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

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.

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

Fig. 1

Selection of the study cohort. ADHD, attention-deficit hyperactivity disorder; PPDIP, public prescription drug insurance plan.

Fig. 2

(a) State distribution plots of attention-deficit hyperactivity disorder (ADHD) medication use 1 year after its initiation (index date). (b) Antipsychotic treatment trajectories and (c) hospital admission trajectories 1 year before and 1 year after the index date, stratified by type of medication. FGA, first-generation antipsychotic; LAI, long-acting injectable; SGA, second-generation antipsychotic. The index date has a 1-year clearance period without ADHD medication.

Fig. 3

Risk of hospital admission for psychosis in the year after attention-deficit hyperactivity disorder (ADHD) medication initiation. aHR, adjusted hazard ratio; AMP, amphetamine; ATX, atomoxetine; GP, general practitioner; MPH, methylphenidate; Rx, medication; SES, socioeconomic status; SUD, substance use disorder. aHR (95% CI) associated with each covariable.