Neurocognitive Effectiveness in Treatment of First-episode Non-affective Psychosis: 1-year Follow-up
Condition: Schizophrenia; Psychotic Disorders
MeSH terms: Schizophrenia; Psychotic Disorders; Mental Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      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, quetiapine and ziprasidone in
      first-episode psychosis at 1 year.
    

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 prospective, randomized, flexible-dose, open-label study.
      Investigators used a simple randomization procedure: a computer-generated randomization list
      was drawn up by a statistician. Dose ranges were 5-30 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.

      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 1 year 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.
    

Intervention name(s): Aripiprazole; Quetiapine; Ziprasidone; Cognitive battery
Intervention type(s): Drug; Drug; Drug; Behavioral
Intervention description(s): Oral, dose range 5-30 mg/day, once or twice a day, during study duration; Oral, dose range 100-600 mg/day, once or twice a day, during study duration; Oral, dose range 40-160 mg/day, once or twice a day, during study duration; Completed in the following standardized sequence: 1-the Rey Auditory Verbal Learning Test (RAVLT); 2-WAIS-III digit symbol subtest; 3-Grooved Pegboard Test; 4-The Zoo Map Test; 5-Tower of London Test (ToL); 6-Rey Complex Figure (RCF); 7-Trail Making Test (TMT); 8-WAIS-III digits forward and backward subtests; 9-WAIS-III letter-number sequencing subtest; 10-WAIS-III vocabulary subtest that was used as measure of premorbid intelligence quotient (IQ); 11-Stroop Test; 12-letter (FAS) and semantic (animal) fluency tests; 14-Eyes Task; 15-Continuous Performance Test (CPT).
Other intervention name(s): Abilify; Seroquel; Zeldox
Intervention MeSH terms: Aripiprazole; Quetiapine Fumarate; Ziprasidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Cognition; Psychosis; Antipsychotic Agents; Treatment; Effectiveness; Aripiprazole; Quetiapine; Ziprasidone; Neurocognition