Treating major depressive episodes with antidepressants can induce or worsen metabolic syndrome: results of the METADAP cohort

Corruble, Emmanuelle; Asmar, Khalil El; Trabado, Séverine; Verstuyft, Céline; Falissard, Bruno; Colle, Romain; Petit, Anne-Cécile; Gressier, Florence; Brailly-Tabard, Sylvie; Ferreri, Florian; Lépine, Jean‐Pierre; Haffen, Emmanuel; Polosan, Mircea; Bourrier, Céline; Perlemuter, Gabriel; Chanson, Philippe; Fève, Bruno; Becquemont, Laurent

doi:10.1002/wps.20260

Cited by 44 publications

(32 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, patients were from the METADAP cohort, a multicenter, observational cohort study of 624 patients diagnosed with MDD and current MDE (http://clinicaltrials.gov identifier: NCT00526383). This cohort study, recruited from six university psychiatry departments between November 2009 and March 2013, has been previously described . Patients with psychotic symptoms, bipolar disorders, psychotic disorders, eating disorders, current substance abuse or dependence, pregnancy, organic brain syndromes, or severe unstable medical conditions were not included.…”

Section: Methodsmentioning

confidence: 99%

“…This cohort study, recruited from six university psychiatry departments between November 2009 and March 2013, has been previously described. 22 Patients with psychotic symptoms, bipolar disorders, psychotic disorders, eating disorders, current substance abuse or dependence, pregnancy, organic brain syndromes, or severe unstable medical conditions were not included. Patients receiving antipsychotics or mood stabilizers before inclusion and/or for a period of 4 months or more during the last year were also excluded.…”

Section: Study Samplesmentioning

confidence: 99%

See 1 more Smart Citation

Peripheral tryptophan, serotonin, kynurenine, and their metabolites in major depression: A case–control study

Colle

Masson

Verstuyft

et al. 2019

Psychiatry Clin Neurosci

Self Cite

View full text Add to dashboard Cite

Aim Tryptophan is the sole precursor of both peripherally and centrally produced serotonin and kynurenine. In depressed patients, tryptophan, serotonin, kynurenine, and their metabolite levels remain unclear. Therefore, peripheral tryptophan and metabolites of serotonin and kynurenine were investigated extensively in 173 patients suffering from a current major depressive episode (MDE) and compared to 214 healthy controls (HC). Methods Fasting plasma levels of 11 peripheral metabolites were quantified: tryptophan, serotonin pathway (serotonin, its precursor 5‐hydroxytryptophan and its metabolite 5‐hydroxyindoleacetic acid), and kynurenine pathway (kynurenine and six of its metabolites: anthranilic acid, kynurenic acid, nicotinamide, picolinic acid, xanthurenic acid, and 3‐hydroxyanthranilic acid). Results Sixty (34.7%) patients were antidepressant‐drug free. Tryptophan levels did not differ between MDE patients and HC. Serotonin and its precursor (5‐hydroxytryptophan) levels were lower in MDE patients than in HC, whereas, its metabolite (5‐hydroxyindoleacetic acid) levels were within the standard range. Kynurenine and four of its metabolites (kynurenic acid, nicotinamide, picolinic acid, and xanthurenic acid) were lower in MDE patients. Conclusion Whilst the results of this study demonstrate an association between the metabolites studied and depression, conclusions about causality cannot be made. This study uses the largest ever sample of MDE patients, with an extensive assessment of peripheral tryptophan metabolism in plasma. These findings provide new insights into the peripheral signature of MDE. The reasons for these changes should be further investigated. These results might suggest new antidepressant therapeutic strategies.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Study Samplesmentioning

confidence: 99%

Peripheral tryptophan, serotonin, kynurenine, and their metabolites in major depression: A case–control study

Colle

Masson

Verstuyft

et al. 2019

Psychiatry Clin Neurosci

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several psychiatric disorders, such as schizophrenia (6), bipolar disorder (7), and depressive disorder (8), have been consistently associated with an increased risk of metabolic and cardiovascular complications, which in turn are thought to contribute to the markedly increased mortality rates associated with these conditions (9,10). The mechanisms by which patients with mental disorders are more prone to developing MetS are complex (11), but factors related to lifestyle choices, such as smoking, a poor diet, and the absence of physical activity (12), as well as the prolonged use of psychiatric medication, particularly antipsychotics (13) and some antidepressants (14)(15)(16)(17)(18), have been described as relevant contributors to the risk.…”

mentioning

confidence: 99%

Metabolic and Cardiovascular Complications in Obsessive-Compulsive Disorder: A Total Population, Sibling Comparison Study With Long-Term Follow-up

Isomura

Brander

Chang

et al. 2018

Biological Psychiatry

View full text Add to dashboard Cite

show abstract

“…The antidepressant treatment had to be a monotherapy. The drug and its dose were left to the treating psychiatrist, using “real‐world” treatment options . The majority of patients were treated with selective serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI) (Table ).…”

Section: Methodsmentioning

confidence: 99%

“…The drug and its dose were left to the treating psychiatrist, using "real-world" treatment options. 25 The majority of patients were treated with selective serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI) ( 26 Patients were included based on the following criteria: aged 18-65 years, with a current MDE (with a minimum score of 18 at the Hamilton Depression Rating Scale-17, HDRS-17) in a context of MDD. Patients with psychotic symptoms, bipolar disorders, psychotic disorders, eating disorders, current substance abuse or dependence, organic brain syndromes, severe unstable medical conditions or pregnancy were not included.…”

Section: Patientsmentioning

confidence: 99%

SOD2 genetic polymorphism (rs4880) has no impact on 6‐month response to antidepressant treatment and inflammatory biomarkers in depressed patients

Tayeb

Becquemont

El‐Asmar

et al. 2020

Basic Clin Pharma Tox

Self Cite

View full text Add to dashboard Cite

Two thirds of patients suffering from a major depressive episode (MDE) do not reach a complete response with antidepressant drugs. This lack of response is due to several factors, including genetic determinants. Since major depressive disorder is associated with inflammatory and oxidative stress abnormalities, the metabolism of superoxide anions might be involved in non‐response to antidepressant drugs. Superoxide anions are metabolized by manganese‐dependent superoxide dismutase (SOD2) in the mitochondria. A functional genetic polymorphism (SOD2, rs4880), responsible of a 40% reduction in enzyme activity, is associated with anti‐inflammatory response of rosuvastatin. We investigated the association of ala‐allele of SOD2 rs4880 and both antidepressant efficacy and inflammatory parameters in patients treated for a MDE with antidepressant drugs. The Hamilton Depression Rating Scale (HDRS) score and levels of plasma CRP and inflammatory cytokines were assessed at baseline, one month (M1), 3 months (M3) and 6 months (M6) after antidepressant treatment. They were compared according to SOD2 genetic polymorphism. Of the 484 patients studied, 361 (74.6%) carried the ala‐allele (Ala group), 123 (25.4%) of them had Val/Val genotype (Val/Val group). No significant difference was observed between the Ala and Val/Val groups neither for baseline clinical characteristics, nor for HDRS scores, response/remission rates, plasma CRP and cytokine levels throughout the study. The rs4880 SOD2 genetic polymorphism was not associated with the clinical response and cytokines levels after antidepressant treatment. These data suggest that SOD2 is not a major genetic determinant of antidepressant response. Other genes of the oxidative stress pathways should be explored in further studies.

show abstract

Treating major depressive episodes with antidepressants can induce or worsen metabolic syndrome: results of the METADAP cohort

Cited by 44 publications

References 10 publications

Peripheral tryptophan, serotonin, kynurenine, and their metabolites in major depression: A case–control study

Peripheral tryptophan, serotonin, kynurenine, and their metabolites in major depression: A case–control study

Metabolic and Cardiovascular Complications in Obsessive-Compulsive Disorder: A Total Population, Sibling Comparison Study With Long-Term Follow-up

SOD2 genetic polymorphism (rs4880) has no impact on 6‐month response to antidepressant treatment and inflammatory biomarkers in depressed patients

Contact Info

Product

Resources

About