Treatment with psychostimulants and atomoxetine in people with psychotic disorders: Reassessing the risk of clinical deterioration in a real-world setting
Commentary by Dr. Lila Amirali*: Combining psychostimulants (such as methylphenidate and amphetamines) and atomoxetine with antipsychotics was associated with a decreased rate of hospital admissions for psychosis and other mental disorders compared to the previous year in a real-world study using a large health database. Individuals exposed to these medications had more complex clinical profiles than those not exposed. This aligns with a previous study on methylphenidate, indicating a protective association with psychosis. The findings challenge the perception of psychostimulant safety in schizophrenia spectrum and other psychotic disorders, suggesting that, when used in certain individuals, these medications may be safer than commonly believed. Possible explanations include improved adherence to antipsychotic medication and minimal interference of psychostimulants with the pharmacodynamics of co-prescribed antipsychotics.
Abstract
Background: Although attention-deficit hyperactivity disorder (ADHD) is often comorbid with schizophrenia spectrum and other psychotic disorders (SZSPD), concerns about an increased risk of psychotic events have limited its treatment with either psychostimulants or atomoxetine.
Aims: To examine whether the risk of hospital admission for psychosis in people with SZSPD was increased during the year following the introduction of such medications compared with the year before.
Method: This was a retrospective cohort study using Quebec (Canada) administrative health registries, including all Quebec residents with a public prescription drug insurance plan and a diagnosis of psychotic disorder, defined by relevant ICD-9 or ICD-10 codes, who initiated either methylphenidate, amphetamines or atomoxetine, between January 2010 and December 2016, in combination with antipsychotic medication. The primary outcome was time to hospital admission for psychosis within 1 year of initiation. State sequence analysis was also used to visualise admission trajectories for psychosis in the year following initiation of these medications, compared with the previous year.
Results: Out of 2219 individuals, 1589 (71.6%) initiated methylphenidate, 339 (15.3%) amphetamines and 291 (13.1%) atomoxetine during the study period. After adjustment, the risk of hospital admission for psychosis was decreased during the 12 months following the introduction of these medications when used in combination with antipsychotics (adjusted HR = 0.36, 95% CI 0.24–0.54; P < 0.0001).
Conclusions: These findings suggest that, in a real-world setting, when used concurrently with antipsychotic medication, methylphenidate, amphetamines and atomoxetine may be safer than generally believed in individuals with psychotic disorders.
*Lila Amirali MD, MMGMT (IMHL), FRCPC, DFAPA is a child and adolescent psychiatrist, CHU Sainte-Justine, Montreal, Quebec.
Journal articles are selected based on their clinical relevance. The commentary reflects the reviewer’s own opinion and is not approved, or necessarily representative, of the opinion of the CADDRA Board.