Number of illness episodes as predictor of residual symptoms in major depressive disorder
Introduction
Major depressive disorder (MDD) is a phenotypically heterogeneous condition that may encompass a myriad of cognitive, affective and somatic manifestations (American Psychiatric Association, 2013). In addition, up to 15.0% of the population may be affected by a lifetime major depressive episode, and MDD is associated with impaired functioning and quality of life as well as significant morbidity and excess mortality (Walker et al., 2015, Kessler and Bromet, 2013, World Health Organization, 2012). Approximately 20% of patients completely recover from depression without any recurrence whereas the remaining 80% experience at least one relapse/recurrence during the lifetime clinical course of this condition (Fava et al., 2006, Petersen et al., 2001)
However, consistent evidence indicated that the course of MDD is significantly heterogeneous, with some individuals presenting a more recurring course associated with cognitive deterioration and functional impairment when compared to others (Musliner et al., 2016, Li et al., 2014, Evans et al., 2014). MDD may be conceptualized as a neuroprogressive disorder, particularly in the subset of patients with a more recurring course characterized by shorter periods of remission, treatment resistance and more severe functional impairment (Moylan et al., 2013, Kessing and Andersen, 2017) even during remission. These patients commonly continue to experience significant functional impairment (Trivedi et al., 2010) which challenges the conventional definition of euthymia (Fava and Bech, 2016).
While according to the study of Tondo et al. (2014), seven factors (a) ≥ 4 previous depressive episodes, (b) suicidal acts, (c) cyclothymic temperament, (d) family history of bipolar disorder, (e) substance-abuse, (f) younger-at-onset, or onset-age < 25, and (g) male sex; four of these (c, d, f, g)) have been reported as significant and independent predictors of bipolar disorder in a large sample (N = 2146) of patients with a first-lifetime depressive episode, addressing differentiation of bipolar from major depressive disorders and contributing to guiding prognosis and clinical management, relatively few studies have investigated factors associated with a more severe course of unipolar depression. Evidence indicates that only 30% of patients with a major depressive episode achieve remission after the initial trial with a first-line antidepressant agent (Carvalho et al., 2014, Greden, 2013, Thase, 2010, Trivedi et al., 2006). Therefore, a meaningful subset of patients with MDD experience residual symptoms of depression, also known as subsyndromal manifestations of MDD. Hence, even during full affective remission, patients with MDD often experience 1 (median: 2–4) affective residual symptoms (Nierenberg et al., 2010, Iovieno et al., 2011, Conradi et al., 2011).
The most frequently endorsed affective symptoms are sleep dysfunctions, lack of energy, cognitive problems, and appetite/weight disturbances (Nierenberg et al., 2010, Iovieno et al., 2011, Conradi et al., 2011). Although evidence suggests that residual symptoms may confer a higher risk for relapses/recurrences as well as significant psychosocial impairment (Culpepper et al., 2015), relatively few studies have investigated potential correlates and predictors of residual symptoms in MDD.
Therefore, the current study aimed first to explore the correlates and associated features related to the presence of MDD residual symptoms in a large outpatient sample after achievement of euthymia. Here, our purpose was mainly to explore the existence of potential predictors associated with residual depressive symptoms with particular regard to lifetime psychotic symptoms, substance abuse, age at illness onset and age at first treatment, recent life events, family history of psychiatric disorders, duration of illness, and number of illness episodes together with their impact on the course of MDD.
Section snippets
Methods
This naturalistic cohort study included a sample of 210 currently euthymic outpatients with MDD, of which 68 males (32.4%) and 142 females (67.6%) with an age ranging from 18 to 65 years (mean = 52.1 ± 15.5). Participants, who were currently in euthymic phase, had the following psychiatric diagnoses when admitted: 93.3% with major depression recurrent episode and 6.7% with dysthymia together with major depression (double depression). Participants were all consecutive outpatients receiving only
Socio-demographic and clinical variables in patients with and without residual interepisodic depressive symptoms
We initially screened a sample of 247 patients; however, only 210 subjects voluntary accepted to participate in the study. Thus, we have a 85.02% participation rate for the present study. The present sample of currently euthymic patients was consecutively recruited at the Section of Psychiatry, outpatient service, Department of Neuroscience (DINOGMI), University of Genoa (Italy), included 68 males (32.4%) and 142 females (67.6%). All participants were recruited directly from our catchment area
Discussion
The present study, conducted on a sample of 210 unipolar depressed patients, found that more than half (exactly, 57.6%) of subjects experienced depressive residual symptoms between episodes. This result is in line with existing reports of the current literature upon the main topic (van der Voort et al., 2015, Rush, 2015, Dennehy et al., 2014, IsHak et al., 2013, Thase, 2010, Trivedi et al., 2010, Trivedi et al., 2009, Trivedi et al., 2006), and confirms that a substantial proportion of unipolar
Acknowledgements
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare no conflicts of interest. The authors sincerely thank Prof. André Carvalho for his help and valuable supervision of the present manuscript.
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