Algorithm Guided Treatment Strategies for Bipolar Depression

Study Overview
=================
Brief Summary
-----------------
The purpose of the AGTs-BD study is to compare the treatment outcome and safety profiles between different mood stabilizers combination treatments in the patients with bipolar disorders, currently suffered from depression episode.

Detailed Description
-----------------
The AGTs-BD study is a randomized, open-label, rater-blind, multicenter study, which including an 8-week acute treatment (Phase I), followed by a 24-week recurrence prevention treatment (Phase II), and a 24-week relapse prevention treatment (Phase III). Patients initially enter an up to 4 weeks screening phase to confirm the randomization to whom met DSM-IV criteria of bipolar I or II disorder, currently depressed with Hamilton Depression Rating Scale-17 items (HAM-D) total score ≥17. The protocol was approved by the each sites' appropriate institutional review boards and ethics committees. After screening, patients were randomly allocated to one of three groups: (1) lithium monotherapy; (2) lithium plus quetiapine; (3) lithium plus a Traditional Chinese Medicine (TCM) named as Shuganjieyu capsule (SGJY, St. John's wort and acanthopanax senticosus combination). After phase I, patients who met stable remission, defined as HAM-D total score ≤7 and Young Mania Rating Scale (YMRS) total score ≤10 in two consecutive visit at least 4 weeks, were qualified into phase II and III. Patients remained on the allocated treatment for up to 48 weeks or until treatment failure. The difference between phase II and phase III was that treatment dose could be decreased (within the study ranges) if side-effects became troublesome in phase III, but not for phase II. All patients will be provided with free care (3 visits) by the investigators, for a period of up to 3 months after the end of the study, in order to help them make the transition into routine clinical care.

Official Title
-----------------
Algorithm Guided Treatment Strategies for Bipolar Depression

Conditions
-----------------
Bipolar Disorder

Intervention / Treatment
-----------------
* Drug: Lithium
* Drug: Quetiapine
* Drug: Shuganjieyu capsule


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age from 18 to 65 years old; Han Chinese; Outpatient and inpatient patients; Patients met DSM-IV criteria of bipolar I or II disorder, currently depressed, ascertained with the Mini International Neuropsychiatric Interview (MINI) HAM-D total score≥17, HAM-D item 1 (depressed mood) score≥2, and YMRS total score≤10 at baseline; Written informed consent was given; Junior high school education and above, with enough audio-visual ability to accomplish the visits; Normally resident in one country and had a residential address, able to follow-up. Exclusion Criteria: Bipolar disorder rapid cycling or mixed episode; Experienced DSM-IV-TR axis I disorders in the 6 months prior to randomization; Severe personality disorder, metal retardation, anorexia/bulimia nervosa; Actively suicide ascertained by research psychiatrist or HAM-D item 3 score≥3(suicidality); Known history of intolerance or hypersensitivity to any of the medications involved in the study, including lithium, quetiapine and SGJY capsule; Female patients who were pregnant, planning to be pregnant or breast feeding; Severe medical or neurological problems.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lithium combined with SGAs<br>SGAs (Second Generation Antipsychotics), quetiapine adjunctive to lithium therapy | Drug: Lithium<br>* Lithium plasma concentration was between 0.6-1.2 mmol/L, dose should be fixed at the end of week 4, and the maximum dosage was judged by the investigator based on the patients' tolerability.<br>Drug: Quetiapine<br>* Quetiapine adjunctively to lithium therapy, target 400 mg/d with a minimum dose of 200 mg/d. Dose should be fixed at the end of week 4, and the maximum dosage was judged by the investigator based on the patients' tolerability.<br>|
| Experimental: lithium combined with TCM<br>TCM (Traditional Chinese Medicine), Shuganjieyu capsule adjunctive to lithium therapy. | Drug: Lithium<br>* Lithium plasma concentration was between 0.6-1.2 mmol/L, dose should be fixed at the end of week 4, and the maximum dosage was judged by the investigator based on the patients' tolerability.<br>Drug: Shuganjieyu capsule<br>* Shuganjieyu capsule adjunctively to lithium therapy, target dose 1440 mg/d.<br>* Other names: SGJY, St.John's wort and acanthopanax senticosus combination;|
| Active Comparator: Lithium monotherpy<br>Lithium monotherapy | Drug: Lithium<br>* Lithium plasma concentration was between 0.6-1.2 mmol/L, dose should be fixed at the end of week 4, and the maximum dosage was judged by the investigator based on the patients' tolerability.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of HAM-D total score only for the phase I |  | baseline and 8 weeks | 
| Time to new intervention for an emerging mood episode | Time to new intervention for an emerging mood episode is only for Phase II and Phase III, including drug treatment (commencement of a new drug, increase in dose of concurrent drug, restarting of a discontinued drug, or increasing the investigational drug dose in response to an emergent mood episode) or admission to hospital. | up to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HAM-D total score ≤7 | Remission rate | 8 weeks for phase I, up to 48 weeks for phase II and III | 
| Mean changes from baseline to EOS in HAM-D total score ≥50% | Response rate | 8 weeks for phase I, up to 48 weeks for phase II and III | 
| Mean changes from baseline to EOS in 16-item Quick Inventory of Depressive Symptomatology-Patient Self-Report (QIDS16-SR) |  | 8 weeks for phase I, up to 48 weeks for phase II and III | 
| Mean changes from baseline to EOS in Clinical Global Impression scale of Bipolar Disorder-Severity (CGI-BP-S) |  | 8 weeks for phase I, up to 48 weeks for phase II and III | 
| Mean changes from baseline to EOS in Sheehan Disability Scale (SDS) | Social function | 8 weeks for phase I, up to 48 weeks for phase II and III | 
| Mean changes from baseline to EOS in 6-item Quality of Life scale (QOL-6) | Social function | 8 weeks for phase I, up to 48 weeks for phase II and III | 
| Young Mania Rating Scale (YMRS) total score ≤10 | Using YMRS total score to monitor the switching from depression to hypomania and mania | 8 weeks for phase I, up to 48 weeks for phase II and III | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
bipolar disorder, lithium, quetiapine, Medicine, Chinese Traditional, efficacy, safety, Recurrence