Elsevier

Psychiatry Research

Volume 262, April 2018, Pages 469-476
Psychiatry Research

Number of illness episodes as predictor of residual symptoms in major depressive disorder

https://doi.org/10.1016/j.psychres.2017.09.026Get rights and content

Highlights

  • More than half of participants experienced depressive residual symptoms between episodes.

  • Insomnia, anxiety, psychomotor retardation, and guilty were the most reported residual interepisodic symptoms.

  • The number of previous illness episodes was a significant predictor of residual symptoms.

Abstract

Notwithstanding major depressive disorder (MDD) is a recurring and chronic condition, relatively few variables have consistently been shown to predict its course. Residual depressive symptoms may be associated with disability and functional impairment but few studies evaluated clinical correlates associated with these symptoms and their impact on functioning after adjustment for potential confounders. Therefore, our study aimed to investigate factors associated with residual depressive symptoms and their impact on the course of MDD. The sample consisted of 210 consecutive MDD euthymic outpatients (67.6% females; mean age = 52.1 ± 15.5), admitted to the Section of Psychiatry, University of Genoa (Italy). Residuals depressive symptoms were significantly associated with female gender; use of short half-life benzodiazepines; longer duration of the current depressive episode; higher number of illness episodes; and higher duration of illness. Conversely, prior treatment with first-generation antipsychotics, later age of illness onset and first hospitalization were less frequently observed among patients with residual symptoms. After multivariate analyses, only duration of current illness episodes (ß = 0.003; p = <0.005) and substance abuse (ß = 0.042; p = <0.05) remained significantly associated with residual symptoms. Our findings indicate that residual depressive symptoms conferred a pernicious illness course in this specific cohort of MDD patients. Future trials mainly targeting these burdensome symptoms are warranted.

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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