Effectiveness of Second Generation Antipsychotics in First Episode Psychosis Patients: 1-year Follow-up (PAFIP3_1Y)
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|ClinicalTrials.gov Identifier: NCT02532491|
Recruitment Status : Enrolling by invitation
First Posted : August 25, 2015
Last Update Posted : February 12, 2020
|Condition or disease||Intervention/treatment||Phase|
|Schizophrenia Psychotic Disorders||Drug: Aripiprazole Drug: Risperidone||Phase 4|
At present there is no evidence of which antipsychotic treatment would be the choice for treating the appearance of a non-affective psychotic disorder. There are a number of second-generation antipsychotic drugs that have proven effective in controlling positive symptoms of the disease but carry a number of variable side effects so there is no evidence on the treatment of choice in the market. Few studies try to assess the adhesion of a first episode of psychosis as prolonged treatment in time. Thus the development of experimental studies comparing the effectiveness of such treatments in clinical practice is of high interest for clinical psychiatrists.
Study setting and financial support: data for the present investigation are being 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 provide 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 flexible-dose study of two neuroleptics (Aripiprazole and Risperidone) assigned at aleatory ratio 1:1. Rapid titration schedule (5-day), until optimal dose is reached, is 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 are allowed for clinical reasons. No antimuscarinic agents are administered prophylactically. Antidepressants (Sertraline) and mood stabilizers (lithium) are permitted if clinically needed.
Clinical assessment: 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) and the Scale for the Assessment of Negative symptoms (SANS) are 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) are used. The same trained psychiatrist (BC-F) completed all clinical assessments.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Open Flexible-dose Randomized Study of the Effectiveness of Second Generation Antipsychotics in First Episode Psychosis Patients: A 1-year Follow-up|
|Actual Study Start Date :||May 2014|
|Actual Primary Completion Date :||May 2018|
|Estimated Study Completion Date :||December 2020|
Active Comparator: Aripiprazole
Oral, dose range 10-30 mg/day, once or twice a day during study duration.
Initial dose: 10 mg.
Other Name: Abilify
Active Comparator: Risperidone
Oral, dose range 1-6 mg/day, once or twice a day during study duration.
Initial dose: 2 mg.
Other Name: Risperdal
- Effectiveness of Aripiprazole and Risperidone at long term as measured by Percentage of discontinuation [ Time Frame: 1 year ]Percentage of discontinuation of the initially assigned treatment: patients who completed the 1 year follow-up assessment and changed initial antipsychotic. 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. Antipsychotic treatment data (doses, discontinuation and concomitant medications) were registered every 3 months. Insufficient efficacy was established at the treating physician's judgment only after at least three weeks of treatment.
- Change in general psychopathology measured by BPRS at medium and long term [ Time Frame: 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, investigators also explored to rate of responders if a cutoff of ≥ 50% reduction of the BPRS total scores at intake was used.
- Change in negative symptoms measured by SANS at medium and long term [ Time Frame: 3 months and 1 year ]Measured by changes in total score of the Scale for the Assessment of Negative Symptoms (SANS).
- Change in positive symptoms measured by SAPS at medium and long term [ Time Frame: 3 months and 1 year ]Measured by changes in total score of the Scale for the Assessment of Positive Symptoms (SAPS).
- Emergence of adverse events by using the Scale of the Udvalg for Kliniske Undersogelser (UKU) [ Time Frame: 3 months and 1 year ]Measured by UKU. Those treatment-emergent adverse events that occurred at a rate of at least 10% in either treatment group are considered.
- Emergence of akathisia by using the Barnes Akathisia Scale (BAS) [ Time Frame: 3 months and 1 year ]Measured by BAS. Treatment-emergent akathisia is assessed by both baseline-to-end changes and newly emergent categorical changes.
- Emergence of extrapyramidal symptoms by using the Simpson-Angus Rating Scale (SARS) [ Time Frame: 3 months and 1 year ]Measured by SARS. Extrapyramidal symptoms is assessed by both baseline-to-end changes and newly emergent categorical changes.
- Remission rate at long term [ Time Frame: 1 year ]Remission was defined according to Andreasen et al. (2005) criteria covering BPRS and SANS scores: 1.- a score of mild or less (≤3) on six predefined BPRS symptom items: grandiosity, suspiciousness, unusual thought content, hallucinations, conceptual disorganization and mannerisms; and 2.- SANS items scores of ≤2 simultaneously in all items. These criteria are required to be maintained for at least 6 months.
- Relapse rate at long term [ Time Frame: 1 year ]Among patients who achieved clinical improvement and stability (CGI rating ≤ 4 and a decrease of at least 30% on BPRS total score and all BPRS key symptom items, by being rated ≤ 3 for more than 4 consecutive weeks at some point during the first 6 months following program entry), relapse was defined as any of the following criteria that occurred during follow-up: 1 - a rating of either 5 or above on any key BPRS symptom items, 2 - CGI rating of ≥ 6 and a change score of CGI of "much worse" or "very much worse", 3 - hospitalization for psychotic psychopathology, or 4 - completed suicide. The key BPRS symptoms were unusual thought content, hallucinations, suspiciousness, conceptual disorganization and bizarre behaviour. Exacerbation was defined as any 2-point increase of any of the key BPRS symptoms, excluding changes in which the rating remained at the non-psychotic level (i.e., <3).
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02532491
|University Hospital Marques de Valdecilla|
|Santander, Cantabria, Spain, 39008|
|Principal Investigator:||Benedicto Crespo-Facorro, Professor||University Hospital Marqués de Valdecilla, IDIVAL, Department of Psychiatry, School of Medicine, University of Cantabria, CIBERSAM Centro Investigación Biomédica en Red Salud Mental, Santander, Spain.|