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Objectives: To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well‐characterized individuals with BD in North America, Europe, and Australia. Methods: Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta‐analyses with generalized linear mixed methods were conducted to identify prescription patterns. Results: This study included 10,351 individuals from North America (n = 3985), Europe (n = 3822), and Australia (n = 2544). Overall, participants were predominantly female (60%) with BD‐I (60%; vs. BD‐II = 33%). Cross‐sectionally, mood‐stabilizing anticonvulsants (44%), second‐generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First‐generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD‐II (47%) compared to BD‐I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort. Conclusions: Mood‐stabilizing anticonvulsants, second‐generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first‐generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence‐based guidelines to help improve treatment practices in BD. [ABSTRACT FROM AUTHOR]

Objective: To explore illness-related factors in patients with major depressive disorder (MDD) recipients of adjunctive minocycline (200 mg/day) treatment. The analysis included participants experiencing MDD from a 12-week, double blind, placebo-controlled, randomized clinical trial (RCT). Methods: This is a sub-analysis of a RCT of all 71 participants who took part in the trial. The impact of illness chronicity (illness duration and number of depressive episodes), systemic illness (endocrine, cardiovascular and obesity), adverse effects and minocycline were evaluated as change from baseline to endpoint (12-week) using ANCOVA. Results: There was a consistent but statistically non-significant trend on all outcomes in favour of the use of adjunctive minocycline for participants without systemic illness, less illness chronicity, and fewer adverse effects. Conclusion: Understanding the relationship between MDD and illness chronicity, comorbid systemic illness, and adverse effects, can potentially better characterise those individuals who are more likely to respond to adjunctive anti-inflammatory medications. [ABSTRACT FROM AUTHOR]

Background The prevalence of posttraumatic stress disorder (PTSD) co-occurring in people with bipolar disorder (BD) is high. People with BD and PTSD may experience different outcomes and quality of life after pharmacologic treatment than those with BD alone. This review systematically explores the impact of PTSD on pharmacologic treatment outcomes for adults with BD. Methods We conducted a systematic search up to November 25, 2021, using MEDLINE Complete, Embase, American Psychological Association PsycInfo, and the Cochrane Central Register of Controlled Trials to identify randomized and nonrandomized studies of pharmacologic interventions for adults with BD that assessed for comorbid PTSD. We used the Newcastle-Ottawa Scale and Cochrane Risk of Bias tool to assess the risk of bias. Results The search identified 5093 articles, and we reviewed 62 full-text articles. Two articles met inclusion criteria (N = 438). One article was an observational study, and the other was a randomized comparative effectiveness trial. The observational study examined lithium response rates and found higher response rates in BD alone compared with BD plus PTSD over 4 years. The randomized trial reported more severe symptoms in the BD plus PTSD group than in those with BD alone following 6 months of quetiapine treatment. There was no significant difference in the lithium treatment group at follow-up. Conclusions Comorbid PTSD may affect quetiapine and lithium treatment response in those with BD. Because of the high risk of bias and low quality of evidence, however, these results are preliminary. Specific studies exploring comorbid BD and PTSD are required to inform pharmacotherapy selection and guidelines appropriately. (International Prospective Register of Systematic Reviews ID: CRD42020182540). [ABSTRACT FROM AUTHOR]

This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Serum samples were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200 mg/day, added to treatment as usual) for adults (n = 71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12; placebo 2.06 ± 1.35 pg/ml; minocycline 1.77 ± 0.79 pg/ml; p = 0.317), LBP (week 12; placebo 3.74 ± 0.95 µg/ml; minocycline 3.93 ± 1.33 µg/ml; p = 0.525) or BDNF (week 12; placebo 24.28 ± 6.69 ng/ml; minocycline 26.56 ± 5.45 ng/ml; p = 0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA; p = 0.021) and quality of life (Q-LES-Q-SF; p = 0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger sample size. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled clinical trials that have investigated minocycline as an adjunctive treatment for major depressive disorder have proved promising. Data from two studies were pooled to evaluate more definitively whether the addition of minocycline to standard treatment for major depressive disorder leads to an improvement of depressive symptoms when compared with placebo. Methods: Both studies were multi-site, double-blinded, placebo-controlled trials of minocycline 200 mg/day added to treatment as usual during a 12-week period. The primary outcome measure was change in depressive symptoms (Montgomery–Asberg Depression Rating Scale in Dean et al. and Hamilton Depression Rating Scale in Husain et al.). Secondary outcomes were change in depression severity (Montgomery–Asberg Depression Rating Scale for Dean et al. and 9-item Patient Health Questionnaire in Husain et al.), anxiety severity (Hamilton Anxiety Rating Scale in Dean et al. and Generalized Anxiety Disorder 7-item scale in Husain et al.) and functional status, which were also evaluated as potential mediators on the primary outcome. Results: A total of 112 participants were included in the pooled data (Dean et al., n = 71; Husain et al., n = 41). A significant change from baseline to week 12 was noted in depressive symptoms – differential change (Placebo vs Minocycline): 9.0, 95% confidence interval = [4.2, 13.9], Cohen's D (95% confidence interval): 0.71 [0.29, 1.14], p < 0.001 – anxiety severity – differential change (Placebo vs Minocycline): 0.38, confidence interval = [0.00, 0.75], Cohen's D (95% confidence interval): 0.41 [0.00, 0.82], p = 0.050) and functional status – differential change (Placebo vs Minocycline): 1.0, 95% confidence interval = [0.4, 1.5], Cohen's D (95% confidence interval): 0.76 [0.34, 1.19], p = 0.001). Duration of illness, current use of benzodiazepine and pain medication were identified as moderators, whereas functional status as a mediator/predictor. Conclusion: The improvement of depressive symptoms, anxiety severity and functional status is promising and suggests that minocycline has potential as an adjunctive treatment for major depressive disorder. However, further studies are warranted to confirm therapeutic effects of minocycline in major depressive disorder. Trial registrations: NCT02263872, registered October 2014, and ACTRN12612000283875, registered March 2012. [ABSTRACT FROM AUTHOR]