Predictors of multiple treatment failure of antipsychotics in early-onset psychosis
Pina-Camacho, L; Dean, H; Lechler, S; et al.Sears, N; Patel, R; Kartoglu, I; Shetty, H; Hotopf, M; Ford, T; Kyriakopoulos, M; Arango, C; MacCabe, J; Hayes, R; Downs, J
Date: 31 October 2016
Conference paper
Publisher
Elsevier for European College of Neuropsychopharmacology
Publisher DOI
Abstract
Background: In adult-onset psychosis, a number of factors are
associated with poor clinical outcomes, which include the severity
of negative symptoms at illness onset, the presence of premorbid
difficulties, and a family history of psychotic disorder [1]. If
and how these factors effect psychosis prognosis in children and
adolescents ...
Background: In adult-onset psychosis, a number of factors are
associated with poor clinical outcomes, which include the severity
of negative symptoms at illness onset, the presence of premorbid
difficulties, and a family history of psychotic disorder [1]. If
and how these factors effect psychosis prognosis in children and
adolescents is unclear [2].
Objective: Using a retrospective cohort design and data from a
large electronic case register, we sought to investigate, in a sample
of children and adolescents with first-episode psychosis (FEP),
the prospective association of demographic and clinical variables
at first presentation to services with reduced antipsychotic effectiveness.
We used multiple treatment failure (MTF) as a proxy for
reduced treatment effectiveness, defined as the initiation of a third
trial of novel antipsychotic as a result of insufficient response, nontolerable
adverse effects or non-adherence. We hypothesized that
presence of premorbid difficulties (e.g. comorbid neurodevelopmental
disorders), baseline negative symptoms and family history
of psychosis would be positively associated with MTF.
Methods: Data were obtained from a clinical cohort of 638
children (51% male) with FEP, aged 10−17 years, referred to
inpatient and community-based services in South London, UK,
using the Clinical Record Interactive Search (CRIS) system. Age,
sex, ethnicity, adaptive function, inpatient status, presence of
negative symptoms at first presentation, first degree family history
of psychosis, co-morbid neurodevelopmental disorders (autism
spectrum disorders [ASD], intellectual disability [ID], and hyperkinetic
disorders), unique antipsychotic medications prescribed in
a 5-year observation period, and reasons for MTF were extracted
from electronic patient records. The effect of neurodevelopmental
comorbidity, presenting with two or more Marder Negative
Symptoms, and family history of psychosis, on the development
of MTF over a 5-year period was modelled using Cox regression.
Results: One hundred and twenty-four children with FEP
(19.3% of the sample) developed MTF prior to the age of eighteen.
Of those, 10.5% (n = 13) showed a persistently insufficient response
to two consecutive trials of different antipsychotics, 14.5%
(n = 18) experienced persistently non-tolerable adverse effects, 4%
(n = 5) showed persistent non-adherence, and 78% (n = 77) showed
a combination of these reasons.
After controlling for a range of potential confounders, a fully
adjusted cox proportional hazards model found that co-morbid
ASD (adjusted hazard ratio [aHR] 1.89; 95% CI 1.03–3.46;
p<0.05) was significantly associated with MTF. The presence
of two or more NS around the first episode (aHR 2.00; 1.16–
3.42; p<0.05), family history of psychosis (aHR 2.08; 1.15–3.75; p<0.05), and Black ethnicity, relative to white British ethnicity
(aHR 2.09; 1.31–3.33; p<0.05) were all significantly associated
with an increased risk of MTF over a 5 year follow-up period.
Adaptive function score was inversely associated with MTF (aHR
0.98; 0.97–0.99, p<0.05).
Conclusion: Prominent negative symptoms, co-morbid ASD
and first degree family history of psychosis at first presentation
can delineate a subset of children and adolescents with psychosis
who have a higher risk of reduced antipsychotic effectiveness.
Children with these risk factors may require early optimisation
of current therapeutic approaches or early alternatives to conventional
antipsychotic treatment to improve their prognosis.
Institute of Health Research
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