Caffeine Consumption and Schizophrenia: A Systematic Review and Meta-analysis of Cognitive, Symptomatic, and Functional Outcomes

Background Schizophrenia is a complex mental disorder characterized by cognitive deficits, persistent symptoms, and functional impairment. Caffeine, a commonly consumed psychoactive substance, has plausible effects on cognition and mood. However, its impact on individuals with schizophrenia remains unclear. This review evaluates caffeine’s impact on cognition, symptomatology, and functional outcomes in schizophrenia.

A systematic literature search was conducted for articles published up to 30 December 2024 across PubMed, Cochrane Library, PsycINFO, Embase, Emcare, and Medline. We included English-language studies in adults with schizophrenia that compared different caffeine intake levels and reported outcomes on cognition, symptoms, or functioning. Cohort, cross-sectional, and clinical trial designs were included. Data were synthesized using a random-effects model with Hedges’ g for effect size and I² statistics for heterogeneity.

Of 252 articles screened, eleven studies (n=1,406) met inclusion criteria. Findings were mixed. Some studies reported improvements in cognitive performance and working memory, while others observed increases in positive symptoms or inconsistent associations with overall symptom management. Meta-analyses revealed a non-significant increase/decrease in overall symptom severity (measured with Brief Psychiatric Rating Scale (BPRS) and Nurses’ Observation Scale for Inpatient Evaluation (NOSIE). Physiologically, caffeine was found to reduce cerebral blood flow, with no statistically significant effects on blood pressure or pulse.

Caffeine may have mixed effects on schizophrenia, with potential positive effects on cognitive and negative symptoms while possibly worsening positive symptoms. Functional and physiological impacts are unclear, warranting further research to guide clinical recommendations. Competing Interest Statement The authors have declared no competing interest. Clinical Protocols https://www.crd.york.ac.uk/PROSPERO/view/CRD42025628484 Funding Statement The author(s) received no financial support for the research, authorship, and/or publication of this article. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used only openly available human data that were located from PubMed, Cochrane Library, PsycINFO, Embase, Emcare, Medline. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Statements and Declarations: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article Funding statement: The author(s) received no financial support for the research, authorship, and/or publication of this article. Data Availability All data produced in the present study are available upon reasonable request to the authors