Sertraline and Mirtazapine Versus Placebo in Subgroups of Depression in Dementia: Findings From the HTA-SADD Randomized Controlled Trial

Marij Zuidersma, Kia-Chong Chua, Jennifer Hellier, Richard Oude Voshaar, Subrata Sekhar Banerjee

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Studies have shown that antidepressants are no better than placebo in treating depression in dementia. The authors examined antidepressant efficacy in subgroups of depression in dementia with different depressive symptom profiles.

This study focuses on exploratory secondary analyses on the randomized, parallel-group, double-blind, placebo-controlled Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial. The setting included old-age psychiatry services in nine centers in England. The participants included 326 patients meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association probable/possible Alzheimer disease criteria, and Cornell Scale for Depression in Dementia (CSDD) scores of 8 or more. Intervention was placebo (n = 111), sertraline (n = 107), or mirtazapine (n = 108). Latent class analyses (LCA) on baseline CSDD items clustered participants into symptom-based subgroups. Mixed-model analysis evaluated CSDD improvement at 13 and 39 weeks by randomization in each subgroup.

LCA yielded 4 subgroups: severe (n = 34), psychological (n = 86), affective (n = 129), and somatic (n = 77). Mirtazapine, but not sertraline, outperformed placebo in the psychological subgroup at week 13 (adjusted estimate: –2.77 [standard error (SE) 1.16; 95% confidence interval: –5.09 to –0.46]), which remained, but lost statistical significance at week 39 (adjusted estimate: –2.97 [SE 1.59; 95% confidence interval: –6.15 to 0.20]). Neither sertraline nor mirtazapine outperformed placebo in the other subgroups.

Because of the exploratory nature of the analyses and the small sample sizes for subgroup analysis there is the need for caution in interpreting these data. Replication of the potential effects of mirtazapine in the subgroup of those with depression in dementia with “psychological” symptoms would be valuable. These data should not change clinical practice, but future trials should consider stratifying types of depression in dementia in secondary analyses.
Original languageEnglish
Pages (from-to)920-931
Number of pages12
JournalAmerican Journal of Geriatric Psychiatry
Issue number9
Early online date6 Apr 2019
Publication statusPublished - 1 Sept 2019


  • Depression
  • dementia
  • latent class analyses
  • mirtazapine
  • randomized controlled trial
  • sertraline


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