Anzalee Khan

A randomized controlled trial of cognitive remediation among inpatients with persistent mental illness.

OBJECTIVE This study evaluated the feasibility and efficacy of a cognitive remediation program in improving cognitive and work functioning for intermediate- to long-stay psychiatric inpatients. METHODS Eighty-five inpatients with predominantly DSM-IV-defined schizophrenia were randomly assigned to cognitive remediation or to a control condition. The cognitive remediation program consisted of 24 hours of computerized practice over a 12-week period and a weekly discussion group to facilitate transfer of cognitive skills to daily activities. A computer control group received similar hours of staff and computer exposure without cognitive training exercises. A comprehensive neuropsychological battery was administered at baseline and posttreatment. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline, midtreatment (six weeks), and posttreatment (12 weeks) and at six- and 12-month follow-ups. Work functioning was tracked during a 12-month follow-up period. RESULTS The average number of 45-minute sessions completed was 23. Patients in the cognitive remediation group demonstrated significantly greater improvements over three months than the control group in the composite measure of overall cognitive functioning, psychomotor speed, and verbal learning. In addition, patients who received cognitive remediation worked more weeks than the control group over the 12-month follow-up period. Patients in both groups showed significant and comparable improvements over the follow-up period on the positive, activation, and depression subscales of the PANSS. CONCLUSIONS Cognitive remediation was a feasible treatment for this group of inpatients and more effective at improving cognitive functioning than a computer control intervention. Longer-term follow-up indicated that cognitive remediation was associated with better work outcomes, suggesting benefits in psychosocial functioning.

Improving Social Cognition in Schizophrenia: A Pilot Intervention Combining Computerized Social Cognition Training With Cognitive Remediation

BACKGROUND Social cognition is significantly impaired in schizophrenia and contributes to poor community functioning. This study examined whether cognitive remediation (CR; COGPACK), shown to improve neurocognition, improves an integral component of social cognition, emotion perception, compared with CR combined with a computerized Emotion Perception intervention (Mind Reading: Interactive Guide to Emotions [MRIGE]). METHODS 59 stable schizophrenia or schizoaffective predominantly inpatients were randomized to either CR (N=27) alone or CR+MRIGE (N=32) for 12 weeks. Assessments included the Facial Emotion Identification Task (FEIT), Facial Emotion Discrimination Task (FEDT), MCCB-MATRICS, Personal and Social Performance Scale, and the Positive and Negative Syndrome Scale. RESULTS There was a significant group-by-time effect on FEIT (F=11.509, P=.004); CR+MRIGE demonstrated significantly greater improvement than CR alone (CR+MRIGE, Z=1.89, P=.05; CR alone Z=0.57, P=.13). There was significant group-by-time effect on FEDT (F=5.663, P=.022); CR+MRIGE demonstrated significantly greater improvement than CR alone (CR+MRIGE, Z=1.90, P=.05; CR alone Z=0.67, P=.21). There was also a significant group by time effect for social cognition, measured by the Mayer-Salovey-Caruso Emotional Intelligence Test (F=5.473, P=.050): CR+MRIGE demonstrated significantly greater improvement than CR alone (CR+MRIGE, Z=1.98, P=.02; CR alone, Z=1.00, P=.05). CONCLUSIONS Combined CR with emotion perception remediation produced greater improvements in emotion recognition, emotion discrimination, social functioning, and neurocognition compared with CR alone in chronic schizophrenia.

Outcome Evaluation of a Structured Educational Wellness Program in Patients With Severe Mental Illness

OBJECTIVE Obesity is increasing at an alarming rate in the United States, as is the obesity rate in patients with schizophrenia. Our study retrospectively evaluated the effectiveness of the Solutions for Wellness and Team Solutions programs, 2 structured educational patient programs, and evaluated the effects on obesity and other metabolic markers in a large, naturalistic inpatient sample. METHOD Between September 18, 2006, and September 15, 2007, 275 inpatients with DSM-IV-TR-diagnosed chronic mental illness admitted to a tertiary care psychiatric facility were included in the 36-week comprehensive and manualized educational program for healthy lifestyles for patients with chronic mental illness incorporating psychoeducational small-group curricula. Patients were tested before and after each of three 12-week group periods by 30 knowledge-assessment questions, and metabolic markers were recorded at baseline, midpoint, and endpoint. RESULTS Of the 275 included inpatients, 50.5% completed more than 5 modules, 20.4% completed less than or equal to 2 or fewer modules, and 5.1% completed all 11 modules. Significant increases in scores were observed for 7 of the 11 modules in the knowledge assessments (P < .001). Eighty-seven patients (43.72%) had a body mass index (BMI) >/=30 (indicating obesity) at the start of the program. There was a significant mean weight loss of 4.88 lb (P = .035) together with a significant decrease in mean BMI (P = .045). Patients with diabetes showed a reduction in mean weight of 5.98 lb. Significant reductions were observed in glucose and triglyceride levels (both P < .05). Patients with impaired glucose tolerance showed a significantly greater decrease in glucose level (P = .000). Sixty-nine patients (25.46%) met criteria for metabolic syndrome at baseline, and this number was reduced to 53 patients (19.56%) at endpoint; this decrease was significant (P = .027). Regarding relationship of change in knowledge after completion of the modules and metabolic changes, we found a significant correlation between reduction in weight and change in Fitness and Exercise score (r = 0.62, P = .001) and a significant correlation between the change score on Nutrition/Healthy Lifestyles and change in glucose values (r = 0.56, P = .001). CONCLUSIONS We found that a structured wellness program using a psychoeducational curriculum can be successfully implemented in a large, naturalistic psychiatric setting with unselected, chronically mentally ill inpatients. Results may help both clinicians and hospital managers to implement similar programs or to include successful components in existing programs for psychiatric patients.

Galantamine augmentation of long-acting injectable risperidone for cognitive impairments in chronic schizophrenia

BACKGROUND Galantamine, a reversible cholinesterase inhibitor with effects on nicotinic receptors, has shown mixed effects on cognitive impairments in patients with schizophrenia. Given these mixed results we examined whether galantamine compared to adjunctive placebo may improve cognitive functions in patients treated concomitantly with a long acting atypical antipsychotic. METHOD The parent study was a 52-week double-blind, randomized study of treatment with long-acting injectable risperidone 25mg or 50mg every two weeks. Adjunctive galantamine or placebo treatment was administered from Month 6 to 12. Outcome measures were neurocognitive, psychopathology, social and quality of life functions. Patients were randomized to blinded galantamine up to 24mg/day or matching placebo tablets. All patients were maintained on their randomized long-acting injectable risperidone regimen for the duration of the trial. RESULTS 32 patients were included in the intent-to-treat analysis. No statistically significant differences were found for Attention Vigilance, Declarative Memory, Processing Speed, Reasoning/Problem Solving, Working Memory domains and the Neurocognitive Composite Score. Group specific analysis showed a statistically significant group interaction (p=0.043) with the Social Cognition domain showing in the galantamine group significantly lower scores at endpoint than placebo patients. The PANSS general psychopathology subscale showed significantly higher scores in the galantamine group at endpoint (p=0.05). ANCOVA model for within treatment group comparisons showed a significant increase of 7.3 points for the total PANSS score for the galantamine group. CONCLUSION Galantamine showed no ameliorative effects on cognitive measures in this 6month, double-blind study of patients with schizophrenia treated with an assured and stable antipsychotic medication delivery system. Galantamine may not be an appropriate augmentation agent for cognitive impairments in patients with schizophrenia at the dose used.

Effects of olanzapine and risperidone on glucose metabolism and insulin sensitivity in chronic schizophrenic patients with long-term antipsychotic treatment: a randomized 5-month study.

BACKGROUND Comparisons of diabetic potential, glucose related metabolic levels, and insulin resistance between olanzapine and risperidone have produced variable results in cross-sectional and epidemiologic studies. Randomized prospective studies of metabolic effects during treatment with these drugs may provide results that are more informative. METHOD Hospitalized patients with chronic schizophrenia (DSM-IV), most of whom had been treated with multiple antipsychotics in the past, were randomly assigned to treatment with a single antipsychotic, olanzapine or risperidone, for a period of 5 months. At baseline and every treatment month thereafter, fasting glucose, insulin, insulin-related metabolic measures, and prolactin were assessed, and an oral glucose tolerance test (OGTT) was performed during baseline and months 1, 2, and 5 of treatment. Weight was assessed monthly, and waist and hip measures were taken at baseline and month 5. Data were analyzed on 23 patients randomly assigned to risperidone and 23 patients randomly assigned to olanzapine. The study was conducted from February 2003 to August 2007. RESULTS Most patients were overweight or obese at baseline (mean body mass index [BMI] = 29.4), but there were no differential drug effects on weight change and no differences between drug groups at the 5-month time point. There were no overall drug treatment differences in fasting glucose or glycohemoglobin or 2-hour glucose levels in OGTT and no differences between the two drug groups at the 5-month time point. There were no consistent drug treatment differences in the number of patients who developed borderline or diabetic glucose levels. Olanzapine-treated patients showed a significantly greater increase than risperidone-treated patients in a fasting measure of insulin resistance (P = .041), and olanzapine patients showed greater decreases in insulin sensitivity during OGTT (P = .023) compared to risperidone-treated patients. Olanzapine-treated patients had a significantly greater increase in 1-hour glucose and insulin levels during OGTT in subsequent months compared to baseline and greater increase in glucose and insulin area under the curve over time than the risperdone-treated patients. Prolactin levels decreased in olanzapine patients and increased in risperidone patients (P values approximately .02). There were no significant drug treatment differences in C-peptide levels or 2 indices proposed as measures of insulin secretion or beta-cell function (homeostasis model assessment of beta-cell function [HOMA-B], BIGTT-acute insulin response surrogate measure [BIGTT-AIR]). Changes in insulin resistance over time were not strongly related to changes in BMI or waist circumference during study drug treatment. CONCLUSIONS The increase in insulin levels during olanzapine treatment may compensate for the increase in insulin resistance and serve to reduce fasting and postprandial glucose levels. This may contribute to the lack of differences between olanzapine and risperidone in indices of diabetic or prediabetic glucose levels or glycohemoglobin. How many years this compensatory mechanism will persist needs further investigation. Periodic OGTT tests measuring glucose and insulin levels would be helpful in assessing the status of beta-cell insulin reserve in patients treated with olanzapine and other second-generation antipsychotics and assessing an individual patients risk for conversion to type 2 diabetes. TRIAL REGISTRATION clinicaltrials.gov Identifier NCT00287820.

Use of NON-PARAMETRIC Item Response Theory to develop a shortened version of the Positive and Negative Syndrome Scale (PANSS)

BackgroundNonparametric item response theory (IRT) was used to examine (a) the performance of the 30 Positive and Negative Syndrome Scale (PANSS) items and their options ((levels of severity), (b) the effectiveness of various subscales to discriminate among differences in symptom severity, and (c) the development of an abbreviated PANSS (Mini-PANSS) based on IRT and a method to link scores to the original PANSS.MethodsBaseline PANSS scores from 7,187 patients with Schizophrenia or Schizoaffective disorder who were enrolled between 1995 and 2005 in psychopharmacology trials were obtained. Option characteristic curves (OCCs) and Item Characteristic Curves (ICCs) were constructed to examine the probability of rating each of seven options within each of 30 PANSS items as a function of subscale severity, and summed-score linking was applied to items selected for the Mini-PANSS.ResultsThe majority of items forming the Positive and Negative subscales (i.e. 19 items) performed very well and discriminate better along symptom severity compared to the General Psychopathology subscale. Six of the seven Positive Symptom items, six of the seven Negative Symptom items, and seven out of the 16 General Psychopathology items were retained for inclusion in the Mini-PANSS. Summed score linking and linear interpolation was able to produce a translation table for comparing total subscale scores of the Mini-PANSS to total subscale scores on the original PANSS. Results show scores on the subscales of the Mini-PANSS can be linked to scores on the original PANSS subscales, with very little bias.ConclusionsThe study demonstrated the utility of non-parametric IRT in examining the item properties of the PANSS and to allow selection of items for an abbreviated PANSS scale. The comparisons between the 30-item PANSS and the Mini-PANSS revealed that the shorter version is comparable to the 30-item PANSS, but when applying IRT, the Mini-PANSS is also a good indicator of illness severity.

Psychiatric patients with histories of aggression and crime five years after discharge from a cognitive-behavioral program

A program evaluation examined a long-term cognitive skills inpatient program (STAIR) in reducing rehospitalization and rearrest rates in mental illness. Psychiatric and criminal histories were obtained. Psychological tests were administered. After discharge, monthly follow-up was obtained. One hundred forty-five patients completed the STAIR program and were followed for a range of six to 60 months after discharge. Thirty-one (21.4%) remained stable, 67 (46.2%) were rehospitalized, and 47 (32.4%) were rearrested and/or rehospitalized. Group membership was predicted by STAIR admission age and outpatient medication compliance. Significantly, fewer arrests, hospitalizations, and days institutionalized occurred post-STAIR. Medication compliance is the single most enduring factor associated with clinical stability and prevention of criminal behavior. Other factors’ impact may vary depending on the length of stay in the community. Long-term inpatient programs (e.g., STAIR) may be helpful to some of these patients.

A randomized, double-blind, parallel-group, fixed-dose, clinical trial of quetiapine at 600 versus 1200 mg/d for patients with treatment-resistant schizophrenia or schizoaffective disorder.

Quetiapine is often prescribed at doses higher than those approved by regulatory authorities, with limited evidence from controlled trials. The objective of this study was to assess the safety, tolerability, and efficacy of high-dose quetiapine (1200 mg/d) compared with a standard dose of 600 mg/d among patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, schizophrenia or schizoaffective disorder hospitalized at 2 state-operated psychiatric facilities. In order to be eligible for randomization, subjects were required to prospectively fail to demonstrate an initial therapeutic response during a 4-week run-in phase with quetiapine at 600 mg/d (immediate release and dosed twice a day). Lack of an adequate initial response was defined a 15% or lower decrease in the Positive and Negative Syndrome Scale total score. Patients were then randomized to either continue quetiapine at 600 mg/d for an additional 8 weeks or to receive 1200 mg/d quetiapine instead. No significant differences were observed between the high dose (n = 29) and standard dose (n = 31) groups in change from baseline to endpoint on extrapyramidal symptoms, electrocardiographic changes, or most laboratory measures between groups. There was a significant difference between groups for triglycerides (P = 0.035), and post hoc tests revealed a decrease in triglycerides from baseline (mean [SD], 162.7 [59.3] mg/dL) to endpoint (mean [SD], 134.8 [62.7] mg/dL) for the 600 mg/d group (P = 0.019). The mean change in the Positive and Negative Syndrome Scale total score did not differ between groups. In conclusion, quetiapine at 1200 mg/d, although reasonably tolerated, did not confer any advantages over quetiapine at 600 mg/d among patients who had failed to demonstrate an adequate response to a prospective 4-week trial of 600 mg/d.

A new Integrated Negative Symptom structure of the Positive and Negative Syndrome Scale (PANSS) in schizophrenia using item response analysis

BACKGROUND Debate persists with regard to how best to categorize the syndromal dimension of negative symptoms in schizophrenia. The aim was to first review published Principle Components Analysis (PCA) of the PANSS, and extract items most frequently included in the negative domain, and secondly, to examine the quality of items using Item Response Theory (IRT) to select items that best represent a measurable dimension (or dimensions) of negative symptoms. METHODS First, 22 factor analyses and PCA met were included. Second, using a large dataset (n=7187) of participants in clinical trials with chronic schizophrenia, we extracted items loading on one or more PCA. Third, items not loading with a value of ≥ 0.5, or loading on more than one component with values of ≥ 0.5 were discarded. Fourth, resulting items were included in a non-parametric IRT and retained based on Option Characteristic Curves (OCCs) and Item Characteristic Curves (ICCs). RESULTS 15 items loaded on a negative domain in at least one study, with Emotional Withdrawal loading on all studies. Non-parametric IRT retained nine items as an Integrated Negative Factor: Emotional Withdrawal, Blunted Affect, Passive/Apathetic Social Withdrawal, Poor Rapport, Lack of Spontaneity/Conversation Flow, Active Social Avoidance, Disturbance of Volition, Stereotyped Thinking and Difficulty in Abstract Thinking. CONCLUSIONS This is the first study to use a psychometric IRT process to arrive at a set of negative symptom items. Future steps will include further examination of these nine items in terms of their stability, sensitivity to change, and correlations with functional and cognitive outcomes.

Psychometric characteristics of the MATRICS Consensus Cognitive Battery in a large pooled cohort of stable schizophrenia patients

The MATRICS Consensus Cognitive Battery (MCCB) was developed to assess cognitive treatment effects in schizophrenia clinical trials, and is considered the FDA gold standard outcome measure for that purpose. The aim of the present study was to establish pre-treatment psychometric characteristics of the MCCB in a large pooled sample. The dataset included 2616 stable schizophrenia patients enrolled in 15 different clinical trials between 2007 and 2016 within the United States (94%) and Canada (6%). The MCCB was administered twice prior to the initiation of treatment in 1908 patients. Test-retest reliability and practice effects of the cognitive composite score, the neurocognitive composite score, which excludes the domain Social Cognition, and the subtests/domains were examined using Intra-Class Correlations (ICC) and Cohens d. Simulated regression models explored which domains explained the greatest portion of variance in composite scores. Test-retest reliability was high (ICC=0.88) for both composite scores. Practice effects were small for the cognitive (d=0.15) and neurocognitive (d=0.17) composites. Simulated bootstrap regression analyses revealed that 3 of the 7 domains explained 86% of the variance for both composite scores. The domains that entered most frequently in the top 3 positions of the regression models were Speed of Processing, Working Memory, and Visual Learning. Findings provide definitive psychometric characteristics and a benchmark comparison for clinical trials using the MCCB. The test-retest reliability of the MCCB composite scores is considered excellent and the learning effects are small, fulfilling two of the key criteria for outcome measures in cognition clinical trials.