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

Abstract

Staging has been increasingly used in unipolar depression since its introduction in the nineties. Several models are available, but their differential features and implications are not completely clear. We systematically reviewed: (a) staging models of longitudinal development of unipolar depression; (b) staging models of treatment-resistant unipolar depression; (c) their applications. MEDLINE, PsycINFO, EMBASE, and Web of Science were examined according to PRISMA guidelines from inception to December 2021. Search terms were: ‘stage/staging’, combined using the Boolean ‘AND’ operator with ‘psychiatric disorder/mental disorder/depressive/mood disorder’. A total of 169 studies were identified for inclusion: 18 described staging models or applications, 151 described treatment-resistant staging models or applications. Staging models of longitudinal development were found to play a key role in formulating sequential treatment, with particular reference to the use of psychotherapy after pharmacotherapy. Staging methods based on treatment resistance played a crucial role in setting entry criteria for randomized clinical trials and neurobiological investigations. Staging is part of clinimetrics, the science of clinical measurements, and its role can be enhanced by its association with other clinimetric strategies, such as repeated assessments, organization of problematic areas, and evaluation of phenomena that may affect responsiveness. In research, it may allow to identify more homogeneous populations in terms of treatment history that may diminish the likelihood of spurious results in comparisons. In clinical practice, the use of staging in a clinimetric perspective allows clinicians to make full use of the information that is available for an individual patient at a specific time.

Clinimetric Integration of Diagnostic Criteria for a Personalized Psychiatry

“…The model for unipolar depression included 5 stages: prodromal phase, acute major depressive episode, residual phase, dysthymia/recurrent major depression, and chronic major depressive episode [34]. This classification retained its basic structure in subsequent proposals [35]. Staging may be based on the longitudinal development of disorders, its progression in terms of severity and complications, or response to treatment.…”

“…For instance, according to the DSM-5 cross-sectional perspective [14], certain symptoms may not reach the diagnostic threshold of a disorder and be discarded as of minor value. Yet, with staging the same symptoms can be interpreted as residual after a course of treatment and may constitute a considerable risk for relapse [35]. Staging is thus uniquely geared to identifying individual trajectories.…”

“…Staging is thus uniquely geared to identifying individual trajectories. It provides room for the primary/ secondary distinction, regardless of the diagnostic threshold required by DSM-5 [35]. There appears to be a relationship between residual and prodromal symptomatology according to the rollback phenomenon: 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 [36].…”

Longitudinal Development of Symptoms and Staging in Psychiatry and Clinical Psychology: A Tribute to Giovanni Fava

“…Finally, only very recently, Cosci and Fava [35] published an updated systematic review of studies concerned with staging models in adult patients with unipolar depression, including an adapted version of their 2013 [17] model of staging unipolar depression: prodromal phase with either nonspecific symptoms or subthreshold depressive symptoms (stage 1); first major depressive episode (stage 2); residual phase, including nonspecific symptoms, residual depressive symptoms, and dysthymia (stage 3); recurrent or double depression (stage 4); and chronic major depressive episode (stage 5). Interestingly, the great majority of studies found in Cosci and Fava’s [35] 2022 review described models of staging treatment resistance, while only a minority dealt with staging models of longitudinal development of symptoms. Also, an additional staging model of tolerance to, and side effects of, antidepressant drugs was proposed by Cosci and Chouinard [36].…”

Discontinuation of Antidepressant Medications: A Significant Healthcare Problem Insufficiently Addressed by the NICE Guidelines

“…In addition, the NICE guidelines do not mention that withdrawal symptomatology may be associated with loss of treatment efficacy despite adequate adherence to the antidepressant treatment and lack of response to a previously effective antidepressant treatment when it was restarted, which is part of treatment resistance [21]. These clinical manifestations can deeply influence the individual trajectories of development of a mental disorder, representing the trigger to move to a different, and more severe or chronic, stage of the same illness [22]. In brief, clinicians must manage what is not mentioned in guidelines; most importantly when a drug is started, clinicians should know what may happen at dose decrease and drug discontinuation.…”