Evaluation of a plasticity-based cognitive training program in schizophrenia: Results from the eCaesar trial.

OBJECTIVE: Cognitive impairment in schizophrenia is a core feature of the disorder. Computerized cognitive training has shown promise in pilot studies. A 26-week randomized blinded placebo-controlled trial was conducted to investigate the effect of a novel computerized cognitive training program on cognitive and functional capacity outcomes. METHOD: The study followed MATRICS guidelines for the evaluation of interventions designed to improve cognitive function in schizophrenia. Participants (N = 150) were randomized to experimental (computerized cognitive training in a game-like format) or active control (computer games) groups. Training was conducted in-clinic, with an intended training schedule of 5 days per week, 1 h per day, for 26 weeks. Co-primary outcome measures were the MATRICS Consensus Cognitive Battery (MCCB) composite score and the UCSD Performance-Based Skills Assessment (UPSA-2) total score, secondary outcome measures included the Cognitive Assessment Interview (CAI) and the Short-Form-12 Mental Composite Score (SF-12 MCS). Target engagement was assessed with task-learning based assessment. RESULTS: At baseline, the groups were well matched. No significant effect of the experimental treatment was seen on the primary or secondary outcome measures compared to the active control. Review of the task learning/target engagement data suggested inadequate target engagement. CONCLUSIONS: Results do not support a cognitive or functional capacity benefit from this implementation of a computerized cognitive training program in people with schizophrenia. In future trials, careful consideration is merited of the assessment of task learning/target engagement, the effects of making the cognitive training game-like on motivation, and the implicit effects of trial requirements on participant selection.

Health Care Utilization of Veterans With Serious Mental Illness.

Outreach regarding veteran-specific factors can help determine which targeted interventions reduce the need for chronic mental illness inpatient hospitalization.

Feasibility and challenges of inpatient psychotherapy for psychosis: lessons learned from a veterans health administration pilot randomized controlled trial.

BACKGROUND: In large health care systems, decision regarding broad implementation of psychotherapies for inpatients with psychosis require substantial evidence regarding effectiveness and feasibility for implementation. It is important to recognize challenges in conducting research to inform such decisions, including difficulties in obtaining consent from and engaging inpatients with psychosis in research. We set out to conduct a feasibility and effectiveness Hybrid Type I pilot randomized controlled trial of acceptance and commitment therapy (ACT) and a semi-formative evaluation of barriers and facilitators to implementation. FINDINGS: We developed a training protocol and refined an ACT treatment manual for inpatient treatment of psychosis for use at the Veterans Health Administration. While our findings on feasibility were mixed, we obtained supportive evidence of the acceptability and safety of ACT. Identified strengths of ACT included a focus on achievement of valued goals rather than symptoms. Weaknesses included that symptoms may limit patient's understanding of ACT. Facilitators included building trust and multi-stage informed consent processes. Barriers included restrictive eligibility criteria, rigid use of a manualized protocol, and individual therapy format. Conclusions are limited by our randomization of only 18 patient participants (with nine completing all aspects of the study) out of 80 planned. CONCLUSIONS: Future studies should include (1) multi-stage informed consent processes to build trust and alleviate patient fears, (2) relaxation of restrictions associated with obtaining efficacy/effectiveness data, and (3) use of Hybrid Type II and III designs.

Do obese depressed patients respond to topiramate? A retrospective chart review.

BACKGROUND: Topiramate, a novel anticonvulsant, has shown promise in preliminary open trials in bipolar disorder, but there are no studies in primary depression. Topiramate's tendency to cause weight loss could be advantageous for many patients with mood disorders. METHODS: A chart review was conducted on 16 female outpatients with a primary major depressive episode and mild to moderate obesity who received open-label adjunctive topiramate. Ongoing psychotropics were continued at previous doses. Self-report symptoms were assessed before and after acute phase (4-8 weeks) treatment in a subset of 11 patients, and clinician ratings were assessed at all visits during extended phase (up to 40 weeks) treatment for the entire group. RESULTS: Patient and clinician symptom ratings dropped significantly during acute phase treatment (5.5+/-1.2 weeks), but only 36% of patients were judged responders. At extended phase endpoint (17.7+/-13.4 weeks), 44% of patients were responders. Body mass index decreased significantly on topiramate, reflecting a mean weight loss of 6.1+/-8.2% from baseline. Central nervous system side effects were prominent. CONCLUSIONS: Topiramate may have potential for the adjunctive treatment of depression in obese patients, but close monitoring of weight and adverse effects is warranted.

A double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine.

BACKGROUND: A previous pilot study of open-label mirtazapine augmentation conducted by the authors in 20 depressed patients yielded a 55% response rate at week 4. A double-blind controlled trial was undertaken to further elucidate the efficacy of this intervention. METHODS: 26 adult outpatients with persistent major depression despite adequate antidepressant monotherapy were randomized to receive 4 weeks of mirtazapine or placebo augmentation. Mirtazapine was begun at 15 mg at bedtime, with possible titration to 30 mg at bedtime per physician's discretion after week 1. RESULTS: Categorical positive response rate at end point was 64% for active drug and 20% for placebo. Remission rates were 45.4% and 13.3% for active drug and placebo groups, respectively, Mirtazapine demonstrated statistically significant superiority to placebo on most major outcome measures, and was associated with improvement in overall functioning and quality of life. There were no significant group differences with regard to emergent side effects, weight change, or serum concentrations of primary antidepressants. CONCLUSIONS: Mirtazapine appears safe and effective for short-term antidepressant augmentation.