Antidepressants Lack Effectiveness for Depression in Dementia

September 7, 2018

By Will Boggs MD

NEW YORK (Reuters Health) - Antidepressants provide little relief for depressed people with dementia, according to a systematic review.

"Studies that have come out in recent years all pointed toward the same conclusion," Dr. Robert Dudas from the University of Cambridge, in the U.K., told Reuters Health by email. "The findings are in line with our clinical experience, which is that antidepressants don't always work well for patients who have dementia in addition to their depression."

Depression appears to be common in people with dementia, though it can be hard to recognize, and it is associated with increased disability, poorer quality of life and shorter life expectancy. Whether antidepressants are effective in this setting remains unclear.

Dr. Dudas's team reviewed 10 studies with a total of 1,592 patients to evaluate the efficacy and safety of any type of antidepressant for patients who had been diagnosed as having dementia of any type and depression as defined by recognized criteria.

Based on high-quality evidence from eight studies, there was little or no difference in scores on depression symptom rating scales between antidepressant and placebo treated groups after six to 13 weeks, the researchers report in the Cochrane Database of Systematic Reviews, online August 31.

Moderate-quality evidence also suggested little or no difference between groups after six to nine months.

Moderate-quality evidence from four studies, however, indicated that remission rates at 12 weeks were significantly higher in the antidepressant group (40%) than in the placebo group (21.7%).

High-quality evidence showed no effect of antidepressants on performance of activities of daily living at weeks six to 13, and moderate-quality evidence showed little or no effect of antidepressants on cognition.

Participants on antidepressants seemed to be more likely to drop out of treatment, and adverse events emerged in significantly more patients on antidepressants (49.2%) than on placebo (38.4%). Heterogeneity in the way different studies reported adverse events limited the confidence of these analyses.

"It is important to be clear about the limited chances of improvement with treatment in this patient group," Dr. Dudas said. "One should be cautious not to overtreat patients. There is no clear evidence that any particular antidepressant is better than the others, so in someone with dementia and depression, you'd probably stop after trying one or two antidepressants."

"The choice is likely to be guided by the side effect profile of the drugs and the clinician's experience of prescribing them," he said. "Therefore, be careful that you aren't just giving the patient side effects from the medication."

"We clearly need more research and studies that are better designed and better reported," Dr. Dudas said.

Dr. Francesco Panza and Dr. Madia Lozupone from the University of Bari Aldo Moro's neurodegenerative disease unit, in Italy, who recently reviewed pharmacotherapy for the treatment of depression in patients with Alzheimer's disease (AD), told Reuters Health, "This (review) should be useful to ponder the prescription of antidepressant drugs in dementia and AD patients. Promising evidences might come from multimodal antidepressants - e.g., vortioxetine demonstrated a significant improvement in cognitive function (verbal memory and executive functioning) in older depressed patients - as novel drugs for treating depression in AD patients, such as from agents affecting glutamate transmission."

"Physicians have to remember that depression in AD may occur on a spectrum ranging from very mild 'sub-threshold' forms to major depression differing only quantitatively regarding severity of symptoms," they said in a joint email. "Moreover, depression in AD often manifests more in cognitive and somatic symptoms (so-called 'depression without sadness') that may not be ascertained by screening tools. Theoretically, this concern has the potential to obscure potentially useful benefits of antidepressants in patient subgroups."

"The lack of effective treatments does imply that a nonresponsive depressive mood (to conventional antidepressants) in dementia could be considered a treatment-resistant form of depression," they added.

Dr. Raj C. Shah from Rush University Medical Center, in Chicago, who has researched various aspects of late-life depression and its treatment, told Reuters Health by email, "The findings highlight the limitation of our current pharmacological treatment options for depression in the presence of mild-to-moderate dementia."

"The decision to start an antidepressant for depression in persons with dementia should be approached using shared decision making," he said. "If a choice is made to initiate an antidepressant, then monitoring should follow procedures in the clinical trials over 6 to 12 weeks and medications should be stopped if no improvement is noted after a particular observation time."

"We need to work on identifying markers to identify the persons living with dementia and symptoms consistent with depression who are most likely to benefit from treatment," Dr. Shah said. "While remission rates were higher in persons on treatment than placebo, the information is derived from a handful of studies and needs more confirmation. Real-world evidence on antidepressant treatment for depression in dementia is needed."


Cochrane Database Syst Rev 2018.

(c) Copyright Thomson Reuters 2018. Click For Restrictions -

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