A novel way to quantify schizophrenia symptoms in clinical trials

Abstract

Background A major problem in quantifying symptoms of schizophrenia is establishing a reliable distinction between enduring and dynamic aspects of psychopathology. This is critical for accurate diagnosis, monitoring and evaluating treatment effects in both clinical practice and trials. Materials and methods We applied Generalizability Theory, a robust novel method to distinguish between dynamic and stable aspects of schizophrenia symptoms in the widely used Positive and Negative Symptom Scale (PANSS) using a longitudinal measurement design. The sample included 107 patients with chronic schizophrenia assessed using the PANSS at five time points over a 24‐week period during a multi‐site clinical trial of N‐Acetylcysteine as an add‐on to maintenance medication for the treatment of chronic schizophrenia. Results The original PANSS and its three subscales demonstrated good reliability and generalizability of scores (G = 0.77‐0.93) across sample population and occasions making them suitable for assessment of psychosis risks and long‐lasting change following a treatment, while subscales of the five‐factor models appeared less reliable. The most enduring symptoms represented by the PANSS were poor attention, delusions, blunted affect and poor rapport. More dynamic symptoms with 40%‐50% of variance explained by patient transient state including grandiosity, preoccupation, somatic concerns, guilt feeling and hallucinatory behaviour. Conclusions Identified dynamic symptoms are more amendable to change and should be the primary target of interventions aiming at effectively treating schizophrenia. Separating out the dynamic symptoms would increase assay sensitivity in trials, reduce the signal to noise ratio and increase the potential to detect the effects of novel therapies in clinical trials.

Cross-cultural validation of the stroke riskometer using generalizability theory

“…across cultures/countries). To date, G-Theory has been applied to establish reliability and generalizability of assessment scores across many different disciplines including medicine 21 , rehabilitation 22 , psychology 17 , psychiatry 23 and education 18 .…”

N‐acetylcysteine as a new prominent approach for treating psychiatric disorders

“…Several published clinical studies, including randomized double‐blind placebo‐controlled trials, showed some beneficial effects of NAC as an efficient therapy for schizophrenia (Table 3). NAC administration for a minimum of 4 weeks in doses ranging from 0.6 to 3.6 g day −1 to patients who underwent clinical antipsychotic therapy or without clinical therapy diminished negative symptoms (Berk, Copolov, Dean, Lu, Jeavons, Schapkaitz, Anderson‐Hunt, Judd, et al, 2008; Breier et al, 2018; Bulut et al, 2009; Di Rosa et al, 2010; Farokhnia et al, 2013; Lavoie et al, 2008; Medvedev et al, 2020; Rossell et al, 2016; Sepehrmanesh et al, 2018; Tharoor et al, 2018; Zhang et al, 2015). A few studies reported the effect of NAC on positive symptoms (Bulut et al, 2009; Di Rosa et al, 2010; Medvedev et al, 2020; Sepehrmanesh et al, 2018; Zhang et al, 2015), but the research data were weaker than those for negative symptoms.…”

“…NAC administration for a minimum of 4 weeks in doses ranging from 0.6 to 3.6 g day −1 to patients who underwent clinical antipsychotic therapy or without clinical therapy diminished negative symptoms (Berk, Copolov, Dean, Lu, Jeavons, Schapkaitz, Anderson‐Hunt, Judd, et al, 2008; Breier et al, 2018; Bulut et al, 2009; Di Rosa et al, 2010; Farokhnia et al, 2013; Lavoie et al, 2008; Medvedev et al, 2020; Rossell et al, 2016; Sepehrmanesh et al, 2018; Tharoor et al, 2018; Zhang et al, 2015). A few studies reported the effect of NAC on positive symptoms (Bulut et al, 2009; Di Rosa et al, 2010; Medvedev et al, 2020; Sepehrmanesh et al, 2018; Zhang et al, 2015), but the research data were weaker than those for negative symptoms. In addition, NAC improves cognitive symptoms, including working memory, mismatch negativity, and global functioning (Berk, Copolov, Dean, Lu, Jeavons, Schapkaitz, Anderson‐Hunt, Judd, et al, 2008; Carmeli et al, 2012; Conus et al, 2018; Di Rosa et al, 2010; Rapado‐Castro et al, 2017; Sepehrmanesh et al, 2018).…”

Communication strategies for nursing research with older adults diagnosed with schizophrenia using life course theory

“…Shortened intervals can show respect for the potential challenges associated with a participant's diminished ability to concentrate (APA, 2013;Manojlovic & Nikolic-Popovic, 2016;Medvedev et al, 2021).…”

“…Instead, they "must be recognized as valuable to society… and as distinct contributors to diversity of thought and experience" (Moore, 2020, p. 250). To facilitate OADWS' expression of their thoughts and ideas, given their unique needs related to potentially diminished concentration, research sessions can be broken up into shorter periods of time (Medvedev et al, 2021;Moore, 2020;Pawełczyk et al, 2018).…”