Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12608000613303
Ethics application status
Approved
Date submitted
28/10/2008
Date registered
5/12/2008
Date last updated
22/04/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Maintenance antidepressants versus treatment cessation in the prevention of depression recurrence.
Scientific title
Stable primary care depression: maintenance vs gradual withdrawal of antidepressants in prevention of depression recurrence in primary care in patients with unipolar depressive disorder.
Secondary ID [1] 289065 0
Nil known
Universal Trial Number (UTN)
Trial acronym
ACT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 3206 0
Condition category
Condition code
Mental Health 3370 3370 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Placebo masked tapered cessation of current selective serotonin reuptake inhibitor antidepressant medication. Participants in the intervention group will have their medication tapered over a month to placebo which will continue for 18 months. The dose of active drug in each capsule will be halved each week for the first four weeks then discontinued. The placebo is a non lactose inert powder filled oral capsule. After the taper period both the active drug and the placebo/taper arm will continue to take one tablet daily for the 18 month study period.
Intervention code [1] 2948 0
Treatment: Drugs
Comparator / control treatment
Continuation of maintenance selective serotonin reuptake inhibitor antidepressant treatment. Patients in the control group will continue receiving their antidepressants at the dose they have been taking over the same 18 month time period. The medication will be encapsulated as a powder which look identical to the taper /placebo arm, taken as a daily dose for the entire 18 months of follow up
Control group
Active

Outcomes
Primary outcome [1] 4579 0
Depression recurrence. Recurrence will be assessed using the interviewer administered Montgomery Asberg Depression Rating Scale (MADRS).
Timepoint [1] 4579 0
This will be assessed at week 1,2 and 4 and then at 3 monthly time points during the 18 months of follow up
Secondary outcome [1] 7737 0
Time to recurrence. Recurrence will be assessed using the interviewer administered Montgomery Asberg Depression Rating Scale (MADRS).
Timepoint [1] 7737 0
This will be assessed at week 1,2 and 4 and then at 3 monthly time points during the 18 months of follow up.
Secondary outcome [2] 7738 0
Occupational and social functioning as measured by the Medical Research Council (MRC) Social Performance Scale.
Timepoint [2] 7738 0
This will be assessed at week 1,2 and 4 and then at 3 monthly time points during the 18 months of follow up
Secondary outcome [3] 8408 0
General psychological functioning, measured using the Kesslar K10 scale.
Timepoint [3] 8408 0
This will be assessed at week 1,2 and 4 and then at 3 monthly time points during the 18 months of follow up
Secondary outcome [4] 8409 0
General Functioning as measured by the SF36.
Timepoint [4] 8409 0
This will be assessed at week 1,2 and 4 and then at 3 monthly time points during the 18 months of follow up
Secondary outcome [5] 8410 0
Subjective assessment of depression using the Montgomery Asberg Depression Rating Scale (MARDS) self report scale.
Timepoint [5] 8410 0
This will be assessed at week 1,2 and 4 and then at 3 monthly time points during the 18 months of follow up

Eligibility
Key inclusion criteria
Aged between 18 and 75 years
Living in the Christchurch, Wellington or Auckland urban areas
Historical diagnosis of unipolar depressive disorder for which current therapy is maintenance antidepressants
Diagnosed and treated for depression in primary care
On treatment with antidepressants for at least 12 months
Currently in remission: Montgomery Asberg Depression Rating Scale (MADRS)
Patient willing to try discontinuation
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Diagnosis / treatment carried out in secondary care setting (inpatient or outpatient referral to psychiatrist) for the index episode
Unipolar depression not primary reason for prescription of SSRI
Bipolar disorder
Psychotic disorder
Substance dependence disorder
Postnatal depression in the last 12 months
Pregnancy
Serious current suicide risk (score >2 on MADRS suicide item)
English language skills inadequate to understand and respond to rating scales
Concurrent use of any other antidepressant

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Partipants will be recruited from primary care. Once they have met the inclusion criteria and consented they will be given the next medication pack from a numbered list. The medication has been packed according to the outlined randomisation procedure.
Allocation concealment
Placebos will be identical to the active drug tablets, and identified by a code which will be attached to the patient’s clinical notes.
The dispensing pharmacists will keep the codes in a sealed envelope. The investigator team, General Practioners (GPs) and biostatistician will have no access to the code until the end of the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The medication has been packed according to the outlined randomisation procedure.
Randomisation procedure:
A non-study biostatistician will provide a computer generated random sequence for the medication packs using random block lengths.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
20/08/2008
Actual
17/12/2008
Date of last participant enrolment
Anticipated
Actual
15/02/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
330
Accrual to date
Final
263
Recruitment outside Australia
Country [1] 994 0
New Zealand
State/province [1] 994 0

Funding & Sponsors
Funding source category [1] 3700 0
Government body
Name [1] 3700 0
Health Research Council of New Zealand(NZ)
Country [1] 3700 0
New Zealand
Primary sponsor type
Government body
Name
Health Research Council of NZ
Address
PO Box 5541
Wellesley Street
Auckland 1141
Country
New Zealand
Secondary sponsor category [1] 3318 0
None
Name [1] 3318 0
Address [1] 3318 0
Country [1] 3318 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5750 0
New Zealand Multiregion Ethics Committee
Ethics committee address [1] 5750 0
Ministry of Health
PO Box 5013
Lambton Quay
Wellington 6145
Ethics committee country [1] 5750 0
New Zealand
Date submitted for ethics approval [1] 5750 0
Approval date [1] 5750 0
12/02/2008
Ethics approval number [1] 5750 0

Summary
Brief summary
Most (85-90%) depression is treated in primary care. Many patients in primary care are now receiving long term maintenance therapy with antidepressants to prevent recurrence. Whilst research indicates long term maintenance treatment benefits some patients referred to and treated in secondary care, there is no similar evidence for patients with milder symptoms treated exclusively in primary care. Recurrence of depressive episodes is lower in primary than secondary care treated patients (35% vs 75%).
This study is a triple blinded randomised controlled trial of continued treatment vs tapered withdrawal of fluoxetine in patients who have been treated in primary care for at least twelve months and who are not currently experiencing depression. Patients will be followed for 18 months to monitor recurrence of depression, side effects, and general social and occupational functioning and the two arms compared. This study will further our understanding of the optimal long term treatment of depression in primary care by assessing whether there is any benefit in using antidpressants for preventing recurrence of depression, or whether the medication can safely be stopped.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28629 0
A/Prof Derelie Mangin
Address 28629 0
Department of Family Medicine
McMaster University, David Braley Health Sciences Centre
100 Main Street West, 5th floor
Hamilton, Ontario
L8P 1H6
Canada
Country 28629 0
Canada
Phone 28629 0
+1 905 525 9140
Fax 28629 0
Email 28629 0
[email protected]
Contact person for public queries
Name 11786 0
A/Prof Dr Dee Mangin
Address 11786 0
Department of Family Medicine
McMaster University, David Braley Health Sciences Centre
100 Main Street West, 5th floor
Hamilton, ON L8P 1H6
Country 11786 0
Canada
Phone 11786 0
+1 905 525 9140 ext 21219
Fax 11786 0
Email 11786 0
[email protected]
Contact person for scientific queries
Name 2714 0
A/Prof Dr Dee Mangin
Address 2714 0
Department of Family Medicine
McMaster University, David Braley Health Sciences Centre
100 Main Street West, 5th floor
Hamilton, ON L8P 1H6
Country 2714 0
Canada
Phone 2714 0
+1 905 525 9140
Fax 2714 0
Email 2714 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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