Depression More Severe, Persistent in the Elderly

Batya Swift Yasgur, MA, LSW

June 21, 2018

Older adults with major depressive disorder (MDD) have a substantially worse prognoses than their younger counterparts, new research suggests.

A 2-year observational study showed that the course of MDD worsened linearly with age, such that individuals aged 70 years and older had the worst outcomes. These findings persisted after the researchers adjusted for clinical, social, and health factors.

"Because the course of major depressive disorder is more unfavorable in old age, it might be worthwhile to treat depression more intensively," lead author Roxanne Schaakxs, PhD, of the Amsterdam Public Health Research Institute, Department of Psychiatry, VU University Medical Center, the Netherlands, told Medscape Medical News.

"For example, we might use a multidisciplinary approach with strict monitoring, in which multiple health professionals are involved and cooperate," she said.

The study was published online June 7 in Lancet Psychiatry.

Inconsistent Methodology

It is expected that almost one fifth of adults will have at least one episode of MDD at some point during their lives, but the course of such episodes "can be highly variable," the authors write.

Previous studies, said Schaakxs, show that the course of MDD is more unfavorable in older age. However, she noted that studies with "solid methodology" that carefully take into account other prognostic factors are lacking.

In previous studies, "age groups were often inconsistent — for example, one study would classify a 55-year-old as 'young,' where another would classify the person as 'old' — making it hard to compare the studies and obtain a clear conclusion," she added.

"We wanted to confirm the idea of a more unfavorable course in older age because, if differences between age groups truly exist, it is important to tailor depression treatment according to age."

The authors note that what was needed was "a large-scale study that includes a broad age range and consistent course assessments."

To accomplish that, they used data from two cohort studies: the Netherlands Study of Depression and Anxiety (NESDA), and the Netherlands Study of Depression in Older Persons (NESDO).

The studies included a total of 1042 participants aged 18 to 88 years (66% women).

Individuals of insufficient capacity to participate in the study, those who had received a primary clinical diagnosis of dementia, or those who had a severe psychiatric disorder other than depressive and anxiety disorders were excluded. Participants were also required to be outpatients.

At baseline, the DSM-IV-based Composite International Diagnostic Interview (CIDI, lifetime version) was used to determine presence of depression, and the self-report Inventory of Depressive Symptomatology (IDS-SR) was used to assess depression severity.

The CIDI and IDS-SR were also used to ascertain the presence of depression and, if present, the severity of depression at the 2-year follow-up. The Life Chart Interview was used to assess for the presence of depressive symptoms between the two time points.

The researchers used four indicators to capture various ways that depression can develop over time: the presence of 6-monthy depression diagnoses (MDD, dysthymia, or both) after 2 years (assessed with the CIDI); a chronic course of depressive symptoms (assessed with the Life Chart Interview); time to remission (assessed with Life Chart Interview data); and depression severity change, defined as the depression severity score at 2-year follow-up minus the baseline depression severity.

The researchers also recorded participants' psychosocial factors (loneliness, social network size, and social support); health factors (functional limitations, pain, chronic diseases, and body-mass index); antidepressant use; the presence of anxiety disorder; and previous history of a MDD episode.

Surprising Findings

Older age was found to be significantly associated with a worse 2-year course for all four indicators (MDD diagnosis: odds ratio [OR], 1.08; 95% confidence interval [CI], 1.00 - .1.17; chronic symptom course: OR, 1.24; 95% CI, 1.13 - 1.35; time to remission: hazard ratio [HR], 0.91; 95% CI, 0.87 - 0.96; depression severity change: regression coefficient, 1.06; P < .0001 [all per 10-year increase]).

The course of MDD worsened linearly with increasing age.

These age-related effects were found in two indicators: the presence of a chronic course of depression, and mean depression severity change; dysthymia was the predominant driver of the presence of depression.

Individuals aged 70 years or older had worse outcomes than those aged 18 to 29 years; the latter group was considered the reference group (MDD diagnosis: OR, 2.02; 95% CI, 1.18 - 3.45; chronic symptom course: OR, 3.9, 95% CI, 1.74 - 5.84; time to remission: HR, 0.60; 95% CI, 0.44 - 0.83).

The depression severity change was -12.64 (SD, 10.85) in those aged 18 to 29 years, compared to -5.57 (SD, 11.14) in those aged 70 years or older (adjusted means).

These results were slightly reduced but still persisted; they remained significant for three of the four indicators, even after the researchers adjusted for prognostic clinical, social, and health factors.

However, for the indicators of any depression (as well as MDD and dysthymia separately), the associations with age lost significance, owing to the adjustment for loneliness.

"The fact that we found older persons to show a more unfavorable course was not really surprising, as we expected this, based on previous studies," Schaakxs commented.

"However, we were surprised to find that none of the prognostic psychosocial, clinical, or health factors included in our study explained this more unfavorable course," she added.

New Treatment Avenues

Commenting on the study for Medscape Medical News, John Zajecka, MD, associate professor of psychiatry and clinical director of the Depression Treatment and Research Center at Rush University Medical Center, Chicago, Illinois, who was not involved in the study, said the study "reinforces the notion that traditional antidepressants may not work in all people."

Recent research into the biological mechanisms of depression, including the role of inflammation, glutamate, and endogenous opioids, may facilitate expansion of the treatment armamentarium into new avenues with potential utility in the geriatric population, he said.

Zajecka suggested a treatment approach similar to that taken in hypertension, cancer, or infectious diseases, "where we may need to combine different treatments to achieve the desired outcome, which is complete remission."

Nonpharmacologic somatic interventions and evidence-based psychotherapies may have utility, especially in combination with pharmacotherapy, he noted.

He advised clinicians to "tailor treatment to individual patients, not only in the elderly but in all of our patients, and think outside the box, since the elderly may be a tougher population to treat."

He added that these patients "must be watched very carefully so we can intervene quickly if we see any early signs of relapse or recurrence."

In an accompanying editorial, Tze Pin Ng, PhD, of the Department of Psychological Medicine, Young Loo Lin School of Medicine, National University of Singapore, notes that the study may have underestimated effects of medical comorbidity in explaining the poorer prognostic outcome and that it did not sufficiently account for cognitive impairment, which "hampers recovery from MDD" and reduces treatment effectiveness.

Schaakxs acknowledged this limitation.

"One factor especially suitable for future research into this association is cognitive decline," she said.

"We could not include this factor in our analyses because it was not assessed in the younger persons, although older persons who were suspected to have dementia were not included in our study," she said.

NESDA was funded by the Netherlands Organization for Health Research and Development, with financial contributions by participating universities and mental health care organizations, which are listed in the original article. NESDO was funded by the Fonds NutsOhra, Stichting tot Steun VCVGZ, NARSAD the Brain and Behaviour Research Fund and participating universities and mental health care organizations, which are listed in the original article. One of the study authors received funding from the European Union 7th Framework Programme. Dr Schaakxs has disclosed no relevant financial relationships. The other authors' disclosures are listed on the original article. Dr Zajecka has received research support from AstraZeneca, Cyberonics, ElMinda, Forest, Hoffman-LaRoche, Otsuka, Shire, and Takeda. Dr Ng has disclosed no relevant financial relationships.

Lancet Psychiatry. Published online June 7, 2018. Abstract, Editorial

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