Psychosis
Conditions
Keywords
Aripiprazole, Quetiapine, Psychosis, Child, Adolescent
Brief summary
The benefits and harms of antipsychotics are relatively well studied in adults. However, there is a lack of scientifically valid studies regarding the benefits and harms of antipsychotics in children and adolescents with psychosis. The main objective of the TEA trial is to compare the efficacy and adverse reactions of two antipsychotics (quetiapine versus aripiprazole) in children and adolescents between 12-17 years of age with psychotic symptoms on psychopathology, cognitive deficits, and daily functioning. Furthermore, the trial will focus on adverse reaction profiles of the two antipsychotics as well as early predictors of later sustained clinical effects of these antipsychotics.
Detailed description
A sex and age matched healthy control group will be included to form a reference group for cognitive and somatic measures. The healthy controls will not receive any trial medication.
Interventions
DRUGAripiprazole
pill, 2,5-20 mg/day, maximum 16 weeks
DRUGQuetiapine
pill, 50-600mg/day, maximum 16 weeks
Sponsors
The Psychiatric Centre for Children and Adolescents in Bispebjerg, Denmark
Psychiatric Centre Copenhagen, Denmark
Copenhagen Trial Unit, Center for Clinical Intervention Research
Albert Einstein College of Medicine
Research Institute for Biological Psychiatry, Sct. Hans Hospital, Denmark
Capital Region Pharmacy, Denmark
The Research Council for Health and Disease, Denmark
Allocated inheritance from Elizabeth Stevn and Niels Rindom, Denmark
AP Moeller Foundation
Tryg Fonden, Denmark
Anne Katrine Pagsberg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
Yes
Inclusion criteria
Patients - Inclusion Criteria: * Diagnosis: Children and adolescents with a non-organic and non-drug-induced psychosis, meeting the criteria for ICD-10 diagnoses: F20, F22-F29 and F30.2, F31.2 F31.5, F32.3 and F33.3. This is verified with a semi-structured psychopathological interview using K-SADS-PL (Kaufmann 1997) four weeks after inclusion into the trial. * Psychopathology: Children and adolescents with psychotic symptoms, scoring ≥ 4 on at least one of the following PANSS items: P1 (delusions), P2 (conceptual disorganisation), P3 (hallucinations), P5 (grandiosity), P6 (suspiciousness/persecution) or G9 (unusual thought content); and a total PANSS score \> 60. The treating physician has decided to prescribe an antipsychotic compound. * Age: 12-17 years (both inclusive). * Sex: Both sexes are included. * Previous treatment: Patients must be antipsychotic-naïve. The maximum accepted previous treatment with antipsychotic compounds is two weeks cumulatively, and during the two weeks prior to inclusion no continuous treatment and a maximum of four dosages in total can have been received. * Somatic illness: No somatic contraindication to planned medication, documented by standard somatic examination * Written informed consent. Patients -
Exclusion criteria
* Compulsory treatment: Patients that are compulsorily hospitalised against their will are excluded. If their status changes to voluntary hospitalisation, patients can be included. If the patient is already included in the trial and is briefly detained, confined, or subjected to other forceful treatment according to the Danish Psychiatric Care Act ('Psykiatriloven'), both the patient and parents have to agree to remain in the trial if exclusion is to be avoided. Compulsory treatment in the form of, e.g., brief forced immobilisation or single instances of forced medication, are not causes for exclusion. * Diagnoses: Patients with drug-induced or organic psychosis, severe chronic somatic illness, or a history of severe head-trauma are not included. Patients that do not have psychotic symptoms but are prescribed antipsychotic treatment on the indication of, e.g., severe behavioural problems or tics are not included. * Pregnancy: Pregnant or lactating patients are not included (a pregnancy test is undertaken at inclusion). Female participants, that are sexually active, must use safe contraception throughout the trial period (see section 6.4) * Substance abuse: People with severe alcohol or drug abuse are not included. Possible abuse is monitored both by interviewing participants and by taking a urine sample at inclusion and at 4, 12 and 52 weeks follow-up (if there is suspicion of substance abuse), testing for the presence of cocaine, amphetamine, cannabis, opiates, metamfetamine (inclusive for extacy), and benzodiazepines. When severe abuse is suspected during the trial, an ad hoc urine sample is taken. Brief periods of large alcohol/cannabis intake are not a cause of exclusion from the trial; however, cognitive and other examinations are not carried out while patients are under the influence of drugs or alcohol. * Aggravation: Patients may be excluded if there is a significant worsening of clinical state during the course of the trial (i.e., increases of 30% or more from baseline on the PANSS total score). * Allergy and intolerance: Patients with allergy towards the investigational drugs, or is lactose intolerant are not included. * Lack of informed consent. Healthy volunteers - Inclusion Criteria: * Matching: Healthy controls (n=100) are included, in the way that they are matched to the first 100 patients included in the study (i.e., corresponding to the number of patients required in each treatment group). They will be matched according to: * age; * sex; and * socioeconomic status (based on a combination of parental education and income, according to criteria from the National Institute of Public Health (earlier Danish Institute of Clinical Epidemiology, DIKE)). * Informed consent. Healthy volunteers -
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Psychopathology: improvement on PANSS positive scale (PANSS 'Positive and Negative Syndrome Scale') | 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognition | 12 weeks | Cognition and functioning (BACS Global Score, SCoRS-DK, Schizophrenia Cognition Rating Scale, BRIEF) |
| Adverse reactions | 12 weeks | Adverse reactions (UKU side effect scale, AIMS, SAS, BARS, and other adverse events) |
| Suicidal ideation | 12 weeks | Suicidal ideation (K-SADS-PL, specific questions for depressive disorders (current) |
| Psychopathology | 12 weeks | Psychopathology (other PANSS scales, DIPI, SGI-S, CGI-I,and GAPD). |
| Prognostic factors | 12 weeks | Prognostic factors (DUP, and PAS) |
| Quality of Life | 52 weeks | Quality of Life (measured with Kidscreen) |
| Stigmatization | 52 weeks | Qualitative interviews |
| Genetic and antipsychotic laboratory tests | 12 weeks | Genetic variants affecting metabolism of antipsychotics |
Countries
Denmark
Outcome results
None listed