Condition category
Mental and Behavioural Disorders
Date applied
27/02/2006
Date assigned
02/03/2006
Last edited
11/07/2013
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Sube Banerjee

ORCID ID

Contact details

Professor of Mental Health and Ageing
Unit PO26
Section of Mental Health and Ageing
Health Services Research Department
The Institute of Psychiatry
King’s College London
De Crespigny Park
London
SE5 8AJ
United Kingdom
+44 (0)20 7848 0012
s.banerjee@iop.kcl.ac.uk

Additional identifiers

EudraCT number

2006-000105-38

ClinicalTrials.gov number

Protocol/serial number

HTA 04/11/02, EudraCT Number: 2006-000105-38

Study information

Scientific title

Acronym

HTA-SADD

Study hypothesis

Primary Objective
1. To determine the clinical and cost effectiveness of two classes of antidepressants for depression in dementia (compared with placebo)
a. To determine whether a selective serotonin reuptake inhibitor (SSRI) (sertraline) is i) more clinically effective and ii) more cost effective than placebo in reducing Cornell depression score 13 weeks post randomisation
b. To determine whether a noradrenergic and specific serotonergic antidepressant (NaSSA) (mirtazapine) is i) more clinically effective and ii) more cost effective than placebo in reducing Cornell Depression score 13 weeks post-randomisation

Secondary Objectives
2. To investigate differences in the clinical and cost effectiveness, and in terms of adverse events, withdrawals from treatment and adherence to treatment between mirtazapine and sertraline for depression in dementia at 13 and 39 weeks post-randomisation
3. To investigate differences in the clinical and cost effectiveness of mirtazapine/sertraline and placebo on patient (e.g. quality of life, cognition) and family carer (e.g. carer burden, carer quality of life) outcomes at 13 and 39 weeks post-randomisation
4. To investigate the influence on clinical and cost effectiveness of clinical characteristics including: dementia severity, dementia type, depression type, depression severity, care arrangements, neuropsychiatric symptoms, and physical illness

As of 30/07/09 this record has been updated. All updates can be found in the relevant field with the above update date. Please also note that the sponsor of this trial has been changed.
Initial sponsor at time of registration:
Department of Health (UK)
Quarry House
Quarry Hill
Leeds
LS2 7UE
United Kingdom
Sheila.Greener@doh.gsi.gov.uk
http://www.dh.gov.uk/en/index.htm

Please note that, as of 04/09/2009, the anticipated end date of this trial has been updated from 30/11/2008 to 31/05/2010.

Ethics approval

Added on 29/07/09: Ethics approval received on the 12th of July 2006

Study design

A multi-centre double-blind placebo-controlled randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Depression in dementia

Intervention

The randomised interventions are:
1. Mirtazapine (a NaSSA) + sertraline placebo with normal clinical care
2. Sertraline (an SSRI) + mirtazapine placebo with normal clinical care
3. Mirtazapine placebo + sertraline placebo with normal clinical care

Interventions will be available in 15 mg tables for mirtazapine and 50 mg capsules for sertraline. The protocol will therefore require each subject to take six tablets per day. This is a double dummy design.

For the first two weeks of treatment, participants will receive:
1. Sertraline 50 mg plus a placebo mirtazapine tablet
2. Mirtazepine 15 mg plus a placebo sertraline tablet
3. A placebo sertraline tablet and a placebo mirtazapine tablet

For the second two weeks, participants will receive:
1. Sertraline 100 mg (2 tablets) plus two placebo mirtazapine tablets
2. Mirtazapine 30 mg (2 tablets) plus two placebo sertraline tablets
3. Two placebo sertraline tablets and two placebo mirtazapine tablets

From week 4 until the end of the trial (ten months in total), participants will receive:
1. Sertraline 150 mg (3 tablets) plus three placebo mirtazapine tablets
2. Mirtazapine 45 mg (3 tablets) plus three placebo sertraline tablets
3. Three placebo sertraline tablets and three placebo mirtazapine tablets

Dose adjustments can be made by reducing back to 2 of each tablet daily or to 1 of each tablet daily in participants experiencing troublesome side effects.

Intervention type

Drug

Phase

Not Specified

Drug names

Mirtazapine and sertraline

Primary outcome measures

1. Depression in dementia - CSDD (Alexopoulos et al 1988)
2. Costs - Client Service Receipt Inventory (CSRI; Beecham et al 2001)

Secondary outcome measures

1. Disease specific quality of life - DEMQOL and DEMQOL-Proxy (Smith et al 2005)
2. Generic measure of quality of life - interview administered to carer (Coucill et al 2001) EQ-5D (EuroQoL Group 1990)
3. Withdrawal from treatment arm
4. Cognitive impairment - MMSE (Folstein et al 1975)
5. Medication adherence
6. Adverse events
7. Carer mental health - General Health Questionnaire - 12 (GHQ-12; Goldberg et al 1988)
8. Carer quality of life - SF-12 v2 (Ware et al 1996)
9. Carer burden - Zarit Carer Burden Scale (Zarit 1980)

Overall trial start date

01/09/2006

Overall trial end date

31/05/2010

Reason abandoned

Eligibility

Participant inclusion criteria

We have designed this study as a pragmatic trial of effectiveness in routine clinical practice. We wish to minimise exclusions from the study in order to maximise the generalisability of the data generated.

The criteria for inclusion are set to be as close to clinical practice as possible. For this reason we do not specify the use of anything other than clinical diagnoses of dementia and depression since standardised instruments (other than the Mini-Mental State Examination [MMSE] as a measure of severity) are not used in routine practice. A detailed characterisation of cases using standardised tools will be completed at the research assessment. We will recruit those in whom a secondary care doctor makes at the point of referral to the RW:
1. A clinical diagnosis of mild to moderate probable or possible Alzheimer's Disease
2. A co-existing depressive illness likely to need treatment with antidepressants
3. Depression should have a duration of more than four weeks

Participant type

Patient

Age group

Senior

Gender

Both

Target number of participants

507

Participant exclusion criteria

We wish to minimise exclusions. We will exclude from the trial those in whom a secondary care doctor finds at the point of referral to the RW are:
1. Currently taking antidepressants
2 Those with severe dementia (defined as MMSE >7)
3. The case is considered as being too critical to be randomised (e.g. because of suicide risk)
4. Displays absolute contraindications to one or more of the trial treatments
5. Not in another trial
6. Those where there is no identifiable family carer or other informant (e.g. a formal/professional carer who spends sufficient time with the person with dementia to be able to give an informed opinion) to give collateral information

We will further exclude from the trial those in whom the RW finds have a Cornell score <8 at the point of randomisation.

Recruitment start date

01/09/2006

Recruitment end date

31/05/2010

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Professor of Mental Health and Ageing
London
SE5 8AJ
United Kingdom

Sponsor information

Organisation

King's College London (UK)

Sponsor details

Gill Dale
Research & Development Department
Box P005
Institute of Psychiatry
King's College London
De Crespigny Park
London
SE5 8AF
United Kingdom
g.dale@iop.kcl.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Health Technology Assessment Programme - HTA (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21764118
2. 2013 results in www.ncbi.nlm.nih.gov/pubmed/23438937
3. 2013 cost-effectiveness analysis in http://www.ncbi.nlm.nih.gov/pubmed/23258767

Publication citations

  1. Results

    Banerjee S, Hellier J, Dewey M, Romeo R, Ballard C, Baldwin R, Bentham P, Fox C, Holmes C, Katona C, Knapp M, Lawton C, Lindesay J, Livingston G, McCrae N, Moniz-Cook E, Murray J, Nurock S, Orrell M, O'Brien J, Poppe M, Thomas A, Walwyn R, Wilson K, Burns A, Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial., Lancet, 2011, 378, 9789, 403-411, doi: 10.1016/S0140-6736(11)60830-1.

  2. Results

    Banerjee S, Hellier J, Romeo R, Dewey M, Knapp M, Ballard C, Baldwin R, Bentham P, Fox C, Holmes C, Katona C, Lawton C, Lindesay J, Livingston G, McCrae N, Moniz-Cook E, Murray J, Nurock S, Orrell M, O'Brien J, Poppe M, Thomas A, Walwyn R, Wilson K, Burns A, Study of the use of antidepressants for depression in dementia: the HTA-SADD trial--a multicentre, randomised, double-blind, placebo-controlled trial of the clinical effectiveness and cost-effectiveness of sertraline and mirtazapine., Health Technol Assess, 2013, 17, 7, 1-166, doi: 10.3310/hta17070.

  3. Romeo R, Knapp M, Hellier J, Dewey M, Ballard C, Baldwin R, Bentham P, Burns A, Fox C, Holmes C, Katona C, Lawton C, Lindesay J, Livingston G, McCrae N, Moniz-Cook E, Murray J, Nurock S, O'Brien J, Poppe M, Thomas A, Walwyn R, Wilson K, Banerjee S, Cost-effectiveness analyses for mirtazapine and sertraline in dementia: randomised controlled trial., Br J Psychiatry, 2013, 202, 121-128, doi: 10.1192/bjp.bp.112.115212.

Additional files

Editorial Notes