Women Twice as Likely to Develop Depression After Stroke

Damian McNamara

February 19, 2019

Women are twice as likely to develop severe depressive symptoms after stroke compared with their male counterparts, new research shows.

In findings that have important clinical implications, investigators found more than 20% of women developed severe depression post-stroke compared to 10% of their male counterparts. The researchers also note that depression severity was linked to a greater mortality risk.

"Although the association between severe depression symptoms and mortality in patients with stroke has been reported, the sex differences and differential trajectories of symptoms over time demonstrated in this study have, to our knowledge, not been previously explored," the researchers note.

"There are heterogeneous patterns of progression in depression symptoms after stroke," principal investigator Salma Ayis, PhD, of the School of Population Health and Environmental Sciences, King's College London, United Kingdom, told Medscape Medical News.

For example, said Ayis, while the severity of symptoms of depression tended to remain the same among women, moderate symptoms in men were more likely to worsen over time.

The study was published online January 7 in the European Journal of Neurology.

Depression After Stroke Common

Depression after a stroke is common, affecting approximately 1 in 3 people. In addition, most studies report a higher prevalence among women compared to men.

"Women are thought to report their symptoms more often than men, and they do have hormonal changes during various stages in life that may have a role in making them more susceptible to depression," Ayis said.

"In addition, women may differ in how they value their social roles that may be challenged by mental and physical limitations as a result of stroke and the harm it causes to the brain."

Due to these and other factors, the investigators hypothesized there would be sex differences with respect to depression after stroke, she added.

Even though previous evidence supports a difference between how men and women experience post-stroke depression, there is "no consistency across studies," Ayis said.

In general, she added, looking at patients as a single group, even in longitudinal studies, does not help reveal important details in the progression of symptoms. Differing methods for assessing depression and patient characteristics also adds to the lack of consensus in the literature, she said.

Instead of merely comparing women to men, the investigators assessed different trajectories of post-stroke depression within each sex.

Longitudinal Data

The researchers analyzed data in individuals from the South London Stroke Register who suffered a stroke between 1998 and 2016. The cohort included 1275 men and 1038 women. In addition to depression trajectories, the investigators also looked at 10-year all-cause mortality.

Sociodemographic, stroke severity and clinical measures were collected during the acute phase. The Hospital Anxiety and Depression Scale (HADS) was used to screen for depression 3 months post-stroke and annually thereafter.

The investigators used group-based trajectory models to identify trajectories of depression and Cox proportional hazard models to study mortality risk.

They identified three distinct trajectories among men in the study: low and stable depressive symptoms (42.1%), moderate increasing symptoms (46.5%), and severe, persistent symptoms (11.4%).

In women, the results showed four trajectories: low symptoms (29.1%), moderate (49.8%), severe (16.3%), and very severe depressive symptoms (4.8%).

Results showed the severe persistent depression group of men and the severe and very severe groups of women had average scores that met HADS criteria for major depression.

Not surprisingly, patients with more depressive symptoms also experienced more incontinence, physical limitations and lack of orientation in the acute phase.

Increased Mortality Risk

Risk of 10-year all-cause mortality increased as symptoms of depression increased for both sexes.

The 10-year adjusted mortality hazard ratios in men were 1.68 (95% confidence interval [CI], 1.38 - 2.04) and 2.62 (95% CI, 1.97 - 3.48) in men with moderate and severe symptoms, respectively, compared with their counterparts who had low/stable depressive symptoms.

In women, the adjusted mortality hazard ratios were 1.38 (95% CI, 1.09 -1.75), 1.65 (95% CI, 1.23 - 2.20) and 2.81 (95% CI, 1.90 - 4.16) for moderate, severe, and very severe symptoms, respectively, compared to women with low symptoms.

Based on these findings and those from other studies, neurologists and other physicians should regularly monitor stroke patients for depression, said Ayis.

The higher prevalence of depression among women may also reflect the higher prevalence in the general population, the researchers note.

Study strengths included the use of long-term follow-up data from an established stroke registry; a completion rate of HADS exceeding 75%; and use of group-based trajectory models "to unmask the heterogeneity in the developmental course of depression by sex."

A loss to follow-up of approximately 20% was a potential limitation. However, the researchers note, "estimates in the main baseline characteristics from patients with complete data showed no significant differences from those lost to follow-up, suggesting that 'missingness' is likely to be missing at random and not systematic."

Randomized controlled trials to establish the efficacy of different interventions could be a next research step, Ayis said. Future studies may reveal interventions that work better for women or men as well.

Anticipated interventions would not necessarily be limited to medications but include a multipronged approach that could encompass social and psychological elements, she added.

Important Clinical Implications

Commenting on the findings for Medscape Medical News, James H. Bernheimer, MD, a neurologist at The Neurology Center at Mercy Medical Center in Baltimore, Maryland, said the study has important clinical implications.

"Survival is always less in patients with severe depression symptoms because of suicide risk, but in stroke it is particularly important because anhedonia — the depression symptom associated with a lack of drive to do anything — can interfere with therapy and recovery," said Bernheimer, who was not involved with the current research.

Treating depression in stroke patients can be very important, Bernheimer said, and "this study suggests we should be more vigilant about screening for depression symptoms in women who have had strokes."

Also commenting on the study findings, Bruce Volpe, MD, professor at the Feinstein Institute for Medical Research in Manhasset, New York, said, previous evidence suggests there are gender-related disadvantages for women with stroke.

"Some studies showed that while women may have a lower age-adjusted incidence of stroke, other studies showed that their outcome was significantly worse than men along scales that measure activity limitations, quality of life, and, apropos the study by Ayis et al., post-stroke depression," said Volpe, who was also not involved with the current study. 

Volpe applauded the investigators for the comprehensive review and "elegantly" analyzing outcomes to confirm that "post-stroke depression in its most severe form affects women preferentially."

One powerful message for the clinician is treat — perhaps aggressively —those with post-stroke depression, Volpe said.

"For the clinician scientist, the report prompts curiosity. With the opportunity offered by the data in over 2000 records, why not also look for serum markers of persistent inflammation?" Volpe said. "Recent studies suggest tantalizing clues for cryptic brain impairment secondary to nonresolving inflammation. Maybe that is their next paper?"

The study was funded by Guy's and St Thomas' Hospital Charity; The Stroke Association; The Department of Health/Healthcare Quality Improvement Partnership, UK; and the National Institute for Health Research Programme.

Ayis, Bernheimer, and Volpe have disclosed no relevant financial relationships.

Eur J Neurol. Published online January 7, 2019. Abstract

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