[The efficacy of esketamine in resistant major depressive disorder: A systematic review of the literature]. / L'efficacité de l'eskétamine dans le trouble dépressif majeur résistant : une revue systématique de la littérature.

OBJECTIVE: Major depression is a significant public health problem since its lifetime prevalence is estimated at 15-18 %. Its standard treatment is based on the use of antidepressant medications but their effectiveness is limited. Indeed, only two thirds of patients with a major depressive episode will reach remission after two lines of conventional treatment. In major depression, there are arguments in favour of disturbances in neuronal glutamatergic transmission. Esketamine appears to have an antidepressant action through modulation of the NMDA receptors involved in this glutamatergic neurotransmission. The aim of this review to systematically investigate the efficacy of esketamine combined with an SSRI or SNRI for major depressive disorder resistant to treatment. METHOD: A systematic review on the efficacy of esketamine in combination with an SSRI or SNRI for resistant major depressive disorder was performed in July 2021 in the PUBMED database according to the PRISMA criteria. The key words used are: "depressed" [All Fields] OR "depression" [MeSH Terms] OR "depression" [All Fields] OR "depressions" [All Fields] OR "depression s" [All Fields] OR "depressive disorder"[MeSH Terms] OR ("depressive"[All Fields] AND"disorder"[All Fields]) OR"depressive disorder"[All Fields] OR"depressivity"[All Fields] OR"depressive"[All Fields] OR "depressively" [All Fields] OR "depressiveness" [All Fields] OR "depressives" [All Fields]) AND ("esketamine" [Supplementary Concept] OR "esketamine" [All Fields] OR "esketamine" [All Fields]. The inclusion criteria were: efficacy on depressive symptoms of intranasal esketamine combined with an SSRI or an SNRI for major depressive disorder resistant to at least two lines of treatment, RCT and meta-analysis, individual≥18 years, articles in English and French. RESULTS: Four randomized double-blind studies were selected on the basis of these criteria. The included studies are of grade A and B which leads to a high level of scientific evidence. CONCLUSIONS: Intranasal esketamine in combination with sertraline, escitalopram, duloxetine or venlafaxine prolonged release is more effective than the monotherapy use of these four molecules for the treatment of resistant depression. It has been shown to be effective for a population aged between 18 and 74 years at doses between 28mg and 84mg. Currently, based on these results, intranasal esketamine should be proposed as a second level of treatment after an unsuccessful trial of two antidepressants. It is nevertheless advisable to be careful in its use in a clinical psychiatric population: exclusion of suicidal ideation or antecedent of suicidal acting, absence of psychotic depression, use exclusively for unipolar major depressive disorder. The different conditions of use are also notified in the product characteristics of the European Medicines Agency. Finally, further comparative studies are needed in the future, in the absence of funding from the pharmaceutical company producing esketamine.

[Atypical depression as a risk factor for obstructive sleep apnea syndrome in young adults]. / La dépression majeure à caractéristique atypique comme facteur de risque du syndrome d'apnées obstructives du sommeil chez le jeune adulte.

OBJECTIVES: In the literature, several studies have investigated the particular relationship between major depression and obstructive sleep apnoea syndrome (OSAS). However, most of these studies have focused primarily on middle-aged to elderly individuals (≥40 years) which means that this problem has been little studied in young adults (<30 years). Nevertheless, in young adults the prevalence of major depression (particularly its atypical subtype) is not negligible, which seems to justify carrying out additional investigations in order to allow a better understanding of the potential role played by major depression in the pathophysiology of OSAS in this particular subpopulation. The aim of this study was therefore to empirically investigate the prevalence of OSAS in young adults and to study the risk of OSAS associated with major depression in this particular subpopulation. METHODS: Polysomnographic and demographic data from 264 young adults were collected from the Erasme Hospital Sleep Laboratory (Brussels, Belgium) database to enable our analyses. During their two-night stay (including a first night of habituation and a night of polysomnography) at the Sleep Laboratory, these individuals underwent a complete somatic assessment (including blood test, electrocardiogram, daytime electroencephalogram and urinalysis), a systematic psychiatric assessment by a unit psychiatrist and an assessment of their complaints related to sleep. These different steps made it possible to systematically diagnose all somatic pathologies, psychiatric disorders according to the diagnostic criteria of the DSM-IV-TR and sleep pathologies according to the diagnostic criteria of the AASM. This allowed the selection of young adults included in our study based on our inclusion and exclusion criteria. Polysomnographic recordings from our Sleep Laboratory were visually scored according to AASM criteria. An obstructive sleep apnoea-hypopnoea index ≥5/hour was used for the diagnosis of OSAS. At the statistical level, in order to allow our analyses, we subdivided our sample of young adults into two groups: a control group without OSAS (n=215) and a patient group with OSAS (n=49). After checking the normal distribution of our data, normally distributed data were analysed with t-tests whereas asymmetrically or dichotomously distributed data were analysed with Wilcoxon tests or Chi2 tests. Univariate regression models were used to study the risk of OSAS associated with major depression (categorized: absent, typical, atypical) in young adults and potential confounding factors. In multivariate regression models, the risk of OSAS associated with major depression (categorized: absent, typical, atypical) in young adults was adjusted only for confounding factors significantly associated with OSAS during univariate analysis. These confounding factors were introduced in a hierarchical manner in the various multivariate regression models constructed. RESULTS: The prevalence of OSAS in our population of young adults was 18.6 %. During univariate analyses, atypical depression [OR 2.51 (95% CI 1.18-5.32), p-value=0.014], male gender [OR 4.53 (95% CI 2.20-9.34), P-value <0.001], presence of snoring [OR 2.51 (95% CI 1.33-4.75), P-value=0.005], presence of at least one cardio-metabolic alteration [OR 2.26 (95% CI 1.19-4.28), P-value=0.012], body mass index>30 kg/m2 [OR 4.55 (95% CI 2.07-10.03), P-value <0.001] and ferritin ≥150 µg/L [OR 3.28 (95% CI 1.69-6.36), P-value<0.001] were associated with increased risk of OSAS in our population of young adults. After adjusting for these major confounding factors associated with OSAS (gender, body mass index, cardio-metabolic alterations, ferritin level, and snoring) in the four models studied, multivariate regression analyses confirmed that unlike typical depression, atypical depression [OR 3.09 (95% CI 1.26-7.54), P-value=0.019] was a risk factor for OSAS in young adults. CONCLUSIONS: In our study, we demonstrated that the prevalence of OSAS was 18.6 % in young adults referred to the Erasme Hospital Sleep Laboratory. In addition, we have shown that unlike typical depression, atypical depression was associated with an increased risk of OSAS in young adults, which seems to justify more systematic research of this pathology in young adults suffering from atypical depression in order to allow the establishment of adapted therapeutic strategies and avoid the negative consequences associated with the co-occurrence of these two pathologies.