Comparative Study of Aripiprazole, Quetiapine and Ziprasidone in the Treatment of First Episode Nonaffective Psychosis (PAFIP2)

March 13, 2017 updated by: Benedicto Crespo-Facorro, Fundación Marques de Valdecilla

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

203

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • University Hospital Marqués de Valdecilla

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Aripiprazole
Oral, dose range 5-30 mg/day, once or twice a day, during study duration
Drug: Aripiprazole
Other Names:
  • Abilify
Active Comparator: Quetiapine
Oral, dose range 100-600 mg/day, once or twice a day, during study duration
Drug: Quetiapine
Other Names:
  • Seroquel
Active Comparator: Ziprasidone
Oral, dose range 40-160 mg/day, once or twice a day, during study duration
Drug: Ziprasidone
Other Names:
  • Zeldox

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effectiveness of antipsychotics (percentage of discontinuation of the initially assigned treatment)
Time Frame: 6 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in general psychopathology measured by the Brief Psychiatric Rating Scale (BPRS)
Time Frame: 6 weeks, 3 months and 1 year
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
Change in positive and negative symptoms measured by the Scale for the Assessment of Negative and Positive Symptoms (SANS and SAPS)
Time Frame: 6 weeks, 3 months and 1 year
Measured by SANS and SAPS.
6 weeks, 3 months and 1 year
Change in the severity of depressive symptoms measured by the Calgary Depression Scale (CDS)
Time Frame: 6 weeks, 3 months and 1 year
Measured by CDS.
6 weeks, 3 months and 1 year
Change in maniac symptoms measured by the Young Mania Rating Scale (YMRS)
Time Frame: 6 weeks, 3 months and 1 year
Measured by YMRS.
6 weeks, 3 months and 1 year
Adherence to treatment
Time Frame: 1 year
1 year

Other Outcome Measures

Outcome Measure
Time Frame
Relapse rate
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundación Marques de Valdecilla

Collaborators

Centro de Investigación Biomédica en Red de Salud Mental
Instituto de Investigación Marqués de Valdecilla

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2005

Primary Completion (Actual)

February 1, 2011

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

November 20, 2014

First Submitted That Met QC Criteria

December 2, 2014

First Posted (Estimate)

December 3, 2014

Study Record Updates

Last Update Posted (Actual)

March 14, 2017

Last Update Submitted That Met QC Criteria

March 13, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AZQ2005
  • CI 2005-0308007 (Other Grant/Funding Number: SENY Fundació Research Grant CI 2005-0308007)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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