Pharmacological treatment profiles in the FACE-BD cohort: An unsupervised machine learning study, applied to a nationwide bipolar cohort✰

Brodeur, Sébastien; Terrisse, Hugo; Pouchon, Arnaud; Godin, O.; Aouizerate, Bruno; Aubin, V.; Bellivier, Frank; Belzeaux, Raoul; Bougerol, Thierry; Courtet, Philippe; Dubertret, Caroline; Gard, Sébastien; Haffen, Emmanuel; Henry, Chantal; Leboyer, Marion; Olié, Émilie; Roux, Paul; Samalin, Ludovic; Schwan, Raymund; Étain, Bruno; Bosson, Jean‐Luc; Polosan, Mircea

doi:10.1016/j.jad.2021.02.036

Cited by 6 publications

(4 citation statements)

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“…Two other studies, although not specifically aimed at comparing BD with vs. without SUDs, reported discrepant results. One study conducted among homeless persons with BD showed that comorbid SUDs were significantly associated with inappropriate prescription regimens ( 32 ), while a nationwide French cohort study (independent from the sample analyzed in the current study) did not observe any difference in preventive BD medication in outpatients with vs. without SUDs ( 33 ). Given the paucity of available literature, knowledge about the sources of variability ( 34 ) and non-compliance to guidelines of pharmacological treatment in BD + SUD remains limited.…”

Section: Introductionmentioning

confidence: 60%

Preventive Medication Patterns in Bipolar Disorder and Their Relationship With Comorbid Substance Use Disorders in a Cross-National Observational Study

et al. 2022

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ObjectiveThe potential role of sub-optimal pharmacological treatment in the poorer outcomes observed in bipolar disorder (BD) with vs. without comorbid substance use disorders (SUDs) is not known. Thus, we investigated whether patients with BD and comorbid SUD had different medication regimens than those with BD alone, in samples from France and Norway, focusing on compliance to international guidelines.MethodsSeven hundred and seventy patients from France and Norway with reliably ascertained BD I or II (68% BD-I) were included. Medication information was obtained from patients and hospital records, and preventive treatment was categorized according to compliance to guidelines. We used Bayesian and regression analyses to investigate associations between SUD comorbidity and medication. In the Norwegian subsample, we also investigated association with lack of medication.ResultsComorbid SUDs were as follows: current tobacco smoking, 26%, alcohol use disorder (AUD), 16%; cannabis use disorder (CUD), 10%; other SUDs, 5%. Compliance to guidelines for preventive medication was lacking in 8%, partial in 44%, and complete in 48% of the sample. Compliance to guidelines was not different in BD with and without SUD comorbidity, as was supported by Bayesian analyses (highest Bayes Factor = 0.16). Cross national differences in treatment regimens led us to conduct country-specific adjusted regression analyses, showing that (1) CUD was associated with increased antipsychotics use in France (OR = 2.4, 95% CI = 1.4–3.9, p = 0.001), (2) current tobacco smoking was associated with increased anti-epileptics use in Norway (OR = 4.4, 95% CI = 1.9–11, p < 0.001), and (3) AUD was associated with decreased likelihood of being medicated in Norway (OR = 1.2, 95% CI = 1.04–1.3, p = 0.038).ConclusionSUD comorbidity in BD was overall not associated with different pharmacological treatment in our sample, and not related to the level of compliance to guidelines. We found country-specific associations between comorbid SUDs and specific medications that warrant further studies.

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Section: Introductionmentioning

confidence: 60%

Preventive Medication Patterns in Bipolar Disorder and Their Relationship With Comorbid Substance Use Disorders in a Cross-National Observational Study

et al. 2022

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“…1) include stable outpatients diagnosed with BD(N=837) within the FondaMental Advanced Centers of Expertise (FACE-BD) cohort. Full description of population, characteristics and treatments can be found elsewhere 3,[23][24][25][26] . Validation cohort (N=255) consists of patients within stable or acute phases of BD (N=26 stable; N=75 acute) and during acute phase of SCZ (N=76) and non-psychiatric community controls (N=55) that were recruited as part of the French National granted I-GIVE (Immuno-Genetics, Inflammation, retro-Virus, Environment) cohort, for full description see 27 .…”

Section: Study Populationmentioning

confidence: 99%

Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder

Zachos,

Choi,

Godin

et al. 2023

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ImportanceExamining translatable mitochondrial blood-based biological markers to identify its association with metabolic diseases in bipolar disorder.ObjectiveTo test whether mitochondrial metabolites, mainly lactate, and cell-free circulating mitochondrial DNA are associated with markers of metabolic syndrome in bipolar disorder, hypothesizing higher lactate but unchanged cell-free circulating mitochondrial DNA levels in bipolar disorder patients with metabolic syndrome.DesignIn a cohort study, primary testing from the FondaMental Advanced Centers of Expertise for bipolar disorder was conducted, including baseline plasma samples and blinded observers for all experimentation and analysis.SettingThe FondaMental Foundation coordinate a multicenter, multidisciplinary French networks aiming at creation of cohorts to improve identification of homogeneous subgroups of psychiatric disorders toward personalized treatments.ParticipantsThe FACE-BD primary testing cohort includes 837 stable bipolar disorder patients. The I-GIVE validation cohort consists of 235 participants: stable and acute bipolar patients, non-psychiatric controls, and acute schizophrenia patients. Participants were randomly selected based on biosample availability.ExposuresAll patients underwent the standard primary care within their center. No intentional exposures were part of this study.Main Outcome and MeasuresThe primary outcome modelled an association with lactate and metabolic syndrome in this population. Reflectivea priorihypothesis.ResultsMultivariable regression analyses show lactate association with triglycerides (Est= 0.072(0.023), p = 0.0065,), fasting glucose (Est = 12(0.025), p= 0.000015) and systolic (Est= 0.003(0.0013), p= 0.031) and diastolic blood pressure (Est = 0.0095±0.0017, p= 1.3e-7). Significantly higher levels of lactate were associated with presence of metabolic syndrome (Est = 0.17±0.049, p=0.00061) after adjusting for potential confounding factors. Mitochondrial-targeted metabolomics identified distinct metabolite profiles in patients with lactate presence and metabolic syndrome, differing from those without lactate changes but with metabolic syndrome. Circulating cell-free mitochondrial DNA was not associated with metabolic syndrome.Conclusion & RelevanceThis thorough analysis mitochondrial biomarkers indicate the associations with lactate and metabolic syndrome, whereas circulating cell-free mitochondrial DNA is limited in the context of metabolic syndrome. This study is relevant to improve the identification and stratification of bipolar patients with metabolic syndrome and provide potential personalized-therapeutic opportunities.Key PointsQuestionCan lactate, a mitochondrial metabolite, indicate metabolic syndrome in bipolar disorder?FindingIn 837 stable bipolar disorder patients, we found high lactate levels significantly associated with metabolic syndrome, unlike circulating cell-free mitochondrial DNA. This pattern also appeared in acute bipolar and schizophrenia cases. Mitochondrial-targeted metabolomics distinguishes patients with high lactate and metabolic syndrome from those without lactate changes, but presence of metabolic syndrome.MeaningThis research underscores lactate as a potential biomarker for identifying bipolar disorder patients with metabolic syndrome. It opens new avenues for personalized treatment strategies, leveraging mitochondrial metabolite profiling to improve patient stratification and therapeutic outcomes.

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“…3,4 The bipolar pharmacopoeia has evolved gradually over the last 25 years. Several studies have explored the pharmacotherapeutic prescription practices in BD and reported variable patterns of pharmacologic treatment, [5][6][7][8] most notably the underutilization of lithium (Li) in the United States. 9 Based on regulatory drug development, the use of secondgeneration antipsychotics (SGAs) has steadily increased.…”

Section: Introductionmentioning

confidence: 99%

Patterns of pharmacotherapy for bipolar disorder: A GBC survey

et al. 2023

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ObjectivesTo 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.MethodsData 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.ResultsThis 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.ConclusionsMood‐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.

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Pharmacological treatment profiles in the FACE-BD cohort: An unsupervised machine learning study, applied to a nationwide bipolar cohort✰

Cited by 6 publications

References 34 publications

Preventive Medication Patterns in Bipolar Disorder and Their Relationship With Comorbid Substance Use Disorders in a Cross-National Observational Study

Preventive Medication Patterns in Bipolar Disorder and Their Relationship With Comorbid Substance Use Disorders in a Cross-National Observational Study

Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder

Patterns of pharmacotherapy for bipolar disorder: A GBC survey

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