The University of Southampton
University of Southampton Institutional Repository

Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial

Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial
Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial
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.

Findings. 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.

Interpretation. 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.
0140-6736
403-411
Banerjee, Sube
c89df0e0-46cf-482b-ac93-6c39333c93b5
Hellier, Jennifer
f3216551-62bd-44f1-b76e-ffb620cc936f
Dewey, Michael
74b151c3-2873-4860-be5c-ad70aa2a2c7c
Romeo, Renee
53fa96fa-1b89-4622-b835-8224fdfd176f
Ballard, Clive
e244c4e5-5dd4-4c66-9efb-6bf2006bdb7e
Baldwin, Robert
a909a8b5-71ee-4b0c-b91f-a9701437a842
Bentham, Peter
3c600094-9382-46a2-9ade-ac945e1a637d
Fox, Chris
06b59c5d-a369-4443-b5ae-d9a06f622d9f
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Katona, Cornelius
307dcc4d-fce2-4f6d-924e-a03dc301c4e6
Knapp, Martin
39b0d60c-30b1-4b9b-bc7f-13c5bdc7e712
Lawton, Claire
2293efb5-80c0-47c5-abe1-8edd164d0530
Lindesay, James
4b6a8efb-00c8-43df-81f8-076829e6ea35
Livingston, Gill
ea18efb5-2f07-42a9-be5e-0d7b5b02f229
McCrae, Niall
8130c014-1d31-4741-8316-18f7d3ed590e
Moniz-Cook, Esme
dc98defb-af8f-4a6d-9809-d182c44b63d3
Murray, Joanna
e4c89a6e-d81c-4378-8786-0e82eeed6b58
Nurock, Shirley
7ad7c7ad-c3f4-47df-8579-6ee9b7c28f67
Orrell, Martin
07952ad1-e889-4dd1-afb2-9ec6e2f0a264
O'Brien, John
0906821d-4431-47e6-8155-27de5d7f9612
Poppe, Michaela
08123f47-83e7-4742-8ddd-d3c459aa7adb
Thomas, Alan
d6e83331-45d6-4622-a8c7-1af212695dda
Walwyn, Rebecca
e5580818-9be9-4ee2-91f6-20d199221432
Wilson, Kenneth
4845c17b-5a8d-42a5-a633-b030c6bd0ed6
Burns, Alistair
3b42ceb2-cc8b-4159-807b-fe1bc095f723
Banerjee, Sube
c89df0e0-46cf-482b-ac93-6c39333c93b5
Hellier, Jennifer
f3216551-62bd-44f1-b76e-ffb620cc936f
Dewey, Michael
74b151c3-2873-4860-be5c-ad70aa2a2c7c
Romeo, Renee
53fa96fa-1b89-4622-b835-8224fdfd176f
Ballard, Clive
e244c4e5-5dd4-4c66-9efb-6bf2006bdb7e
Baldwin, Robert
a909a8b5-71ee-4b0c-b91f-a9701437a842
Bentham, Peter
3c600094-9382-46a2-9ade-ac945e1a637d
Fox, Chris
06b59c5d-a369-4443-b5ae-d9a06f622d9f
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Katona, Cornelius
307dcc4d-fce2-4f6d-924e-a03dc301c4e6
Knapp, Martin
39b0d60c-30b1-4b9b-bc7f-13c5bdc7e712
Lawton, Claire
2293efb5-80c0-47c5-abe1-8edd164d0530
Lindesay, James
4b6a8efb-00c8-43df-81f8-076829e6ea35
Livingston, Gill
ea18efb5-2f07-42a9-be5e-0d7b5b02f229
McCrae, Niall
8130c014-1d31-4741-8316-18f7d3ed590e
Moniz-Cook, Esme
dc98defb-af8f-4a6d-9809-d182c44b63d3
Murray, Joanna
e4c89a6e-d81c-4378-8786-0e82eeed6b58
Nurock, Shirley
7ad7c7ad-c3f4-47df-8579-6ee9b7c28f67
Orrell, Martin
07952ad1-e889-4dd1-afb2-9ec6e2f0a264
O'Brien, John
0906821d-4431-47e6-8155-27de5d7f9612
Poppe, Michaela
08123f47-83e7-4742-8ddd-d3c459aa7adb
Thomas, Alan
d6e83331-45d6-4622-a8c7-1af212695dda
Walwyn, Rebecca
e5580818-9be9-4ee2-91f6-20d199221432
Wilson, Kenneth
4845c17b-5a8d-42a5-a633-b030c6bd0ed6
Burns, Alistair
3b42ceb2-cc8b-4159-807b-fe1bc095f723

Banerjee, Sube, Hellier, Jennifer, Dewey, Michael, Romeo, Renee, Ballard, Clive, Baldwin, Robert, Bentham, Peter, Fox, Chris, Holmes, Clive, Katona, Cornelius, Knapp, Martin, Lawton, Claire, Lindesay, James, Livingston, Gill, McCrae, Niall, Moniz-Cook, Esme, Murray, Joanna, Nurock, Shirley, Orrell, Martin, O'Brien, John, Poppe, Michaela, Thomas, Alan, Walwyn, Rebecca, Wilson, Kenneth and Burns, Alistair (2011) Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial. The Lancet, 378 (9789), 403-411. (doi:10.1016/S0140-6736(11)60830-1). (PMID:21764118)

Record type: Article

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.

Findings. 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.

Interpretation. 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.

Full text not available from this repository.

More information

e-pub ahead of print date: 18 July 2011
Published date: 30 July 2011
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337605
URI: https://eprints.soton.ac.uk/id/eprint/337605
ISSN: 0140-6736
PURE UUID: cb3698c9-44b1-46da-b327-bb233e5a4a44
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912

Catalogue record

Date deposited: 01 May 2012 09:27
Last modified: 20 Feb 2019 01:36

Export record

Altmetrics

Contributors

Author: Sube Banerjee
Author: Jennifer Hellier
Author: Michael Dewey
Author: Renee Romeo
Author: Clive Ballard
Author: Robert Baldwin
Author: Peter Bentham
Author: Chris Fox
Author: Clive Holmes ORCID iD
Author: Cornelius Katona
Author: Martin Knapp
Author: Claire Lawton
Author: James Lindesay
Author: Gill Livingston
Author: Niall McCrae
Author: Esme Moniz-Cook
Author: Joanna Murray
Author: Shirley Nurock
Author: Martin Orrell
Author: John O'Brien
Author: Michaela Poppe
Author: Alan Thomas
Author: Rebecca Walwyn
Author: Kenneth Wilson
Author: Alistair Burns

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×