title: Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Depression is common in dementia but the evidence base for appropriate drug treatment is sparse and equivocal. We aimed to assess efficacy and safety of two of the most commonly prescribed drugs, sertraline and mirtazapine, compared with placebo.
  
  
  METHODS
  We undertook the parallel-group, double-blind, placebo-controlled, Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial in participants from old-age psychiatry services in nine centres in England. Participants were eligible if they had probable or possible Alzheimer's disease, depression (lasting ≥4 weeks), and a Cornell scale for depression in dementia (CSDD) score of 8 or more. Participants were ineligible if they were clinically critical (eg, suicide risk), contraindicated to study drugs, on antidepressants, in another trial, or had no carer. The clinical trials unit at King's College London (UK) randomly allocated participants with a computer-generated block randomisation sequence, stratified by centre, with varying block sizes, in a 1:1:1 ratio to receive sertraline (target dose 150 mg per day), mirtazapine (45 mg), or placebo (control group), all with standard care. The primary outcome was reduction in depression (CSDD score) at 13 weeks (outcomes to 39 weeks were also assessed), assessed with a mixed linear-regression model adjusted for baseline CSDD, time, and treatment centre. This study is registered, number ISRCTN88882979 and EudraCT 2006-000105-38.
  
  
  RESULTS
  Decreases in depression scores at 13 weeks did not differ between 111 controls and 107 participants allocated to receive sertraline (mean difference 1·17, 95% CI -0·23 to 2·58; p=0·10) or mirtazapine (0·01, -1·37 to 1·38; p=0·99), or between participants in the mirtazapine and sertraline groups (1·16, -0·25 to 2·57; p=0·11); these findings persisted to 39 weeks. Fewer controls had adverse reactions (29 of 111 [26%]) than did participants in the sertraline group (46 of 107, 43%; p=0·010) or mirtazapine group (44 of 108, 41%; p=0·031), and fewer serious adverse events rated as severe (p=0·003). Five patients in every group died by week 39.
  
  
  CONCLUSIONS
  Because of the absence of benefit compared with placebo and increased risk of adverse events, the present practice of use of these antidepressants, with usual care, for first-line treatment of depression in Alzheimer's disease should be reconsidered.
  
  
  BACKGROUND
  UK National Institute of Health Research HTA Programme.
authors.affiliation: Institute of Psychiatry, Health Services and Population Research Department, King's College London, London, UK. sube.banerjee@kcl.ac.uk
authors.forename: Sube
authors.initials: S
authors.lastname: Banerjee
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hellier
authors.forename: Michael
authors.initials: M
authors.lastname: Dewey
authors.forename: Renee
authors.initials: R
authors.lastname: Romeo
authors.forename: Clive
authors.initials: C
authors.lastname: Ballard
authors.forename: Robert
authors.initials: R
authors.lastname: Baldwin
authors.forename: Peter
authors.initials: P
authors.lastname: Bentham
authors.forename: Chris
authors.initials: C
authors.lastname: Fox
authors.forename: Clive
authors.initials: C
authors.lastname: Holmes
authors.forename: Cornelius
authors.initials: C
authors.lastname: Katona
authors.forename: Martin
authors.initials: M
authors.lastname: Knapp
authors.forename: Claire
authors.initials: C
authors.lastname: Lawton
authors.forename: James
authors.initials: J
authors.lastname: Lindesay
authors.forename: Gill
authors.initials: G
authors.lastname: Livingston
authors.forename: Niall
authors.initials: N
authors.lastname: McCrae
authors.forename: Esme
authors.initials: E
authors.lastname: Moniz-Cook
authors.forename: Joanna
authors.initials: J
authors.lastname: Murray
authors.forename: Shirley
authors.initials: S
authors.lastname: Nurock
authors.forename: Martin
authors.initials: M
authors.lastname: Orrell
authors.forename: John
authors.initials: J
authors.lastname: O'Brien
authors.forename: Michaela
authors.initials: M
authors.lastname: Poppe
authors.forename: Alan
authors.initials: A
authors.lastname: Thomas
authors.forename: Rebecca
authors.initials: R
authors.lastname: Walwyn
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wilson
authors.forename: Alistair
authors.initials: A
authors.lastname: Burns
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications*; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003704:Dementia / Q000150:complications*; D003866:Depressive Disorder / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000188:drug therapy*; D008803:Mianserin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000078785:Mirtazapine; D016032:Randomized Controlled Trials as Topic; D020280:Sertraline / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D008803:Mianserin; D000078785:Mirtazapine; D020280:Sertraline