Mood Changes When Starting Atomoxetine

Critical Safety Monitoring Required

The FDA recommends close monitoring of children and adolescents taking atomoxetine for suicidality, clinical worsening, and unusual changes in behavior, especially during the first few months of treatment or at times of dose changes, due to the increased risk of suicidal ideation in pediatric patients receiving atomoxetine compared to placebo 1, 2.
The American Academy of Pediatrics suggests that analyses of twelve placebo-controlled trials have shown a greater risk of suicidal ideation in pediatric patients receiving atomoxetine compared to placebo, leading to a black box warning for increased risk of suicidal thoughts in this population 1, 2.
Notably, similar analyses in adults did not demonstrate this increased risk, highlighting the importance of close monitoring in pediatric patients 1.

The therapeutic effect of atomoxetine is delayed, requiring 6-12 weeks to achieve full symptom control, during which time mood-related side effects may persist, according to the FDA 3.
Common adverse effects during initiation include initial somnolence, irritability, and gastrointestinal symptoms, particularly if dosage is increased too rapidly, as reported by the American Academy of Pediatrics 2.
Mood disturbances and behavioral changes warrant immediate clinical attention rather than waiting for spontaneous resolution, as emphasized by the FDA 1.

If mood changes emerge when starting atomoxetine, immediately assess for suicidal ideation, aggressive behavior, or hostility, which require urgent intervention and possible medication discontinuation, as recommended by the FDA and the American Academy of Pediatrics 1, 2.
Evaluate dosing schedule and consider split dosing to reduce side effects and improve tolerability, as suggested by the FDA 3.
Review titration speed and slow the titration schedule if somnolence or irritability is prominent, as recommended by the American Academy of Pediatrics 2.

Do not assume mood changes will spontaneously resolve, as the black box warning exists precisely because these effects can be serious and persistent, according to the FDA and the American Academy of Pediatrics 1, 2.
Do not confuse therapeutic lag with tolerability issues, as while ADHD symptom improvement takes 6-12 weeks, concerning mood changes require immediate evaluation, as emphasized by the FDA 3.
Do not overlook the impact of CYP2D6 metabolism, as approximately 7% of the population are poor metabolizers with significantly higher plasma levels and longer half-lives, leading to increased adverse effects including mood disturbances, as reported by the FDA 1.

Beyond mood changes, monitor for other serious adverse effects including emergent psychotic or manic symptoms, particularly in patients with underlying bipolar disorder, as recommended by the FDA 1.
Cardiovascular parameters, such as heart rate and blood pressure, should also be monitored, as atomoxetine can cause mild increases, according to the American Academy of Pediatrics 2.