the known increased risk of post-partum depression in women with a history of mental illness (as well as previously unaffected women). The media turned its focus to this study and news reports aired to inform the populace of the dangers of SSRIs while pregnant. Pharmacists began (and still do) label SSRIs as a risk in the 3rd trimester of pregnancy. However, if you read the study in detail, you will read this… “ The crude risk of PPHN associated with the use of any antidepressant at any time in pregnancy was not significantly elevated (odds ratio, 1.3; 95 percent confidence interval, 0.7 to 2.2), nor was the use of SSRIs alone at any time in pregnancy significantly associated with PPHN (odds ratio, 1.5; 95 percent confidence interval, 0.8 to 2.9). However, when the comparison was stratified according to the timing of exposure in pregnancy, use of any antidepressant after the 20th week of gestation was significantly associated with PPHN (odds ratio, 2.9; 95 percent confidence interval, 1.3 to 6.5).”2 In effect, the first quoted sentence negates the entire study, even though the authors continue to draw conclusions from their data. If you read only the abstract, it will seem like there is an actual difference in the incidence of PPHN among infants born to mothers taking SSRIs compared to mothers not taking any antidepressant medication, but this conclusion, per their own data, is inaccurate. The first quoted sentence was in the full text version of the research report, but absent from the abstract.

I understand that data evolves, and medical recommendations continue to change with time. We continue to learn from research and will need to adjust our recommendations constantly. But, our alarmist society does not need physicians to follow suit. We, for the most part, have remained steadfast in our defense of vaccines, perhaps because many physicians still remember children in the ICU with Haemophilus influenza meningitis. We still see babies with pertussis, some of whom do not survive. So, we persevere, despite the fear among our patient families. Yet, as has always been the case with mental ailments, issues we cannot see and touch, the bias has been to not treat, or to simply refer the issue to someone else. Side effects are certainly possible, but our patients need us to address the health of their whole being. There are simply not enough child and adolescent psychiatrists available to do this for us.

Recommendations for providers:

  1. Use a teen screen or ask a general question or two during well child check-ups to ascertain whether or not your patient is suffering from functionally impairing anxiety and/or depression.
  2. Discuss treatment options with parent and patient. A cognitive behavioral therapist is an excellent first step in treatment or an effective adjunct to pharmacotherapy.
  3. If an SSRI is warranted, have a plan for slow titration and a scheduled phone call or visit weekly or bi-monthly for the first couple of months to discuss any side effects or patient/parent concerns.
  4. If the patient’s case is not straightforward or unusual side effects occur, refer to a child/adolescent psychiatrist.


Recommendations for parents/patients:

  1. Know that a lot of what we recommend is based on personal bias coupled to medical fact. There are almost always a couple different approaches to take regarding treatment.
  2. If your child is suffering, it is imperative to seek help. I had a patient transfer to me a few years ago because her pediatrician refused to prescribe an SSRI for her anxiety. The family was and is very informed and supportive, but didn’t believe their daughter’s straightforward case of anxiety required a psychiatrist. She improved markedly once medicated on a low dose of an SSRI. In her case, and many others, it has completely changed her life.
  3. I don’t believe that parents or patients in general take medications lightly. I believe we all would rather not, but sometimes medications are simply warranted. It is important to know and understand the benefits and true risks of any treatment. Your doctor should be able to guide you through this. If you feel you have learned something through your own research with Dr. Google, ask your pediatrician about it! If he doesn’t know, he can look into it. If it’s not medically sound, she can tell you. But, of course, be wary – there is some crazy stuff on the Internet!
  4. Homeopathic alternatives do exist and for some people are truly helpful. In my opinion, personal more than medical, alternative medicine is a fabulous adjunct to traditional medical treatment, but rarely outright cures disease. It helps, but as sole treatment is generally not enough.


1. 2.N Engl J Med. 2006 Feb 9;354(6):579-87. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. Chambers CD1, Hernandez-Diaz S, Van Marter LJ, Werler MM, Louik C, Jones KL, Mitchell AA. 3.

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