Combining across stimulant medications, during double-blind, placebo-controlled trials, placebo was not associated with any toxicosis events in 3,990 subjects with a combined duration of treatment of over 425 years. For therapeutic doses of active medication, there were 13 reports of toxicosis in 5,717 subjects with a combined treatment duration of over 800 years. In open-label trials, stimulants were associated with 45 reports of toxicosis in 15,999 subjects with a combined treatment duration of almost 9,400 years. Although there are methodological problems in summing across stimulant medications and across studies that may have different sensitivities for identifying psychotic-like and manic-like symptoms, these numbers suggest as a preliminary estimate that toxicosis will occur in approximately 0.25% of children treated with stimulants, or about 1 in 400—a proportion suggesting an infrequent but not rare effect of therapeutic dosing. - ajp.psychiatryonline.org