Psychosis with use of amphetamine drugs, methylphenidate and atomoxetine in adolescent and adults.

Background: Use of psychostimulants and relative drugs has increased worldwide in treatment of attention-deficit hyperactivity disorder (ADHD) in adolescents and adults. Recent studies suggest a potential association between use of psychostimulants and psychotic symptoms. The risk may not be the same between different psychostimulants.

Objective: To assess whether amphetamine or atomoxetine use is associated with a higher risk of reporting symptoms of psychosis than methylphenidate use in adolescents and adults, particularly in patients with ADHD.

Methods: Using VigiBase, the WHO's pharmacovigilance database, disproportionality of psychotic symptoms reporting was assessed among adverse drug reactions related to methylphenidate, atomoxetine and amphetamines, from January 2004 to December 2018, in patients aged 13-25 years. The association between psychotic symptoms and psychostimulants was estimated through the calculation of reporting OR (ROR).

Findings: Among 13 863 reports with at least one drug of interest, we found 221 cases of psychosis with methylphenidate use, 115 with atomoxetine use and 169 with a prescription of an amphetamine drug. Compared with methylphenidate use, amphetamine use was associated with an increased risk of reporting psychotic symptoms (ROR 1.61 (95% CI 1.26 to 2.06)]. When we restricted the analysis to ADHD indication, we found a close estimate (ROR 1.94 (95% CI 1.43 to 2.64)). No association was found for atomoxetine.

Conclusion: Our study suggests that amphetamine use is associated with a higher reporting of psychotic symptoms, compared with methylphenidate use.

Clinical implications: The prescription of psychostimulants should consider this potential adverse effect when assessing the benefit-risk balance.