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Bipolar disorder is associated with high rates of alcohol use disorder. However, little is known about the treatment of this dual diagnosis population. Previous studies suggest that ondansetron decreases alcohol use, particularly in people with specific single nucleotide polymorphism (SNP) alleles. A 12-week, randomized, double-blind, placebo-controlled trial of ondansetron was conducted in 70 outpatients with bipolar spectrum disorders and early onset alcohol use disorder. Outcome measures included alcohol use, assessed with the Timeline Followback method, Penn Alcohol Craving Scale (PACS), Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology-Self-report, and Young Mania Rating Scale. SNPs rs1042173, rs1176713 and rs1150226 were explored as predictors of response. Participants had a mean age of 44.9 ± 9.4 years, were mostly men (60.0%), and African American (51.4%). Mean ondansetron exit dose was 3.23 ± 2.64 mg. No significant between-group differences in alcohol use measures were observed. However, a significant reduction in HRSD scores was observed (p = 0.045). Inclusion of SNPs increased effect sizes for some alcohol-related outcomes and the HRSD. Ondansetron was well tolerated. This proof-of-concept study is the first report on ondansetron in bipolar people with bipolar disorders and alcohol use disorder. Alcohol use did not demonstrate a significant between-group difference. However, the findings suggest that ondansetron may be associated with reduction in depressive symptom severity in persons with bipolar illnesses and alcohol use disorder. A larger trial is needed to examine the effects of ondansetron on bipolar depression., (Copyright © 2020. Published by Elsevier B.V.)

Background: Past studies suggest that brexpiprazole is an effective adjunctive treatment for major depressive disorder and schizophrenia; however, no studies have examined brexpiprazole for bipolar depression. In this study, we examined the effects of brexpiprazole on mood, cognition, and quality of life in outpatients with bipolar depression., Methods: Twenty-one adults with bipolar disorder (most recent episode depressed) and scoring at least a 25 on the Montgomery-Åsberg Depression Rating Scale (MADRS) were recruited. Brexpiprazole was titrated up to 4 mg/day over the 8-week period. Depressive symptoms were measured using MADRS and Inventory of Depressive Symptomatology Self-report (IDS-SR 30 ). Manic symptoms were measured using Young Mania Rating Scale, quality of life with the Quality of Life in Bipolar Disorder (QOLBD), and cognition with Rey Auditory Verbal Learning Test, Stroop Color Word Test, and Trail Making Test., Results: MADRS and IDS-SR 30 scores decreased from baseline at weeks 4 and 8. YMRS and cognitive scores did not change significantly. QOLBD scores increased from baseline to week 8., Limitations: A limitation to this study is the open-label design., Conclusion: To our knowledge, this is the first study to examine the effects of brexpiprazole on bipolar depression. We found a significant reduction in depressive symptoms and an increase in quality of life., (Copyright © 2019. Published by Elsevier B.V.)

Purpose/background: In animal models, levels of the neurosteroid pregnenolone increase after tetrahydrocannabinol (THC) administration and pregnenolone appears to attenuate the brain effects of THC. Given these interactions between pregnenolone and THC, we evaluated baseline neurosteroid levels in participants with a history of a cannabis use disorders (CUDs)., Methods/procedures: Bipolar depressed participants were enrolled in a randomized placebo-controlled clinical trial to evaluate the efficacy of add-on pregnenolone for depression and before receiving pregnenolone or placebo. Baseline serum levels of neurosteroids (pregnenolone, allopregnanolone, pregnanolone, and androsterone) were analyzed in 53 participants with highly sensitive and specific gas chromatography/mass spectrometry. Current, active substance use disorders, or a positive baseline urine drug screen, were exclusionary. Participants were classified by past cannabis abuse or dependence diagnosis using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Data were analyzed by independent t tests for separate neurosteroids., Findings/results: Participants with a history of CUD had higher serum pregnanolone, lower allopregnanolone, a higher pregnanolone to allopregnanolone ratio, and a lower pregnenolone to pregnanolone ratio compared with those without a history of cannabis use. Similar findings were not observed based on a history of other substance use disorders with the exception of lower allopregnanolone in those with opioid use disorders. Notably, the majority of those with an opioid use disorder also had a CUD (75%)., Implications/conclusions: These findings potentially suggest either enduring changes in neurosteroids in people with past CUDs or represent a vulnerability marker for a CUD.

Objective: Although drug dependence is common in patients with bipolar disorder, minimal data are available on the treatment of drug dependence in this patient population. The authors previously reported a decreased risk of relapse to cocaine use in a pilot study of citicoline in patients with bipolar disorder and cocaine dependence. The primary aim of the present study was to determine whether citicoline reduces cocaine use in outpatients with bipolar I disorder and current cocaine dependence and active cocaine use., Method: A total of 130 outpatients with bipolar I disorder (depressed or mixed mood state) and cocaine dependence received citicoline or placebo add-on therapy for 12 weeks. Results of thrice-weekly urine drug screens were analyzed using a generalized linear mixed model that was fitted to the binary outcome of cocaine-positive screens at each measurement occasion for 12 weeks. Mood was assessed with the Inventory of Depressive Symptomatology-Self Report, the Hamilton Depression Rating Scale, and the Young Mania Rating Scale., Results: In the intent-to-treat sample (N=61 in both groups), significant treatment group and group-by-time effects were observed, whether or not missing urine screens were imputed as cocaine positive. The group effect was greatest early in the study and tended to decline with time. No between-group differences in mood symptoms or side effects were observed., Conclusions: Citicoline was well tolerated for treatment of cocaine dependence in patients with bipolar disorder. Cocaine use was significantly reduced with citicoline initially, although treatment effects diminished over time, suggesting the need for augmentation strategies to optimize long-term benefit.

Although bipolar disorder and substance dependence are both associated with treatment non-adherence and cognitive impairment, no studies have investigated relationships between treatment adherence and cognitive functioning in this population. As part of a clinical trial, baseline performance on two neuropsychological tests in 120 outpatients with bipolar disorder and cocaine dependence was used to examine whether cognitive functioning was associated with appointment attendance, medication adherence, and return of medication bottles. This study found that higher baseline cognitive functioning measured by the Stroop Color-Word condition predicted better treatment adherence. However, this study also reports measurement sensitivity of cognition as it relates to treatment adherence when applied to this dual diagnosis population. Poorer performance in simple visual attention tasks as assessed by the Stroop Word condition was inversely associated with some measures of adherence. Future studies are warranted that include a comprehensive neuropsychological battery and advanced medication adherence measures to confirm these findings., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Depression in bipolar disorder (BPD) is challenging to treat. Therefore, additional medication options are needed. In the current report, the effect of the neurosteroid pregnenolone on depressive symptoms in BPD was examined. Adults (n=80) with BPD, depressed mood state, were randomized to pregnenolone (titrated to 500 mg/day) or placebo, as add-on therapy, for 12 weeks. Outcome measures included the 17-item Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology-Self-Report (IDS-SR), Hamilton Rating Scale for Anxiety (HRSA), and Young Mania Rating Scale (YMRS). Serum neurosteroid levels were assessed at baseline and week 12. Data were analyzed using a mixed model ANCOVA with a between factor of treatment assignment, a within factor (repeated) of visit, and the baseline value, as well as age and gender, as covariates. In participants with at least one postbaseline visit (n=73), a significant treatment by week interaction for the HRSD (F(5,288)=2.61, p=0.025), but not IDS-SR, was observed. Depression remission rates were greater in the pregnenolone group (61%) compared with the placebo group (37%), as assessed by the IDS-SR (χ(2)(1)=3.99, p=0.046), but not the HRSD. Large baseline-to-exit changes in neurosteroid levels were observed in the pregnenolone group but not in the placebo group. In the pregnenolone group, baseline-to-exit change in the HRSA correlated negatively with changes in allopregnanolone (r(22)=-0.43, p=0.036) and pregNANolone (r(22)=-0.48, p=0.019) levels. Pregnenolone was well tolerated. The results suggest that pregnenolone may improve depressive symptoms in patients with BPD and can be safely administered.

Background: Alcohol dependence is common in bipolar disorder (BPD) and associated with treatment nonadherence, violence, and hospitalization. Quetiapine is a standard treatment for BPD. We previously reported improvement in depressive symptoms, but not alcohol use, with quetiapine in BPD and alcohol dependence. However, mean alcohol use was low and a larger effect size on alcohol-related measures was observed in those with higher levels of alcohol consumption. In this study, efficacy of quetiapine in patients with BPD and alcohol dependence was examined in patients with higher mean baseline alcohol use than in the prior study., Methods: Ninety outpatients with bipolar I or II disorders, depressed or mixed mood state, and current alcohol dependence were randomized to 12 weeks of sustained release quetiapine (to 600 mg/d) add-on therapy or placebo. Drinking was quantified using the Timeline Follow Back method. Additional assessment tools included the Hamilton Rating Scale for Depression, Inventory of Depressive Symptomatology-Self-Report, Young Mania Rating Scale, Penn Alcohol Craving Scale, liver enzymes, and side effects. Alcohol use and mood were analyzed using a declining-effects random-regression model., Results: Baseline and demographic characteristics in the 2 groups were similar. No significant between-group differences were observed on the primary outcome measure of drinks per day or other alcohol-related or mood measures (p > 0.05). Overall side effect burden, glucose, and cholesterol were similar in the 2 groups. However, a significant weight increase was observed with quetiapine at week 6 (+2.9 lbs [SE 1.4] quetiapine vs. -2.0 lbs [SE 1.4], p = 0.03), but not at week 12. Scores on the Barnes Akathisia Scale increased significantly more (p = 0.04) with quetiapine (+0.40 [SE 0.3]) than placebo (-0.52 [SE 0.3]) at week 6 but not week 12. Retention (survival) in the study was similar in the groups., Conclusions: Findings suggest that quetiapine does not reduce alcohol consumption in patients with BPD and alcohol dependence., (Copyright © 2014 by the Research Society on Alcoholism.)