Comparative Study of Aripiprazole, Quetiapine and Ziprasidone in the Treatment of First Episode Nonaffective Psychosis

Schizophrenia Clinical Trial

— PAFIP2  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02305823
• Other study ID #: AZQ2005
• Secondary ID: CI 2005-0308007
• Status: Completed
• Phase: Phase 4
• First received: November 20, 2014
• Last updated: March 13, 2017
• Start date: October 2005
• Est. completion date: May 2014

Study information

• Verified date: March 2017
• Source: Fundación Marques de Valdecilla
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 203
• Est. completion date: May 2014
• Est. primary completion date: February 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 15 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Mental Disorders
• Psychotic Disorders
• Schizophrenia

Intervention

Drug:
• Aripiprazole

• Quetiapine

• Ziprasidone

Locations

Country	Name	City	State
Spain	University Hospital Marques de Valdecilla	Santander	Cantabria

Sponsors (3)

Lead Sponsor	Collaborator
Fundación Marques de Valdecilla	Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Investigación Marqués de Valdecilla

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Relapse rate		1 year
Primary	Effectiveness of antipsychotics (percentage of discontinuation of the initially assigned treatment)	The main outcomes of effectiveness were the percentage of discontinuation of the initially assigned treatment (patients who completed the 6 weeks follow-up assessment and changed initial antipsychotic) and the mean time to all-cause medication discontinuation. Four reasons for the discontinuation were recorded: 1.- insufficient efficacy; 2.- marked side-effects; 3.- patient reported non-adherence and 4.- other causes. If more than one reason for discontinuation was present, the most important reason according to the above ranking was selected. Data on antipsychotic treatment (doses, discontinuation and concomitant medications) were registered weekly during the first 4 weeks and at 6 week. Insufficient efficacy was established at the treating physician´s judgment only after at least three weeks of treatment.	6 weeks
Secondary	Change in general psychopathology measured by the Brief Psychiatric Rating Scale (BPRS)	Measured by BPRS. The patients were defined as responders to the optimum dose of antipsychotic at 6 weeks if a >40% reduction of the BPRS scores at intake and had a CGI severity score of = 4. In addition, we also explored to rate of responders if a cutoff of = 50% reduction of the BPRS total scores at intake was used.	6 weeks, 3 months and 1 year
Secondary	Change in positive and negative symptoms measured by the Scale for the Assessment of Negative and Positive Symptoms (SANS and SAPS)	Measured by SANS and SAPS.	6 weeks, 3 months and 1 year
Secondary	Change in the severity of depressive symptoms measured by the Calgary Depression Scale (CDS)	Measured by CDS.	6 weeks, 3 months and 1 year
Secondary	Change in maniac symptoms measured by the Young Mania Rating Scale (YMRS)	Measured by YMRS.	6 weeks, 3 months and 1 year
Secondary	Adherence to treatment		1 year