In my clinical work, I often encounter parents who are concerned about putting their kids on psychiatric medications. In the case of anti-depressants, such concerns are grounded on a large literature that has linked anti-depressant use by adolescents with a mild increase in the risk of suicide. Contrary to some common explanations, it is not simply that kids who are more likely to attempt suicide (those who are clinically depressed) are also more likely to receive anti-depressant medication, since the increased risk for suicide has been observed during randomized clinical trials (RTCs). That is, in many RTCs, those clinically depressed kids who are randomly assigned to a medication have been found to be more likely to attempt suicide than their equally depressed peers who happened to be randomly assigned to a placebo. It is indeed the exposure to the active treatment that leads to the increase risk for suicide. Although there are some questions still being debated (e.g., effect of age, type of medication, type of disorder, etc), there is a general agreement that anti-depressant medication use during adolescence leads to a mild but real increase in the risk for suicide. The more pertinent questions are 1) why is this the case? And more importantly… 2) what are the implications for clinical practice ? I’m going to touch on these two questions during the next few weeks. Today, I want to discuss a recent article published in the Journal Pediatrics that examined the risk of suicide among adolescents taking anti-depressant medications in Canada. The main goal of the study was to examine whether the kind of medication (brand or type) resulted in different levels of risk. In other words, are all medications created equal in terms of their effects on suicide risk for adolescents?

In this study, the authors examined the medical records of all residents of British Columbia who were 10 to 18 years of age and who started to use an anti-depressant medication between 1997 and 2005. The British Columbia Ministry of Health keeps detailed records of all medical services provided to British Columbia residents. This allowed the investigators to identify all children who were provided (and filled) a prescription for an anti-depressant medication during those years. The researchers also indentified all suicidal attempts and suicide completions during the same years, and obtained key medical information on these children, such as the diagnosis, past use of anti-depressants, gender, etc. With this information, the researchers examined whether the risk for suicide varied based on the specific medication used after controlling for other factors.

The results:

During the study period, 20,906 children and adolescents started taking an anti-depressant medication. 2% of these children had already attempted suicide before starting the medication.

The medications were divided into 5 groups:

1. SSRI, including Citalopram (celexa), Fluoxetine (Prozac), Fluvoxamine (Luvox), Paroxetine (Paxil), Sertaline (Zoloft)

2. SNRIs, including Venlafaxine (Effexor)

3. Triclyclic Antidepressants, including Amitriptyline, Amoxapine, Clomipramine, Desipramine, Doxepin, Imipramine, Maprotiline, Nortiptyline, Protriptyline, and trimipranime.

4 Atypical New Agents, including Mirtazapine, Nefazodone, and Trazodone

5. MAOIs, including Moclobemide, Phenelzine, and Tranyclypromine

During the 12 months after the children/adolescents started using the medication, the researchers identified 268 children who attempted suicide, including 3 who completed suicide. That is, only 1.2% of those children who started the medication had a suicide attempt during the first 12 months. This rate was actually surprisingly low given that 2% of these kids had already attempted suicide before starting treatment. However, if we consider only those kids who had not been previously on anti-depressant medication, the rate increased to 2.5%.

Was one medication safer or riskier than others? Apparently the answer is no. The researchers did not identify any difference in suicide risk among all the medications. The rates of suicide attempts were comparable across all medications. One exception was MAOI’s. No suicide attempts were observed among children taking MAOI’s. However, likely due to MAOIs’ other significant risks, only 37 children (0.17% of the sample) were prescribed MAOI’s, which prevented a proper statistical examination of risk for suicide when taking MAOIs.

But what does this have to do with my initial questions? This helps narrow the answer as to why there is an increase risk of suicide when taking anti-depressant medications. Some have proposed that the increased risk was due to the use of a specific type of medication (e.g., SSRIs such as Prozac) because of some unknown effect on brain functioning. But these data suggest that all anti-depressant medication, not only SSRIs, have lead to an equal increase in the risk for suicide. It appears that this risk is not unique to any type or brand of medication. Some have suggested that the increase in suicide risk is due to the therapeutic effect of the drug. Specifically, as patients begin to feel better, there is an increase in behavioral activity and self-confidence. In theory, this could increase the risk of suicide among those who were so depressed that they lacked motivation even to attempt suicide (either because of a lack of energy/motivation or the belief that even suicide wouldn’t help). But under this hypothesis, there also should be an increase in the risk for suicide after adolescents engage in psychotherapy. Unfortunately, there are significantly fewer (and much smaller) studies of psychotherapy with children and adolescents than of anti-depressant medications, which has prevented researchers from examining this question in an adequately large sample. So, the question remains as to whether the increased risk for suicide is an unfortunate byproduct of the therapeutic effect of effect interventions and not just of antidepressant drugs.
Schneeweiss, S., Patrick, A., Solomon, D., Dormuth, C., Miller, M., Mehta, J., Lee, J., & Wang, P. (2010). Comparative Safety of Antidepressant Agents for Children and Adolescents Regarding Suicidal Acts PEDIATRICS, 125 (5), 876-888 DOI: 10.1542/peds.2009-2317

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3 Responses to Antidepressant medications and risk for suicide in children and adolescents: all drugs are created equal.

  1. sam bryks says:

    This is an interesting and thoughtful review of this controversial but critical issue but the use of the word “mild” to describe an increase in suicide ideation and/or attempts is truly a poor choice of language. There is nothing “mild” about suicide risk.
    The increase in suicide ideation has been known for many years and has been well reviewed by David Healy an expert in these drugs from Cardiff University in Wales, U.K., I believe.
    there is a long history of drug companies protecting their interests and literally “fudging” findings to show best results. Many of the drug company studies have excluded at risk subjects even though there was a famous case of a subject in a study who did not have any history whatsoever of depression and who killed herself during a study involving prozac, the first SSRI drug.
    Healy wrote an incisive study on how the medical model of drugs curing a disease has been applied badly to psychiatric practice even though the impact of these drugs is much more complex than a simplistic model of “you feel depressed.. here, take this, and you’ll feel better” and the truly stupid practice “oh, you feel worse after this “mild” dose, here take this stronger “mild” dose when sometimes the “feeling worse” is actually a side effect of the drug and taking more can result in suicide because of putting the patient into an even worse state than they wer ein before they had the drug.
    The word “mild” should never be used in context of effects of drugs that are potentially life threatening.


    • Thanks for the comment Sam. The use of the word “Mild” reflects the findings. It is also the conclusion of the three large studies that have reviewed this issue. It is a technical term that describes the size of the effect. Across all trials, the effect is mild (not moderate or severe; around a 66% increase) and no effect was observed in completed suicides. As you mentioned, this is a controversial issue and more complex than we think. For example, following the SSRI warning label, there was in significant decrease in SSRI use by adolescents, which then was followed by the largest yearly increase in completed adolescent suicides in the USA of the last 40 years. This brings the question of clinical significance and ethical practices… How do we compare the clinical significant and implications for treatment and clinical decision the increase in ideation (but not actual suicides) due to medication use vs. the increase in actual suicides due to decreases in medication use?

  2. Manaka says:

    It was interesting to know why “anti-depressant medication use during adolescence leads to a mild but real increase in the risk for suicide”. In my country, a lot of people commit suicide. Therefore, I wanted to know whether there is a correlation between anti-depressant medication use during adolscene and the risk for suicide.

    I’m researching about teen depression at school. I sent you an email because I wanted to find out more about teen depression. I hope you can reply me back. Thank you so much.

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