Background:
In Iceland, treatment with ADHD medication can only be initiated by psychiatrists or pediatricians with experience in diagnosing neurodevelopmental disorders. The diagnostic evaluation is most often carried out by a psychologist or psychiatrist, and must be confirmed by a psychiatrist.
Some previous studies have suggested a small but significant increased risk of psychosis or mania associated with ADHD medication, while others have not.
Iceland has a single-payer national healthcare insurance system that tracks virtually its entire population. An Icelandic research team accessed two administrative databases with nationwide coverage – the Icelandic Prescription Medicines Register and the Icelandic Hospital Discharge Register – to explore this relationship among all adults from 2010 through 2022.
They included three categories of ADHD medications prescribed in Iceland: amphetamines, including dexamphetamine and lisdexamphetamine; methylphenidate; and atomoxetine. In Iceland, methylphenidate or atomoxetine must be prescribed and tried first before switching to lisdexamphetamine or dexamphetamine.
Method:
Diagnoses of mania or psychosis recorded in electronic health records were used to identify individuals who were admitted to a psychiatric ward within one year of starting treatment with a specific class of ADHD medication. First-onset psychosis or mania was defined as the emergence of these conditions in individuals with no prior history, diagnosis, or hospitalization for psychosis or mania.
A total of 16,125 adults began using an ADHD medication for the first time during the 13-year study period.
Methylphenidate was the most used ADHD medication among those admitted for psychosis or mania (25 out of 61; 41%), reflecting its status as the most frequently prescribed stimulant during the study period. It was followed by amphetamines (21 out of 61; 34.4%) and atomoxetine (15 out of 61; 24.6%).
Half of those hospitalized had previously received a diagnosis of substance use disorder. One in nine (11%) of those hospitalized acknowledged misuse of the type of ADHD medication they had been prescribed.
Within a year of discharge, 42 out of the 61 patients (68.9%) had been prescribed an ADHD medication again. Among those, one in four (11 out of 42; 26%) were readmitted for psychosis or mania within the following year.
The team noted, “It is concerning that most patients (68.9%) in our study resumed ADHD drug treatment within a year of hospital discharge … However, some studies have reported that the use of psychostimulants or atomoxetine to treat ADHD in individuals with psychotic disorders did not increase the risk of hospitalisation for psychosis if used concurrently with antipsychotic medication or that such use might even reduce this risk.”
Findings:
By comparison with the general population, adults initiating ADHD medications had eight times the relative risk of being admitted for psychosis or mania within the first year.
The absolute risk was low: 0.38% overall for those initiating ADHD medication. Adjusting for the general population risk of hospitalization for first-onset psychosis or mania, more than 300 patients would need to be initiated to ADHD medication to generate one hospital admission for psychosis or mania.
The team conceded, “Confounders of real-life clinical settings, such as non-disclosed ADHD drug abuse or misuse or some degree of substance abuse, may have influenced our findings.”
A further, unmentioned, limitation is that the team did not perform any of the usual adjustments for confounding variables, critically including co-occurring (comorbid) psychiatric disorders known to be common with ADHD, and likely to have a major effect on the relative risk of hospitalization.
Given the very small increase in risk along with the methodological flaws, the team’s suggestion of a “potential causal role of ADHD drugs in the development of first-onset psychosis or mania” is unsubstantiated and speculative. This is especially so given other studies suggesting no increased risk for psychosis due to these medications.
In any event, causation cannot be established through observational studies.
Ragna Kristin Gudbrandsdottir, Engilbert Sigurdsson, Þorsteinn Ivar Albertsson, Halldora Jonsdottir, and Oddur Ingimarsson, “Risk of hospitalisation for first-onset psychosis or mania within a year of ADHD medication initiation in adults with ADHD,” BMJ Mental Health (2025), 28: 1–7, https://doi.org/10.1136/bmjment-2024-301521.
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