Sarah Bilali

Medical and substance use comorbidity in bipolar disorder.

OBJECTIVE National Comorbidity Survey data indicate that bipolar disorder is characterized by high lifetime rates of co-occurring anxiety and substance use disorders (SUDs). Although compelling evidence suggests SUD comorbidity predicts non-response to treatment, the relationship between medical comorbidity and treatment response has not been studied adequately. In an attempt to understand the impact of medical comorbidity on treatment outcome, an analysis was conducted to inform the relationship between co-occurring medical illness, the phenomenology of bipolar disorder, and response to treatment with mood stabilizers. METHOD A total of 98 adult outpatients with rapid-cycling bipolar I or II disorder and co-occurring SUDs were prospectively treated with the combination of lithium and valproate for up to 24 weeks. A logistic regression analysis was conducted to explore the relationship between phenomenology, response to mood stabilizers, and medical comorbidity as assessed by the Cumulative Illness Rating Scale (CIRS). High and low medical comorbidity burden were defined as a CIRS total score > or = 4 and < or = 3, respectively. RESULTS Every patient enrolled into this study had at least 1 medical illness (most commonly respiratory, 72%) and on average had 4.9 different medical conditions. Over half of patients (52%) exhibited illnesses across four or more different organ systems, 24% had uncontrollable medical illnesses, and the mean overall total CIRS score was 5.56. The average body mass index (BMI) was 28.1 with 38% being overweight and 29% being obese. High medical burden was observed in 64% and was most strongly predicted by a diagnosis of bipolar I disorder (OR=34.9, p=0.002, 95%CI=3.9-316.1). A history of attempted suicide (OR=10.3, p=0.01, 95%CI=1.7-62.0), a history of physical abuse (OR=7.6, p=0.03, 95%CI=1.3-45.7) and advancing age (OR=1.2, p<0.001, 95%CI=1.1-1.3) also independently predicted a high burden of general medical problems. Only 21% (N=21) of subjects enrolled into this study showed a bimodal response to treatment with lithium plus valproate, and neither BMI nor any summary CIRS measure predicted response. CONCLUSION Rapid cycling with co-occurring substance use is not only associated with poor response to mood stabilizers, but is also a harbinger of serious medical problems. A high burden of medical comorbidity was associated with the bipolar I subtype, a history of attempted suicide, a history of physical abuse, and advancing age.

Independent Predictors for Lifetime and Recent Substance Use Disorders in Patients with Rapid-Cycling Bipolar Disorder: Focus on Anxiety Disorders

We set out to study independent predictor(s) for lifetime and recent substance use disorders (SUDs) in patients with rapid-cycling bipolar disorder (RCBD). Extensive Clinical Interview and Mini-International Neuropsychiatric Interview were used to ascertain DSM-IV Axis I diagnoses of RCBD, anxiety disorders, and SUDs. Data from patients enrolling into four similar clinical trials were used. Where appropriate, univariate analyses with t-test or chi-square were applied. Stepwise logistic regression was used to examine the relationship among predictor variables and lifetime and recent SUDs. Univariate analysis showed that patients with co-occurring anxiety disorders (n = 261) had significantly increased rates of lifetime (odds ratio [OR]= 2.1) and recent (OR = 1.9) alcohol dependence as well as lifetime (OR = 3.4) and recent (OR = 2.5) marijuana dependence compared to those without co-occurring anxiety disorder (n = 303). In logistic regression analyses, generalized anxiety disorder (GAD) was associated with increased risk for lifetime SUDs (OR = 2.34), alcohol dependence (OR = 1.73), and marijuana dependence (OR = 3.36) and recent marijuana dependence (OR = 3.28). A history of physical abuse was associated with increased risk for lifetime SUDs (OR = 1.71) and recent marijuana dependence (OR = 3.47). Earlier onset of first mania/hypomania was associated with increased risk for lifetime SUDs (5% per year), and recent marijuana dependence (12% per year) and later treatment with a mood stabilizer were also associated with increased risk for recent SUDs (8% per year). Positive associations between GAD, later treatment with a mood stabilizer, and early childhood trauma and history of SUDs suggest that adequate treatment of comorbid anxiety, early treatment with a mood stabilizer, and prevention of childhood trauma may reduce the risk for the development of SUDs in patients with bipolar disorder.