Supplementary Material for: Prodromal Symptoms in Depression: A Systematic Review

<b><i>Introduction</i></b>: Appraisal of prodromal symptoms of unipolar depression may complement the traditional cross-sectional approach and provide a longitudinal perspective, according to a staging model of the illness. <b><i>Objective:</i></b> To provide an updated systematic review of clinical studies concerned with prodromal symptoms of unipolar depression, according to PRISMA guidelines. <b><i>Methods:</i></b> Keyword searches were conducted in PubMed, Scopus, and Web of Science. Longitudinal studies on prodromal symptoms and signs in adult patients primarily diagnosed with unipolar depression were selected. Findings were examined separately according to study design (i.e., retrospective or prospective). <b><i>Results:</i></b> Twenty-five studies met the criteria for inclusion in this systematic review. Findings indicate that a distinct prodromal symptomatology – commonly characterized by anxiety, tension, irritability, and somatic complaints – exists before the onset of unipolar depression. The duration of the prodromal phase was highly variable across studies, ranging from less than a month to several years. Prodromal symptoms profile and duration were consistent within individuals across depressive episodes. There was a close relationship between prodromal and residual symptoms of the same depressive episode. <b><i>Conclusions:</i></b> The present systematic review addresses an important, and yet relatively neglected, clinical issue that deserves further investigation and may be of immediate practical value. The findings provide challenging insights into the pathogenesis and course of unipolar depression, which may result in more timely and effective treatment of recurrences. The definition of a prodromal phase in depression would benefit from the joint use of symptom identification, biomarkers, and neuroimaging.