Prodromal Symptoms in Depression: A Systematic Review

Abstract

<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.

Treating Insomnia with High Risk of Depression Using Therapist-Guided Digital Cognitive, Behavioral, and Circadian Rhythm Support Interventions to Prevent Worsening of Depressive Symptoms: A Randomized Controlled Trial

“…Table 1 summarizes demographic and clinical characteristics, and Table 2 summarizes the characterization of participants in view of the staging model of depression [49, 50]. At baseline, 12.9% could be considered to be in stage 0 (no current or past MDD, IDS-SR ≤13); 31.8% in stage 1 (possible prodromal depression (see Benasi et al [51] for a critical review) without current or past MDD, IDS-SR >13); and 55.3% in stage 3 (residual depression without current MDD, with history of MDD in the past). It should be noted that the discrimination between stage 0 and stage 1 based on an IDS-SR cut-off remains to be validated for use in ID [30].…”

Staging of unipolar depression: systematic review and discussion of clinical implications

“…Staging calls for a reassessment of basic pathophysiological models of pathogenesis of unipolar depression, that neglect intermediate phenomenological steps in the balance between health and disease. The pathophysiological model that is entailed by the existence of a prodromal phase (Benasi et al, 2021; Fava, 1999) is in line with the concept of allostatic load (the cost of chronic exposure to fluctuating or heightened physiologic responses resulting from repeated or chronic stress) in the balance between health and disease (Guidi, Lucente, Sonino, & Fava, 2021). When environmental challenges exceed the individual ability to cope, allostatic overload ensues.…”

“…There appears to be a relationship between residual and prodromal symptomatology according to the rollback phenomenon that was substantiated in mood disorders: as the illness remits, it progressively recapitulates, even though in a reverse order, many of the stages and symptoms that were seen during the time it developed (Detre & Jarecki, 1971;Fava, 1999). Since prodromal symptoms of relapse tend to mirror those of the initial episode, symptoms occurring in the prodromal phase deserve more clinical attention than others (Benasi, Fava, & Guidi, 2021;Fava et al, 1994). Indeed, in clinimetrics major and minor symptoms can be differentiated (Fava et al, 2012a(Fava et al, , 2012b, unlike in the psychometric model endorsed by DSM, where all items are weighed the same.…”

“…Allostatic load may cause a transition from one stage to another and trigger enhanced vulnerability to relapse. For instance, stressful life events have been associated with onset of depression in conjunction with prodromal symptomatology (Benasi et al, 2021) and relapse during maintenance treatment 1624 Fiammetta Cosci and Giovanni A. Fava with antidepressant drugs in the residual phase (Paykel Tanner, 1976). Table 1 does not include a stage 0, as suggested by other investigators to characterize an asymptomatic stage (Hetrick et al, 2008;McGorry et al, 2006;Nelson et al, 2021).…”

“…Allostatic load may cause a transition from one stage to another and trigger enhanced vulnerability to relapse. For instance, stressful life events have been associated with onset of depression in conjunction with prodromal symptomatology (Benasi et al, 2021) and relapse during maintenance treatment with antidepressant drugs in the residual phase (Paykel & Tanner, 1976).

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