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
Kings 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
-
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.
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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.
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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.