Clarification on Black Box Warnings for Atomoxetine
I apologize for any confusion, but there is no black box warning for homicidal ideation associated with atomoxetine (Strattera)—the existing black box warning is specifically for suicidal ideation, not homicidal ideation. 1
Current Black Box Warning
Atomoxetine carries a black box warning for increased risk of suicidal ideation in children and adolescents with ADHD, based on analyses of twelve placebo-controlled trials. 1
Key Facts About the Suicidal Ideation Warning:
The warning stems from meta-analyses showing suicidal ideation occurred in 0.37% (5/1357) of pediatric patients taking atomoxetine versus 0% (0/851) in the placebo group. 2
No completed suicides occurred in any of the clinical trials that formed the basis for this warning. 2, 3
More recent and comprehensive analyses have challenged the strength of this association:
- A 2014 meta-analysis of 23 placebo-controlled studies (N=3883) found no statistically significant association between atomoxetine and suicidality (MHRR=1.57; p=0.42). 3
- A large register-based study calculated a hazard ratio of 0.96 for suicide-related events during atomoxetine treatment, suggesting no increased risk. 4
- A 2017 observational cohort study in England (n=4509) found no evidence of increased risk of suicidal ideation during treatment compared to the period before starting atomoxetine (RR: 0.71; CI: 0.48-1.07; P=0.104). 5
Warnings Related to Aggressive Behavior/Hostility
The FDA label and regulatory bodies do include warnings about "aggressive behavior or hostility" as potential adverse effects requiring monitoring, but this is distinct from homicidal ideation and is not part of a black box warning. 1
- Meta-analyses show aggression/hostility frequency was not statistically significantly higher with atomoxetine: 1.6% (21/1308) with atomoxetine versus 1.1% (9/806) with placebo. 4
Required Clinical Monitoring
All children being treated with atomoxetine should be monitored closely for suicidality, clinical worsening, and unusual changes in behavior, especially during the first few months of treatment or at times of dose changes. 1
Common Pitfall to Avoid:
Do not confuse "aggressive behavior or hostility" warnings with homicidal ideation—these are separate clinical entities, and atomoxetine does not carry a black box warning for homicidal thoughts or behaviors. 1, 4