Methylphenidate is one of the most commonly prescribed stimulants for treating ADHD. Methylphenidate has 2 known mechanisms of action: 1) inhibition of catecholamine reuptake at the presynaptic dopamine reuptake inhibitor, and 2) binding to and blocking intracellular dopamine transporters, inhibiting both dopamine and norepinephrine reuptake.5,6 Because increased levels of synaptic dopamine are implicated in the generation of psychotic symptoms, the pharmacologic mechanism of methylphenidate also implies a potential to induce psychotic symptoms.7
How common is this problem?
On the population level, there is no detectable difference in the event rate (incidence) of psychosis in children treated with stimulants or children not taking stimulants.8 However, there are reports that individual patients can experience psychosis due to treatment with stimulants as an unusual adverse medication reaction. In 1971, Lucas and Weiss9 were among the first to describe 3 cases of methylphenidate-induced psychosis. Since then, many articles in the scientific literature have reported cases of psychosis related to stimulant medications.
A brief review of the literature between 2002 and 2010 revealed 14 cases of stimulant-related psychosis, in patients ranging from age 7 to 45. Six of the patients were children, age 7 to 12; 1 patient was an adolescent, age 15; 4 were young adults, age 18 to 25; and 3 were older adults. Of all 14 individuals, 7 reported visual hallucinations, 4 had tactile hallucinations, 4 had auditory hallucinations, and 3 displayed paranoid delusions.10 With the aim of exploring possible etiologic factors associated with psychotic symptoms, such as type of drug and dosage, it was found that 9 patients received methylphenidate, with total daily doses ranging from 7.5 to 74 mg (3 patients received short-acting methylphenidate; 1 patient received methylphenidate extended release (ER); 1 patient received both; 4 patients received dextroamphetamine, with doses of 30 to 50 mg/d; and 1 patient received amphetamine, 10 mg/d). In terms of family history, 1 patient had a positive family history of schizophrenia; 1 patient had a family history of bipolar disorder; and 6 patients were negative for family history of any psychotic disorder.10
In 2006, due to growing concerns about adverse psychiatric effects of ADHD medications, the FDA Center for Drug Evaluation and Research Office of Surveillance and Epidemiology requested the electronic clinical trial databases of manufacturers of drugs approved for the treatment of ADHD, or those with active clinical development programs for the same indication.11 In that study, Mosholder et al11 analyzed data from 49 randomized, controlled clinical trials that were in pediatric development programs and found that there were psychotic or manic adverse events in 11 individuals in the pooled active drug group. These were observed with methylphenidate, dexmethylphenidate, and atomoxetine. There were no events in the placebo group, which reinforced the causality between the ADHD medication and these symptoms, as participants with untreated ADHD did not develop them.11
It is important to note that ADHD medications taken in excessive doses are much more likely to provoke psychotic adverse effects than when taken at therapeutic doses. However, as seen in our clinical case, patients such as R could develop acute psychosis even with a lower dosage of stimulant medications. An article by Ross2 suggested rates of .25% for this psychiatric adverse effect (1 in 400 children treated with therapeutic doses of stimulants will develop psychosis), which is consistent with the data from the Mosholder et al11 study.
Continue to: TREATMENT Discontinuation and re-challenge