An independent meta-analysis by Bridge et al12 examined the pediatric trial data used in the FDA meta-analysis plus 7 additional studies. Its findings differ in 2 important ways from those of the FDA review:
- Antidepressants—including others besides fluoxetine—showed efficacy in treating anxiety disorders and depression in children and adolescents.
- The frequency of suicide-related adverse events (no trial patients committed suicide) was approximately 3% on active medication—25% lower than the FDA estimated rate—and 2% on placebo, similar to the FDA estimate.
Antidepressants and suicide risk, 1985 to 2007
|Case reports suggest link between suicide and SSRI use||FDA analysis finds no association between SSRIs and increased suicide risk||UK agency warns of suicide-related events in children treated with paroxetine and venlafaxine||FDA conducts meta-analysis, requires black-box warnings of risk of suicidality in youth taking antidepressants||FDA meta-analysis finds age-dependent effect of antidepressants on suicidality risk in adults||FDA expands warning of increased suicidality risk with antidepressants to adults age|
|Antidepressant prescriptions quadruple; age-adjusted suicide rate drops 22.5% for women and 12.8% for men||Pediatric depression diagnoses and antidepressant prescriptions decline; suicides increase 11%||Bridge et al meta-analysis finds 25% lower rate of suicide-related events in youth than the FDA found|
What about adults?
Overall effect. A subsequent FDA meta-analysis of antidepressant clinical trial data in adults13 found 8 suicides in 372 trials totaling nearly 100,000 persons. All occurred in the 295 trials with psychiatric indications. Among these psychiatric trials, 59% had a suicidal behavior/ideation event in either the test-drug or placebo arm, and 41% had none. Eleven antidepressants were included in the meta-analysis:
- 6 SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline)
- 2 SNRIs (duloxetine and venlafaxine)
- 3 others (bupropion, mirtazapine, and nefazodone).
Age-specific findings. When the FDA analysis was stratified by age, however, antidepressants’ benefit appeared greater for patients age ≥25 than for those age 18 to 24. The data suggested:
- elevated suicidality risk among adults age
- neutral or possibly protective effect for adults age 25 to 64
- protective effect in adults age ≥65 ( Table 1 ).13
FDA meta-analysis: Suicide rates by age in antidepressant trials
|Age group (yr)||Suicide rate (%)(test drug/placebo)||Suicide attempt rate (%)(test drug/placebo)|
|18 to 24||0.03/0.00||0.55/0.27|
|25 to 30||0.00/0.03||0.23/0.11|
|31 to 64||0.01/0.00||0.13/0.15|
|Source: Reference 13|
The odds ratio for suicidal behavior (preparatory acts, attempt, or suicide) for subacts, attempt, or suicide) for subjects age 18 to 24 on test drug vs placebo was 2.31 (95% CI: 1.02, 5.64) [event rate/sample: 23/3810 vs 8/2604]. NNH was 333, which means 333 adults in this age group would need to be treated with an antidepressant for 1 to experience a suicidal behavior event that would not have happened with placebo.