The Use of Cognitive Screening in Pharmacotherapy Trials for Cognitive Impairment Associated With Schizophrenia

Abstract

There are currently no regulatory approved pharmacological treatments for cognitive impairment associated with schizophrenia (CIAS). One possibility is that trial methodology itself is hindering their development. Emerging evidence suggests that patients with schizophrenia may show limited benefit from pro-cognitive interventions if they already exhibit intact cognitive performance, relative to normative thresholds. The aim of this report was to examine the extent to which objectively assessed cognitive performance has been used as an eligibility and/or stratification criterion in CIAS pharmacotherapy trials. On 16th January 2019, we conducted a systematic search of studies listed on ClinicalTrials.gov to identify randomized, double-blind, placebo-controlled, add-on pharmacotherapy trials conducted in patients with a diagnosis of schizophrenia, in which a paper-and-pencil or computerized cognitive task (or battery) was specified as a primary outcome measure. Of the 87 trials that met our inclusion criteria, 10 (11.5%) required the presence of an objectively assessed cognitive deficit as part of their patient eligibility criteria. No studies reported stratifying patients according to the presence or degree of cognitive impairment they exhibited. These results suggest that the vast majority of CIAS trials may have been underpowered due to the inclusion of cognitively “normal” patients. Purposive screening for cognitive impairment could increase CIAS trial success.

An α7 nAChR approach for the baseline-dependent modulation of deviance detection in schizophrenia: A pilot study assessing the combined effect of CDP-choline and galantamine

“…An initial baseline session will allow for the predesignation of lower sensory processing baseline individuals most likely to benefit from this treatment approach and will prevent treatment administration to individuals with higher sensory processing levels. Patients with lower baseline deviance detection should also be prioritized as the inclusion of patients with more efficient or intact deviance processing might underpower the results ( Cotter et al, 2019 ). Furthermore, our stratification strategy may help explain the failure for AVL-3288 (a selective α7 type 1 PAM, previously shown to ameliorate cognition) to enhance cognitive measures in SCZ, as this study selected individuals with higher cognitive processing levels at baseline ( Gee et al, 2017 ; Kantrowitz et al, 2020 ).…”

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“…No pharmacologic treatment has been indicated for the treatment of cognitive impairment associated with schizophrenia. Trial design modifications, such as screening trial participants for cognitive impairment and stratifying results based on level of cognitive impairment, have been recommended to increase the chance of finding effective treatment for cognitive impairment associated with schizophrenia ( Cotter et al, 2019 ; Keefe et al, 2013 ; Zhu, 2020 ).…”

Effects of 7.5% Carbon Dioxide and Nicotine Administration on Latent Inhibition

“…Since DSM-5 criteria neither determine the presence of cognitive impairments cognitive ability nor classify according to underlying neurobiological abnormalities, it is not surprising that these drugs have failed to universally improve cognition among such a heterogeneous group. To date, 87 novel agents have been unsuccessfully trialed for cognitive impairment associated with schizophrenia [see (54)]: a tool to enhance the prediction of treatment efficacy for a core area of schizophrenia where no treatments currently exist has the potential to greatly improve the chances of an effective drug becoming available.…”