Challenges and Strategies for the Recruitment of Patients With Schizophrenia in a Research Setting.

BACKGROUND: With numerous potentially novel targets and pharmacodynamic biomarkers for schizophrenia entering late-stage testing, the next decade will bring an urgent need for well-conducted clinical trials. A critically important step for the successful execution of clinical research trials is timely and appropriate recruitment of participants. Patients with schizophrenia can be especially challenging to recruit because of the disability inherent in psychotic spectrum disorders. Research on how best to recruit for clinical trials is understudied. Clearly defining a model for recruitment procedures would be valuable for researchers and, by extension, the patient populations that may benefit from the insight gained by future clinical research. METHODS: This article aims to offer suggestions for recruitment based on years of experience at the Columbia Schizophrenia Research Clinic (CSRC), a hub for clinical trials focusing on the etiology and treatment of various psychotic disorders. RESULTS: The present report provides practical, step-by-step recommendations for implementing the highly effective CSRC recruitment model, including the benefits of 2 recruitment initiatives that were instituted in 2018: hiring a dedicated recruiter and targeted chart reviews at affiliated clinics. Other topics discussed include our umbrella protocol and database, advertising, and tips for collaborating with external sites. CONCLUSIONS: Despite ongoing complications from coronavirus disease 2019, these strategies have been successful, increasing the rate of both consents and study enrollments by approximately 40% and enabling the CSRC to conduct multiple studies simultaneously.

Pharmacological treatment of violence in schizophrenia.

Chronic aggression and violence in schizophrenia are rare, but receive disproportionate negative media coverage. This contributes to the stigma of mental illness and reduces accessibility to mental health services. Substance Use Disorders (SUD), antisocial behavior, non-adherence and recidivism are known risk factors for violence. Treatment with antipsychotic medication can reduce violence. Aside from clozapine, long-acting injectable antipsychotics (LAI) appear to be superior to oral antipsychotics for preventing violence, addressing adherence and recidivism. LAI also facilitate the implementation of functional skills training. For the high-risk recidivist target population with schizophrenia, better life skills have the potential to also reduce the risk for contact with the legal system, including an improved ability to live independently in supported environments and interact appropriately with others. High-risk patients who are resistant to treatment with other antipsychotics should receive treatment with clozapine due to its direct positive effects on impulsive violence, along with a reduction in comorbid risk factors such as SUDs.

Confidence, performance, and accuracy of self-assessment of social cognition: A comparison of schizophrenia patients and healthy controls.

Impairments in self-assessment in schizophrenia have been shown to have functional and clinical implications. Prior studies have suggested that overconfidence can be associated with poorer cognitive performance in people with schizophrenia, and that reduced awareness of performance may be associated with disability. However, overconfidence is common in healthy individuals as well. This study examines the correlations between performance on a social cognitive test, confidence in performance, effort allocated to the task, and correlates of confidence in patients with schizophrenia and healthy controls (HC). Measures included self-reports of depression, social cognitive ability, and social functioning. A performance-based emotion recognition test assessed social cognitive performance and provided the basis for confidence judgments. Although schizophrenia patients had reduced levels of overall confidence, there was a substantial subset of schizophrenic patients who manifested extreme overconfidence and these people had the poorest performance and reported the least depression. Further, a substantial number of HC over-estimated their performance as well. Patients with schizophrenia, in contrast to HC, did not adjust their effort to match task difficulty. Confidence was minimally related to task performance in patients but was associated with more rapid decisions in HC, across both correct and incorrect responses. Performance on social cognitive measures was minimally related to self-reports of social functioning in both samples. These data suggest global self-assessments are based on multiple factors, with confidence affecting self-assessments in the absence of feedback about performance.

New discoveries for an old drug: a review of recent olanzapine research.

Objective: Based on a substantial literature, olanzapine appears to be one of the most efficacious antipsychotics marketed in the United States, with only clozapine clearly more advantageous. However, olanzapine is marred by an equally substantial literature demonstrating a metabolic burden of olanzapine, particularly for weight gain. With the publication of successful strategies to limit olanzapine induced weight gain, a reassessment of the clinical utility of olanzapine appears warranted. The purpose of this paper is to review recent evidence for olanzapine, highlighting use in both schizophrenia and other conditions, safety and supporting the use of olanzapine above 20 mg/day, focusing on studies published since our previous reviews in 2008 and 2009.Data Sources: The US National Library of Medicine's PubMed resource (https://www.ncbi.nlm.nih.gov/pubmed/) was searched using the text word 'olanzapine' for all English-language articles published between 2008 to July 2019, inclusive with a specific focus on double-blind randomized controlled trials and meta-analyses. In addition, we examined the review articles for other reports of interest that may have been missed by our initial search.Data Extraction: The studies were evaluated based on efficacy and safety data.Results: Use of olanzapine may be decreasing but remains common overall. Evidence continues to support both the relative efficacy advantage and weight gain/metabolic disadvantages of olanzapine in schizophrenia, and recent research supports olanzapine's use in treating anorexia nervosa and chemotherapy-induced nausea. The evidence for high dose olanzapine dosages >20 mg remains limited. Non-pharmacological options, such as dietary counseling and exercise, appear to be efficacious in addressing antipsychotic-induced weight gain. Topiramate, metformin and possibly the olanzapine-samidorphan combination also appear helpful.Conclusions: Olanzapine remains a useful antipsychotic, but requires with careful monitoring. Further research is needed to compare the different options available to mitigate olanzapine-induced weight gain and to evaluate potential synergism between pharmacological and non-pharmacological treatments.

Autism symptoms, depression, and active social avoidance in schizophrenia: Association with self-reports and informant assessments of everyday functioning.

Autistic traits are a feature of schizophrenia and has been found to impair social functioning and social cognition. Other influences on social outcomes in schizophrenia include depression and social avoidance. However, challenges in self-assessment of abilities and functioning (i.e., introspective accuracy) and self-assessment bias also contribute to disability. Depression has been studied for its association with introspective accuracy and bias, but autistic traits have not. Participants were 177 patients with schizophrenia who self-reported their everyday functioning and social cognitive ability as well as their depression. All were rated with the PANSS and a separate rater generated all-sources ratings of everyday functioning and social cognitive ability. Correlations between self-reported everyday functioning and social cognitive ability, ratings of everyday functioning and social cognitive ability, and the discrepancies between those ratings were examined for correlations with depression, autistic features and social avoidance. Accuracy was defined by the absolute value of the difference between self-reports and all-sources ratings and bias was defined by the direction of discrepancy (positive vs. negative). There was a statistically significant difference between sources on every measure. Bias was not directional on average, but patients with the lowest levels of depression overestimated their abilities on every measure and those with the highest depression underestimated. Autistic traits were associated with impairments in everyday functioning and underestimation of those impairments, while social avoidance was associated with impaired social functioning and accurate self-assessment. Features of schizophrenia have differential implications for impaired functioning and self-assessment, with autistic features and low levels of depression associated with consistent self-assessment biases.

Predictors of social functioning in patients with higher and lower levels of reduced emotional experience: Social cognition, social competence, and symptom severity.

BACKGROUND: Deficits in social functioning in schizophrenia are primarily predicted by negative symptoms, social cognition deficits, and social skills deficits. Here we examine those predictive variables across variations in the severity of reduced emotional experience. We hypothesized that in patients with high symptom severity, factors such as social cognition would have reduced importance for predicting social outcomes. METHODS: Participants with schizophrenia (n = 312) were tested using five different measures of social cognition. Performance-based assessments and clinical ratings of reduced emotion experience were used to assess social competence. High contact informants rated interpersonal functioning and social acceptability of behavior, while unaware of other patient data. Patients were divided into higher and lower reduced emotional experience using previously validated criteria. RESULTS: 33% of the patients had at least moderate symptoms of reduced emotional experience. Patients with greater severity had more social functioning impairment, but not poorer social competence and social cognition. In the patients with lower severity, social cognition accounted for 9% of the variance in interpersonal functioning, while in patients with higher severity, social cognition did not predict any variance. In the patients with lower severity, social cognition accounted for 4% of the variance in social acceptability of behavior, while in patients with higher severity, social cognition also did not predict any variance. IMPLICATIONS: The influence of social cognition on social outcomes appears greater in patients with less severe symptoms of reduced emotional experience. As there are treatments for both these symptoms and social cognition with demonstrated efficacy, these data suggest differential application of these interventions based on symptom severity.

Social Cognition and Neurocognition in Schizophrenia and Healthy Controls: Intercorrelations of Performance and Effects of Manipulations Aimed at Increasing Task Difficulty.

Social cognition (SC) and neurocognition appear to predict different aspects of functional outcome in people with schizophrenia. However, the correlations between performance on these domains have not been tested extensively and compared cross-diagnostically with healthy controls. Further, some social cognitive measures appeared to have potential ceiling effects, particularly for healthy people, in previous research, so increasing their difficulty is of interest. In this paper we report on two studies wherein we examined the correlations between neurocognitive ability and performance on SC tests. In the first study the correlations between measures of social perception, emotion processing, and theory of mind and performance on a brief neuropsychological (NP) assessment were examined in 179 schizophrenia (SCZ) patients and 104 healthy controls (HC). In the second study, we instructed participants to perform a subset of the tasks as rapidly as possible in order to increase task difficulty, and we examined the effects of those instructions on task difficulty, task psychometrics, and correlations between SC and NP tests in 218 SCZ patients and 154 HC. In the first study, both HC and SCZ manifested a domain specific pattern of correlation between NP and SC test performance. Controlling for group differences in NP performance did not eliminate SC performance differences between the groups. In the second study, no differences in task performance, intercorrelations other SC tests, or test-retest stability were induced by the difficulty manipulation in the samples who performed the tasks with speed demands compared to the performance of the previous sample. These data suggest that simple manipulations aimed at increasing task difficulty may not have the desired effect and that despite consistent correlations between SC and NP test performance, impairments in social cognitive functioning are not fully explained by NP performance deficits.