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author:("bilaii, Sarah")
1.  Clinical Correlates of Patients With Rapid-Cycling Bipolar Disorder and a Recent History of Substance Use Disorder: A Subtype Comparison From Baseline Data of 2 Randomized, Placebo-Controlled Trials 
The Journal of clinical psychiatry  2008;69(7):1057-1063.
To compare clinical variables in patients with rapid-cycling bipolar I or II disorder and a recent history of substance use disorder (SUD).
Cross-sectional data from 2 studies of patients with rapid-cycling bipolar I disorder or rapid-cycling bipolar II disorder and a recent history of SUD were used to retrospectively assess the differences in clinical variables between the subtypes. The studies were conducted from November 1997 to February 2007 at University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio. Extensive clinical interview and the Mini-International Neuropsychiatric Interview were used to ascertain DSM-IV diagnoses of rapid-cycling bipolar disorder, SUDs, and other Axis I disorders and to collect clinical variables. The Addiction Severity Index (ASI), Global Assessment Scale (GAS), and the Medical Outcomes Study 36-ltem Short-Form Health Survey were used to measure the severity of impairment at the initial assessment. One-way analysis of variance or χ2 was used for significance tests. A Bonferroni adjustment was applied for multiple comparisons.
Of 245 patients with rapid-cycling bipolar disorder (rapid-cycling bipolar I disorder, N = 191; rapid-cycling bipolar II disorder, N = 54) and a recent history of SUD, the demographics were similar. A significantly higher rate of panic disorder was observed in patients with rapid-cycling bipolar I disorder than in those with rapid-cycling bipolar II disorder (odds ratio = 3.72, 95% CI = 1.66 to 8.32, p = .008). A significantly higher psychiatric composite score on the ASI was also found in patients with rapid-cycling bipolar I disorder than in those with rapid-cycling bipolar II disorder even after Bonferroni adjustment (p = .0007). There were no significant differences between the subtypes in the rates of previous hospitalization or suicide attempt, early childhood verbal, physical, or sexual abuse, lifetime substance abuse or dependence, the number of SUDs or mood episodes in the last 12 months, and total or other subscale scores on ASI and GAS.
Except for the significantly higher rate of comorbid panic disorder and higher psychiatric composite scores on the ASI in patients with rapid-cycling bipolar I disorder than in those with rapid-cycling bipolar II disorder, the other clinical variables were similar between the 2 groups.
PMCID: PMC4285700  PMID: 18588360
2.  A 6-Month, Double-Blind, Maintenance Trial of Lithium Monotherapy Versus the Combination of Lithium and Divalproex for Rapid-Cycling Bipolar Disorder and Co-Occurring Substance Abuse or Dependence 
To assess whether combination treatment with lithium and divalproex is more effective than lithium monotherapy in prolonging the time to mood episode recurrence in patients with rapid-cycling bipolar disorder (RCBD) and comorbid substance abuse and/or dependence.
A 6-month, double-blind, parallel group comparison was carried out in recently manic/hypomanic/mixed patients who had demonstrated a persistent bimodal response to combined treatment with lithium and divalproex. Subjects were randomly assigned to remain on combination treatment or to discontinue divalproex and remain on lithium monotherapy.
Of 149 patients enrolled into the open-label acute stabilization phase, 79% discontinued prematurely (poor adherence: 42%; nonresponse: 25%; intolerable side effects: 10%). Of 31 patients (21%) randomly assigned to double-blind maintenance treatment, 55% relapsed (24% into depression and 76% into a manic/hypomanic/mixed episode), 26% completed the study, and 19% were poorly adherent or exited prematurely. The median time to recurrence of a new mood episode was 15.9 weeks for patients receiving lithium monotherapy and 17.8 weeks for patients receiving the combination of lithium and divalproex (p=NS). The rate of relapse into a mood episode for those receiving lithium monotherapy or the combination of lithium and divalproex was 56% and 53%, respectively. The rate of depressive relapse in both arms was 13%, while the rate of relapse into a manic, hypomanic, or mixed episode was 44% for lithium monotherapy and 40% for the combination of lithium and divalproex.
A small subgroup of patients in this study stabilized after six months of treatment with lithium plus divalproex. Of those who did, the addition of divalproex to lithium conferred no additional prophylactic benefit over lithium alone. Although depression is regarded as the hallmark of RCBD in general, these data suggest that recurrent episodes of mania tend to be more common in presentations accompanied by comorbid substance use.
PMCID: PMC3587136  PMID: 19192457
Bipolar disorder; Rapid cycling; Dual-diagnosis; Substance use disorder; Maintenance trial; Placebo-controlled trial; Lithium; Divalproex; Combination pharmacotherapy
3.  Correlates of Historical Suicide Attempt in Rapid-Cycling Bipolar Disorder: A Cross-Sectional Assessment 
The Journal of clinical psychiatry  2009;70(7):1032-1040.
A rapid-cycling course in bipolar disorder has previously been identified as a risk factor for attempted suicide. This study investigated factors associated with suicide attempts in patients with rapid-cycling bipolar I or II disorder.
Cross-sectional data at the initial assessment of patients who were enrolled into 4 clinical trials were used to study the factors associated with suicide attempt. An extensive clinical interview and the Mini-International Neuropsychiatric Interview were used to ascertain DSM-IV diagnoses of rapid-cycling bipolar disorder, substance use disorders, anxiety disorders, psychosis, and other clinical variables. Chi-square, t test, and logistic regression or Poisson regression were used to analyze the data where appropriate, with odds ratios (ORs) for relative risk estimate. The data were collected from September 1995 to June 2005.
In a univariate analysis, 41% of 561 patients had at least 1 lifetime suicide attempt. Earlier age of depression onset, bipolar I subtype, female sex, unmarried status, and a history of drug use disorder, panic disorder, sexual abuse, and psychosis were associated with significantly higher rates of attempted suicide (all p<.05). After considering 31 potential confounding factors in the stepwise logistic regression model (n = 387), any Axis I comorbidity (OR=2.68, p = .0219), female sex (OR= 2.11, p = .0005), psychosis during depression (OR = 1.84, p = .0167), bipolar I subtype (OR= 1.83, p = .0074), and history of drug abuse (OR = 1.62, p = .0317) were independent predictors for increased risk of attempted suicide. However, white race was associated with a lower risk for suicide attempt (OR = 0.47, p = .0160). Psychosis during depression (p = .0003), bipolar I subtype (p = .0302), and physical abuse (p = .0195) were associated with increased numbers of suicide attempts by 248%, 166%, and 162%, respectively; white race was associated with a 60% decrease in the number of suicide attempts (p=.0320).
In this highly comorbid group of patients with rapid-cycling bipolar disorder, 41% had at least 1 suicide attempt. Among the demographics, female sex was positively associated, but white race was negatively associated, with the risk for suicide attempt. Independent clinical variables for increased risk and/or number of attempted suicides were any Axis I comorbidity, psychosis during depression, bipolar I subtype, a history of drug abuse, and physical abuse.
PMCID: PMC3457055  PMID: 19653978
4.  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 disorder (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 (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 generalized anxiety disorder, later treatment with a mood stabilizer, and early childhood trauma and history of SUDs suggests 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.
PMCID: PMC2924768  PMID: 20716307
5.  Medical and Substance Use Comorbidity in Bipolar Disorder 
Journal of affective disorders  2008;116(1-2):64-69.
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.
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 ≥ 4 and ≤ 3, respectively.
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.
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.
PMCID: PMC2866135  PMID: 19100627
6.  Differential Interactions between Comorbid Anxiety Disorders and Substance Use Disorder in Rapid Cycling Bipolar I or II Disorder 
Journal of affective disorders  2008;110(1-2):167-173.
Anxiety disorders (AD) and substance use disorders (SUD) commonly co-occur with bipolar disorder. This study was undertaken to assess AD-SUD-bipolar subtype interactions.
Extensive clinical interview and MINI were used to ascertain DSM-IV diagnoses of rapid cycling bipolar I (RCBPDI) or II (RCBPDII) disorder, SUDs, and ADs including generalized anxiety disorder (GAD), panic disorder (PD), and obsessive-compulsive disorder (OCD). Data at the initial assessment of four studies was used to compare the prevalence differences in ADs between RCBPDI and RCBPDII by using protocol-defined SUD categories, “Never,” “Lifetime, but not recent,” or “Recent.”
Five-hundred sixty-six of 568 patients (RCBPDI n=320, RCBPDII n=246) were eligible for analyses. In the “Never” group (n=191), patients with RCBPDI and RCBPDII had similar risk for ADs. In the “Lifetime, but not recent” group (n=195), RCBPDI patients had significantly higher risks for GAD (OR=3.29), PD (OR=2.95), but not OCD, compared with their RCBPDII counterparts. Similarly, in the “Recent” group (n=180), RCBPDI patients also had significantly higher risks for GAD (OR=3.6), PD (OR=3.8), but not OCD, compared with their RCBPDII counterparts.
Data were cross-sectional and not all ADs were included.
In this large cohort of patients with rapid cycling bipolar disorder, risk for having GAD, PD, but not OCD increased significantly in patients with bipolar I disorder compared to their bipolar II counterparts when a history of SUD was present. However, there were no significant differences in the risk for GAD, PD, or OCD between the subtypes among patients without a history of SUD.
PMCID: PMC2561239  PMID: 18234350
Rapid cycling bipolar disorder; anxiety disorder; substance use disorder; comorbidity; interaction
7.  Screening for Bipolar Disorder in a County Jail at the Time of Criminal Arrest 
Journal of psychiatric research  2007;42(9):778-786.
This study assessed the operating characteristics of the Mood Disorder Questionnaire (MDQ) among offenders arrested and detained at a county jail.
The MDQ, a brief self-report instrument designed to screen for all subtypes of bipolar disorder (BP I, II and NOS) was voluntarily administered to adult detainees at the Ottawa County Jail in Port Clinton, Ohio. A confirmatory diagnostic evaluation was also performed using the Mini-International Neuropsychiatric Interview (MINI). The MDQ was scored using a standard algorithm requiring endorsement of 7/13 mood items as well as two items that assess whether manic or hypomanic symptoms co-occur and cause moderate to severe functional impairment. In addition to the standard algorithm for scoring the MDQ, modifications were also tested in an attempt to improve overall sensitivity.
Among 526 jail detainees who completed the MDQ, 37 (7%) screened positive for bipolar disorder. Of 164 detainees who agreed to a research diagnostic evaluation, 32 (19.5%) screened positive on the MDQ, while 55 (33.5%) met criteria for bipolar disorder according to the MINI. When administered to the sample of 164 adult jail detainees, the sensitivity of the MDQ was 0.47 and the specificity was 0.94. The MDQ was significantly better at detecting BP I (0.59) than BP II/NOS (0.19; p = 0.008). Modification of scoring the MDQ improved the sensitivity for detection of BP II from 0.23 to 0.54 with minimal decrease in specificity (0.84). The optimum sensitivity and specificity of the MDQ was achieved by decreasing the item threshold to 3/13 and eliminating the symptom co-occurrence and functional impairment items.
The MDQ was found to have limited utility as a screening tool for bipolar disorder in a correctional setting, particularly for the BP II subtype.
PMCID: PMC2475656  PMID: 17935734
Bipolar Disorder; Mood Disorder Questionnaire; Jail; Screening; Bipolar II; Psychometrics

Results 1-7 (7)