Neurocognitive Effectiveness in Treatment of First-episode Non-affective Psychosis: 3-years Follow-up (PAFIP3_nc3Y)

Neurocognitive Effectiveness in Treatment of First-episode Non-affective Psychosis: a Randomized Comparison of Aripiprazole and Risperidone Over 3 Years

Cognitive enhancement is a primary goal in treating individuals with schizophrenia. Cognitive deficits are already present at the first break of the illness, seem to remain stable during early phases and noticeably influence daily functioning. Differences among antipsychotics in terms of cognitive effectiveness have turned out to be a topic of increasing research interest. The initially postulated superior neurocognitive effectiveness of second-generation antipsychotics (SGAs) compared to first-generation antipsychotics (FGAs) is currently under debate. Long-term studies would be of great value to evaluate the differential benefits exerted by antipsychotic drugs on cognitive performance. The aim of this study is to investigate the cognitive effects of aripiprazole and risperidone in first-episode psychosis at 3 years.

Study Overview

• Status: Unknown
• Conditions: Psychotic Disorders; Schizophrenia; Psychosis
• Intervention / Treatment: Drug: Aripiprazole; Drug: Risperidone

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. No pharmaceutical company supplied any financial support.

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), 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. These clinical data are described at AZQ2005 study.

Neuropsychological assessment. Cognitive functioning was assessed in patients at 2 points: baseline and 3 years after the initialization of antipsychotic treatment. The cognitive assessment at baseline was carried out at 12 weeks after recruitment because this time is considered optimal for patients' stabilization. The evaluation required approximately 2 h and was carried out in the same day by the same neuropsychologist (R.A.-A and E.G.-R). The neuropsychological battery comprises 9 cognitive domains: information processing speed, motor dexterity, working memory, verbal learning, visuospatial abilities, delayed memory, attention, executive function and theory of mind.

• Study Type: Interventional
• Enrollment (Anticipated): 115
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients followed in the First Episode Psychosis Clinical Program (PAFIP III) from January 2015 to December 2020.
• Experiencing their first episode of psychosis (First Episode of Psychosis is defined as that psychopathological state in which for the first time and regardless of its duration, the patient has enough severe psychotic symptoms to allow a diagnosis of psychosis, having received no specific psychiatric treatment for him).
• Living in the catchment area (Cantabria).
• 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 with loss of consciousness.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aripiprazole; Oral, dose range 10-30 mg/day, once or twice a day during study duration.	Drug: Aripiprazole; Initial dose: 10 mg.; Other Names: Abilify
Active Comparator: Risperidone; Oral, dose range 1-6 mg/day, once or twice a day during study duration.	Drug: Risperidone; Initial dose: 2 mg.; Other Names: Risperdal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global cognitive index	In order to calculate a measure of Global Cognitive Functioning (GCF) raw cognitive scores were reversed when appropriate before standardization so they all have the same direction (the higher, the better). According to previous methodology, the GCF was calculated as T-scores, with raw scores of a healthy comparison sample. T scores were converted to deficit scores that reflect presence and severity of cognitive impairment. Deficit scores on all tests were then "averaged" to create the GCF score.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in information processing speed	Measured by Wechsler Adult Intelligence Scale (WAIS)-III digit symbol subtest (standard total score).	3 years
Change in information processing speed	Measured by Trail Making Test (TMT) trail A.	3 years
Change in information processing speed	Measured by Continuoys Performace Test (CPT) reaction time.	3 years
Change in motor dexterity	Measured by Grooved Pegboard Test (time to complete with dominant hand).	3 years
Change in working memory	Measured by WAIS-III letter-number sequencing test (standard total score).	3 years
Change in working memory	Measured by WAIS-III digits forward (standard total score).	3 years
Change in verbal learning	Measured by the Rey Auditory Verbal Learning Test (RAVLT) (trials 1-5).	3 years
Change in visuospatial abilities	Measured by the Rey Complex Figure (RCF) (copy figure).	3 years
Change in delayed memory	Measured by the Rey Auditory Verbal Learning Test (RAVLT) (list recall and list recognition discrimination subscore).	3 years
Change in delayed memory	Measured by the Rey Complex Figure (RCF) (delayed recall).	3 years
Change in attention	Measured by Continuoys Performace Test (CPT) (discrimination subscores).	3 years
Change in executive function	Measured by Trail Making Test (TMT) trail B.	3 years
Change in executive function	Measured by Stroop Test (color-word).	3 years
Change in executive function	Measured by the Zoo Map Test (first and second conditions).	3 years
Change in executive function	Measured by the Tower of London Test (ToL) (total correct and total moves score).	3 years
Change in executive function	Measured by FAS Word Fluency and semantic (animal) fluency tests.	3 years
Change in theory of mind	Measured by Eyes Task (total correct score).	3 years

Collaborators and Investigators

• Sponsor: Fundación Marques de Valdecilla
• Collaborators: Centro de Investigación Biomédica en Red de Salud Mental; Instituto de Investigación Marqués de Valdecilla
• Investigators: 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: March 13, 2019
• First Submitted That Met QC Criteria: March 19, 2019
• First Posted (Actual): March 20, 2019

Study Record Updates

• Last Update Posted (Actual): January 14, 2020
• Last Update Submitted That Met QC Criteria: January 13, 2020
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Treatment; Aripiprazole; Risperidone; Cognition; Effectiveness; Antipsychotic Agents
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mental Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole; Risperidone
• Other Study ID Numbers: ROAC2018_nc3Y

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