Cognitive Enhancement Therapy for Early-Stage Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 3

Summary: 
      This study will determine the effectiveness of cognitive enhancement therapy (CET) in
      treating cognitive abnormalities in people experiencing the early stages of schizophrenia.
    

Detailed description: 
      In this study, we wish to determine the neurobiological predictors and the relative efficacy
      of Cognitive Enhancement Therapy (CET) in ameliorating specific cognitive abnormalities
      presumably mediated by PFC and related brain structures, among younger, early-course
      schizophrenia patients who potentially have a better prognosis. A series of recent-onset
      schizophrenic patients, whose psychotic symptoms have successfully been stabilized on an
      atypical antipsychotic drug for one year following initiation of treatment, will be
      randomized to CET combined with an enriched supportive therapy (EST) or EST alone, and
      treated for two years. Subjects will have been assessed on neurobehavioral and clinical
      indices immediately prior to beginning CET or EST (corresponding with the CNMD 1-year
      follow-up) and in the proposed study will again be assessed after 1 and 2 years of
      psychosocial treatment. In a smaller subset of patients, we will also seek to collect
      preliminary data on the efficacy of CET in reversing the neurobiological alterations in the
      PFC. The hypotheses of this study are:

        1. The presence of relatively well preserved PFC structure and function (PFC volume,
           activation with fMRI, and metabolism as measured by proton MRS) at baseline will predict
           a better response to CET (Neurobiological Prediction Hypothesis).

        2. CET combined with "enriched" supportive psychotherapy (EST) will be more effective than
           EST alone in ameliorating social and non-social cognitive deficits of patients with
           early schizophrenic illness whose psychotic symptoms have been stabilized on maintenance
           chemotherapy (The Treatment Efficacy Hypothesis).

        3. CET will result in additive, positive effects on neurocognitive parameters that were not
           observed following one year of antipsychotic medication, using a "sequential" treatment
           design in a subset of patients in whom we have pre-neuroleptic baseline data from CNMD
           studies (The Treatment Specificity Hypothesis).

      Study Design: Subjects will be randomly assigned, once stabilized clinically, to CET plus EST
      (n = 30) or EST alone (n = 30) and then treated for up to two years. Clinical,
      neuropsychological, neurological and functional neuroimaging assessments will be administered
      at baseline and at two annual follow-ups. At the end of CET or EST treatment, subjects will
      be asked to come back quarterly to meet informally with either their Cognitive Enhancement
      Therapy clinicians and former group members, or with their Enriched Supportive Therapy
      clinician. The purpose of these visits is for us to learn more about the successes that
      patients have had, or about the difficulties that they might have had since leaving the
      program. Clinician(s) will also share information obtained during this follow-up which might
      help patient in overcoming these difficulties. At the end of the one-year period post EST or
      CET treatment, subjects will be assessed on all measures, except for diagnostic, imaging and
      blood studies.
    

Intervention name(s): Cognitive enhancement therapy (CET); Enriched supportive therapy (EST)
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Using 80 to 100 hours of graduated exercises in computer assisted training, coupled with structured but unrehearsed in vivo social group interactions, CET tries to shift an early developmental reliance on effortful, serial and verbatim cognitive processing to a more gistful, less effortful and spontaneous abstraction of social themes. CET uses attention, memory and problem solving software from three exercises from Ben-Yishay's Orientation Remediation Module (the Attention Reaction Conditioner, Zero Accuracy Conditioner, and Time Estimates) that are graduated in difficulty and designed to enhance vigilance, selective attention, the ability to shift between auditory and visual modalities, and rapid decision-making.; EST is the commonly recommended (Spaulding 1992) treatment for control and experimental subjects in psychosocial trials. EST is a two-staged treatment that requires weekly one-hour sessions in Phase 1 and biweekly sessions in Phase 2. Some practice principles (e.g., psychoeducation and relaxation training) are provided during the group exercises for CET patients, but individually for EST patients. No attempt is made to control for hours of contact between EST and CET, since offering three hours of supportive therapy to EST subjects is neither logistically feasible nor faithful to the goals and methods of supportive therapy. Further, neurobiological hypotheses related to treatment specificity would be best tested by clear differences in treatment intensity and content.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Schizophrenia; Cognition; Enhancement; Randomized