Clinical trial and postmarketing surveillance data for drugs used in treatment of attention deficit hyperactivity disorder were analyzed to determine the frequency of hallucinations and other psychotic side effects, in a study at the US Food and Drug Administration, and Department of Health and Human Services, Maryland. In a search of electronic databases of 49 randomized, controlled clinical pediatric trials, a total of 11 cases of psychosis/mania occurred during 743 person-years of double-blind treatment with these drugs. In contrast, no cases occurred in a total of 420 person-years of placebo exposure. Methylphenidate transdermal patch formulation and atomoxetine accounted for 4 cases each, modafinil 2 cases, and dextromethylphenidate 1 case. Hallucinations occurred during double-blind treatment with every class of compound except Adderall XR, but psychosis/mania events were reported with open-label Adderall XR. The rate per 100 person years in the pooled active drug group was 1.48. Analyses of spontaneous postmarketing data uncovered >800 case reports of psychosis or mania. Hallucinations involved visual and/or tactile sensations of insects, snakes, or worms in affected children. 
COMMENT. Hallucination as an adverse event during treatment of children with ADHD has received little attention until recently, although isolated reports of cases are cited in the literature for the past 40 years. In my practice, a neurology-based clinic for ADHD, reports of hallucinations are very rare. Perhaps, patients attending a psychiatric clinic are more susceptible to psychiatric side effects of these medications. In the above FDA study, approximately 10% cases had a previous history of a similar psychiatric condition, and <3% of patients suffered from drug abuse. Younger children were affected more often than adolescents, almost half of the cases occurring at <10 years of age. A review of the data also appears to show that the frequency of psychiatric adverse events is correlated with the duration of exposure. A dose effect was not studied, but this may be a factor. The number of person years of exposure is greater with drugs (methylphenidate patch and atomoxetine) that account for the higher number of hallucinatory reports.
An FDA warning was added to package inserts for ADHD drugs regarding psychiatric and cardiovascular adverse effects in 2006. Patients and physicians should be aware of the possible psychiatric adverse events, especially hallucinations, when prescribing stimulants or the nonstimulant, atomoxetine, for the treatment of ADHD in children. An incidence of 1 in 400 cases is estimated in one report . Physicians should be especially vigilant when treating younger children with the newer agents. The relative freedom from psychosis/mania events during double-blind treatment with Adderall XR is of interest, although isolated reports occur with open-label trials.