AGTs-MDD: Algorithm Guided Treatment Strategies for Major Depressive Disorder

Sponsor

Shanghai Mental Health Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT01764867

Collaborator

(none)

1,080

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare treatment outcomes between measurement based Algorithm Guided Treatment and Treatment As Usual strategies in a Chinese population with major depressive disorder.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Escitalopram Drug: Mirtazapine Other: modified electroconvulsive therapy Other: repetitive transcranial magnetic stimulation Drug: Fluoxetine Drug: Citalopram Drug: Escitalopram Drug: Paroxetine Drug: Sertraline Drug: Fluvoxamine Drug: Venlafaxine Drug: Duloxetine Drug: Mirtazapine Drug: Bupropion Drug: Trazodone	Phase 4

Detailed Description

The AGT arm includes a 2-step medication monotherapy and a combination treatment algorithm. The first step (level 1) includes two medication monotherapy options: escitalopram and mirtazapine. For those participants who don't remit with the initial intervention after up to 6 to 12-week treatment, the second step (level 2) with a variety of treatment options will be provided. In level 2 intervention, a switch strategy for those who don't remit with escitalopram will be switched to mirtazapine, or for those who don't remit with mirtazapine will be switched to escitalopram, combination strategy (i.e. escitalopram plus mirtazapine) and augmentation strategy (i.e. escitalopram or mirtazapine plus either rTMS or mECT). Participants who don't get remission in level 1 intervention will be encouraged to enter level 2 interventions based on intend-to-treatment principle. The TAU arm as control intervention is performed using the psychiatrist's individual discretion based on his/her expertise and knowledge.

Participants will be recruited consecutively in 8 psychiatric settings across China and randomized into any of the two initial interventions of AGT or TAU arm. Follow-up interviews will be performed monthly for all participants who finish any acute treatment of AGT or TAU. The follow-up period will last up to 6 months.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1080 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Algorithm Guided Treatment Strategies for Major Depressive Disorder

Study Start Date :

Jun 1, 2012

Anticipated Primary Completion Date :

Oct 1, 2014

Anticipated Study Completion Date :

Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Algorithm Guided Treatment (AGT) Algorithm Guided Treatment (AGT) strategies include two steps. In the first step, participants will be randomly assigned to escitalopram (10-20mg/d) or mirtazapine (30-45mg/d) group. In the second step those non-remitted will be allocated into a set of different intervention groups including mirtazapine monotherapy (only for those taken escitalopram in the first step), escitalopram monotherapy (only for those taken mirtazapine in the first step), or combination therapies (i.e. escitalopram plus mirtazapine, escitalopram or mirtazapine plus either modified electroconvulsive therapy with 6-10 sessions or repetitive transcranial magnetic stimulation with 20 sessions respectively) according to intent-to-treat principle. Medication dosage in combination therapy has the same range as the first.	Drug: Escitalopram Recommended dosage range of escitalopram is 10-20mg per day. The duration will last up to 6-12 weeks until progression or unacceptable intolerability develops. Other Names: Lexapro Drug: Mirtazapine Recommended dosage range of mirtazapine is 30-45mg per day. The duration will last up to 6-12 weeks until progression or unacceptable intolerability develops. Other Names: Remeron Other: modified electroconvulsive therapy Up to 6-10 sessions of mECT will be performed for selected participants who fails to remit to initial AGT intervention during 6 to 12-week period. Other Names: mECT Other: repetitive transcranial magnetic stimulation Up to 20 sessions of rTMS will be performed for selected participants who fails to remit to initial AGT intervention during 6 to 12-week period. Other Names: rTMS
Active Comparator: Treatment As Usual (TAU) This control arm refers to routine antidepressant treatment strategies for participants. Any of the new-generation antidepressants including fluoxetine, citalopram, escitalopram, paroxetine, sertraline, fluvoxamine, venlafaxine, duloxetine, mirtazapine, bupropion, or trazodone, which are all available in Chinese psychiatric clinics, may be used for participants who are randomly assigned to this treatment arm based on clinician's expertise and clinical judgement. The dosage range of any of the above antidepressants depends on clinician's judgement. The follow-up period will last up to 6-12 weeks. During follow-ups, clinician can decide to continue current treatment or start a switch or combination strategy based on his/her own clinical judgement.	Drug: Fluoxetine Fluoxetine may be prescribed for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement. Drug: Citalopram Citalopram may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement. Drug: Escitalopram Escitalopram may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement. Drug: Paroxetine Paroxetine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement. Drug: Sertraline Sertraline may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement. Drug: Fluvoxamine Fluvoxamine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement. Drug: Venlafaxine Venlafaxine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement. Drug: Duloxetine Duloxetine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement. Drug: Mirtazapine Mirtazapine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement. Drug: Bupropion Bupropion may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement. Drug: Trazodone Trazodone may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.

Arm

Intervention/Treatment

Active Comparator: Algorithm Guided Treatment (AGT)

Algorithm Guided Treatment (AGT) strategies include two steps. In the first step, participants will be randomly assigned to escitalopram (10-20mg/d) or mirtazapine (30-45mg/d) group. In the second step those non-remitted will be allocated into a set of different intervention groups including mirtazapine monotherapy (only for those taken escitalopram in the first step), escitalopram monotherapy (only for those taken mirtazapine in the first step), or combination therapies (i.e. escitalopram plus mirtazapine, escitalopram or mirtazapine plus either modified electroconvulsive therapy with 6-10 sessions or repetitive transcranial magnetic stimulation with 20 sessions respectively) according to intent-to-treat principle. Medication dosage in combination therapy has the same range as the first.

Drug: Escitalopram

Recommended dosage range of escitalopram is 10-20mg per day. The duration will last up to 6-12 weeks until progression or unacceptable intolerability develops.

Other Names:

Lexapro

Drug: Mirtazapine

Recommended dosage range of mirtazapine is 30-45mg per day. The duration will last up to 6-12 weeks until progression or unacceptable intolerability develops.

Other Names:

Remeron

Other: modified electroconvulsive therapy

Up to 6-10 sessions of mECT will be performed for selected participants who fails to remit to initial AGT intervention during 6 to 12-week period.

Other Names:

mECT

Other: repetitive transcranial magnetic stimulation

Up to 20 sessions of rTMS will be performed for selected participants who fails to remit to initial AGT intervention during 6 to 12-week period.

Other Names:

rTMS

Active Comparator: Treatment As Usual (TAU)

This control arm refers to routine antidepressant treatment strategies for participants. Any of the new-generation antidepressants including fluoxetine, citalopram, escitalopram, paroxetine, sertraline, fluvoxamine, venlafaxine, duloxetine, mirtazapine, bupropion, or trazodone, which are all available in Chinese psychiatric clinics, may be used for participants who are randomly assigned to this treatment arm based on clinician's expertise and clinical judgement. The dosage range of any of the above antidepressants depends on clinician's judgement. The follow-up period will last up to 6-12 weeks. During follow-ups, clinician can decide to continue current treatment or start a switch or combination strategy based on his/her own clinical judgement.

Drug: Fluoxetine

Fluoxetine may be prescribed for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.

Drug: Citalopram

Citalopram may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.

Drug: Escitalopram

Escitalopram may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.

Drug: Paroxetine

Paroxetine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.

Drug: Sertraline

Sertraline may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.

Drug: Fluvoxamine

Fluvoxamine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.

Drug: Venlafaxine

Venlafaxine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.

Drug: Duloxetine

Duloxetine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.

Drug: Mirtazapine

Mirtazapine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.

Drug: Bupropion

Bupropion may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.

Drug: Trazodone

Trazodone may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.

Outcome Measures

Primary Outcome Measures

Remission defined as endpoint 17-item Hamilton Rating Scale for Depression (HRSD-17) total score ≤ 7 [12 weeks]
Acute treatment will last at least 6 weeks if remission occurs, or up to 12 weeks. Endpoint total score in HRSD-17 at up to 12 weeks will be measured to determine wether remission occurs.

Secondary Outcome Measures

Remission defined as endpoint the Quick Inventory of Depressive Symptomatology (16-item) (QIDS-SR16) total score ≤ 5 [12 weeks]
Frequency and intensity of adverse events [12 weeks]
Self-report and clinician rating frequency and intensity of adverse events will be measured at up to 12 weeks.
Quality of life [12 weeks]
Change from baseline in 6-item Quality of life Inventory will be measured at up to 12 weeks.

Other Outcome Measures

Relapse rate [6 months]
Relapse rate will be measured at the end of 6 months after remission.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Meets Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for single or recurrent nonpsychotic major depressive disorder
Age 18-75
Written informed consent completed
Scores 14 or higher on the 17-item Hamilton Depression Rating Scale
Initial treatment with escitalopram or mirtazapine or other antidepressants is clinically appropriate

Exclusion Criteria:

History of bipolar disorder
Concurring psychotic disorders
Scores 3 or higher on item 3 (suicidal) of HRSD-17
History of nonresponse to an adequate trial of escitalopram and/or mirtazapine
Has general medical condition, which contraindicates any leve 1 or 2 treatment option
Is on concomitant medication, which contraindicates any leve 1 or 2 treatment option
Any contraindication for mECT or rTMS
Is pregnant or breast feeding or is planning to get pregnant