Caitlin McIntosh, 12, hanged herself with shoelaces weeks after starting treatment for depression with a selective serotonin reuptake inhibitor (SSRI). Matt Miller, 13, hanged himself in his bedroom closet after taking his seventh SSRI dose. Michael Shivak, 11, slashed his wrists in class—but survived—while taking an SSRI.
These adolescents’ parents testified at an FDA hearing Feb. 2 about possible increased risk of suicidality with SSRIs in depressed children and adolescents.
Other families related positive experiences. Sherri Walton said her daughter, Jordan, 14, has achieved “enormous benefit” from taking SSRIs for obsessive-compulsive disorder. Suzanne Vogel-Scibilia told the FDA panel she is convinced that her two children with psychiatric disorders lead full lives because of SSRIs.
Sensitive to the anguish of grieving families but not wanting to deprive seriously depressed children of effective treatment, the FDA is proceeding methodically with its inquiry—probably at least until summer.
In the meantime, this article offers resources to help you answer questions from parents concerned about their children starting or continuing SSRIs. We include pediatric antidepressant dosing recommendations and data on benefits and risks of SSRIs and other reuptake inhibitors in young patients.
Why the FDA inquiry?
SSRI-associated behavioral activation and suicidal ideation in children and adolescents were reported anecdotally, as case reports, in the early 1990s,1 and more recently.2 No convincing evidence has shown, however, that SSRIs increase the risk of suicide. In fact, widespread use of SSRIs has been associated with reduced suicide rates.3
In May 2003, unpublished data submitted to the FDA from placebo-controlled trials suggested an increased risk of “possibly suicide-related” events and “suicide attempts” in pediatric patients taking paroxetine for major depression. No suicides were reported.
The Medicines and Healthcare Products Regulatory Agency (MHRA)—the United Kingdom’s equivalent of the Food and Drug Administration—responded by warning British physicians against prescribing paroxetine for depressed patients younger than 18. It also ordered a labeling change for paroxetine, contraindicating its use in pediatric major depression.
The FDA advised U.S. doctors against using paroxetine for children under age 18 with major depressive disorder and began investigating data on pediatric use of antidepressants, including all approved SSRIs. Since then:
- In the United States, venlafaxine’s manufacturer changed the drug’s labeling to include increased reports of hostility and suicidality in pediatric trial data. A “Dear Health Care Professional” letter in August 2003 indicated that venlafaxine is not recommended in depressed pediatric patients.
- Britain’s MHRA added pediatric con-traindications to labeling of venlafaxine, sertraline, citalopram, and escitalopram in December 2003. The agency opined that fluoxetine is the only SSRI with a favorable risk-benefit profile for pediatric major depression.
- At press time, the FDA had not changed any SSRI labeling.
At the Feb. 2 public hearing, the FDA’s Psycho-pharmacological Drugs Advisory Committee and Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee heard public comments from patients, families, and physicians and reviewed the inquiry’s progress. To locate the Web site containing the FDA’s memorandum on this hearing, see Related resources.
For the next several months, an expert group at Columbia University is under contract with the FDA to develop a system to classify events that might represent suicidality. The group will then analyze data from 24 studies involving more than 4,000 depressed pediatric patients and nine antidepressants (paroxetine, fluoxetine, sertraline, fluvoxamine, citalopram, bupropion, venlafaxine, nefazodone, and mirtazapine).
Independent findings. In January, an American College of Neuropsychopharmacology (ACNP) report concluded that SSRIs do not increase suicidal thoughts or suicide attempts in youth (Table 1). An ACNP task force examined the use of SSRIs in more than 2,000 children and adolescents, including all published clinical trial data, unpublished data from several pharmaceutical companies, and data reported to Britain’s MHRA. An executive summary is available on the ACNP’s Web site (see Related resources).
Table 1
Suicide deaths, behavior, or ideation in clinical trials of youth with major depressive disorder
| Medication | Total youth* in trials | No. of suicide deaths | % of youth with suicidal behavior or ideation** | P value | Statistical significance | |
|---|---|---|---|---|---|---|
| Antidepressant | Placebo | |||||
| Citalopram | 418 | 0 | 8.9%(19) | 7.3% (15) | 0.5 | No |
| Fluoxetine | 458 | 0 | 3.6%(9) | 3.8% (8) | 0.9 | No |
| Paroxetine | 669 | 0 | 3.7%(14) | 2.5% (7) | 0.4 | No |
| Sertraline | 376 | 0 | 2.7%(5) | 1.1% (2) | 0.3 | No |
| Venlafaxine | 334 | 0 | 2%(NA) | 0% | 0.25 | No |
| * Total number of youth given antidepressants and placebo | ||||||
| ** Number inside parenthesis is actual number of youth | ||||||
| NA = Not available | ||||||
| Source: Data from published clinical trials, unpublished clinical trials provided by drug sponsor, and clinical data compiled by the Medicines and Healthcare Products Regulatory Agency of the United Kingdom. | ||||||
| Reprinted with permission of the American College of Neuropsychopharmacology from Preliminary report of the Task Force on SSRIs and Suicidal Behavior in Youth (executive summary), January 2004:18. | ||||||
Depression’s impact on children
The prevalence of depression in youth age 18 and younger is 8.3%,4 and the rate increases with patient age. Before puberty, common signs of depression include somatic symptoms such as abdominal pain, headaches, and irritability, whereas adolescents are more likely to express feelings of depression and exhibit suicidal behavior. Girls and boys are equally at risk for depression until puberty, when girls begin to outnumber boys and the presentation begins to resemble adult depression.