Tolerability and Effects of Antipsychotics in Children and Adolescents with Psychosis (The TEA Trial)

​Project Research Manager, Senior Researcher Anne Katrine Pagsberg.

The main objective of the project is to examine the effects of antipsychotics in children and adolescents between 7-18 years of age with psychotic symptoms on psychopathology, cognitive deficits, daily functioning, and side-effects, particularly metabolic changes. In the period 2010-2015 we included 113 patients with psychosis between the ages 12-17 years, as well as 60 healthy controls. Reports are currently published or underway.

TEA substudy 1

Cardiac and metabolic adverse events during treatment with aripiprazole or quetiapine ER in children or adolescents with psychosis. PhD Project (thesis completed), PhD Karsten Gjessing Jensen, Senior researcher Anne Katrine Pagsberg.

We examined the cardiometabolic risk factors in 113 youths with psychosis before and during treatment with aripiprazole versus quetiapine extended release (ER) in the setting the independently funded, randomized, controlled multi-center TEA trial. We found that patients entering the trial had significantly higher waist circumference (WC) and plasma lipids than the matched, healthy controls. We also found that a family history with type 2 diabetes or dyslipidemia was associated with higher cardiometabolic risk. Our results from the 12 week intervention period revealed statistically and clinically significant increases in weight, waist circumference (WC), body mass index (BMI), insulin resistance, plasma lipids and corrected
QT interval during treatment with quetiapine ER, while aripiprazole was associated with smaller, yet still clinically relevant, increases in weight, BMI and WC.

TEA substudy 2

Children and Adolescents with Psychosis: Quality of Life and Stigmatization, PhD project, PhD student Dea Gowers Klauber, Senior researcher Anne Katrine Pagsberg.

The project aims to examine subjectively experienced consequences of psychosis and medical antipsychotic treatment in children and adolescents. The project consists of two parts, the first measuring Health Related Quality of Life (HRQoL). The second is focused on how psychosis and exposure for daily medication influences the social relations and the daily life of the children and adolescents, and whether the children experience stigmatization. The project will use two different methodological approaches, where the HRQoL is measured quantitatively by using questionnaires. To ensure an in-depth understanding of the subjective experiences of daily life, social relations and stigmatization, this part will use qualitative interviews of the children and adolescents. The use of different methods will help to improve the understanding of how the study participants experience their life as young individuals who live with a psychotic disorder.
The project is an integral part of the TEA trial. The TEA Trial is a randomized controlled multicenter 12 week trial followed by a 1 year reassessment, that investigates and compares the effects of  two  antipsychotics (aripiprazole and quetiapine), that are frequently used in Danish children and adolescents with psychosis.

TEA substudy 3

Computerised quantification of motions in patients with psychiatric disorders
A spin-off project from the TEA trial. PhD Project, PhD student Ditte Rudå, senior researcher Anne Katrine Pagsberg.
Antipsychotic-induced movement disorders are associated with poor treatment compliance and reduced quality of life. Current assessments in clinical practice are limited to clinical impressions and/or side effect rating scales. In cooperation with the Danish Technical University we developed and tested the Microsoft Kinect sensor to assess performance times related bradykinesia and rigidity associated with antipsychotic-induced parkinsonism. The software was initially tested in a group of adult patients with Parkinson’s disease and healthy controls to enhance signal detection. Data are validated against clinical assessments on neuromotor symptom ratingscales. The aim is to develop a cheap, easy implementable, precise and objective instru,ment for the identification and quantification of motor symptoms in patients with schizophrenia. We expect that such an instrument will be especially suited for use in children and adolescents and improve motivation for participating in assessments of neuromotor adverse effects.

TEA substudy 4

The phenomenology of early-onset Schizophrenia and related psychoses - and the early treatment response to antipsychotic medication. PhD Project (thesis completed), PhD Marie Stentebjerg Olesen, senior researcher Anne Katrine Pagsberg.

The PhD thesis reviewed the phenomenology and outcome of early onset schizophrenia spectrum psychosis, and analysed the predictive validity of an early response (ER) to treatment with antipsychotic (AP) medication for later clinical response, called ultimate response (UR). 
We summarized the phenomenology and outcome of EOS across 35 studies, covering 28 independent samples, including a total of 1506 participants. Youth with EOS were functionally impaired and had moderate to severe levels of positive and negative symptoms and disorganization. During a mean follow-up time of 2.2 years, global function and symptom scale scores improved significantly. A longer duration of untreated psychosis (DUP) was significantly associated with less improvement in functioning over time. Four studies compared DUP in EOS and AOS patients directly and found that EOS patients had a longer mean DUP compared to adult onset patients.

We explored ER as a predictor of UR in youth patients treated with AP medication, and found that the majority of symptomatic improvement was already achieved after 2-4 weeks of treatment, and that ER/ENR significantly predicted UR/UNR and remission. Thus, results from adult studies were replicated and extended to youth patients with EOS. The ER measured at 3 weeks using an ER threshold of at least 20% BPRS-C reduction had the best predictive power for UR. Using the CGI-I score of at least “minimally improved” to define the ER resulted in predictive values comparable to the ER defined by a 20% BPRS-C reduction. The ER remained a robust and significant predictor of UR, even after adjustment for other predictors of ER/ENR or UR/UNR like age, gender, a diagnosis of schizophrenia, AP naïvity, and extrapyramidal symptoms .

PhD Thesis Marie Stentebjerg-Olesen, MD

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