Algorithm Guided Treatment Strategies for Major Depressive Disorder

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Algorithm Guided Treatment Strategies for Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Algorithm Guided Treatment (AGT)<br>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<br>* 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.<br>* Other names: Lexapro;Drug: Mirtazapine<br>* 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.<br>* Other names: Remeron;Other: modified electroconvulsive therapy<br>* 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.<br>* Other names: mECT;Other: repetitive transcranial magnetic stimulation<br>* 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.<br>* Other names: rTMS;|
| Active Comparator: Treatment As Usual (TAU)<br>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<br>* Fluoxetine may be prescribed for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.<br>Drug: Citalopram<br>* Citalopram may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.<br>Drug: Escitalopram<br>* Escitalopram may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.<br>Drug: Paroxetine<br>* Paroxetine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.<br>Drug: Sertraline<br>* Sertraline may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.<br>Drug: Fluvoxamine<br>* Fluvoxamine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.<br>Drug: Venlafaxine<br>* Venlafaxine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.<br>Drug: Duloxetine<br>* Duloxetine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.<br>Drug: Mirtazapine<br>* Mirtazapine may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.<br>Drug: Bupropion<br>* Bupropion may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.<br>Drug: Trazodone<br>* Trazodone may be used for participants who are randomly assigned to the Treatment As Usual (TAU) arm based on clinician's judgement.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission defined as endpoint 17-item Hamilton Rating Scale for Depression (HRSD-17) total score ≤ 7 | 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. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Self-report and clinician rating frequency and intensity of adverse events will be measured at up to 12 weeks. | 12 weeks | 
| Quality of life | Change from baseline in 6-item Quality of life Inventory will be measured at up to 12 weeks. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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major depressive disorder, algorithm guided treatment, treatment as usual, escitalopram, mirtazapine, transcranial magnetic stimulation (rTMS), modified electroconvulsive therapy (mECT), remission, relapse, quality of life