Treatment with psychostimulants and atomoxetine in people with psychotic disorders: reassessing the risk of clinical deterioration in a real-world setting

Br J Psychiatry. 2024 Mar;224(3):98-105. doi: 10.1192/bjp.2023.149.


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.

Keywords: Attention-deficit hyperactivity disorders; CNS stimulants; comorbidity; drug or substance interactions and side-effects; psychotic disorders/schizophrenia.

MeSH terms

  • Amphetamines / adverse effects
  • Antipsychotic Agents* / therapeutic use
  • Atomoxetine Hydrochloride / adverse effects
  • Attention Deficit Disorder with Hyperactivity* / drug therapy
  • Attention Deficit Disorder with Hyperactivity* / epidemiology
  • Central Nervous System Stimulants* / adverse effects
  • Clinical Deterioration*
  • Humans
  • Methylphenidate* / adverse effects
  • Psychotic Disorders* / drug therapy
  • Psychotic Disorders* / epidemiology
  • Retrospective Studies


  • Atomoxetine Hydrochloride
  • Antipsychotic Agents
  • Central Nervous System Stimulants
  • Methylphenidate
  • Amphetamines