The prevalence of depression in patients with dementia is more than 20%, as reported by Ballard and colleagues in the June 1996 issue of the International Journal of Geriatric Psychiatry. The first-line treatment is often a selective serotonin reuptake inhibitor or a noradrenergic and specific serotonergic antidepressant. However, a 2002 Cochrane review by Bains and colleagues found that the evidence of the effectiveness of antidepressants in dementia was weak.
This multicenter, parallel-group, double-blind, placebo-controlled, randomized trial by Banerjee and colleagues assesses the efficacy and safety of sertraline, a selective serotonin reuptake inhibitor, and mirtazapine, a noradrenergic and specific serotonergic antidepressant, compared with placebo for the treatment of depression in patients with dementia.
Antidepressants may provide little benefit but appear to increase adverse effects in individuals with dementia and comorbid depression, suggesting that clinicians should reconsider use of these agents in this population, new research suggests.
In a randomized, controlled trial of more than 300 elderly patients with probable or possible Alzheimer’s disease (AD), those who were treated with sertraline or mirtazapine showed no significant difference in depression reduction after 3 months compared with the placebo group. In addition, individuals receiving active treatment reported more moderate and severe treatment-associated adverse events.
“I am surprised by just how unequivocal our findings are,” lead author Sube Banerjee, MD, professor of mental health and aging at King’s College London, Institute of Psychiatry, United Kingdom, told Medscape Medical News.
On the basis of these results, the investigators recommend clinicians “reframe” the way they treat these patients and “reconsider routine prescription of antidepressants.”
“The present practice of use of these antidepressants with usual care for first-line treatment of depression in Alzheimer’s disease should be reconsidered,” they write.
The study was published online July 18 in The Lancet.
Commonly Prescribed Agents
According to the study, dementia affects 35 million people worldwide and costs “1% of global gross domestic product every year.” There is also a more than 20% prevalence of depression in these patients.
“Depression is one of the most important comorbidities in dementia. It is a source of great distress yet the treatments we use are not proven,” said Dr. Banerjee.
The study’s aim was to assess efficacy and safety of “2 of the most commonly prescribed drugs,” explain the researchers.
The Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) included 326 elderly patients (mean age, 79 years) between January 2007 and December 2009 from 9 centers providing old-age psychiatry services in England.
All participants were diagnosed with comorbid depression for 4 or more weeks and had a score of 8 or more on the Cornell scale for depression in dementia (CSDD). Participants were randomly assigned to receive 150 mg of sertraline (n = 107, 68% female), 45 mg of mirtazapine (n = 108, 71% female), or placebo (n = 111, 64% female) daily.
Reduction in CSDD score at 13 weeks was the primary outcome measure. CSDD score and adverse events at 39 weeks were among the secondary outcomes.
No Between-Group Benefits
Results showed that although the CSDD scores decreased for all groups at 13 weeks, there were no significant differences between those receiving sertraline or mirtazapine compared with those receiving placebo (mean difference, 1.17 and 0.01, respectively) or compared with each other (mean difference, 1.16).
There were also no significant between-group differences in CSDD scores at the 39-week check-point.
In addition, significantly fewer patients receiving placebo reported adverse reactions compared with those receiving sertraline (26% vs 43%; P = .010) or mirtazapine (41%; P = .031).
Gastrointestinal reactions, especially nausea, were the most common events reported by those receiving sertraline, and drowsiness and sedation were the most commonly reported by those receiving mirtazapine.
Compared with both treatment groups, the placebo group also had significantly less severe adverse events (P = .003).
A total of 15 participants died by the 39th week, 5 in each treatment group.
“The message is to think before using antidepressants for depression in dementia. It may well be that these symptoms will resolve with the problem-solving and information-giving that is implicit in good-quality dementia care,” added Dr. Banerjee.
Furthermore, the investigators suggest that antidepressants be reserved for “individuals whose depression has not resolved within 3 months of referral, apart from those in whom drug treatment is indicated by risk or extreme severity.”
Largest Trial to Date
In an accompanying editorial, Henry Brodaty, MD, from the Brain and Aging Research Program and Primary Dementia Collaborative Research Center at the University of New South Wales in Sydney, Australia, notes this study is the “largest trial of antidepressant drugs in dementia ever and almost equalling the combined total of previously published work.”
Although negative, he adds, the findings are important because depression in dementia is common and results from previous trials looking at this issue are “unconvincing.”
“The absence of efficacy of antidepressants in the [study’s] dementia population raises questions about whether there are different pathogenic mechanisms at play in depression in Alzheimer’s disease,” writes Dr. Brodaty.
He points out that the study recommends “a stepped care approach of watchful waiting, followed-up by low-intensity psychosocial interventions and, if unsuccessful, by more complex and intense interventions.”
Dr. Brodaty also stresses that the trial does not advocate the abandonment of antidepressants in these patients.
Rather, he notes, the trial data underscore “the need for clinicians to think about creative alternatives to drug treatment for management of depression in people with dementia, and to use evidence-based techniques and partnerships with family carers.”
The study was funded by the United Kingdom National Institute of Health Research HTA Program. The study authors report several disclosures, which are listed in full in the original article. Dr. Brodaty has disclosed no relevant financial relationships.
The Alzheimer’s Society provides a variety of online resources on recognition, diagnosis and management of depression, including a large number of downloadable fact sheets helpful for patient education.