Caffeine exposure is associated with higher anxiety scores but no clear effect on depressive symptomsCaffeine intake shows no clear effect on depressive symptoms

BackgroundCaffeine is one of the most widely consumed psychoactive dietary components worldwide. However, its effects on affective symptoms remain uncertain, with inconsistent findings regarding depressive and anxiety outcomes. This systematic review and meta-analysis aimed to evaluate the effects of quantified caffeine intake on affective symptoms based exclusively on randomized controlled trial (RCT) evidence.MethodsThe review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement and was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024564399). PubMed/MEDLINE, Embase, the Cochrane Library, Web of Science, CBM, VIP, CNKI, and Wanfang Data were searched from inception to May 16, 2026. Random-effects meta-analyses used restricted maximum likelihood estimation with Hartung–Knapp adjustment. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) and, where appropriate, 95% prediction intervals (PIs) were reported. Clinical coherence was examined according to exposure pattern and psychiatric status, and dose-stratified analyses were exploratory.ResultsFifteen RCTs involving 668 participants contributing to the selected comparisons were included. For depressive symptoms, the broad pooled estimate did not show clear evidence of a difference between caffeine and control conditions [SMD = −0.49, 95% CI: (−1.33, 0.34); I2 = 92.89%; 95% PI: (−2.87, 1.88)]. Anxiety scores were higher on average after caffeine exposure [SMD = 0.51, 95% CI: (0.12, 0.89); I2 = 90.30%], although the 95% PI crossed the null (−0.95, 1.96). In acute non-psychiatric comparisons, pooled estimates were −0.15 [95% CI: (−2.12, 1.81)] for depressive symptoms and 0.38 [95% CI: (−0.02, 0.79)] for anxiety. Exploratory dose stratification showed higher anxiety scores in the >200 mg category [SMD = 0.97, 95% CI: (0.55, 1.39)] but not in the ≤200 mg category [SMD = −0.05, 95% CI: (−0.41, 0.30)]. Certainty of evidence was very low for both outcomes, and small-study effects were detected for anxiety.DiscussionRandomized evidence does not support a uniform effect of caffeine across settings. The positive broad anxiety estimate should be interpreted cautiously because of substantial heterogeneity, a prediction interval spanning the null, and very-low-certainty evidence. Dose-category findings remain exploratory and do not establish a clinical threshold or continuous dose–response relationship.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=564399, PROSPERO CRD42024564399.