Efficacy and Mechanism of IPSRT for Bipolar II Disorder

The Efficacy and Mechanism of Different Intervention Strategy for Bipolar II Disorder Patients With Rhythm Disturbance

This project is based on the biphasic instability model and social timing theory, utilizing IPSRT to help regulate social interactions and establish regular daily habits, alleviate emotional symptoms, and prevent. The included patients with bipolar II disorder who did not take medication for the first time or relapsed within the past month were randomly divided into a medication only group (Q group), a only IPSRT group (I group). Group Q received treatment with quetiapine alone (starting at 50mg/day, with an additional 50mg to 300mg/day per week, and the dosage can be flexibly adjusted); Group I received 12 weeks of interpersonal and social rhythm therapy (12 sessions, once a week, 40 minutes each time, with relatively fixed tasks and agendas for each meeting). Compare the changes in various clinical evaluation scales and skin potential before and after treatment, explore the safety and effectiveness of drug therapy and psychotherapy for patients with bipolar II disorder with rhythm disorders, and investigate the potential biological mechanism of IPSRT by collecting data on salivary cortisol and melatonin, peripheral circadian rhythm genes (PER1/PER2/PER3/BMAL1), and magnetic resonance.

Study Overview

• Status: Not yet recruiting
• Conditions: Bipolar Disorder II
• Intervention / Treatment: Drug: Quetiapine (drug); Behavioral: Psychopharmacological treatment

• Study Type: Interventional
• Enrollment (Estimated): 216
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Huang Manli, Professor; Phone Number: 13957162975 Ext. 86; Email: huangmanli@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The First Affiliated Hospital of Zhejiang University
      • Contact: Huang Manli, M.D; Phone Number: 13957162975 Ext. 86; Email: huangmanli@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1: a primary diagnosis of bipolar II disorder in accordance with DSM-V criteria, in a current major depressive episode;

  2: scoring ≥17 on the 17-item Hamilton Rating Scale for Depression (HAMD-17)

  3: scoring <12 on the Young Mania Rating Scale (YMRS)

  4: medication-free (≥4 weeks without psychotropics)

  5: with rhythm disturbance, scoring >26 on the Biological Rhythm Interview for Neuropsychiatry (BRIAN)

  6: Understand written language and be able to conduct questionnaire survey

  7: 18 to 60 years old, gender is not limited

  8: the patient voluntarily participates, signs a written informed consent form, is willing to participate in the study and undergo evaluation

  9: Han Chinese

  10: Right-handedness

Exclusion Criteria:

• 1: diseases that may significantly increase research risks or interfere with the evaluation of results

  2: patients with rapid-cycling bipolar disorder (with >4 episodes within the past year);

  3: any psychiatric or organic mental disorder, bipolar I disorder (BD I), current alcohol or drug dependence, borderline or antisocial personality disorder

  4: patients currently receiving any psychological treatment or melatonin treatment intervention

  5: patients with active suicidal ideation, HAMD-17 item 3 score ≥3

  6: pregnant

  7: patients with metal objects in the body (pacemaker, cochlear implant, implanted teeth, braces, metal foreign bodies, cardiac stent/intravascular coil, orthopedic steel plate, etc.) and other MRI examination contraindications (claustrophobia or inability to cooperate with the examination).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group Q; Patients received treatment with quetiapine alone (starting at 50mg/day, with an additional 50mg to 300mg/day per week, and the dosage can be flexibly adjusted)	Drug: Quetiapine (drug); Patients received treatment with quetiapine alone (starting at 50mg/day, with an additional 50mg to 300mg/day per week, and the dosage can be flexibly adjusted)
Experimental: Group I; Patients received 12 weeks of interpersonal and social rhythm therapy (12 sessions, once a week, 40 minutes each time, with relatively fixed tasks and agendas for each meeting)	Behavioral: Psychopharmacological treatment; Patients received 12 weeks of interpersonal and social rhythm therapy (12 sessions, once a week, 40 minutes each time, with relatively fixed tasks and agendas for each meeting); Other Names: Interpersonal and Social Rhythm Therapy (IPSRT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Scale (17-items) Total Score Change	The Hamilton Depression Scale (17-items), is a 17 item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. It's considered the gold standard for rating depression severity and used frequently in clinical trials. Higher HAM-D17 score indicates more severe depression. A reduction of 50% or more in total score from Baseline indicates clinical response.	Baseline，4，8，12 weeks after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of The Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) score	The BRIAN comprises 18 items, which are divided in 3 areas: sleep and social rhythms, activities and eating pattern. The total score ranged from 18 to 72, a higher score suggested a more severe biological rhythm disturbance.	Baseline，4，8，12 weeks after treatment
Neuroimaging	MRI	Baseline，12 weeks after treatment
Skin potential	In a quiet environment, the subject's left hand was pre connected to a portable skin potential acquisition device to collect skin potential signals under different types of emotional stimulation task paradigms. After denoising, 10 time-domain eigenvalues and 8 time-frequency domain eigenvalues were obtained for each task.	Baseline，12 weeks after treatment
Polysomnography	overnight polysomnography	Baseline，12 weeks after treatment
Change of the Brief Social Rhythm Scale (BSRS) score	The BSRS assess the irregularity with which participants engage in basic daily activities during the workweek and on the weekend, using a scale ranging from 1 (very regularly) to 6 (very irregularly）	Baseline，4，8，12 weeks after treatment
Neuropsychological tests	Software testing (Prisoner's Dilemma game, Social searching task)	Baseline，12 weeks after treatment
Change of Beck Scale of Suicidal Ideation score	Beck Scale of Suicidal Ideation is a 21-item self-report instrument that detects and measures the intensity of a patient's specific attitudes, behaviors, and suicide plans during the past week. The BSI score ranges from 0 to 63, with higher scores indicating worse outcomes and lower scores indicating better outcomes.	Baseline，4，8，12 weeks after treatment
Change of the Pittsburgh Sleep Quality Index (PSQI) score	The PSQI is a validated self-report questionnaire assessing sleep quality and disturbance over 1 month, quantifying 7 sleep-related domains, with higher scores indicating worse sleep quality.	Baseline，4，8，12 weeks after treatment
Change of the Young Mania Rating Scale (YMRS) score	The Young Mania Rating Scale (YMRS) , is a 11 item diagnostic questionnaire used to measure the severity of mania symptom in patients with mood disorders.	Baseline，4，8，12 weeks after treatment
Change of Hamilton Anxiety Scale score	Hamilton Anxiety Scale is a 17 item diagnostic questionnaire used to measure the severity of anxiety episodes in patients. Each item on the scale is rated on a 5-point scale from 0 (not present) to 4 (severe), with the total score ranging from 0 to 68. The HAMA-17 is often used in clinical and research settings to assess the severity of anxiety symptoms and to evaluate the effectiveness of treatments for anxiety.	Baseline，4，8，12 weeks after treatment
Change of the Sociaty Adaptive Scale score	SAS is a self-rating scale used to assess an individual's social functioning in areas such as work, study, interpersonal communication, and family life.	Baseline，4，8，12 weeks after treatment
blood	Blood samples are collected to analyze the expression levels of peripheral circadian clock genes (PER1/PER2/PER3/BMAL1).	Baseline，12 weeks after treatment
saliva samples	Saliva is employed for the analysis of cortisol and melatonin	Baseline，12 weeks after treatment

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Collaborators: Shanghai Mental Health Center; Second Xiangya Hospital of Central South University; Zhejiang Provincial Tongde Hospital; Brain Hospital Affiliated to Guangzhou Medical University; The Affiliated Hospital of Hangzhou Normal University; Hunan Mental Hospital; First Affiliated Hospital of Kunming Medical University; Brain Hospital Hunan Province

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: June 12, 2026
• First Submitted That Met QC Criteria: June 12, 2026
• First Posted (Actual): June 17, 2026

Study Record Updates

• Last Update Posted (Actual): June 17, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: bipolar disorder II; interpersonal and social rhythm therapy
• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Mood Disorders; Bipolar Disorder; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Dibenzothiazepines; Thiazepines; Thiepins; Quetiapine Fumarate; Pharmaceutical Preparations
• Other Study ID Numbers: IIT20250074C-R2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No