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Trial registered on ANZCTR


Registration number
ACTRN12609000052235
Ethics application status
Approved
Date submitted
5/12/2008
Date registered
22/01/2009
Date last updated
4/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Differential Treatment Effectiveness in Patients with the melancholic sub-type of depression
Scientific title
Differential Treatment Effectiveness in Patients with the melancholic sub-type of depression
Universal Trial Number (UTN)
Trial acronym
TOMEDS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melancholic Depression 4075 0
Condition category
Condition code
Mental Health 4283 4283 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There are three treatment groups in this trial. Current routine management for patients who present with melancholic depression include prescribing citalopram (SSRI) or referral to undergo cognitive behavioural therapy. This study will compare these two management options with a treatment developed through clinical experience, the Sequencing Drug-based Algorithm.

Sequencing Drug-based Algorithm (SDA): Those receiving the SDA protocol will initially receive the dual action antidepressant drug venlafaxine (i.e. impacting on serotonergic and noradrenergic functioning), initially daily at 75 mg and progressively titrated up to maximum dose of 300 mg over three weeks – subject to side-effects and response. If no ‘response’ (operationalised as 50% or more improvement in Hamilton score), augmentation by the low dose atypical antipsychotic olanzapine (i.e. 2.5 mg daily) will be initiated in the fourth week, with the latter ceased (at the end of the fifth week) if the subject’s depression remits and the dual action antidepressant maintained. If no ‘response’ or, if a recurrence after ceasing the augmenting drug, the venlafaxine drug will be tapered and ceased over two weeks, and the tricyclic antidepressant drug nortriptyline introduced in the eighth week will be taken daily, and again augmented with an atypical antipsychotic drug if no formal ‘response’ after two weeks for a maximum of two weeks while the tricyclic will be maintained until the end of the twelfth week. [Nortriptyline is chosen as the tricyclic drug, as it has been the most common tricyclic comparator compared to cognitive behaviour therapy]. Each participant will attend eight, 30 minute consultations over the twelve week treatment intervention period.
Intervention code [1] 3798 0
Treatment: Drugs
Comparator / control treatment
There are two comparator groups that are considered standard care:
Individual cognitive behavioural therapy (CBT): Participants in this group will receive weekly individual CBT for the first 8 weeks and then two fortnightly sessions for the last 4 weeks from a therapist trained in CBT, with each session lasting a minimum of 45 minutes. CBT will be orthodox, manual-based, focused on problem formulation and staged interventions and conform to best practice. The total number of CBT sessions will be ten sessions conducted over the 12 week period.

SSRI alone: Participants assigned to this arm will receive the SSRI citalopram (progressively titrated from half recommended starting dose to full dose as judged by the treating clinician). Each participant will take citalopram daily for twelve weeks and attend seven, 30 minute consultations with their clinician over twelve weeks.

All participants will complete three questionnaires at baseline and weeks 2, 4, 6, 8, 10 and 12 including: 16 item Quality of Life Enjoyment and Satisfaction Questionnaire (QOL), QIDS-SR, 5 item Work Productivity and Activity Impairment (WPAI). Each participant will also complete daily mood charting either online or pencil and paper.
Control group
Active

Outcomes
Primary outcome [1] 5170 0
To measure severity of participants' symptoms of melancholic depression.
Timepoint [1] 5170 0
The Hamilton Rating Scale for Depression (HRSD) and The CORE Assessment of Psychomotor Change will be administered by a blind assessor at baseline, and weeks 4, 8 and 12. The total HRSD score will be the primary outcome along with the endogenous subscale of the HRSD.
Secondary outcome [1] 8703 0
Effect of depression on participants life
Timepoint [1] 8703 0
16 item Quality of Life Enjoyment and Satisfaction Questionnaire (QOL), Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR), 5 item Work Productivity and Activity Impairment (WPAI) will be completed at baseline, weeks 2, 4, 6, 8, 10 and 12. 16 item Quality of Life Enjoyment and Satisfaction Questionnaire (QOL) and 5 item Work Productivity and Activity Impairment (WPAI) both measure the extent to which the participant's depression affects their everyday life, and work performance, respectively. Each participant will also complete daily mood charting via the Daily Rating Scale (DRS) questionnaire.

Eligibility
Key inclusion criteria
1. Age between 18 and 65 years. 2. Current episode of depression, duration between 4 weeks and 2 years. 3. Diagnostic Statistical Manual IV (DSM-IV) diagnosis of Major Depressive Disorder (with melancholic features) and having a QIDS-SR score of 11 or more (= a score of 14 or more on the Hamilton Depression Scale).
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. More than one failed antidepressant treatment trial. 2. Currently pregnant or breast feeding. 3. Taken antidepressant medication within twelve months. 4. Currently seeing a psychologist. 5. Undergone cognitive behavioural therapy in the last five years. 6. Suicide risk. 7. Comorbid diagnoses of obsessive compulsive disorder, psychosis, bipolar disorder or eating disorder. 8. Current substance abuse or dependence.

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)
Enrolling a subject: Each potential participant was screened via telephone to ensure they met the inclusion/exclusion criteria. The participant was then assessed according to a semi-structured interview to ensure they met criteria for a DSM-IV of melancholic depression. The participant then attended the clinic on a separate day to be assessed by a psychiatrist.

Allocating Treatment: An ‘envelope’ method was used in this study. Prior to the study the sequence of 300 allocations was placed into 300 similarly-ordered numerically-labelled envelopes. When a participant was admitted into the study the psychiatrist opened the sealed envelope to identify which treatment group the participant would enter. This system was overseen by a researcher who entered the psychiatrist’s office randomly to ensure the envelopes were being opened in the correct order.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The sequence will be created using computer-generated randomisation of treatments in blocks.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
21/01/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 4253 0
University
Name [1] 4253 0
UNSW Gold Star
Country [1] 4253 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
UNSW Research Services
The University of New South Wales
UNSW, Sydney, 2052
New South Wales
Country
Australia
Secondary sponsor category [1] 3826 0
None
Name [1] 3826 0
Address [1] 3826 0
Country [1] 3826 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6305 0
University of New South Wales Human Research Ethics Committee
Ethics committee address [1] 6305 0
UNSW Research Services
Rupert Myers Building, Level 3
The University of New South Wales, 2052
Sydney, NSW
Ethics committee country [1] 6305 0
Australia
Date submitted for ethics approval [1] 6305 0
Approval date [1] 6305 0
12/08/2008
Ethics approval number [1] 6305 0
HREC08175

Summary
Brief summary
The evidence-based strategies most commonly recommended in treatment guidelines for clinical depression do not distinguish between patients with melancholic depression and those without. This study seeks to demonstrate that a strategy which reflects the different neurobiology of melancholic depression will produce a far better treatment response. Participants will be randomly assigned to one of three groups for 12 weeks of therapy. The first two treatments (an SSRI antidepressant and CBT) are drawn from treatment guidelines, while the third (a Sequencing Drug-based Algorithm [SDA]) has been developed through clinical experience.

The principal hypotheses to be tested, which address the comparable effectiveness implied by a sub-typing as against a generic treatment model, are that for individuals with melancholic depression:
1. Those assigned to SDA will show superior remission and responder rates (outcome) to those receiving the SSRI only or CBT only.
2. Those assigned to SSRI only will have a superior outcome to those in CBT only.
3. Differences between treatment arms will not be accounted for by non-specific therapist-based differences.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29203 0
Address 29203 0
Country 29203 0
Phone 29203 0
Fax 29203 0
Email 29203 0
Contact person for public queries
Name 12360 0
Bianca Blanch
Address 12360 0
Black Dog Institute
Hospital Road
Prince of Wales Hospital
Randwick, 2031
Country 12360 0
Australia
Phone 12360 0
+61 2 9382 9268
Fax 12360 0
+61 2 9382 8207
Email 12360 0
[email protected]
Contact person for scientific queries
Name 3288 0
Professor Gordon Parker
Address 3288 0
Black Dog Institute
Hospital Road
Prince of Wales Hospital
Randwick, 2031
Sydney
Country 3288 0
Australia
Phone 3288 0
+61 2 9382 4372
Fax 3288 0
+61 2 9382 4343
Email 3288 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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