Q. Are SSRIs safe to use in children and adolescents?
A. The ACNP’s task force reviewed 15 clinical trials, including published and unpublished data on SSRIs and other new antidepressant medications. A total of more than 2000 subjects were involved. No study participant committed suicide, and even though the definition of suicidality was left up to the individual investigators and could differ across studies, there was no significant difference between suicidal behavior in patients on SSRIs and those on placebo. The UK study reports an increased risk of ≤2% in suicidal behavior, a finding that was not statistically significant for any of the SSRIs.17 The conclusion of the task force was that five SSRIs are more effective than placebo in the treatment of depression in at least one study: Prozac, Zoloft, Paxil, Celexa, and nefazodone. The task force concluded there is sufficient evidence that SSRIs overall are effective in treating depression in children and adolescents.18
Another safety factor to consider, one which has not been clearly defined, is that of low vs. high lethality in suicide attempts. Low-lethality attempts are more frequent in women within the context of an interpersonal crisis and not often fatal. High-lethality attempts, which are more common in men, are usually well-planned and more often result in death.18
The ACNP also reports on other interesting data that support the safety of SSRIs and their effect of actually decreasing suicide. One toxicology study demonstrated that of 49 adolescents who committed suicide, none tested positive for SSRIs, even though some had been prescribed these antidepressants. Another similar study of 100 adults who committed suicide demonstrated that most of the victims had not taken an SSRI before their death. Epidemiologic studies in the United States and other countries have also shown a decrease in suicide over the past 14-15 years. This coincides with the advent of, and increases in, the prescription of SSRIs. In fact, suicide rates in 15 countries have declined by 33% in the past 15 years.18
Recently, investigators in Britain examined 2791 patients ages 10 to 69 who were first-time users of antidepressants and compared the risks of suicidal ideation and behaviors of those taking SSRIs (Paxil and Prozac) with those taking TCAs (amitriptyline [Elavil, Endep] or dothiepin).19 While they concluded that the rate of suicide was increased during the first month of treatment on any agent, particularly during the first nine days, they found no substantial differences in the suicide rate among the drugs, particularly when used in adolescents ages 10-19.
Q. How should pediatric depression be addressed?
A. As recommended in Bright Futures in Practice: Mental Health, screening of mental health should be a routine part of all well-child and adolescent exams.20 Bright Futures in Practice: Mental Health is a comprehensive guide to instituting this aspect of care into your practice. It is published by the National Center for Education in Maternal and Child Health at Georgetown University in Washington, D.C.
Many practitioners may be reluctant to introduce mental-health assessment into their practice. This may be due to the fact that they have not been trained, or they may feel uncomfortable with psychological issues. Once a diagnosis like depression is suspected, the practitioner is then obligated to act on this knowledge to help the patient. If the practitioner is reluctant to initiate treatment and mental-health providers are available and accessible to the patient, then a prompt referral is appropriate. If, however, finding a mental-health professional is difficult, then the practitioner will have to make a decision: Is it reasonable to delay care for depression when there is no one accessible for the patient to see? Is it reasonable to treat a young patient with SSRIs in the primary-care setting? What if there is no one accessible to provide psychological services? These questions are being raised more and more often in everyday practice.
If you decide to treat a child or adolescent for depression, the ACNP recommends that he or she be given the option of therapy with an SSRI. It is imperative to discuss the issues addressed in this article and answer any questions or concerns the patient may have from hearing about SSRIs in the popular press. Bringing up the SSRI controversy initially will increase awareness and, hopefully, early identification of potential problems.
John Walkup, MD, and Michael Labellarte, MD, psychiatrists at The Johns Hopkins Children’s Center in Baltimore, devised a mnemonic to assist clinicians in early recognition of potential complications of treatment with SSRIs.21
As previously noted, the addition of psychotherapy may improve the possibility of a successful outcome.22 If access to a trained psychotherapist is limited, then close follow-up is the next best thing. Contact should include frequent monitoring of side effects, ADRs, and of course, suicide risk.
Q. Which SSRI should be used and which should be avoided for initial pediatric therapy?
A. Of the five SSRIs that may be effective in children and adolescents, Prozac, Zoloft, Paxil, Celexa, and nefazodone,18 Prozac has the longest track record and the most studies to support its use. It is also the only drug approved by the FDA to treat depression in children aged 8-17. If you decide to treat with an SSRI, then Prozac is recommended as first-line therapy, especially in children. This does not mean that the other SSRIs should not be used or are not effective. However, all risks considered, this is the most prudent choice. One might avoid using Paxil as an initial therapy until more data are available. Remember to start therapy with a low dose and increase it slowly to decrease the risk of ADRs. And don’t forget to follow up frequently until an optimal dose is reached. If there is no improvement in depression or if symptom change after two months is minimal, consult with a psychiatric clinician or psychiatrist about the possibility of changing medications, or refer the patient for further treatment.
Q. How long should a child continue with SSRI therapy?
A. Not enough long-term studies have been done to answer this question. However, Pine presents preliminary recommendations that appear prudent.3 For children who respond to an SSRI, it is reasonable to consider a medication-free trial at some point after one year of therapy. Ideally, withdrawal should be during a period of lower stress for the patient. But if the child exhibits signs and symptoms of relapse, the medication should be restarted.
One thing all the experts agree on is the need for more studies in children and adolescents on the best treatment options for depression, both pharmacologic and psychological. There is also a critical need for long-term studies on the safety and efficacy of all therapies, including the SSRIs.
Fortunately, data from the Treatment for Adolescents with Depression Study, which is evaluating both psychological therapy and drug treatment, should be forthcoming.23 Also, The Child and Adolescent Psychiatry Trials Network is planning to conduct large practical trials in community-based sites hopefully to answer some of these current questions about SSRI use in children and adolescents.24
Ms. Waldrop is clinical assistant professor at the University of North Carolina School of Nursing and practices in the Pediatrics Department at UNC Hospitals and Clinics, both in Chapel Hill. She is also a contributing editor to The Clinical Advisor.
1. Kessler RC, Walters EE. Epidemiology of DSM-III-R major depression and minor depression among adolescents and young adults in the National Comorbidity Survey. Depress Anxiety. 1998;7:3-14.
2. Anderson RN. Deaths: Leading Causes for 2000. Hyattsville, Md.: National Center for Health Statistics; 2002. National Vital Statistics Reports 50.
3. Pine DS. Treating children and adolescents with selective serotonin reuptake inhibitors: how long is appropriate? J Child Adolesc Psychopharmacol. 2002;12:189-203.
4. Hazell P, O’Connell D, Heathcote D, Henry D. Tricyclic drugs for depression in children and adolescents. Cochrane Database Syst Rev. 2002;(3):CD002317.
5. Curry JF. Specific psychotherapies for childhood and adolescent depression. Biol Psychiatry. 2001;49:1091-1100.
6. Carey B. Pills or talk therapy? If you’re confused, no wonder. New York Times. June 8, 2004:F1.
7. Nemeroff CB, Heim CM, Thase ME, et al. Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma. Proc Natl Acad Sci USA. 2003;100:14293-14296.
8. Treatment for Adolescents With Depression Study (TADS) Team. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression. JAMA. 2004;292:807-820.
9. Kapur S, Mieczkowski T, Mann JJ. Antidepressant medications and the relative risk of suicide attempt and suicide. JAMA. 1992;268:3441-3445.
10. Medawar C, Herxheimer A. A comparison of adverse drug reaction reports from professionals and users, relating to risk of dependence and suicidal behavior with paroxetine. Int J Risk Safe Med. 2003;16:5-19.
11. Medicines and Healthcare products Regulatory Agency. Seroxat must not be used for treatment of children.
12. Duff G. Selective serotonin reuptake inhibitors: use in children and adolescents with major depressive disorder.
13. Health Canada advises Canadians under the age of 18 to consult physicians if they are being treated with newer antidepressants. Health Canada Web site.
14. Whittington CJ, Kendall T, Fonagy P, et al. Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet. 2004;363:1341-1345.
15. Jureidini JN, Doecke CJ, Mansfield PR, et al. Efficacy and safety of antidepressants for children and adolescents. BMJ. 2004;328:879-883.
16. The Food and Drug Administration. FDA issues public health advisory on cautions for use of antidepressants in adults and children. Rockville, Md.: March 22, 2004. Talk Paper T04-08.
17. Brent DA, Birmaher B. British warnings on SSRIs questioned. J Am Acad Child Adolesc Psychiatry. 2004;43:379-380.
18. American College of Neuropsychopharmacology. Executive summary: preliminary report of the task force on SSRIs and suicide behaviour in youth.
19. Jick H, Kaye JA, Jick SS. Antidepressants and the risk of suicidal behaviors. JAMA. 2004;292:338-343.
20. Jellinek M, Patel BP, Froehle MC, eds. Bright Futures in Practice: Mental Health. Arlington, Va.: National Center for Education in Maternal and Child Health; 2002.
21. Walkup J, Labellarte M. Complications of SSRI treatment. J Child Adolesc Psychopharmacol. 2001;11:1-4.
22. Emslie GJ, Mayes TL, Laptook RS, Batt M. Predictors of response to treatment in children and adolescents with mood disorders. Psychiatr Clin North Am. 2003;26:435-456.
23. Treatment for Adolescents with Depression Study Team. Treatment for adolescents with depression study (TADS): rationale, design, and methods. J Am Acad Child Adolesc Psychiatry. 2003;42:531-542.
24. March JS, Silva SG, Compton S, et al. The Child and Adolescent Psychiatry Trials Network (CAPTN). J Am Acad Child Adolesc Psychiatry. 2004;43:515-518.