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Are Antidepressants Safe to Use in Youth?

Raymond W. Lam, MD, FRCPC

Reprinted from "Treatments for young people" issue of Visions Journal, 2006, 3 (1), p. 7-9

Suicide is a tragic outcome of clinical depression and is a highly emotional topic. So, it is not surprising that there has been so much emotion and confusion over recent reports that newer antidepressant medications like SSRIs (selective serotonin reuptake inhibitors),1 thought to treat depression, might actually cause suicidal thoughts and behaviours in young people. Health Canada and the United States Food and Drug Administration (FDA) recently issued strong warnings to physicians that antidepressants may be associated with increased suicidal ideas or behaviours in youth (children and teenagers).

Are SSRIs safe to use in youth? Like many mental health issues, this simple question is quite complicated—but it needs to be answered scientifically rather than emotionally. It is a complicated question because suicidal ideas are commonly experienced in depression, but can vary in intensity over time. Also, while suicidal ideas are common, suicidal behaviours (attempts or deaths by suicide) are thankfully rare compared to the number of people who are treated for depression. Therefore, whether a treatment causes or worsens suicidal ideas is difficult to separate from the effects of the underlying illness.

The Health Canada and FDA warnings were based on an analysis of the pediatric antidepressant clinical trials submitted to the FDA and drug regulatory agencies in other countries (not including Canada).3 In these clinical trials, youth with depression agreed to be randomly assigned (like with a fl ip of a coin) to taking an antidepressant drug or a placebo (an inactive substance, like a sugar pill). Neither they nor the doctors knew which treatment they were taking. Depressive symptoms and side effects were measured weekly, and after eight to 12 weeks the effects of the drug were found by comparing patients taking the drug to those taking placebo.

In the 24 studies (involving a total of about 5000 youths), there were no deaths by suicide, and no individual study showed any increase in suicidal behaviour in those youths who were taking the antidepressant.3 However, when all the studies were combined, there were slightly more suicidal behaviours in patients taking an antidepressant compared to those who took a placebo. The estimate was that for every 100 youths treated with a placebo, one might expect one to three of them to show suicidal behaviours in the fi rst two months of treatment, while for every 100 patients treated with an antidepressant, two to six youths would show suicidal behaviours.

Unfortunately, clinical trials have limitations that make these results inconclusive. For example, patients participating in clinical trials may not reflect the “typical” patient with depression being treated in doctors’ offi ces because there are so many strict rules for participation.4 Combining results from so many studies is also a problem, because all the studies had different methods, medications, people, locations, and so on. Because of these problems, the accuracy of these results is questionable.

If antidepressants really do worsen suicidal behaviour, other types of studies should also show the same results as the combined clinical trials. “Observational” studies track large numbers of people who are prescribed antidepressants to see whether they made a suicide attempt or died by suicide.

Four large observational studies of depressed youth treated with antidepressants were reported, two in England and two in the United States. These studies each involved tens of thousands of youth treated or not treated with antidepressants, and none found evidence for increased suicide behaviours with antidepressant treatment.5-8 In fact, one study showed that the risk for suicide attempt was highest in the week before starting an antidepressant, with the risk falling sharply in the weeks after starting a medication.

In one of the English studies tracking three million patients, there were 15 youth who died by suicide— none of them had been treated with antidepressants.5 Similarly, in a Danish study, drug testing was done on blood samples taken from almost 15,000 deaths by suicide over an eight-year period. In the unfortunate 52 youths who died by suicide, none had SSRI antidepressants in their blood at the time of death.9 Many other studies have shown that in areas where more antidepressants are prescribed, the suicide rate is lower.

These large observational studies confirm that antidepressants, in general, help to reduce suicide by treating the underlying depression. In contrast to the fi ndings in the combined clinical trials, they provide evidence for the safety of antidepressants in youth. However, these studies cannot tell us if there are rare cases where individuals have a bad reaction to the medication.

So, are antidepressants really safe to use in youth? The answer is “Yes, but…” All drugs have side effects. Most of these side effects are mild and do not interfere with functioning, but there may be rare, unpredictable side effects that have serious consequences (such as allergic reactions to penicillin, gastrointestinal bleeding with aspirin, etc.). But, we need to remember that depression is a serious illness that severely disrupts lives and that, in extreme cases, can cause death by suicide. For depression, as for any other medical condition, you need to weigh the potential benefits of a medication with any small risk of serious side effects. Your doctor can help with that decision.

Summary recommendations

Of the canadian psychiatric association for using antidepressants in youth:

  • All patients (whatever the age) beginning any treatment for depression should be watched closely for worsening of depression and suicidal thoughts

  • For youth with uncomplicated depression of mild to moderate severity, psychological treatments should be used first.

  • Antidepressants can be used if the depression is moderate to severe, if there are other complicating medical or psychiatric conditions, or if psychological treatment is not helpful. Psychological treatment should be used along with the antidepressant treatment.

  • If treated with an antidepressant, patients and families should be educated about possible common and uncommon side effects, including anxiety, restlessness, and increased thoughts of suicide.

  • Fluoxetine (Prozac) is recommended as the first antidepressant, unless there are medical reasons not to use it.

Summary recommendations

Of the canadian psychiatric association for using antidepressants in youth:

  • All patients (whatever the age) beginning any treatment for depression should be watched closely for worsening of depression and suicidal thoughts

  • For youth with uncomplicated depression of mild to moderate severity, psychological treatments should be used first.

  • Antidepressants can be used if the depression is moderate to severe, if there are other complicating medical or psychiatric conditions, or if psychological treatment is not helpful. Psychological treatment should be used along with the antidepressant treatment.

  • If treated with an antidepressant, patients and families should be educated about possible common and uncommon side effects, including anxiety, restlessness, and increased thoughts of suicide.

  • Fluoxetine (Prozac) is recommended as the first antidepressant, unless there are medical reasons not to use it.

disclosure

Dr. Lam conducts research on new medication and non medication treatments for depression. His research is funded by the Canadian Institutes of Health Research, other non-profit funding agencies, and pharmaceutical companies. He has also received speakers’ and consulting fees from several companies, including ones that manufacture antidepressants.

Related Resources

Bender, K.J. (2006). Antidepressants: Youth suicide warnings increasingly questioned. Psychiatric Times, (23)4.

Kutcher, S.P. (n.d.). Ask the Expert: Q & A.

Centre for the Advancement of Children’s Mental Health, Columbia University. (2003). Guidelines for Adolescent Depression in Primary Care (GLAD-PC). These are the first evidence-based guidelines for treating adolescent depression for family doctors. It includes a physician toolkit

 

Raymond is Professor and Head, Division of Clinical Neuroscience, Department of Psychiatry at UBC, and is a member of Visions’ editorial board

Footnotes
  1. Author note: Antidepressants work by altering certain neurotransmitters (chemical messengers that transmit signals between brain cells), such as serotonin and noradrenaline, in areas of the brain that regulate mood, sleep and appetite. Older medications like tricyclic antidepressants also affect many other neurotransmitters, which can lead to side effects. Newer medications like the SSRIs work selectively on neurotransmitters (e.g., only on serotonin), so they are generally safer and have fewer side effects than the older medications.

  2. Kondro, W. (2004). UK bans, Health Canada warns about antidepressants. Canadian Medical Association Journal, 171(1):23.

  3. Hammad, T.A., Laughren, T. & Racoosin, J. (2006). Suicidality in pediatric patients treated with antidepressant drugs. Archives of General Psychiatry, 63(3):332-339

  4. Author note: Participants in depression trials are usually excluded if they have: a chronic (more than 6 months or a year) depression, a coexisting psychiatric diagnosis (such as an anxiety disorder, or ADHD), a co-existing personality disorder, a co-existing medical condition, co-existing substance use/abuse, active suicidal ideas, psychotic symptoms, any history of hypomania or mania, or if they are taking other medications for any other condition. Also, they must be willing and able to attend clinic visits at least once a week and spend two to three hours at each visit, and be willing to take a placebo. This means that patients participating in clinical trials often have only simple, mild depressions— which may explain why the placebo response is so high in many studies, since these depressions are more likely to resolve spontaneously.

  5. Jick, H., Kaye, J.A. & Jick, S.S. (2004). Antidepressants and the risk of suicidal behaviors. Journal of the American Medical Association, 292(3):338-43

  6. Martinez, C., Rietbrock, S., Wise, L. et al. (2005). Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: Nested case-control study. British Medical Journal, 330:389.

  7. Valuck, R.J., Libby, A.M., Sills, M.R. et al. (2004). Antidepressant treatment and risk of suicide attempt by adolescents with major depressive disorder: A propensity-adjusted retrospective cohort study. CNS Drugs, 18(15): 1119-1132.

  8. Simon, G.E., Savarino, J., Operskalski, B. et al. (2006). Suicide risk during antidepressant treatment. American Journal of Psychiatry, 163:41-47.

  9. Isacsson, G., Holmgren, P. & Ahlner, J. (2005). Selective serotonin reuptake inhibitor antidepressants and the risk of suicide: A controlled forensic database study of 14,857 suicides. Acta Psychiatrica Scandinavica, 111(4):286-290.

  10. Olfson, M., Shaffer, D., Marcus, S.C. et al. (2003). Relationship between antidepressant medication treatment and suicide in adolescents. Archives of General Psychiatry, 60(10):978-982.

  11. Gibbons, R.D., Hur, K., Bhaumik, D.K. et al. (2005). The relationship between antidepressant medication use and rate of suicide. Archives of General Psychiatry, 62(2):165-172.

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