Background
Late-life depression is a complex mood disorder with various etiological pathways [
1] and high comorbidity with psychiatric and physical diseases, and cognitive decline [
2-
5]. Late-life depression often has a chronic course and high relapse rates [
6-
15], probably worse compared to younger age groups [
16]. Previous studies were predominantly performed in community based or primary care samples, and some of them were targeting depressive symptoms or sub threshold depression, and not depression diagnoses according to formal diagnostic criteria. However, Beekman et al. [
6] showed a gradient with respect to the prognosis of late-life depression, in which those with sub threshold disorders had the best outcome, followed by those with major depressive disorder (MDD), dysthymia and double depression (MDD and dysthymia). Only a few studies investigated the naturalistic course of late-life-depression in a large sample of older persons with formal depression diagnoses. Magnil et al. [
15] observed the two-year course of depression in a cohort of primary care patients aged 60 years and older and found that, 15 of the 51 depressed patients (29%) had a remitting course, 25 (49%) remained depressive, and 11 (22%) had a fluctuating course. Hybels et al. [
13] were the first to study the course of severe depression in older patients. They found that it took patients with a double depression longer to reach partial or full remission, and that they had higher MADRS (Montgomery–Åsberg Depression Rating Scale) scores after 3 years, compared to those with major depression alone. So, the results suggest that the course of late-life depression in patients from mental health institutions may be as poor as in patients from general practitioners or community based samples. However, more studies among clinically depressed patients are necessary to confirm this assumption.
For a better scientific and clinical understanding of the poor prognosis of late-life depression, it is important to study the clinical determinants of its course. This may help us to improve the treatment of late-life depression and to develop tailor made interventions. Among younger adults, clinical characteristics of the depression such as the severity of the depressive disorder, comorbid anxiety symptoms and age of onset are consistently found to be important predictors of the course [
16-
18]. Increased time to recovery from late-life depression is previously found to be associated with severity of depressive symptoms [
19], but also with chronicity, later age of onset, cognitive decline [
19,
20] and medical comorbidity [
21]. To date there are few longitudinal studies that included sufficient numbers of clinically depressed older persons enabling to study the course and determinants of the course of late-life depression. In the Netherlands Study on Depression in Older Persons (NESDO) depressed patients were included from both mental health care facilities and general practitioners, thus including depressed patients in various developmental and severity stages [
22]. We now have 2-year follow-up data available, which offers us the possibility to study the two-year course of late-life depression and its determinants in our cohort.
The aims of the present study were twofold. First, we examined the course of depression during 2-year follow-up in a sample of clinically depressed patients, and second we studied which socio-demographic and clinical characteristics predicted a depression diagnoses at 2-year follow-up. Based on the literature we expected to find a high percentage of persons that are also depressed after 2-year, and that the severity of the depression and physical comorbidity would be important determinants of the poor outcome.
Discussion
Our study showed that in a sample of clinically depressed older patients nearly 50% still had a depression diagnoses at 2-year follow-up. Of our patients 61% showed a chronic course of the depressive symptoms during the two-year period. Patients with more severe depressive symptoms, comorbid dysthymia, younger age of onset and more chronic diseases were more likely to be depressed at 2-year follow-up.
Our findings are largely in line with expectations from community based, primary care and other clinical samples of older persons [
6,
10,
13,
15,
32]. Consistent with the findings of Hybels et al. [
13], we found that the persons with a double depression (MDD and dysthymia) had the poorest prognosis, with 59% still suffering from a depressive disorder at two years follow-up. Compared to studies among adults aged 18 to 65 years, our remission rates seem somewhat lower. In the Netherlands Study on Depression and Anxiety (NESDA) [
18], which has a comparable design and uses largely the same instruments as in NESDO, about 80% of the purely depressed patient reached remission within 2 years, whereas from the persons with a comorbid anxiety disorder only 50% reached remission within that time frame. In our study, 36.8% of the depressed persons had a comorbid anxiety disorder, however, comorbidity was no predictor of a depression diagnoses at follow-up. Thus, we may conclude that our study confirms the poorer prognosis of depression in terms of chronicity among older persons compared to younger adults.
Since we assessed the severity of depressive symptoms every 6 months, it was possible to study the course of depression in more detail. Of the depressed patients, 61% showed a chronic course of the depressive symptoms during the two years of follow-up, whereas 20% had intermittent depressive symptoms. These findings suggest that most patients had clinically relevant levels of depressive symptoms all the time during this 2-year period, further stressing the persistence and chronicity of the depressive symptoms, despite the fact that most of them were being treated in mental health care facilities. Only 19% of the depressed older people reached complete remission, whereas 56% of the persons without a depression diagnoses at follow-up still had residual depressive symptoms.
With respect to the determinants of the prognosis of depression we found that patients with more severe depression at baseline, comorbid dysthymia, younger age of onset and more chronic diseases were more likely to be depressed at 2-year follow-up. None of the socio-demographic variables appeared to be a predictor of the prognosis, neither was comorbid anxiety disorder or cognitive functioning. Our findings are partly in line with previous studies that reported severity and chronicity of depressive symptoms [
19] and medical comorbidity [
21] to be related with an increased time to recovery. In contrast with Alexopoulos [
19] however, we found an early onset of depression to be associated with poor prognosis. Also in contrast with our results, Bogner [
14] showed in the PROSPECT study that married patients had a favourable course of depression, suggesting that depressed persons with a supportive relationship improve more quickly. In our study, partner status was not statistically significant. This may be the due to the severity of depression, our sample was mainly recruited in in- and outpatients facilities, whereas the PROSPECT sample was recruited in primary care.
Although we included important socio-demographic, and clinical characteristics as possible determinants for the prognosis of depression, additional key biological, health and psychosocial determinants may be of relevance for the prognosis of depression. However, before conducting such in-depth analyses in the NESDO sample, we needed detailed insight in the course of late-life depression and its socio-demographic and clinical determinants, as was the aim of the present paper.
Attrition is an inevitable problem in studies among vulnerable older persons. We made extensive efforts to contact and invite persons to participate in the study and offering them shortened interviews when necessary. We kept in touch with all participants every half year and send them yearly newsletters. Nevertheless, the attrition at 2-year follow-up was highest in the depressed group 24.6% compared to 12.1% in the non-depressed control group. In the depressed group 28% died and 37.6% did not want to participate due to mental reasons. Unfortunately attrition was selective; attrition was higher among persons who were depressed at baseline and who had severe psychopathology, lower cognitive functioning, and were recruited from outpatient or inpatients mental health care settings. In the aforementioned comparable NESDA study among younger adults aged 18–65, the two-year attrition rate was 12.9% which was relatively low compared to other epidemiological studies in psychiatric samples and was mainly due to refusal to further participate [
33]. Among older adults, attrition rates are expected to be higher, because of a higher risk for death and diseases compared to younger adults. In the Longitudinal Aging Study Amsterdam, a population based cohort study among older persons age 55 years and older, three-year attrition rates were around 19% and was mainly due to death [
34]. We may therefore conclude that the attrition rate in our study is not extremely high, when taking age and disease status of our sample into account, but it may limit the generalizability of the findings to some extent and needs to be reflected upon in future studies.
It should be noted that our findings cannot be generalized to community-dwelling older persons, as most of our patients were recruited from specialized mental health facilities and may represent a group with more refractory depression at baseline. However, we were especially interested in this group because patients with clinical depression are often underrepresented in community based samples. Thus far, few studies investigated the naturalistic course of late-life-depression in a large sample of older persons with formal depression diagnoses. Our findings are therefore important for clinical practice.
Clinical implications
As most of the diagnosed patients (85.3%) were under treatment when they entered the NESDO study, the results may tell us something about the adequacy of the depression treatment in this older age group. Regular interventions are mainly adapted from guidelines that are based on research performed in younger adults, assuming that depression in older persons has the same underlying mechanism as depression in younger adults. Although pharmacological and psychotherapy are effective treatments for late-life depression [
35,
36], it is suggested that antidepressants may be less efficacious in in older depressed patients compared to younger ones [
37,
38]. Moreover, studies are generally limited to the youngest old, reflected by average samples ages below 70 years and minimal physical comorbidity [
36].
In older persons, depression treatment may need to be tailored to address underlying etiological factors and comorbidity as well. The group of Alexopoulos [
39] developed a personalized intervention for depressed patients with severe chronic obstructive pulmonary dysplasia (COPD) and showed that this intervention reduced depressive symptoms and dyspnea-related disability more than usual care over 28 weeks. However, thus far there is only limited evidence that such a multifactorial personalized treatment is more effective than the regular treatment. Nevertheless, personalizing depression treatment seems necessary to improve the treatment of depression, especially in this older age group. Our results suggest that physical comorbidity may be candidate for adjusted and intensified treatment strategies of older depressed patients with chronic and complex pathology.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
HCC, principle investigator of NESDO, was responsible for the conception and the design of the study and the acquisition of the data. She wrote the paper and supervised the data-analyses. JN supervised the data collection, performed the overall data management, and carried out the data-analyses. RK contributed to the local data collection and co-authored the paper. HWJM was involved in the design of the study and co-authored the paper. RCM was involved in the conception and the design of the study, supervised the local data collection and co-authored the paper. PN was involved in the conception and the design of the study, supervised the local data collection and co-authored the paper. ROV was involved in the conception and the design of the study, supervised the local data collection and co-authored the paper. PV contributed to the local data collection and co-authored the paper. MWMW contributed to the local data collection and co-authored the paper. MLS was involved in the conception and the design of the study, supervised the local data collection and co-authored the paper. All authors read and approved the final manuscript.