A systematic review and synthesis of 489 studies investigating treatments for negative symptoms in the schizophrenia spectrum: Trial designs, demographics and clinical characteristics
- PMID: 40015036
- DOI: 10.1016/j.psychres.2025.116406
A systematic review and synthesis of 489 studies investigating treatments for negative symptoms in the schizophrenia spectrum: Trial designs, demographics and clinical characteristics
Abstract
Negative symptoms in schizophrenia spectrum are associated with minimal treatment responses. The search for effective treatments is potentially hampered by heterogenous study-designs and sample characteristics depending on the intervention category. This PRISMA-compliant systematic review/synthesis aims to describe the literature on negative symptoms interventions for schizophrenia spectrum disorders by comparing 12 study design, demographical and clinical variables in different intervention categories: antipsychotics (AP), other pharmacological agents (OPA), brain stimulation (BS), psychological/psychosocial (PSI), lifestyle (LS), mixed interventions. Kruskal-Wallis and Chi-square tests measured differences between intervention-groups. Out of 19,935 articles, 489 (AP=149/OPA=187/BS=49/PSI=79/LS=19/mixed=6) were selected for data extraction. Concerning study designs, AP had the largest average arm size (mean ± SD=91.1 ± 122.8participants), OPA the highest double/triple-blinding (97.9 %) rates, PSI the longest follow-up (26.7 ± 21.8weeks). Age/gender demographical differences were significant but of negligible magnitude. OPA illness duration (14.8 ± 9.0years) was longer compared to AP (11.4 ± 6.7years). Positive and Negative Syndrome Scale (PANSS) negative scores were milder in PSI (18.6 ± 6.9) compared to AP/OPA/BS (23.8 ± 6.4/23.4 ± 4.9/24.2 ± 9.2). PANSS total scores were worse in AP (83.6 ± 18.2) than in OPA/BS/PSI (77.1 ± 20.5/75.5 ± 14.7/67.0 ± 23.3). The same was true for dropout rates (AP=25.5 %, OPA/BS/PSI=14.3/9.7/14.5 %). Prevalent treatment as usual was "none" for AP (36.7 %) and "antipsychotic" for other categories (42.3-82.8 %). Implementing cross-over, factorial or multi-arm designs may increase the comparability between studies investigating different intervention categories. Concerning clinical differences, reporting individual treatments at baseline and clinical severity, evaluating cognitive profiles and considering patients' perspectives will allow to better understand the efficacy of the available treatments and develop tailored interventions.
Keywords: Antipsychotics; Brain stimulation; Guidelines; Lifestyle; Pharmacotherapy; Psychotherapy; Treatment.
Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Aldo D'imperio, Laura Fusar-Poli, Cecilia Maria Esposito, Silvana Galderisi, Paolo Fusar-Poli reports financial support was provided by Italian Ministry of University and Research (MUR). Rashmi Patel reports financial support was provided by National Institute for Health and Care Research. Rashmi Patel reports financial support was provided by Medical Research Council. Evangelos Papanastasiou reports a relationship with HMNC Holding GmbH that includes: employment. Rashmi Patel reports a relationship with Janssen Pharmaceuticals Inc that includes: funding grants. Rashmi Patel reports a relationship with Holmusk, Akrivia Health, Columbia Data Analytics, Clinilabs, Boehringer Ingelheim, Teva and Otsuka that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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