Study: antidepressants and dementia: more risk than benefits?

reference

Banerjee S., Hellier J., Dewey M. et al. Sertraline or Mirtazapine against depression in dementia (HTA-SADD): a randomized, multicenter, double-blind, placebo-controlled study.Lancet.2011;378(9789):403-411.

design

A parallel, double-blind, placebo-controlled health technology assessment study of antidepressant use for depression in dementia (HTA-SADD) with participants from geriatric mental health services in 9 centers in England.

Participant

Participants were provided with geriatric psychiatric services at 9 centers in England. Participants were eligible if they had probable or possible Alzheimer's disease, depression (duration ≥4 weeks), and a Cornell Scale for Depression in Dementia (CSDD) score of 8 or more. Participants were ineligible if they were clinically critical (e.g., suicide risk), had medication contraindicated for study, were taking antidepressants, were participating in another study, or did not have a caregiver.

Study medication and dosage

sertraline (target dose 150 mg per day), mirtazapine (45 mg) or placebo

Target parameters

The primary endpoint was reduction in depression (CSDD score) at 13 weeks (outcomes through 39 weeks were also assessed), assessed with a mixed linear regression model adjusted for CSDD baseline, time and treatment center.

Key findings

Decrease in depression scores at 13 weeks did not differ between 111 controls and 107 participants receiving sertraline (mean difference, 1.17; 95% CI: -0.23-2.58;P=0.10) or mirtazapine (0.01; 95% CI: -1.37–1.38;P= 0.99) or between participants of the Mirtazapin and Sertralin group (1.16; 95 %-KI: -0.25–2.57;P=0.11); These findings lasted up to 39 weeks. Fewer controls had side effects (29 of 111). [26%]) than the participants in the sertraline group (46 of 107). [43%];P= 0.010) or Mirtazapin group (44 of 108). [41%];P= 0.031) and less serious undesirable events that were classified as serious (control group) (P=0.003). Five patients in each group died at week 39.

Effects on practice

Antidepressants did not improve outcomes compared to placebo; However, they increased the risk of adverse events. Therefore, the current practice of using antidepressants with usual care as the first-line treatment of depression in Alzheimer's disease should be reconsidered. “Usual care” in this study included referral to psychiatric care in the elderly.

comment

The study says: "Despite these results, the current practice is to use antidepressants, often sertraline, as an initial treatment for depression in dementia." What were the findings? When searching in the literature, which in their opinion was "sparse and ambiguous", the authors of article found six relevant studies (systematic overviews from the Pubmed and Cochrane Library databases) for the treatment of depression in people with dementia, only three meta -analyzed. A study had balanced results (with the tricyclic antidepressant clomipramine in 24 people).¹The second was negative (using the tricyclic antidepressant imipramine in 61 people)²and the third positively (using the selective serotonin reuptake inhibitor Sertralin in 44 people).³The review concluded that there was only weak evidence of the effectiveness of antidepressants in dementia. Tricyclics are medications that are not commonly used in the population (depression in dementia) and that cause anticholinergic side effects. Another relevant randomized trial looked at 67 people given sertraline compared to 64 people given a placebo.^4.5After 12 or 24 weeks, no benefit from Sertralin was reported.

Despite the results of these studies, current practice uses antidepressants, often sertraline, as initial treatment for depression in dementia. Knowing how serious and challenging a public health problem it is, and that depression is common in dementia, the authors of the current study wanted to determine whether or not this subgroup of depressed patients would be better served with antidepressants. And after 13 weeks of the study, they found that the greatest absolute improvement occurred with placebo.

“Due to the lack of benefit compared to placebo and the increased risk of adverse events, the current practice of using these antidepressants with usual care for the first-line treatment of depression in Alzheimer's disease should be reconsidered,” the authors concluded.

The supervisors of these patients with depressive dementia performed better with the quality of life and mental health if their relatives received a placebo.

Antidepressants as a category of drugs have proven side effects such as increased suicidal thoughts and potentially serious mood changes. Since mood swings are also prevalent in dementia patients, the use of such a drug in dementia patients is problematic from the outset. Additionally, many of our elderly take multiple prescription medications, and antidepressants have a long list of drug interactions. Unfortunately, dementia patients may not be able to adequately communicate new or changing symptoms due to these interactions.

Interestingly, the supervisors of these depressive dementia patients perform better in quality of life and mental health if their relatives received a placebo instead of sertraline. The supervisors of the participants of the Mirtazapin Group also had higher quality of life than those of the Sertralin Group, at least after 13 weeks.

And who did best overall? Remember that “usual care” in this study included referral to geriatric mental health services. The depressed dementia patients referred to geriatric mental health services showed a strong, consistent pattern of improvement in depression at 13 and 30 week follow-up. Maybe our elders just need someone to spend time with them, not yet another pill to pop. Perhaps our dependence on technology has overwhelmed our reason and common sense. If we spent time talking and actually living with our elders, perhaps they wouldn't develop dementia in the first place. If we focused on real prevention—eating real food, drinking clean water, exercising daily in ways we enjoy, cultivating healthy relationships, keeping the mind active, maintaining supportive social structures—perhaps we would all have a better chance of growing old without disease affecting our wisdom as we age.