Alcohol Response for Bipolar Disorder

(Long_BACS Trial)

Overseen By Research Coordinator

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas at Austin

Must not be taking: Psychotropics

Disqualifiers: Significant illness, Neurologic abnormality, IQ <85, others

Compensation: Varies

Number of Visits: 4

100 Participants Needed

Trial Summary

What is the purpose of this trial?

Alcohol use disorders (AUDs) affect up to 60% of individuals with bipolar disorder during their lifetime and is associated with worse illness outcomes, yet few studies have been performed to clarify the causes of this comorbidity. Understanding biological risk factors that associate with and predict the development of AUDs in bipolar disorder could inform interventions and prevention efforts to reduce the rate of this comorbidity and improve outcomes of both disorders. Identifying predictors of risk requires longitudinal studies in bipolar disorder aimed at capturing the mechanisms leading to the emergence of AUDs. Previous work in AUDs suggest that subjective responses to alcohol and stress-related mechanisms may contribute to the development of AUDs. In bipolar disorder, altered developmental trajectory of critical ventral prefrontal networks that modulate mood and reward processing may alter responses to alcohol and stressors; consequently, the disruption in typical neurodevelopment may be an underlying factor for the high rates of comorbidity. No longitudinal data exist investigating if this developmental hypothesis is correct. To address this gap, the investigators will use a multimodal neuroimaging approach, modeling structural and functional neural trajectories of corticolimbic networks over young adulthood, incorporating alcohol administration procedures, clinical phenotyping, and investigating effects of acute stress exposure and early life stress. Research aims are to identify biological risk factors-i.e., changes in subjective response to alcohol and associated neural trajectories-that are associated with the development of alcohol misuse and symptoms of AUDs over a two-year longitudinal period in young adults with bipolar disorder and typical developing young adults. Longitudinal data will be collected on 160 young adults (50% with bipolar disorder, 50% female; aged 21-26). This study is a natural extension of the PI's K01 award. How acute exposure to stress and childhood maltreatment affects subjective response to alcohol and risk for prospective alcohol misuse and symptoms of AUDs will be investigated. The investigators will test our hypothesis that developmental differences in bipolar disorder versus typical developing individuals disrupt corticolimbic networks during young adulthood, increase sensitivity to stress, and lead to changes in subjective response to alcohol and placebo response increasing risk for developing AUDs.

Will I have to stop taking my current medications?

The trial requires that participants with bipolar disorder must be stable on their medications for at least 4 weeks before joining. This means you should not stop taking your current medications.

Is alcohol generally safe for people with bipolar disorder?

The studies suggest that people with bipolar disorder may have different responses to alcohol, but they do not provide specific safety data. It's important to consult with a healthcare provider for personalized advice. ^{1 2 3 4 5}

How does the alcohol treatment differ from other treatments for bipolar disorder?

This treatment is unique because it involves administering alcohol to study its effects on individuals with bipolar disorder, which is not a standard approach for treating this condition. The focus is on understanding how alcohol affects mood and behavior in people with bipolar disorder, rather than directly treating the disorder itself. ^{1 5 6 7 8}

Research Team

Elizabeth Lippard, PhD

Principal Investigator

University of Texas at Austin

Eligibility Criteria

This study is for young adults aged 21-26, both with bipolar disorder and typical development. Participants must have had a certain level of alcohol use in the past year but not severe alcohol use disorders or other significant medical conditions. They should be stable on medications if any, and able to undergo MRI scans.

Inclusion Criteria

Participants must have consumed at least 4 (men) or 3 (women) drinks on a single occasion over the last year

Participants must be euthymic at the time of enrollment

I am between 21 and 26 years old.

Exclusion Criteria

I have a history of heart issues, high blood pressure, diabetes, or liver disease.

I have had a significant head injury with unconsciousness for 5 minutes or more.

History of significant medical illness, particularly if possible changes in cerebral tissue

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline clinical, MRI, and placebo-controlled alcohol administration sessions

4 weeks

1 visit (in-person)

Longitudinal Follow-up

Participants are monitored for changes in subjective response to alcohol and neural trajectories over a two-year period

2 years

2 visits (in-person) at 1-year and 2-year follow-up

Psychosocial Stress Task

A subset of participants complete a psychosocial stress and neutral fMRI task followed by an alcohol session

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Alcohol vs. Placebo beverage conditions

Trial Overview The trial investigates how individuals with bipolar disorder respond to alcohol compared to a placebo beverage. It aims to understand biological risk factors for developing alcohol misuse by using neuroimaging techniques over two years.

Participant Groups

Group I: Alcohol Active Control 1 Intervention

Participants will be provided alcohol during study visits and changes in behavior/neural activity after consuming alcohol will be examined.

Group II: Placebo Placebo Group 1 Intervention

placebo beverage condition

Who Is Running the Clinical Trial?

University of Texas at Austin

Lead Sponsor

Trials

387

Recruited

86,100+

Findings from Research

Unmedicated young males with a history of hypomanic experiences (bipolar phenotype participants) reported significantly lower subjective intoxication effects from alcohol compared to healthy controls, indicating a potential biomarker for alcohol use disorders (AUDs).

Despite their lower subjective responses, these participants had higher expectations of alcohol's positive effects, suggesting that diminished intoxication may contribute to increased alcohol misuse among those at risk for bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced subjective response to acute ethanol administration among young men with a broad bipolar phenotype. Yip, SW., Doherty, J., Wakeley, J., et al.[2022]

About 23% of patients with bipolar disorder (BD) also have a lifetime diagnosis of alcohol use disorder (AUD), with significant differences in demographics and clinical characteristics between those with and without AUD.

Key factors associated with a lifetime AUD diagnosis in BD patients include male gender, rapid cycling, history of substance use disorders, PTSD, and younger age at onset of bipolar disorder, indicating that these factors can help identify patients at higher risk for AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and clinical correlates of alcohol use disorders among bipolar disorder patients: results from the Brazilian Bipolar Research Network. Nery, FG., Miranda-Scippa, A., Nery-Fernandes, F., et al.[2018]

In a study of 137 outpatients with bipolar disorder over 52 weeks, neither moderate nor excessive alcohol use was found to negatively impact the course or outcome of their illness, contradicting previous research.

The study measured various clinical outcomes, including mood severity and overall functioning, and found no significant differences among patients based on their alcohol consumption levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of moderate and excessive alcohol use on the course and outcome of patients with bipolar disorders: a prospective cohort study. van Zaane, J., van den Brink, W., Draisma, S., et al.[2010]

In a study of 89 adults with bipolar disorder, 57.8% of those with bipolar I disorder were found to have substance or alcohol abuse dependence, indicating a high prevalence of comorbidity.

Bipolar I subjects showed higher rates of substance abuse compared to bipolar II subjects, with alcohol being the most commonly abused substance, although further research is needed to confirm these findings due to the small number of bipolar II participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lifetime prevalence of substance or alcohol abuse and dependence among subjects with bipolar I and II disorders in a voluntary registry. Chengappa, KN., Levine, J., Gershon, S., et al.[2019]

Young adults with bipolar disorder reported a greater stimulating effect and enjoyment from alcohol compared to healthy young adults, indicating a heightened subjective response to alcohol that may increase their risk for alcohol use disorder (AUD).

Despite expecting to feel less relaxed when drinking, participants with bipolar disorder actually felt more mellow and relaxed during alcohol consumption, which was linked to higher recent alcohol use, suggesting a complex relationship between mood, alcohol response, and drinking behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subjective response to alcohol in young adults with bipolar disorder and recent alcohol use: a within-subject randomized placebo-controlled alcohol administration study. Lippard, ETC., Kirsch, DE., Kosted, R., et al.[2023]

In a study of 46 adolescents and young adults with bipolar disorder, reductions in risky alcohol use were linked to improvements in NMDA receptor function, as measured by changes in mismatch negativity (MMN) over an average follow-up of about 18 months.

Larger MMN amplitudes at baseline predicted higher alcohol use at follow-up, suggesting that monitoring MMN could help identify individuals at risk for alcohol misuse in bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The N-methyl-D-aspartate receptor as a neurobiological intersection between bipolar disorder and alcohol use: a longitudinal mismatch negativity study. Chitty, KM., Lagopoulos, J., Kaur, M., et al.[2018]

A study of 30 patients with bipolar disorder revealed significant alcohol consumption, averaging 18.4 drinking days per month and nearly 10 drinks per day, indicating a high prevalence of alcohol use in this population.

The findings showed that patients with rapid cycling bipolar disorder consumed more alcohol per day compared to those with non-rapid cycling bipolar disorder, suggesting that different bipolar subtypes may have varying patterns of alcohol use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of alcohol consumption in bipolar patients comorbid for alcohol abuse or dependence. McKowen, JW., Frye, MA., Altshuler, LL., et al.[2007]

In a study of 284 bipolar disorder patients followed for 4 years, alcohol use disorders were found to be more prevalent in bipolar II patients (26.8%) compared to bipolar I patients (14.9%), highlighting a significant association between alcohol use and bipolar disorder severity.

The presence of alcohol use disorders significantly increased the risk of depressive relapse in bipolar I patients, with a hazard ratio of 2.7, indicating that addressing alcohol use is crucial for improving long-term outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and impact of comorbid alcohol use disorder in bipolar disorder: A prospective follow-up study. Simhandl, C., Radua, J., König, B., et al.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Reduced subjective response to acute ethanol administration among young men with a broad bipolar phenotype. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Prevalence and clinical correlates of alcohol use disorders among bipolar disorder patients: results from the Brazilian Bipolar Research Network. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

The effect of moderate and excessive alcohol use on the course and outcome of patients with bipolar disorders: a prospective cohort study. [2010]

4. Denmark pubmed.ncbi.nlm.nih.gov

Lifetime prevalence of substance or alcohol abuse and dependence among subjects with bipolar I and II disorders in a voluntary registry. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Subjective response to alcohol in young adults with bipolar disorder and recent alcohol use: a within-subject randomized placebo-controlled alcohol administration study. [2023]

6. England pubmed.ncbi.nlm.nih.gov

The N-methyl-D-aspartate receptor as a neurobiological intersection between bipolar disorder and alcohol use: a longitudinal mismatch negativity study. [2018]

7. Denmark pubmed.ncbi.nlm.nih.gov

Patterns of alcohol consumption in bipolar patients comorbid for alcohol abuse or dependence. [2007]

8. England pubmed.ncbi.nlm.nih.gov

Prevalence and impact of comorbid alcohol use disorder in bipolar disorder: A prospective follow-up study. [2016]