Algorithm Guided Treatment Strategies for Bipolar Depression (AGTs-BD)

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.

Study Overview

• Status: Unknown
• Conditions: Bipolar Disorder
• Intervention / Treatment: Drug: Lithium; Drug: Quetiapine; Drug: Shuganjieyu capsule

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.

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lithium combined with SGAs; SGAs (Second Generation Antipsychotics), quetiapine adjunctive to lithium therapy	Drug: Lithium; 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.; Drug: Quetiapine; 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.
Experimental: lithium combined with TCM; TCM (Traditional Chinese Medicine), Shuganjieyu capsule adjunctive to lithium therapy.	Drug: Lithium; 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.; Drug: Shuganjieyu capsule; Shuganjieyu capsule adjunctively to lithium therapy, target dose 1440 mg/d.; Other Names: SGJY, St.John's wort and acanthopanax senticosus combination
Active Comparator: Lithium monotherpy; Lithium monotherapy	Drug: Lithium; 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.

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

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Investigators: Principal Investigator: Yiru Fang, M.D., Ph.D., Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2012
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: September 5, 2013
• First Submitted That Met QC Criteria: September 9, 2013
• First Posted (Estimate): September 10, 2013

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: October 3, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: safety; quetiapine; bipolar disorder; Recurrence; lithium; efficacy; Medicine, Chinese Traditional
• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Quetiapine Fumarate
• Other Study ID Numbers: 2012BAI01B04-BD; 2012BAI01B04 (Other Grant/Funding Number: 2012BAI01B04)