Are there differences in the clinical course of bipolar I and bipolar II disorder with and without comorbid alcohol use disorder?
There is evidence for an increased prevalence of comorbid substance use disorders (SUDs) in patients with bipolar disorder (BD), even when compared with other psychiatric disorders.1 The epidemiological catchment area study found that the lifetime prevalence of alcohol abuse or dependence in bipolar I and II disorder was 46% and 39%, respectively. A more recent epidemiologic survey of 43,000 respondents found a 24% 12-month and 56% lifetime prevalence of any alcohol use disorders (AUD) in patients with bipolar I disorder.2 There is also evidence that comorbid AUD is associated with a more complicated illness course and poorer outcomes in patients with BD.3
Most studies of comorbid BD and AUD have been retrospective, and few prospective studies have differentiated between bipolar I and II disorders. Using the COGA sample (Collaborative Study on Genetics in Alcoholism), Preuss and colleagues4 directly compared patients who had bipolar I and II disorders with and without comorbid alcohol dependence. These patients were assessed at baseline and then prospectively reinterviewed after 5 years.
COGA enrolls treatment-seeking probands with DSM-IV alcohol dependence (and their relatives) at 6 centers in the United States. Exclusion criteria are life-threatening medical disorders, repeated intravenous drug use, and an inability to speak English. Patients were interviewed at baseline, as well as after approximately 5 years using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). The SSAGA contains an assessment of 17 DSM-IV diagnoses, including BD, as well as the timing of symptom onset and remission.
Altogether, 228 participants with bipolar I disorder or bipolar II disorder were identified. One-hundred seventy-two patients had a comorbid diagnosis of alcohol dependence (N = 56 with bipolar II [Group 2] and 116 with bipolar I [Group 4]). Fifty-six individuals did not have comorbid alcohol dependence (N = 20 with bipolar II [Group 1] and N = 36 with bipolar I [Group 3]). One-hundred twenty-one (53%) of patients were reassessed at a mean of 5.7 years after the initial interview, including 13, 30, 17, and 61 patients in Groups 1, 2, 3, and 4, respectively. All participants were in a euthymic mood state at the time of the SSAGA interview. Between-group differences were evaluated using chi-square tests for categorical data and 1-way analysis of variance (ANOVA). Repeated-measures ANOVA was used to compare continuous variables over time.
At baseline, the mean age was 36 years; 52% were female, and 74% were Caucasian. Regarding patients with alcohol dependence, those with bipolar II disorder had a higher rate of alcohol-related liver disease than those with bipolar I disorder (10.7% versus 1.7%). Individuals with bipolar I disorder were significantly more likely to have had outpatient treatment than those with bipolar II disorder (48% versus 29%). Otherwise, there were no differences in age of onset of alcohol dependence, treatment, alcohol-related violence and physical problems, and other psychiatric comorbidity.
There were no significant differences in age of onset of mania/hypomania and depression between all groups. There were also no significant difference in the proportion of patients with lifetime suicidal ideation and suicide attempt between patient groups. However, patients with bipolar I or II disorder and comorbid alcohol dependence had a greater number of lifetime suicide attempts than patients without alcohol comorbidity (5 versus 1.5), although this finding was not statistically significant. Patients with bipolar I disorder and alcohol dependence had a significantly lower global assessment of functioning score (58) than the other groups (range 67-75).
During the 5-year follow-up, regarding patients with alcohol dependence, subjects with bipolar I disorder had a significantly higher prevalence of binge drinking than those with bipolar II disorder (31.1% versus 13.3%). Individuals with comorbid bipolar I disorder and AUD had a significantly higher prevalence of suicidal ideation (46% versus 10% to 29%) and suicide attempt (18% versus 0%) than the other groups. Patients with bipolar I disorder and alcohol dependence also had more affective symptoms and significantly lower global assessment of functioning score (59) than the other groups (range 62-77).
The authors concluded that individuals with bipolar I disorder and comorbid alcohol dependence had a worse course of mood illness. One limitation of the present study include that the target of the COGA study was patients with alcohol dependence, and therefore only about one-quarter of the patients with BD did not have comorbid alcohol dependence. Another limitation is that almost half of the participants could not be re-interviewed after 5 years, and there is the potential for selective recall bias in those who were interviewed. A primary strength of the study is consideration of patients with bipolar I and bipolar II disorders, separately.
The bottom line
There is evidence from this prospective study that there is a more severe course of bipolar illness in patients with bipolar I disorder and comorbid alcohol dependence. These patients may require comprehensive treatment for psychiatric and SUDs in order to improve symptomatic and functional outcomes.
Dr Miller is professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric TimesTM. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Stanley Medical Research Institute.
1. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse: results from the epidemiologic catchment area (ECA) study. JAMA. 1990;264:2511-2518.
2. Grant BF, Stinson FS, Hasin DS, et al. Prevalence, correlates, and comorbidity of bipolar I disorder and axis I and II disorders: results from the National epidemiologic survey on alcohol and related conditions. J Clin Psychiatr. 2005;66:1205-1215.
3. Salloum IM, Thase ME. Impact of substance abuse on the course and treatment of bipolar disorder. Bipolar Disord. 2000;2:269-280.
4. Preuss UW, Hesselbrock MN, Hesselbrock VM. A prospective comparison of bipolar I and iI subjects with and without comorbid alcohol dependence from the COGA dataset. Front Psychiatry. 2020;11:522228.