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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.)

In animals, stress and corticosteroid excess are associated with decreases in memory performance and hippocampal volume that may be prevented with agents that decrease glutamate release. Humans also demonstrate changes in memory and hippocampus with corticosteroids. In this report the effects of glutamate-release inhibitor lamotrigine on hippocampal structure and memory were examined in people receiving medically needed prescription corticosteroid therapy. A total of 54 outpatient adults (n = 28 women) receiving chronic (≥ 6 months) oral corticosteroid therapy were randomized to lamotrigine or placebo for 48 weeks. Declarative memory was assessed using the Rey Auditory Verbal Learning Test (RAVLT); structural magnetic resonance imaging (MRI) as well as single-voxel proton MR spectroscopy ( 1 HMRS) focused on hippocampus were obtained at baseline and week 48. Utilizing a mixed-model approach, structural and biochemical data were examined by separate ANOVAs, and memory was assessed with a multi-level longitudinal model. RAVLT total scores demonstrated significantly better declarative memory performance with lamotrigine than placebo (p = 0.047). Hippocampal subfield volumes were not significantly different between the treatment groups. In summary, lamotrigine was associated with less decline in declarative memory performance than placebo in corticosteroid-treated patients. Findings suggest that, in humans as well as in animal models, glutamate release inhibitors may attenuate some of the effects on the human memory associated with corticosteroids., (Copyright © 2018. Published by Elsevier B.V.)

Background: In animal models, corticosteroids are associated with changes in hippocampal structure and functioning that are prevented by glutamate release inhibitors or N-methyl-D-aspartate (NMDA) receptor antagonists. Cushing's disease and prescription corticosteroid administration are also associated with memory impairment and hippocampal atrophy. Use of NMDA receptor antagonists to attenuate corticosteroid effects in humans has not been investigated. We examine the NMDA receptor antagonist memantine in patients receiving corticosteroids., Methods: Twenty outpatients receiving long-term oral corticosteroid therapy were randomized to 8 weeks of memantine (maximum dose 20 mg/day) and 8 weeks of placebo in a double-blind fashion, with a 4-week washout period between courses. Declarative memory was assessed with the Hopkins Verbal Learning Test (HVLT) and mood with the Hamilton Rating Scale for Depression and Young Mania Rating Scale. Changes in outcome measures were compared during memantine and placebo exposure., Results: Seventeen participants completed both treatment phases and were used in the analysis. Significant improvement (p < .05) in total and delayed recall on the HVLT was observed with memantine as compared with placebo. No significant changes in mood were observed., Conclusions: Memantine therapy was associated with improvement in declarative memory but not mood in patients receiving prescription corticosteroids.