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A systematic review and synthesis of 489 studies investigating treatments for negative symptoms in the schizophrenia spectrum : Trial designs, demographics and clinical characteristics

Damiani, Stefano ; D'Imperio, Aldo LU orcid ; Radua, Joaquim ; Fortea, Lydia ; Calò, Matteo ; Crippa, Andrea ; Esposito, Cecilia Maria ; Lumer, Estella Linda Luisa ; Patron, Sara and Peviani, Alessandro , et al. (2025) In Psychiatry Research 347.
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.... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antipsychotics, Brain stimulation, Guidelines, Lifestyle, Pharmacotherapy, Psychotherapy, Treatment
in
Psychiatry Research
volume
347
article number
116406
publisher
Elsevier
external identifiers
  • pmid:40015036
  • scopus:85218875816
ISSN
0165-1781
DOI
10.1016/j.psychres.2025.116406
language
English
LU publication?
yes
id
b5764b76-d14f-4b6a-9f9d-90c9dd270742
date added to LUP
2025-06-19 08:42:16
date last changed
2025-06-19 08:43:20
@article{b5764b76-d14f-4b6a-9f9d-90c9dd270742,
  abstract     = {{<p>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.</p>}},
  author       = {{Damiani, Stefano and D'Imperio, Aldo and Radua, Joaquim and Fortea, Lydia and Calò, Matteo and Crippa, Andrea and Esposito, Cecilia Maria and Lumer, Estella Linda Luisa and Patron, Sara and Peviani, Alessandro and Piccolo, Alessandro and Provenzani, Umberto and Santilli, Fabrizio and Spallarossa, Cecilia and Fusar-Poli, Laura and Papanastasiou, Evangelos and Cella, Matteo and Patel, Rashmi and Galderisi, Silvana and Leucht, Stefan and Stahl, Daniel and Fusar-Poli, Paolo}},
  issn         = {{0165-1781}},
  keywords     = {{Antipsychotics; Brain stimulation; Guidelines; Lifestyle; Pharmacotherapy; Psychotherapy; Treatment}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Psychiatry Research}},
  title        = {{A systematic review and synthesis of 489 studies investigating treatments for negative symptoms in the schizophrenia spectrum : Trial designs, demographics and clinical characteristics}},
  url          = {{http://dx.doi.org/10.1016/j.psychres.2025.116406}},
  doi          = {{10.1016/j.psychres.2025.116406}},
  volume       = {{347}},
  year         = {{2025}},
}