The Association Between Comorbid Autism Spectrum Disorders and Antipsychotic Treatment Failure in Early-Onset Psychosis

Abstract

Objective: In a sample of children and adolescents with first-episode psychosis, we investigated whether multiple treatment failure (MTF, defined as the initiation of a third trial of novel antipsychotic due to nonadherence, adverse effects, or insufficient response) was associated with comorbid autism spectrum disorders. Methods: Data were from the electronic health records of 638 children (51% male) aged from 10 to 17 years with firstepisode psychosis (per ICD-10 criteria) from January 1, 2008, to November 1, 2014, referred to mental health services in South London, United Kingdom; data were extracted using the Clinical Record Interactive Search (CRIS) system. The effect of autism spectrum disorder comorbidity on the development of MTF during a 5-year period was modeled using Cox regression. Results: There were 124 cases of MTF prior to the age of 18 (19.4% of the sample). Comorbid autism spectrum disorders were significantly associated with MTF (adjusted hazard ratio = 1.99; 95% CI, 1.19-3.31; P = .008) after controlling for a range of potential confounders. Other factors significantly associated with MTF included higher age at first presentation (P = .001), black ethnicity (P = .03), and frequency of clinical contact (P < .001). No significant association between other comorbid neurodevelopmental disorders (hyperkinetic disorder or intellectual disability) and MTF was found. Conclusions: Children with first-episode psychosis and comorbid autism spectrum disorders at first presentation are less likely to have a beneficial response to antipsychotics.

Negative Symptoms in Early-Onset Psychosis and Their Association With Antipsychotic Treatment Failure

“…A complete description of the study design and sample selection is provided elsewhere. 29 In brief, the sample consisted of a clinical cohort of all those individuals with a first episode of any psychotic disorder who were referred to child and adolescent mental health services (CAMHS)—including inpatient, outpatient, and early intervention for psychosis services—in South London and Maudsley NHS Foundation Trust (SLaM), United Kingdom, from January 1, 2008 to December 31, 2014. Over this time, SLaM delivered all aspects of inpatient and community-based child mental healthcare to approximately 250000 children residing in 4 London boroughs, and specialist provision to children resident outside the boroughs where local area services (such as inpatient facilities) were unavailable.…”

“…To explore NS as potential prognostic indicator, we examined whether NS at first episode predicted antipsychotic treatment failure, using a pragmatic measure of treatment failure, as defined by initiation of a third trial of novel antipsychotic (due to prior insufficient response, intolerable adverse-effects or non-adherence), which we termed multiple treatment failure (MTF). 29 Previous work in adult-onset samples, suggests that NS characterize psychotic disorders with non-hyperdopaminergic pathophysiology, 30,31 which is supported by clinical evidence that NS in the first-episode are associated with poorer response to antidopaminergic effects of current antipsychotic treatment. 30,32 Therefore, we predicted that EOP patients with NS at presentation would be more likely to experience MTF.…”

Social Cognition in a Research Domain Criteria Perspective: A Bridge Between Schizophrenia and Autism Spectra Disorders

“…ASD symptoms are more frequent in subjects diagnosed with SSD than in healthy controls (33,34), and appear to play a relevant role in the clinical situation of patients with SSD, as more severe ASD symptoms represent an individual predictor of worse SC performance (35,36) and poorer real-world social functioning (37), and are correlated with greater impairments in the ability to judge the quality of everyday functioning (38). Individuals diagnosed with SSD and showing prominent ASD features could represent a particular sub-population with specific clinical characteristics, including lower IQ and poorer cognitive performance (39,40) and worse response to antipsychotic treatment (41).…”

Treatment of first-episode psychosis in patients with autism-spectrum disorder and intellectual deficiency

“…4 They are also less likely to have a beneficial response to antipsychotic treatment, showing higher rates of persistent insufficient response and adverse effects than those without ASD. [4][5][6] The risks of ineffective antipsychotic treatment and multiple treatment failures are much higher in young people dually affected by ASD and early-onset psychosis. [4][5][6] Dystonic reactions are extremely distressful for patients and can lead to refusal of antipsychotic medication.…”

“…[4][5][6] The risks of ineffective antipsychotic treatment and multiple treatment failures are much higher in young people dually affected by ASD and early-onset psychosis. [4][5][6] Dystonic reactions are extremely distressful for patients and can lead to refusal of antipsychotic medication. When making treatment decisions in an emergency setting, it should be kept in mind that people with ID and ASD appear more susceptible to adverse effects -particularly on movement -and may be less responsive to antipsychotic medication.…”