BackgroundSpeech contains neuromuscular, physiological and cognitive components, and so is a potential biomarker of mental disorders. Previous studies indicate that speaking rate and pausing are associated with major depressive disorder (MDD). However, results are inconclusive as many studies are small and underpowered and do not include clinical samples. These studies have also been unilingual and use speech collected in controlled settings. If speech markers are to help understand the onset and progress of MDD, we need to uncover markers that are robust to language and establish the strength of associations in real-world data. MethodsWe collected speech data in 585 participants with a history of MDD in the United Kingdom, Spain, and Netherlands as part of the RADAR-MDD study. Participants recorded their speech via smartphones every two weeks for 18 months. Linear mixed models were used to estimate the strength of specific markers of depression from a set of 28 speech features. ResultsIncreased depressive symptoms were associated with speech rate, articulation rate and intensity of speech elicited from a scripted task. These features had consistently stronger effect sizes than pauses. LimitationsOur findings are derived at the cohort level so may have limited impact on identifying intra-individual speech changes associated with changes in symptom severity. The analysis of features averaged over the entire recording may have underestimated the importance of some features. ConclusionsParticipants with more severe depressive symptoms spoke more slowly and quietly. Our findings are from a real-world, multilingual, clinical dataset so represent a step-change in the usefulness of speech as a digital phenotype of MDD.