The effect of therapeutic drug monitoring of risperidone and aripiprazole on weight gain in children and adolescents: the SPACe 2: STAR (trial) protocol of an international multicentre randomised controlled trial
Open accessAbstract
BACKGROUND: Antipsychotic drugs are an important part of the treatment of irritability and aggression in children with an autism spectrum disorder (ASD). However, significant weight gain and metabolic disturbances are clinically relevant side effects of antipsychotic use in children. In the SPACe study, we showed positive correlations between both risperidone and aripiprazole plasma trough concentrations and weight gain over a 6-month period. The trial SPACe 2: STAR is designed as a follow-up study, in which we aim to research whether therapeutic drug monitoring in clinical practice can prevent severe weight gain, while retaining clinical effectiveness. METHODS: SPACe 2: STAR is an international, multicentre, randomised controlled trial (RCT). One hundred forty children aged 6 to 18 who are about to start risperidone or aripiprazole treatment for ASD related behavioural problems will be randomised into one of two groups: a therapeutic drug monitoring (TDM) group, and a care as usual (CAU) group. Participants will be assessed at baseline and 4, 10, 24, and 52 weeks follow-up. In the TDM group, physicians will receive dosing advice based on plasma levels of risperidone and aripiprazole and its metabolites at 4 and 10 weeks. Plasma levels will be measured in dried blood spots (DBS). The primary outcome will be BMI z-score at 24 weeks after start of antipsychotic treatment. Among the secondary outcomes are effectiveness, metabolic laboratory measurements, levels of prolactin, leptin and ghrelin, extrapyramidal side effects, and quality of life. DISCUSSION: This will be the first RCT evaluating the effect of TDM of antipsychotic drugs in children and adolescents. Thus, findings from SPACe 2: STAR will be of great value in optimising treatment in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05146245. EudraCT number: 2020-005450-18. Sponsor protocol name: SPACe2STAR. Registered 8 June 2021. Protocol Version 6, Protocol date: 18 august 2022.
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Medications such as clozapine and valproate affect patients' levels of aggression as well as their blood lipids and blood cells.
“Medications such as clozapine and valproate have an impact on patients’ levels of aggression as well as on their blood lipids and blood cells [80,81,82].”
From The Predictive Value of Monocyte/High-Density Lipoprotein Ratio (MHR) and Positive Symptom Scores for Aggression in Patients with Schizophrenia (2023) · cites this paper as [82]
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- Authors
- Hermans, R. A., Ringeling, L. T., Liang, K., Kloosterboer, S. M., de Winter, B. C. M., Hillegers, M. H. J., Koch, B. C. P., & Dierckx, B.
- Affiliations
- Erasmus MC (NL)
- Corresponding author
- Ringeling, Lisa T.
- ORCID
- Venue
- BMC Psychiatry
- Published
- 2022-12-20
- Volume
- 22
- Issue
- 1
- Pages
- 814-814
- ISSN
- 1471-244X (ISSN-L)
- PMC
- PMC9769061
- OpenAlex
- W4312080237
- Cited by
- 10
- References
- 28
- Citations by year
- 2026: 3 · 2025: 3 · 2023: 4
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- ZonMw (1140022010011)
- Stichting de Merel
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- therapeutic drug monitoring, risperidone, aripiprazole, weight gain, autism spectrum disorder, children and adolescents, antipsychotic adverse effects, irritability, aggression, trough concentration, dried blood spots, BMI z-score, prolactin, leptin, ghrelin, extrapyramidal symptoms, quality of life
- MeSH terms
- Aripiprazole, Adolescent, Child, Humans, Antipsychotic Agents, Multicenter Studies as Topic, Weight Gain, Randomized Controlled Trials as Topic, Drug Monitoring, Risperidone
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