Clinical trial NCT02305823: Comparative Study of Aripiprazole, Quetiapine and Ziprasidone in the Treatment of First Episode Nonaffective Psychosis
Official title: Phase IV Study of the Effectiveness of Aripiprazole, Quetiapine, and Ziprasidone in the Treatment of First Episode of Non-affective Psychosis Individuals Included in the First Episode Psychosis Clinical Program II (PAFIP II)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Psychotic Disorders
Keywords: psychosis
antipsychotic agents
treatment
effectiveness
Lead sponsor: Fundación Marques de Valdecilla
Sponsor class: OTHER
Collaborators: name: Centro de Investigación Biomédica en Red de Salud Mental
name: Instituto de Investigación Marqués de Valdecilla
First posted: 2014-12-03
Enrollment: 203
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The selection of antipsychotic in early stages of the illness is mainly determined by its clinical effectiveness. Second generation antipsychotics (SGAs) are the first line drug treatment for individuals suffering from schizophrenia. It is clear that SGAs are not a homogeneous group and clinical effects and profile of side effects differ between SGAs. Differences among antipsychotics in terms of effectiveness have turned out to be a topic of increasing research interest, although comparisons between the different SGAs are scarce. In first episode of psychosis, SGAs have shown a higher treatment effectiveness compared to first generation antipsychotics (FGAs) (findings primarily driven by Haloperidol). Less evident seems to be the notion that some of the SGAs might be more effective (in terms of treatment discontinuation) than others. Most of the medium-term randomized studies have shown similar rates of all-cause treatment discontinuation in first episode patients treated with different SGAs. It may be concluded that more randomized controlled trails should be accomplished to determine the position of frequently used SGAs in clinical practice. The investigators undertook this study with the major objective of comparing the clinical effectiveness of three widely utilized SGAs (Aripiprazole, Ziprasidone and Quetiapine) in the acute treatment of first-episode non-affective psychosis individuals.

Detailed description: Study setting and financial support: data for the present investigation were obtained from an ongoing epidemiological and three-year longitudinal intervention program of first-episode psychosis (PAFIP) conducted at the outpatient clinic and the inpatient unit at the University Hospital Marqués de Valdecilla, Spain. Conforming to international standards for research ethics, this program was approved by the local institutional review board. Patients meeting inclusion criteria and their families provided written informed consent to be included in the PAFIP. The Mental Health Services of Cantabria provided funding for implementing the program. None pharmaceutical company supplied any financial support to it.

Study design: this is a prospective, randomized, flexible-dose, open-label study. At study intake, all patients but eight were antipsychotic naïve. Dose ranges were 5-20 mg /day Aripiprazole, 40-160 mg/day Ziprasidone and 100-600 mg/day Quetiapine. Rapid titration schedule (5-day), until optimal dose was reached, was as a rule used unless severe side effects occur. At the treating physician´s discretion, the dose and type of antipsychotic medication could be changed based on clinical efficacy and the profile of side effects during the follow-up period. Antimuscarinic medication, Lormetazepam and Clonazepam were permitted for clinical reasons. No antimuscarinic agents were administered prophylactically. Antidepressants (Sertraline) and mood stabilizers (lithium) were permitted if clinically needed.

The severity scale of the Clinical Global Impression (CGI) scale, the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive symptoms (SAPS), the Scale for the Assessment of Negative symptoms (SANS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Young Mania Rating Scale (YMRS) were used to evaluate symptomatology. To assess general adverse event experiences the Scale of the Udvalg for Kliniske Undersogelser (UKU), the Simpson-Angus Rating Scale (SARS) and the Barnes Akathisia Scale (BAS) were used. The same trained psychiatrist (BC-F) completed all clinical assessments.

The adverse events were evaluated using the UKU Side effect rating scale. Those treatment-emergent adverse events that occurred at a rate of at least 10% in either treatment group are considered. Treatment-emergent akathisia (BAS) and extrapyramidal symptoms (SARS) were assessed by both baseline-to-end changes and newly emergent categorical changes.

Eligibility criteria: Inclusion Criteria:

* 15-60 years.
* Living in the catchment area.
* Experiencing their first episode of psychosis.
* No prior treatment with antipsychotic medication or, if previously treated, a total life time of adequate antipsychotic treatment of less than 6 weeks.
* Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for brief psychotic disorder, schizophreniform disorder, schizophrenia, or schizoaffective disorder.

Exclusion Criteria:

* Meeting DSM-IV criteria for drug dependence
* Meeting DSM-IV criteria for mental retardation
* Having a history of neurological disease or head injury.

Primary outcomes:
measure: Effectiveness of antipsychotics (percentage of discontinuation of the initially assigned treatment)
timeFrame: 6 weeks
Secondary outcomes:
measure: Change in general psychopathology measured by the Brief Psychiatric Rating Scale (BPRS)
timeFrame: 6 weeks, 3 months and 1 year
measure: Change in positive and negative symptoms measured by the Scale for the Assessment of Negative and Positive Symptoms (SANS and SAPS)
timeFrame: 6 weeks, 3 months and 1 year
measure: Change in the severity of depressive symptoms measured by the Calgary Depression Scale (CDS)
timeFrame: 6 weeks, 3 months and 1 year
measure: Change in maniac symptoms measured by the Young Mania Rating Scale (YMRS)
timeFrame: 6 weeks, 3 months and 1 year
measure: Adherence to treatment
timeFrame: 1 year
Other outcomes:
measure: Relapse rate
timeFrame: 1 year
Locations:
city: Santander
country: Spain
facility: University Hospital Marques de Valdecilla
state: Cantabria
Study officials:
affiliation: University Hospital Marqués de Valdecilla, IDIVAL, Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain. CIBERSAM Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain
name: Benedicto Crespo-Facorro, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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