Antidepressant Treatments and Cognitive Function of Bipolar Patients

The Impact of Systemic Antidepressant Treatments in Early Stage on Neurocognitive Function of Euthymic Patients With Bipolar Depression

Patients with bipolar disorder (BD) have a wide range of neurocognitive dysfunction, which lead to impaired psychosocial function and reduced quality of life. Therefore, improving neurocognitive function has become an important goal of BD treatment. Aiming at this, some clinical studies have been performed but failed to illustrate significant positive efficacies of pharmacological therapy or non-pharmacological therapy, which could attribute in part to insufficient understanding on the risk factors that affect the neurocognitive function of BD patients. Delayed diagnosis of BD is so common that a lot of patients receive long-term antidepressant treatment before of diagnosis of unipolar depression. There is controversy about whether antidepressant treatment in early stage would affect the neurocognitive function of BD patients. In view of the high prevalence of delayed diagnosis and the use of antidepressants, it is of great scientific significance and clinical value to clarify this matter and other factors that may potentially affect the neurocognitive function of BD patients.

Study Overview

• Status: Recruiting
• Conditions: Bipolar Disorder; Cognition

Detailed Description

Subjects will not be engaged with any interventions in this study. Two senior psychiatrists are in attendance of screening the patients with the inclusion/exclusion criteria, and then all patients who meet both criteria and are willing to participate in this study will sign the informed consent before enrollment. The participants will be divided into AT or NT group according to their history of antidepressant treatment in early stage, which is done by the two senior psychiatrists. Then these senior psychiatrists will also collect additional study parameters, such as age, sex, nation, age of onset, and score of Premorbid Adjustment Scale (PAS). Furthermore, the information about history of treatments and diagnosis will be further confirmed with medical documentary and patients' guardians. Afterwards, other investigators will finish the rating work of the rest of scales. The whole procedure should be done within 180 min. Finally, ten milliliters of venous blood are adopted for measuring NSE

• Study Type: Observational
• Enrollment (Anticipated): 124

Contacts and Locations

• Study Contact: Name: Chenghao Yang, Doctor; Phone Number: +86 13752539531; Email: yts83420@163.com

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Tianjin Anding Hospital
    • Contact: Jie Li, Doctor; Email: jieli@tjmhc.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This study will consist of a sample of 124 patients with bipolar disorder who initiated with a depressive episode and being a euthymic state for 4 weeks at least before enrollment.All participants are divided into two groups according to whether they had received systemic antidepressant treatment or not in the early stage.

Description

Inclusion Criteria:

1. A diagnosis of BD diagnosed according to the Diagnostic and Statistical Manual of Mental disorders, Fourth Edition (DSM-IV-TR) diagnosed with Structured Clinical Interview for DSM-IV (SCID); a current state of euthymia is defined by both scores of Montgomery-Åsberg Depression Scale (MADRS) and Young Manic Rating Scale (YMRS) <7, lasting for 4 weeks at least before recruitment
2. Initiated with a depressive episode
3. Aged between 18~50 years
4. Patients comply with all procedures of study
5. Participants must sign the informed consent

Exclusion Criteria:

1. A history of psychiatric symptoms
2. A comorbidity of attention deficit and hyperactivity disorder (ADHD)
3. Neurological trauma or neurological diseases which could cause cognition injury
4. History of substance dependence/abuse
5. Received modified electroconvulsive therapy (MECT) in the past 12 months
6. Severe physical disease affecting cognitive function or increasing peripheral NSE
7. Recent drug use that affects cognition, such as tricyclic antidepressants, anticholinergic drugs, amphetamines, etc.
8. IQ <70
9. Use benzodiazepines 4 hours before scale evaluation

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
antidepressant treatment group; participants who had received systemic antidepressant (consecutive treatment with adequate antidepressants for 6 weeks at least)treatment in the early stage (from initial depressive onset to first manic/hypomani episode).
non-antidepressant treatment group; participants who had not received systemic antidepressant (consecutive treatment with adequate antidepressants for 6 weeks at least)treatment in the early stage (from initial depressive onset to first manic/hypomani episode).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective cognitive measures	cognitive complaints in Bipolar Disorder Rating Assessment (COBRA)	before 11AM
Objective cognitive measures	the Stroop Color and Word Test (SCWT), the categorical verbal fluency test (CVFT) (animal naming), and the Trail Making Test Part B (TMT-B), the Digital Span Forward and Backward subtest (DSFB) and the Digit Symbol Coding subtest (DSC) of the Wechsler Adult Intelligence Scale-Revised by China (WAIS-RC) and Trail Making Test Part A (TMT-A), the Visual Reproduction subtest (VRP) and the Visual Recognition subtest (VRC) of the Wechsler Memory Scale-Revised (WMS-R)	before 11AM

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Assessment Function (GAF)	to assess patients' functions psychologically, socially and professionally	before 11AM
Methods Checklist on Quality of Life issued by World Health Organization-Brief version,WHOQOL-BRIEF	to assess the quality of life	before 11AM
Peripheral neuron-specific enolase (NSE)	to test the potential injury of neuron	before 11.30AM

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pittsburgh Sleep Quality Index,PSQI	to evaluate the quality of sleep	before 11AM
Positive and Negative Affect Scale,PANAS	to detect the change in positive and negative affect	before 11AM

Collaborators and Investigators

• Sponsor: Tianjin Anding Hospital
• Investigators: Principal Investigator: Chenghao Yang, Doctor, Tianjin Anding Hospital

Publications and helpful links

General Publications

• Yang H, Liu Y, Yang C, Lin X. The effect of systemic antidepressant treatments in early stage on neurocognitive function of euthymic bipolar patients initiated with a depressive onset: An observational, cross-sectional, single-blind study protocol. Brain Behav. 2021 Oct;11(10):e2360. doi: 10.1002/brb3.2360. Epub 2021 Sep 14.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): October 30, 2022

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): December 13, 2021
• Last Update Submitted That Met QC Criteria: December 8, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: bipolar depression; antidepressant treatment; neurocognitive function; euthymic state
• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder
• Other Study ID Numbers: TJAH2020-18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Request based on researcher's consent
• IPD Sharing Time Frame: the data will be available openly after the study finished with no termination.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

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