▸ Atomoxetine initiation. The use of atomoxetine can be simplified and compliance might be improved with small deviations from the original package insert instructions.
Dr. Rubin recommended a titration schedule of 0.5 mg/kg per day the first week, 1.0 mg/kg per day the second week, and 1.5 mg/kg per day the third week. He said this allows only one pill size, but noted that the titration can be done as 40, then 80, then 120 mg in larger patients.
The basic visit schedule should include a visit at week 2 to evaluate tolerability and compliance, a visit at week 4 to look for response signals. Early tolerability problems can often be ameliorated with slower titrations, dose time change, or dose splitting to b.i.d., and a visit at week 6 to evaluate for extent of response and treatment moderators. Stimulant augmentation is useful for partial responders.
An alternate treatment should be considered in nonresponders. Initial evening postdinner dosing has the best tolerability, but a later switch to morning or twice-daily dosing may provide better efficacy. Some late adolescents, particularly college students, may adhere best with noon dosing along with lunch. While rare in adolescents, noradrenergic side effects are relieved by a 50% slower titration.
▸ Long-term stimulant side effects. There is no evidence of major adverse events with long-term stimulant use. Side effects that tend to persist include insomnia, decreased appetite and/or weight loss, and headache. Growth rate may be affected, but no evidence exists of an ultimate adult height reduction. However, if weight or height drops 10 or more percentile points after 1 year of treatment, a medication change should be considered.
▸ Sudden cardiac death and ADHD treatment. After Canada's withdrawal of MAS because of sudden cardiac death concerns and the drug's subsequent reinstatement, a Canadian physician advisory report advised strenuous exercise, use of other stimulants, and family history should be considered in risk-benefit assessment for individual patients.
▸ Atomoxetine and liver injury. Although a package insert warning was announced in December 2004, no Food and Drug Administration or psychiatric guideline for screening in healthy individuals has been issued.
If liver enzymes are measured, it is important to recognize that other factors, such as alcohol intake, acetaminophen, viral syndromes, and obesity can cause temporary changes.
An increase in liver enzymes to more than two times the baseline is a guide used in clinical trials for determining clinical significance. Any increase in bilirubin level is a red flag needing further evaluation.