Excess body weight as a predictor of response to treatment with antidepressants in patients with depressive disorder

Puzhko, Svetlana; Aboushawareb, Sarah A.E.; Kudrina, Irina; Schuster, Tibor; Barnett, Tracie A.; Renoux, Christel; Bartlett, Gillian

doi:10.1016/j.jad.2020.01.113

Cited by 27 publications

(20 citation statements)

References 62 publications

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“…These players may have an impact on drug metabolism and dysregulation of hypothalamic pituitary axes and cell signaling pathways which modifies the response to therapy. Different response to certain groups and types of AD in patients with excess weight, as compared to normal weight patients, was reported in several studies and described in two recent reviews (6,41). Our findings, therefore, may reflect physicians' difficulties with selection of an effective AD medication for obese patients with depression.…”

Section: Discussionsupporting

confidence: 53%

“…In support of the former, obesity was associated with more severe depression (34)(35)(36), especially in extremely obese patients (37). Patients with obesity may need dose adjustment and a longer treatment duration to reach the same level of response as nonobese patients (38)(39)(40)(41). Since our population is a population of prevalent users and our analysis is cross-sectional, longer treatment duration for obese patients may have contributed to the prevalence of both obesity and AD prescribing in this group.…”

Section: Discussionmentioning

confidence: 66%

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Evaluating Prevalence and Patterns of Prescribing Medications for Depression for Patients With Obesity Using Large Primary Care Data (Canadian Primary Care Sentinel Surveillance Network)

et al. 2020

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Introduction: Depression is a serious disorder that brings a tremendous health and economic burden. Many antidepressants (AD) have obesogenic effects, increasing the population of obese patients at increased risk for a more severe disease course and poor treatment response. In addition, obese patients with depression may not be receiving the recommended standard of care due to "obesity bias." It is important to evaluate prescribing pharmacological treatment of depression in patients with obesity. Objectives: To describe the prevalence and patterns of AD prescribing for patients with depression and comorbid obesity compared with normal weight patients, and to examine the association of prescribing prevalence with obesity class. Methods: Study sample of adult patients (>18 years old) with depression was extracted from the national Canadian Primary Care Sentinel Surveillance Network (CPCSSN) Electronic Medical Records database for 2011-2016. Measures were prescribing of at least one AD (outcome) and body mass index (BMI) to categorize patients into weight categories (exposure). Data were analyzed cross-sectionally using descriptive statistics and mixed effects logistic regression model with clustering on CPCSSN networks and adjusting for age, sex, and the comorbidities. Results: Of 120,381 patients with depression, 63,830 patients had complete data on studied variables (complete cases analysis). Compared with normal weight patients, obese patients were more likely to receive an AD prescription (adjusted Odds Ratio [aOR] = 1.17; 95% Confidence Interval [CI]: 1.12-1.22). Patients with obesity classes II and III were 8% (95% CI: 1.00, 1.16) and 6% (95% CI: 0.98, 1.16) more likely, respectively, to receive AD. After imputing missing data using Multiple Imputations by Chained Equations, the results remained unchanged. The prevalence of prescribing >3 AD types was higher Puzhko et al. Antidepressants Prescribing in Patients With Obesity in obese category (7.27%, [95% CI: 6.84, 7.73]) than in normal weight category (5.6%; [95% CI: 5.24, 5.99]). Conclusion: The association between obesity and high prevalence of AD prescribing and prescribing high number of different AD to obese patients, consistent across geographical regions, raises a public health concern. Study results warrant qualitative studies to explore reasons behind the difference in prescribing, and quantitative longitudinal studies evaluating the association of AD prescribing patterns for obese patients with health outcomes.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 66%

Evaluating Prevalence and Patterns of Prescribing Medications for Depression for Patients With Obesity Using Large Primary Care Data (Canadian Primary Care Sentinel Surveillance Network)

et al. 2020

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“…18 In a recent scoping review, excess body weight predicted nonresponse to treatment with antidepressants. 19 Given the enormous public health impact of MDD and obesity and given the evidence of antidepressive effects of statins, a controlled trial of adjunct statin treatment in comorbid patients appears warranted.…”

Section: The 12 Monthsmentioning

confidence: 99%

Simvastatin add-on to escitalopram in patients with comorbid obesity and major depression (SIMCODE): study protocol of a multicentre, randomised, double-blind, placebo-controlled trial

et al. 2020

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IntroductionMajor depressive disorder (MDD) and obesity are both common disorders associated with significant burden of disease worldwide. Importantly, MDD and obesity often co-occur, with each disorder increasing the risk for developing the other by about 50%–60%. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomised controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Importantly, this is a difficult-to-treat population that often exhibits a chronic course of MDD and is more likely to be treatment resistant. Thus, in this confirmatory randomised controlled trial, we will determine whether add-on simvastatin to standard antidepressant medication with escitalopram is more efficacious than add-on placebo over 12 weeks in 160 patients with MDD and comorbid obesity.Methods and analysisThis is a protocol for a randomised, placebo-controlled, double-blind multicentre trial with parallel-group design (phase II). One hundred and sixty patients with MDD and comorbid obesity will be randomised 1:1 to simvastatin or placebo as add-on to standard antidepressant medication with escitalopram. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 12. Secondary outcomes include MADRS response (defined as 50% MADRS score reduction from baseline), MADRS remission (defined as MADRS score <10), mean change in patients’ self-reported Beck Depression Inventory (BDI-II) and mean change in high-density lipoprotein, low-density lipoprotein and total cholesterol from baseline to week 12.Ethics and disseminationThis protocol has been approved by the ethics committee of the federal state of Berlin (Ethik-Kommission des Landes Berlin, reference: 19/0226—EK 11) and by the relevant federal authority (Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), reference: 4043387). Study findings will be published in peer-reviewed journals and will be presented at (inter)national conferences.Trial registration numbersNCT04301271, DRKS00021119, EudraCT 2018-002947-27.

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“…Additionally, to the glucose homeostasis, we aimed to answer the question, if BMI and ECT remission are associated as recent research associated antidepressant treatment response with BMI. In a recent review, Puzhko and colleagues pointed out, that obesity goes in line with lowgrade inflammation such as C-reactive protein (CRP) and that inflammation was linked to an altered antidepressant treatment response (Haroon et al 2018;Puzhko et al 2020). Antidepressant medication, ketamine, and ECT all have an anti-inflammatory impact and may unfold their effect through this way (Freeman et al 2020;Liu et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…The aforementioned hyperactive HPA axis can also contribute to an increase in body weight. Recent studies reported overweight patients to experience a superior response to antidepressant treatment than non-overweight ones, particularly in the case of, e.g., pharmacotherapy (Dreimüller et al 2019;Puzhko et al 2020), including ketamine (Freeman et al 2020), or ECT (Moss and Vaidya 2006). The current study asks whether BMI or levels of adiposity-associated parameters (such as lipids, glucose, and insulin) are affected by ECT or related to treatment outcome.…”

Section: Introductionmentioning

confidence: 97%

Electroconvulsive therapy and adiposity-related parameters in treatment-resistant depressed patients

et al. 2022

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Obesity is often accompanied by major depressive disorder (MDD), and vice versa. Latest research findings suggest the body mass index (BMI) to play a role in antidepressant treatment response in general. Our study aims to examine whether adiposity-related parameters such as BMI, glucose homeostasis, or serum lipids are associated with remission to electroconvulsive therapy (ECT). A pilot study (PS, n = 9) and a glucose study (GS, n = 29) were conducted. Blood was withdrawn directly before and 15 min (GS) as well as 1 h (PS) after the first ECT and directly before the last one (usually an ECT series comprised up to twelve sessions). BMI was associated with remission in the PS (remitters: M = 28, SD = 2.5; non-remitters: M = 22, SD = 2.08; t(7) = 3.325, p < 0.001, d = 0.24) but not in the GS or when pooled together. Glucose and insulin levels increased significantly after a single ECT session (GS: glucose: F (2,25.66) = 39.04, p < 0.001; insulin: PS: F (2,83) = 25.8, p < 0.001; GS: F (2,25.87) = 3.97, p < 0.05) but no chronic effect was detectable. Serum lipids were neither significantly altered after a single ECT session nor during a whole course of ECT. There was no difference between remitters and non-remitters in insulin, glucose, or serum lipid levels. Our study is lacking the differentiation between abdominal and peripheral fat distribution, and the sample size is small. Unexpectedly, BMI, glucose homeostasis, and lipid serum levels did not differ in patients remitting during ECT. In contrast to recently published studies, we cannot confirm the hypothesis that BMI may have an impact on ECT response.

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Excess body weight as a predictor of response to treatment with antidepressants in patients with depressive disorder

Cited by 27 publications

References 62 publications

Evaluating Prevalence and Patterns of Prescribing Medications for Depression for Patients With Obesity Using Large Primary Care Data (Canadian Primary Care Sentinel Surveillance Network)

Evaluating Prevalence and Patterns of Prescribing Medications for Depression for Patients With Obesity Using Large Primary Care Data (Canadian Primary Care Sentinel Surveillance Network)

Simvastatin add-on to escitalopram in patients with comorbid obesity and major depression (SIMCODE): study protocol of a multicentre, randomised, double-blind, placebo-controlled trial

Electroconvulsive therapy and adiposity-related parameters in treatment-resistant depressed patients

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