Methylphenidate and the risk of psychosis in adolescents and young adults: a population-based cohort study

Abstract

Summary Background There is a clinical concern that prescribing methylphenidate, the most common pharmacological treatment for attention-deficit hyperactivity disorder (ADHD), might increase the risk of psychotic events, particularly in young people with a history of psychosis. We aimed to determine whether the risk of psychotic events increases immediately after initiation of methylphenidate treatment or, in the longer term, 1 year after treatment initiation in adolescents and young adults with and without a previously diagnosed psychotic disorder. Methods In this cohort study, we used population-based observational data from the Swedish Prescribed Drug Register, the National Patient Register, and the Total Population Register, three population-based registers containing data on all individuals in Sweden, to attain data on sex, birth, death, migration, medication use, and psychotic events for all eligible participants. We screened individuals on these registers to identify those receiving methylphenidate treatment, and who were aged 12–30 years at the start of treatment, for their inclusion in the study. We used a within-individual design to compare the incidence of psychotic events in these individuals during the 12-week periods immediately before and after methylphenidate initiation. Longer term risk was assessed by comparing the incidence of psychotic events 12 weeks before methylphenidate initiation and during a 12-week period one calendar year before the initiation of methylphenidate with the incidence of these events during the 12-week period one calendar year after methylphenidate initiation. We estimated the incidence rate ratios (IRR) and 95% CIs of psychotic events after the initation of methylphenidate treatment, relative to the events before treatment, which were defined as any hospital visit (inpatient admission or outpatient attendance, based on data from the National Patient Register) because of psychosis, using the International Classification of Diseases version 10 definition. Analyses were stratified by whether the individual had a history of psychosis. Findings We searched the Swedish Prescribed Drug Register to find eligible individuals who had received methylphenidate between Jan 1, 2007 and June 30, 2012. 61 814 individuals were screened, of whom 23 898 (38·7%) individuals were assessed and 37 916 (61·3%) were excluded from the study because they were outside of the age criteria at the start of treatment, they had immigrated, emigrated, or died during the study period, or because they were administered other ADHD medications. The median age at methylphenidate initiation was 17 years, and a history of psychosis was reported in 479 (2·0%) participants. The IRR of psychotic events in the 12-week period after initiation of methylphenidate treatment relative to that in the 12-week period before treatment start was 1·04 (95% CI 0·80–1·34) in adolescents and young adults without a history of psychosis and 0·95 ...

Association of psychiatric comorbidities with the risk of transport accidents in ADHD and MPH

“…sex and genetic factors) and possible indication bias for the same patient before and during the follow-up. We defined the effective period of MPH exposure as 0–90 days after the prescription of the drug (Man et al ., 2017 ; Hollis et al ., 2019 ). We further divided the effective period into three 1-month effective periods: 0–30, 31–60 and 61–90 days after MPH initiation (Shin et al ., 2016 ).…”

Sleep disorders predict the one-year onset, persistence, but not remission of psychotic experiences in pre-adolescence: a longitudinal analysis of the ABCD cohort data

“…Given the well-established association between dopamine agonist stimulant medication and psychotic experiences (Tost, Alam, & Meyer-Lindenberg, 2010), it is likely that a proportion of this association can be accounted for as an adverse effect of the medication. However, confounding by indication is likely also to play a role and children who may fulfil criteria for prescribing may also have shared risk factors for psychotic experiences that manifest through other causal pathways (Hollis et al, 2019).…”

Suicidal and non-suicidal self-injurious behaviour in patients with bipolar disorder and comorbid attention deficit hyperactivity disorder after initiation of central stimulant treatment: a mirror-image study based on the LiSIE retrospective cohort

“…Hence the study could not determine whether the risk of psychotic events was moderated by antipsychotic treatment. 15 …”

“…However, this study did not explore BD as a comorbidity. 15 Concerning prevention of suicidal and non-suicidal self-injurious behaviour, CS do not seem to increase such risk in patients with only ADHD. 16,17 Rather, CS may reduce the risk.…”