HTA Study of Antidepressants for Depression in Dementia: A definitive multi-centre pragmatic randomised controlled double-blind trial of the clinical and cost effectiveness of mirtazapine and sertraline versus placebo for the treatment of depression in dementia presenting in secondary care

ISRCTN	ISRCTN88882979
DOI	https://doi.org/10.1186/ISRCTN88882979
EudraCT/CTIS number	2006-000105-38
Secondary identifying numbers	HTA 04/11/02, EudraCT Number: 2006-000105-38

Submission date: 27/02/2006
Registration date: 02/03/2006
Last edited: 11/07/2013

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Mental and Behavioural Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Sube Banerjee
Scientific

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

Phone	+44 (0)20 7848 0012
Email	s.banerjee@iop.kcl.ac.uk

Study information

Study design	A multi-centre double-blind placebo-controlled randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Scientific title
Study acronym	HTA-SADD
Study objectives	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(s)	Added on 29/07/09: Ethics approval received on the 12th of July 2006
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Mirtazapine and sertraline
Primary outcome measure	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 study start date	01/09/2006
Completion date	31/05/2010

Eligibility

Participant type(s)	Patient
Age group	Senior
Sex	Both
Target number of participants	507
Key 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
Key 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.
Date of first enrolment	01/09/2006
Date of final enrolment	31/05/2010

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Professor of Mental Health and Ageing

London
SE5 8AJ
United Kingdom

Sponsor information

King's College London (UK)
University/education

Gill Dale
Research & Development Department
Box P005
Institute of Psychiatry
King's College London
De Crespigny Park
London
SE5 8AF
England
United Kingdom

Email	g.dale@iop.kcl.ac.uk
"ROR"	https://ror.org/0220mzb33

Funders

Funder type

Government

NIHR Health Technology Assessment Programme - HTA (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Peer reviewed?	Patient-facing?
Results article	results	30/07/2011	Yes	No
Other publications	cost-effectiveness analysis	01/02/2013	Yes	No
Results article	results	01/02/2013	Yes	No