Negative symptoms in schizophrenia: Methodological challenges and emerging solutions for outcome measurement

Negative symptoms (NS) affect approximately 60% of individuals with schizophrenia and are associated with poor outcomes. They remain an important unmet therapeutic need, not adequately addressed by available antipsychotic drugs, and they are poorly assessed in most clinical and research settings. In 2005, a consensus conference identified the relevant domains of NS and provided impetus for the development of new outcome measurement instruments. However, after two decades, the new assessment tools still lack regulatory endorsement, and their uptake in clinical practice and research settings is still limited. Two multidisciplinary ECNP workshops (>25 experts) provided qualitative data, which were thematically analyzed, on the limitations of negative symptom assessment and the future perspective of digital phenotyping. Key methodological challenges in assessment are described in the paper, including: a) the heterogeneity of negative symptoms, with at least five distinct domains to be assessed, b) the primary or secondary nature of negative symptoms with respect to other factors, such as extrapyramidal side effects, and severity of psychotic or depressive symptoms; c) the persistence over time of these symptoms. The limitations of legacy scales and new assessment instruments are reviewed, and possible future perspectives related to digital phenotyping are discussed. The experts' suggested steps to improve the assessment of negative symptoms are reported, including the development of patient-centered outcome measures, the validation of digital phenotyping, and the engagement of regulators and other stakeholders in the development or validation of new assessment instruments.