Atomoxetine’s receptor profile resembles that of antidepressants, which also are labeled with a black box warning describing increased suicidality risk when used in children and adolescents. Risk of suicidal behavior is highest within 10 days of starting antidepressants, and a significant risk remains throughout the first month. The suicidality rate appears to drop after that time.9,10
Follow FDA patient monitoring guidelines for antidepressants when prescribing atomoxetine to youths—particularly given the prospective labeling change. Atomoxetine’s manufacturer is expected to release a patient monitoring guideline unique to this drug.
Table 1
FDA guidelines for monitoring pediatric antidepressant use
| After starting an antidepressant, patients should see their doctor: |
|
| Source: Reference 8 |
Suicidality: finding other causes
Suicidality is more prevalent in bipolar disorder than in other mental disorders,2,4 and ADHD and mania often co-exist (Box 1).11,12 Mania induced by medication might explain suicidality or other behavior changes in some youths, but activation, mania, behavior change, or suicidality can result from the primary or comorbid disorder rather than the medication.
No deaths by suicide were reported among the FDA-reviewed studies of antidepressant use in children and adolescents. Fatal suicidal behavior has been reported in adolescents not treated with medications.14
FDA cites 12 features that point to suicide risk in youths (Box 2).8-10 Seven features suggest both ADHD and mania, which overlap to the point of diagnostic distraction.
Youths with ADHD, depression may also have mania
As many as 20% of children diagnosed with ADHD also meet DSM-IV-TR criteria for bipolar disorder.
When bipolar disorder is the initial diagnosis, 30% to 40% of adolescents and 70% to 90% of prepubertal children may meet ADHD criteria.
Prepubescent major depression carries a 50% lifetime risk of developing mania.
Source: References 3, 11-13
FDA: 12 features that suggest suicide risk
- New or more thoughts of suicide
- Suicide attempts
- New or worsened depression
- New or worsened anxiety
- Feeling agitated or restless*
- Panic attacks
- Difficulty sleeping (insomnia)*
- New or worsened irritability*
- Aggressive, angry, or violent behavior*
- Acting on dangerous impulses*
- Extreme hyperactivity in actions and talking (hypomania or mania)*
- Other unusual behavior changes*
* Suggest both ADHD and mania
Source: References 8-10
The authors’ observations
Consider a broad differential diagnosis when evaluating inattention, hyperactivity, and impulsivity in children. Family medical history, corroborative clinical interviews, past and current behavioral rating scores, and psychological testing can help confirm an ADHD diagnosis (Table 2).
A careful patient interview, watching for diagnostic clues, taking a confirmatory history, and attention to key symptoms can help you discern ADHD from mania. Rule out unexplored diagnoses such as substance abuse, disturbed relationships, medical illness, and other mental disorders. Having the family and teachers track the youth’s longitudinal mood, energy, sleep, and actions may confirm a mood disorder.
Elated mood or grandiosity indicate mania. Irritable hyperactivity is seen more frequently in mania, whereas general hyperactivity tends to be present in ADHD. Childhood depression often heralds bipolar disorder.
Suspected medication-induced suicidality may call for stopping the offending agent, but determining whether a mental disorder or medication is causing suicidal thoughts can be difficult.
Try stopping the suspected offending drug first. If the youth remains suicidal after 1 week, a thorough biopsychosocial reassessment may guide future options including inpatient care, intensive outpatient psychotherapy, monitoring, and cautious use of antidepressant and/or antimanic medications.
Suicide risk requires clinician vigilance. As we learn from the FDA’s warnings, each treatment episode confers new risk and underscores the importance of watching for risk factors that may predict suicide (Table 3).
Table 2
What to include in an ADHD evaluation
| Histories: psychosocial, developmental, medical, educational, substance use and/or family |
| Clinical interviews with the child or adolescent. Corroborative interviews with parents, guardians, teachers, others |
| Rating scales assessing past behavior: Instruments completed by multiple sources such as the youth, family members or guardian, former teachers, others |
| Rating scales of current behavior: Instruments completed by youth, parents or guardian, former teachers, siblings, significant others |
| Psychological testing: Psychoeducational evaluation, personality inventory, intelligence assessment, and/or a continuous performance test. ADHD diagnosis remains clinical, and no evaluation should rely too heavily on “objective tests” for a definitive diagnosis |
Table 3
Risk factors that may predict suicide in youths
| Older (pubertal) age |
| Male gender |
| Mania |
| Mixed mood state |
| Psychosis |
| Victim of sexual or physical abuse |
| Co-occurring disruptive disorders |
| Comorbid substance abuse |
| Impulsivity |
| Easy access to means, such as firearms, lethal toxins, or medications |
| Lack of family support |
| Acute stressors |
| Family history of suicide |
| Source: Adapted from reference 2. |
Continued treatment: no more medication
Mark’s psychiatrist immediately stops atomoxetine. The boy’s mother, a psychiatric nurse, declines a trial of divalproex because she fears drug toxicity. Mark’s suicidality and agitation resolve over 1 week, and he returns to baseline function, leading us to believe his mania was medication-induced.