Treatment of schizotypal disorder: A systematic review and GRADE evaluation of the certainty of evidence.
| Title: | Treatment of schizotypal disorder: A systematic review and GRADE evaluation of the certainty of evidence. |
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| Authors: | Gundersen KB; VIRTU Research Group, Mental Health Center Copenhagen, Copenhagen University Hospital - Mental Health Services, CPH, Denmark; Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center, Glostrup, Copenhagen University Hospital - Mental Health Services CPH, Copenhagen, Denmark; Department of Psychology, University of Copenhagen, Copenhagen, Denmark. Electronic address: Kristina.ballestad.gundersen@regionh.dk.; Arnfred B; VIRTU Research Group, Mental Health Center Copenhagen, Copenhagen University Hospital - Mental Health Services, CPH, Denmark.; Albert N; EMPIRA Research Group, Mental Health Center Copenhagen, Copenhagen University Hospital - Mental Health Services, CPH, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Rasmussen AR; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Mental Health Center Amager, University of Copenhagen, Copenhagen, Denmark; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.; Ebdrup BH; Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center, Glostrup, Copenhagen University Hospital - Mental Health Services CPH, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Polari A; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.; Nelson B; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Orygen, 35 Poplar Rd, Parkville 3052, Australia.; Glenthøj LB; VIRTU Research Group, Mental Health Center Copenhagen, Copenhagen University Hospital - Mental Health Services, CPH, Denmark; Department of Psychology, University of Copenhagen, Copenhagen, Denmark. |
| Source: | Schizophrenia research [Schizophr Res] 2026 Feb; Vol. 288, pp. 3-17. Date of Electronic Publication: 2025 Dec 19. |
| Publication Type: | Journal Article; Systematic Review |
| Language: | English |
| Journal Info: | Publisher: Elsevier Science Publisher B. V Country of Publication: Netherlands NLM ID: 8804207 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-2509 (Electronic) Linking ISSN: 09209964 NLM ISO Abbreviation: Schizophr Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam : Elsevier Science Publisher B. V., c1988- |
| MeSH Terms: | Antipsychotic Agents*/therapeutic use ; Schizotypal Personality Disorder*/therapy ; Schizotypal Personality Disorder*/drug therapy ; Psychotherapy*; Humans |
| Abstract: | Background: Evidence to guide treatment for schizotypal disorder is scarce, and clinical guidelines remain undeveloped. This systematic review synthesized current evidence on pharmacological and psychotherapeutic interventions targeting clinical symptoms, cognition, and functioning in schizotypal disorder.; Methods: We searched PsychINFO, Embase, Medline, and Cochrane Register of Controlled Trials (25/03/2025) without date restrictions, supplemented by handsearching. Eligible studies were screened, quality appraised, and data extracted by two independent authors. Due to substantial heterogeneity, findings were synthesized narratively, and evidence certainty was rated using GRADE.; Results: Twenty-one studies met inclusion criteria. Most had some concerns regarding risk of bias. Pharmacological trials most frequently investigated antipsychotics, with preliminary evidence suggesting benefits of thiothixene and, to a lesser extent, risperidone, olanzapine, and haloperidol in reducing general psychiatric symptoms, although effects on depressive symptoms were mixed. Dopamine agonists and central alpha-2A agonists showed domain-specific cognitive improvements, particularly when combined with cognitive remediation therapy and social skills training. Among psychotherapeutic approaches, metacognitively oriented and evolutionary systems therapies demonstrated consistent symptom reductions, while integrated interventions temporarily reduced negative symptoms and psychosis risk. Functional improvements were most evident in multimodal interventions combining pharmacological and psychosocial components. Across interventions, the overall certainty of evidence was graded very low to low.; Conclusions: Current treatment evidence for schizotypal disorder is limited and heterogeneous. Larger, high-quality randomized controlled trials are needed to establish efficacy across clinical, cognitive, and functional domains and to inform development of evidence-based treatment guidelines.; (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest Bjørn H. Ebdrup is part of the Advisory Board of Boehringer Ingelheim, Lundbeck Pharma A/S, and Orion Pharma A/S; and has received lecture fees from Boehringer Ingelheim, Otsuka Pharma Scandinavia AB, and Lundbeck Pharma A/S. All other authors have no declaration of interests. |
| Contributed Indexing: | Keywords: Clinical guidelines; Evidence limitations; Pharmacotherapy; Psychotherapy; Schizotypal Personality Disorder; Treatment guidelines |
| Substance Nomenclature: | 0 (Antipsychotic Agents) |
| Entry Date(s): | Date Created: 20251220 Date Completed: 20260119 Latest Revision: 20260120 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.schres.2025.12.008 |
| PMID: | 41421074 |
| Database: | MEDLINE |
Journal Article; Systematic Review