Efficacy of Sertraline Plus Placebo or Add-On Celecoxib in Major Depressive Disorder: Macrophage Migration Inhibitory Factor as a Promising Biomarker for Remission After Sertraline—Results From a Randomized Controlled Clinical Trial

Simon, Maria S.; Burger, Bianka; Weidinger, Elif; Arteaga-Henríquez, Gara; Zill, Peter; Musil, Richard; Drexhage, Hemmo A.; Müller, Norbert

doi:10.3389/fpsyt.2021.615261

Cited by 16 publications

(25 citation statements)

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“…In the comparison group treated with a serotonergic plus an anti-inflammatory drug, an opposite effect was observed: a trend for high MIF levels was found in responders and no effect regarding remission. However, the small study consisted of only 43 MDD patients separated into two groups [ 53 ]. In our study, a limitation could be that the observation period of three weeks was too short compared with six weeks in the mentioned studies.…”

Section: Discussionmentioning

confidence: 99%

“…A strength of our study was the three MDD scales which were rated by a clinician or by self-evaluation. In comparison, Musil et al [ 29 ] in 2011 and Simon et al [ 53 ] in 2021 used only either HAM-D or MADRS, rated by clinicians. Interestingly, a better long-term improvement (change in MADRS at 1-year follow-up) for predominantly female patients with mild to moderate depression and high versus low plasma MIF levels was also reported for non-pharmacological treatment in a mindfulness-based group therapy setting with a similar, albeit non-significant, trend after 8 weeks [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

“…On the contrary, Musil et al examined MDD patients during five weeks of reboxetine and add-on celecoxib or placebo treatment and reported no significant MIF change between inclusion and study endpoint, and also no association between MIF course and HAM-D course [ 29 ]. A following study of the same group treated MDD patients for six weeks with sertraline, and additionally celecoxib or a placebo, but no coherent results about MIF change and connection to the MDD course were found [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

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Macrophage Migration Inhibitory Factor in Major Depressive Disorder: A Multilevel Pilot Study

Swoboda

Deloch

Zimmermann

et al. 2022

IJMS

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Macrophage migration inhibitory factor (MIF) is a controversially discussed inflammatory marker in major depressive disorder (MDD). While some studies show an association of high MIF protein levels with depression, animal models have yielded conflicting results. Thus, it remains elusive as to whether MIF plays an anti- or pro-depressive role. Therefore, we aimed to examine the potential of MIF at the genetic, expression and protein levels as a risk factor and biomarker to diagnose, monitor, or predict the course of MDD. Patients with a current major depressive episode (n = 66 with, and n = 63 without, prior medication) and remitted patients (n = 39) were compared with healthy controls (n = 61). Currently depressed patients provided a second blood sample after three weeks of therapy. Depression severity was assessed by self-evaluation and clinician rating scales. We genotyped for three MIF polymorphisms and analyzed peripheral MIF expression and serum levels. The absence of minor allele homozygous individuals in the large group of 96 female patients compared with 10–16% in female controls suggests a protective effect for MDD, which was not observed in the male group. There were no significant group differences of protein and expression levels, however, both showed predictive potential for the course of depression severity in some subgroups. While MIF protein levels, but not MIF expression, decreased during treatment, they were not associated with changes in depression severity. This project is the first to investigate three biological levels of MIF in depression. The data hint toward a genetic effect in women, but do not provide robust evidence for the utility of MIF as a biomarker for the diagnosis or monitoring of MDD. The observed predictive potential requires further analysis, emphasizing future attention to confounding factors such as sex and premedication.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Macrophage Migration Inhibitory Factor in Major Depressive Disorder: A Multilevel Pilot Study

Swoboda

Deloch

Zimmermann

et al. 2022

IJMS

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“…Monotherapy in patients with active osteoarthritis was also successful, similar to naproxen or ibuprofen, even if the celecoxib dose was lower than in other studies (200 versus 400 mg/day) [ 42 ]. The connection between treatment response and immunological biomarkers is supported by the correlation between interleukin (IL)-6 reduction and Hamilton Depression Rating Scale (HAM-D) score reduction [ 43 ], together with a tendency towards higher baseline macrophage migration inhibitory factor (MIF) levels in responders [ 44 ]. On the other hand, a recent RCT failed to show any benefit of celecoxib added to vortioxetine, even when patients were stratified by high-sensitive C-reactive protein (hsCRP), but it is worthy of note that other biomarkers were not examined [ 45 ].…”

Section: Conventional Anti-inflammatory Drugsmentioning

confidence: 99%

Current Perspectives on Pharmacological and Non-Pharmacological Interventions for the Inflammatory Mechanism of Unipolar Depression

et al. 2022

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Since depression remains a major public health issue there is a constant need for new and more efficient therapeutic strategies based on the mechanisms involved in the aetiology of depression. Thus, the pathogenic link between depression and inflammation is considered to play a potential key role in the development of such therapies. This review summarizes the results of various pharmacological (non-steroidal anti-inflammatory drugs, aspirin, cyclooxygenase inhibitors, cytokine inhibitors, corticosteroids, statins, minocycline, N-acetyl cysteine, omega-3 fatty acids and probiotics) and non-pharmacological interventions (electroconvulsive therapy, physical exercise and psychological therapy) and outlines their efficacy and discusses potential challenges. Both conventional and non-conventional anti-inflammatory drugs showed promising results according to the specific group of patients. The pre-existing pro-inflammatory status was, in most cases, a predictor for clinical efficacy and, in some cases, a correlation between clinical improvement and changes in various biomarkers was found. Some of the non-pharmacological interventions (physical exercise and electroconvulsive therapy) have also showed beneficial effects for depressive patients with elevated inflammatory markers. Treatments with anti-inflammatory action may improve clinical outcomes in depression, at least for some categories of patients, thus opening the way for a future personalised approach to patients with unipolar depression regarding the inflammation-related mechanism.

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“…Inflammation has been discussed as a major contributor to non-response to established antidepressants. [19][20][21] Thus, antiinflammatory treatment approaches have been introduced and were tested in numerous clinical trials to treat depression. These studies investigated anti-inflammatory agents as single agents or as add-on regimen to standard therapy and in patients diagnosed with major depressive disorder or with depressive symptoms (eg, Freeman et al, Müller et al).…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Treatment Efficacy in Major Depressive Disorder: A Systematic Review of Meta-Analyses

Simon¹,

Arteaga-Henríquez²,

Algendy³

et al. 2023

NDT

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Immune imbalances in major depressive disorder (MDD) have been targeted by anti-inflammatory treatment approaches in clinical trials to increase responsiveness to therapy. However, even after several meta-analyses, no translation of evidence into clinical practice has taken place. We performed a systematic review to evaluate meta-analytic evidence of randomized controlled trials on the use of anti-inflammatory agents for MDD to summarize efficacy estimates and elucidate shortcomings. Methods: Pooled effect estimates and heterogeneity indices were primary outcomes. Characteristics of the included meta-analyses were extracted. Scientific quality of meta-analyses was assessed using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR). Results: N=20 meta-analyses met the eligibility criteria. Study characteristics like outcome scales, composition of patient populations, and add-on or monotherapy regimen varied very little for celecoxib studies, varied little for minocycline studies, and were rather variable for omega 3 fatty acids studies. R-AMSTAR scores ranged from 26 to 39 out of 44 points indicating variable quality, where a comprehensive literature search was the strongest and the consideration of scientific quality in the conclusions was the weakest domain across all meta-analyses. For minocycline and celecoxib, superiority was demonstrated with medium to large effect size with substantial heterogeneity and with large to very large effect size with negligible heterogeneity, respectively. For omega 3 fatty acids, superiority was also demonstrated with mainly small and medium effect sizes with substantial heterogeneity. However, for minocycline and omega 3 fatty acids, non-significant meta-analyses were found also. Conclusion: Even in our synthesized approach, no clear recommendations could be derived on the use of anti-inflammatory treatment for MDD due to several critical aspects like heterogeneity, diversity of patient populations, treatment regimen, and outcomes, and limited scientific quality. However, we observed clear inter-substance differences with meta-analytic evidence being strongest for celecoxib and weakest for omega 3 fatty acids.

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Efficacy of Sertraline Plus Placebo or Add-On Celecoxib in Major Depressive Disorder: Macrophage Migration Inhibitory Factor as a Promising Biomarker for Remission After Sertraline—Results From a Randomized Controlled Clinical Trial

Cited by 16 publications

References 73 publications

Macrophage Migration Inhibitory Factor in Major Depressive Disorder: A Multilevel Pilot Study

Macrophage Migration Inhibitory Factor in Major Depressive Disorder: A Multilevel Pilot Study

Current Perspectives on Pharmacological and Non-Pharmacological Interventions for the Inflammatory Mechanism of Unipolar Depression

Anti-Inflammatory Treatment Efficacy in Major Depressive Disorder: A Systematic Review of Meta-Analyses

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