History: impulsive and distractible
For 2 years Mark, age 11, has been treated for attention-deficit/hyperactivity disorder (ADHD). His initial symptoms included inattention, hyperactivity, distractibility, short attention span, failure to follow instructions, poor organization, and intruding on others. He often picks fights with his 7-year-old brother, mildly injuring him on one occasion. His teacher recently punished him for roaming the classroom and distracting his classmates.
None of Mark’s symptoms suggest mania. His family has no history of mood disorders, but his father has been diagnosed with substance dependence.
Mark’s psychiatrist had prescribed an extended-release amphetamine salts preparation, 10 mg/d. Soon after, Mark began experiencing stomachaches, insomnia, facial flushing, and headaches. The dosage was reduced to 5 mg/d, but Mark stopped taking the medication after less than 3 weeks. Cognitive-behavioral therapy and classroom modifications were then tried for 11 months, but Mark’s behavior worsened. His symptoms now include inattention, distractibility, excessive talking, restlessness, and impulsivity.
The authors’ observations
Children and adolescents often present with excessive talking, distractibility, increased activity or restlessness, and loss of normal functioning. Distinguishing these ADHD symptoms from those of bipolar, disruptive, learning, movement, anxiety, substance-related or other mental disorders can be challenging.How to reduce mania risk when prescribing stimulants,” October 2005, at www.currentpsychiatry.com.)
Pediatric bipolar disorder often goes undetected because DSM-IV-TR criteria—established for adults—may not apply to youths. Children are more likely to present with a mixed mood state, less-distinct periods between episodes, grandiosity, irritability, and a chronic, continuous course.2 By contrast, bipolar adults often present with a sudden classic manic episode, elation, and euphoria.2 Adults also usually have relatively stable periods between episodes and tend to have comorbid substance dependence, panic, or eating disorders.
Mark’s symptoms still suggest ADHD. His inattention started before age 7, and his teacher is mostly concerned about his hyperactive, impulsive, and disruptive behavior. Mark’s mother, teacher, and psychiatrist feel confident that the ADHD diagnosis is correct, so we decide against comprehensive reassessment or prescribing a mood stabilizer. Mark’s mother opts to try the nonstimulant ADHD medication atomoxetine rather than a different stimulant.
Treatment: a moving experience
Mark’s psychiatrist prescribes atomoxetine, 18 mg/d for 4 days, then increases the dosage to 25 mg/d after finding that the boy could tolerate the medication.
Two weeks after starting atomoxetine, Mark becomes agitated and activated, and voices suicidal thoughts on one occasion. Without warning, while his mother is driving him to school, he opens the door of the moving vehicle and tries to jump out. His mother stops him by calling his name, yelling “No,” and slamming on the brakes. Mark tells her that he is “bad” and wants to die. She has no idea what prompted this behavior.
Mark also has become more oppositional and defiant, and his temper tantrums and destruction of household items are more frequent. He continues to behave aggressively toward his younger brother, often breaking some of his favorite toys. Mark also shows elevated and expansive mood, irritability, pressured speech, inflated self-esteem, and psychomotor agitation—symptoms consistent with a manic episode. At one visit, Mark tells his psychia trist, “I feel great! I can do anything.”
The authors’ observations
Mark, who had been diagnosed as having ADHD, began showing manic activation and suicidal thinking 2 weeks after starting atomoxetine. Whether he showed de novo suicidal behavior or reckless behavior associated with mania is unclear.
Atomoxetine-induced mania is not a new finding.2,5 During clinical trials, 2% of patients reported mood swings and 8% reported irritability. Subsequent experience indicates the risk of mood destabilization may be as high as 33%.5
Atomoxetine, a nonstimulant medication indicated for treating pediatric and adult ADHD, is a potent norepinephrine reuptake inhibitor. Reanalysis of the atomoxetine clinical trial database showed a slightly but statistically significant higher risk of suicidal behavior and thoughts in children and adolescents compared with placebo.6 No deaths from suicide were reported. The FDA subsequently ordered a black box warning on atomoxetine’s label instructing physicians, patients, and families to watch closely for suicidality symptoms with atomoxetine use.
Atomoxetine is safe and effective for pediatric ADHD, provided youths are properly monitored. Be careful, however, when prescribing atomoxetine to youths with a personal or family history of mood disorder.
FDA also is reviewing data on all drugs indicated for treating ADHD to determine whether they cause suicidality, new-onset mental disorders, or other psychiatric adverse events.7
Assessing medication risk
All youths being treated for a mood disorder and/or ADHD must be assessed for suicide risk, but how to most effectively perform this assessment is unclear. Organizations representing pediatrics and child and adolescent psychiatry have not yet incorporated FDA’s medication guidelines regarding pediatric suicidality—released earlier this year—into their guidelines (Table 1). As a result, most physicians follow pediatric patients less frequently than FDA now advises.