Best Treatment for Post-Stroke Depression Still Unclear

Damian McNamara

February 07, 2020

Choosing the best treatment option for post-stroke depression remains more art than science, with little evidence to support one therapeutic approach over another, new research shows.

A Cochrane review showed "very low certainty of evidence" when evaluating pharmacologic treatments, noninvasive brain stimulation, psychological strategies, or a combination of these approaches, the investigators report. However, there was a suggestion that combining antidepressants with other therapies may offer a small edge, senior investigator Maree Hackett, PhD, told Medscape Medical News.

"We now have evidence of a small benefit of talk therapies, noninvasive brain stimulation, and combination treatments for reducing depressive symptoms, such as combining antidepressants with talk therapy or noninvasive brain stimulation," she added.

In addition, the picture remains unclear with respect to adverse effects of various treatment types, she said.

In many cases, "risks were not well recorded in those trials," said Hackett, who is head of the mental health program and professor on the Faculty of Medicine at the University of New South Wales, Sydney, Australia.

The findings were published online January 28 in the Cochrane Database of Systematic Reviews.

Common Shortcomings

Hackett noted that many new randomized controlled trials have "the same shortcomings of older trials," including small numbers of participants, very select participants, poor recording or reporting of adverse events and other risks, and multiple measures for the depression endpoints without a priori identification of a primary depression outcome measure.

"This makes it very difficult to be certain the results from these trials will be applicable to the wide range of people who have stroke," she said.

The researchers state that they conducted an updated Cochrane review because, "[a]lthough depression may influence recovery and outcomes following stroke, many (perhaps most) people with stroke do not receive effective treatment because their mood disorder is undiagnosed or is inadequately treated."

Previous research suggests that 25% of stroke patients are not screened for depression. In addition, only 60% who are diagnosed with depression receive support, including antidepressant prescriptions after hospital discharge. Other studies have suggested that some patients benefit from long-term prescription of antidepressants, but that there is "little attempt to match prescribing to need."

To learn more, the investigators reviewed the evidence to determine which treatments reduced the prevalence of diagnosable post-stroke depression. Neurologic function and health-related quality of life were secondary outcomes.

The review included 49 trials from Asia, Europe, North America, and Australia that had a total of 3342 participants (mean age range, 55 – 78 years).

Few or No Data

Some trials featured more than one comparison. Of 56 total comparisons in the review, 20 were pharmacologic comparisons; eight were noninvasive brain stimulation comparisons; 16, psychological therapy comparisons; and 12, combination therapy trials. Most trials included participants with ischemic stroke.

In general, when the investigators compared the evidence among different treatment strategies for reducing symptoms of post-stroke depression, after improving neurologic function and/or decreasing risk for adverse events, they came up short.

Most outcomes had a "very low certainty of evidence" or no available data, including the main outcome of pharmacologic treatment vs placebo for post-stroke depression.

When examining noninvasive brain stimulation and comparing it to sham brain stimulation and/or usual care, either no data were available, or there was a very low certainty of evidence.

The situation was similar for comparisons of various combinations of psychological therapy, medications, and noninvasive brain stimulation.

In addition, there was very low certainty of evidence that the various treatment options improved health-related quality of life.

Proceed With Caution

Because the evidence does not provide strong guidance on the best therapeutic option, "cautious treatment for those with obvious depression is justified," Hackett said.

"Antidepressant drugs may benefit people with persistent depressive symptoms after stroke, but care is required in their use, as little is known about their side effects" in this population, the researchers write. They add that psychological therapy could also be considered.

The investigators note that future studies of post-stroke depression should include larger numbers of patients and that more research is needed before any recommendations about optimal treatment choice can be made.

"We need research to identify who might benefit without unacceptable risks," Hackett said. Moreover, high-quality trial results are needed to assess newer interventions, said Hackett.

"There are other treatment options that can be explored in people with stroke ― home transcranial direct current stimulation, electronic interventions, including teletherapy, and online self-help, guided or not," she said.

"We also have very little idea about what might work in low-resource settings, especially where there isn't reliable and affordable access to talking therapies or antidepressants."

Worthwhile Research

Commenting on the findings for Medscape Medical News, Bruce Volpe, MD, professor at the Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, said that any research into a difficult question is worthwhile.

"Depression is a serious problem after a life-altering catastrophe like having a stroke," said Volpe, who was not involved with the research.

Because the trends were positive across all the studies, "it behooves investigators to try a combination of treatments ― drugs plus cognitive therapy plus device treatment," he said.

The systematic review does not analyze the quality or degree of depression and provides no guidance about when treatment is warranted.

"It might be a normal response to a life-altering event to feel 'down' or 'blue,' " he said.

Volpe also noted that the review does not address of the influence of gender on post-stroke depression and its potential impact on treatment response. As previously reported by Medscape Medical News, women are twice as likely to suffer from post-stroke depression as men.

The research was supported by the George Institute for International Health, Australia; the Stroke Society of Australasia; the Academic Unit of Psychiatry at the University of Leeds in the United Kingdom; the Department of Clinical Neurosciences at the University of Edinburg; and the Clinical Trials Research Unit at the University of Auckland, New Zealand. Hackett and Volpe have reported no relevant financial relationships.

Cochrane Database Syst Rev. Published online January 28, 2020. Abstract

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