It is not clear that this patient has severe, persisting major depressive disorder; she has had no response to incremental dosing of sertraline over 7 weeks, and she has continuing, bothersome adverse effects. The clinical features support discontinuing sertraline and observing her over time (“watchful waiting”).
Approximately 20% of patients with dementia experience concomitant depression. Research casts doubt on the efficacy of antidepressant agents for this population. Although earlier small studies reported mixed results, a 2002 Cochrane review concluded that there was only weak evidence for the effectiveness of antidepressants in dementia. The 2010 DIADS-2 (Depression in Alzheimer Disease Study–2) reported no benefit of sertraline at 12 and 24 weeks, and a 2011 meta-analysis confirmed that evidence for use of antidepressants in dementia was “equivocal.” Finally, a multicenter, randomized, double-blind, placebo-controlled trial was commissioned by the U.K. National Institute for Health Research to test the clinical effectiveness of sertraline, an SSRI, and mirtazapine, a noradrenergic and specific serotonergic antidepressant, as compared with placebo to reduce depression in patients with dementia. The landmark Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) enrolled 326 participants from 9 geriatric psychiatry centers in England. At 13 weeks, decreases in depression scores did not differ between placebo controls and patients receiving active drugs (SOE=A). The absence of benefit relative to placebo persisted to 39 weeks. Adverse reactions occurred in >40% of patients treated with an antidepressant and in 25% of patients who received placebo. Authors concluded that “antidepressants should not be prescribed as a first-line treatment for people with depression in Alzheimer’s disease,” because many cases will resolve with usual care without antidepressants. They further suggest a reframing of clinical thinking, with 3 months of observation (“watchful waiting”) with stepped psychosocial interventions, after which—if depression has not improved—antidepressants might be considered.
There is some evidence that among older patients with depression—but without dementia—who are treated with antidepressants, those who manifest a notable response after 6–8 weeks might benefit from continuing treatment for an additional 4–6 weeks. There is no comparable evidence for this approach in older depressed patients with dementia, and findings suggest that these patients should not take antidepressants as first-line therapy anyway.
In depressed older patients, switching or augmenting antidepressant agents yields about a 50% improvement rate (even higher if persistent, sequential strategies are used), but there are no comparable findings for depressed patients with dementia.
- Banerjee S, Hellier J, Dewey M, et al. Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomized, multicentre, double-blind, placebo-controlled trial. Lancet. 2011;378(9789):403–411.
- Nelson JC, Devanand DP. A systematic review and meta-analysis of placebo-controlled antidepressant studies in people with depression and dementia. J Am Geriatr Soc. 2011;59(4):577–585.
- Rosenberg PB, Drye LT, Martin BK, et al; DIADS-2 Research Group. Sertraline for the treatment of depression in Alzheimer’s disease. Am J Geriatr Psychiatry. 2010;18(2):136–145.
- Weintraub D, Rosenberg PB, Drye LT, et al; DIADS-2 Research Group. Sertraline for the treatment of depression in Alzheimer’s disease: Week-24 outcomes. Am J Geriatr Psychiatry. 2010;18(4):332–340.