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Life
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Novel Pharmacological Approaches to the Treatment of Depression
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Novel Pharmacological Approaches to the Treatment of Depression

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Pharmaceutical Science".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 41677

Special Issue Editors

Dr. Anna Serefko

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Guest Editor
Laboratory of Preclinical Testing, Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland
Interests: depression; anxiety; epilepsy; neuroscience; preclinical studies
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ewa Poleszak

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Guest Editor
Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, 20-093 Lublin, Poland
Interests: depression; anxiety; preclinical study; neuropharmacology; neuropsychopharmacology; toxicological and biochemical analysis
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Aleksandra Szopa

E-Mail Website
Guest Editor
Department of Clinical Pharmacy and Pharmaceutical Care, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland
Interests: depression; anxiety; epilepsy; neuroscience; preclinical studies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Depression is a common chronic neuropsychiatric disorder highly prevalent in Western countries. It can affect people of all ages, genders, racial/ethnic/cultural backgrounds. Depression negatively influences quality of life of an individual but it also belongs to the largest contributors to global disability and suicide deaths. Though there are several therapeutic options for depression, management of this disease is still challenging. Clinical efficiency of the available antidepressant drugs is not sufficient since a number of patients with depression do not respond to the prescribed therapy, do not achieve complete remission, and they suffer relapses. Furthermore, conventional antidepressants may induce bothersome side effects that can result in patients non-compliance. Therefore, constant attempts have been made to develop new, more effective agents or treatment strategies with faster onset of the antidepressant effect and better safety profile. Research teams focus on novel compounds but also they evaluate unique combinations of known substances with an antidepressant potential. Simultaneously, intensive studies on the pathomechanism of depressive disorders have been carried out in order to identify innovative drug targets. In this Special Issue on Novel Pharmacological Approaches to the Treatment of Depression we would like to bring together experts working in the depression field and invite them to present their recent results from both pre-clinical and clinical studies related to pharmacotherapy of depressive disorders. Review articles and short communications on the latest achievements in the management of depression would be also welcome.

You may choose our Joint Special Issue in Psych.

Dr. Anna Serefko
Prof. Dr. Ewa Poleszak
Dr. Aleksandra Szopa
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antidepressant
  • depression/mood disorders
  • neuroscience
  • preclinical studies
  • clinical studies

Published Papers (10 papers)

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Research

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13 pages, 783 KiB  
Article
Influence of Smallanthus sonchifolius (Yacon) on the Activity of Antidepressant Drugs in Mice
by Sylwia Wośko, Anna Serefko, Aleksandra Szopa, Sylwia Kardaś, Jarosław Widelski, Tomasz Mroczek, Ewelina Rostkowska, Jolanta Szymańska and Ewa Poleszak
Life 2021, 11(11), 1117; https://0-doi-org.brum.beds.ac.uk/10.3390/life11111117 - 21 Oct 2021
Cited by 1 | Viewed by 1791
Abstract
Depression is one of the most common mental disorders in the world that negatively affects the daily functioning of patients. Numerous studies are currently being conducted to examine the antidepressant potential of innovative synthetic compounds and herbal substances. Yacon, Smallantchus sonchifolius, belongs [...] Read more.
Depression is one of the most common mental disorders in the world that negatively affects the daily functioning of patients. Numerous studies are currently being conducted to examine the antidepressant potential of innovative synthetic compounds and herbal substances. Yacon, Smallantchus sonchifolius, belongs to plants with numerous health-beneficial properties. Yacon-based products are regarded as a functional food. In our study, we attempted to check whether administration of Yacon tuber extract would have an antidepressant effect in the forced swim test (FST) in mice and whether its intake could influence the activity of conventional antidepressant drugs with different mechanisms of action, i.e., imipramine hydrochloride, fluoxetine hydrochloride, and reboxetine mesylate. The spontaneous locomotor activity of the tested mice was also investigated to eliminate any false-positive results. We demonstrated that an intragastric administration of the Yacon tuber extract at a dose of 100 mg/kg induced the antidepressant-like behavior in the FST in mice and that a combined administration of the sub-effective doses of the Yacon extract (50 mg/kg) with imipramine hydrochloride (7.5 mg/kg), fluoxetine hydrochloride (20 mg/kg), or reboxetine mesylate (5 mg/kg) significantly reduced the immobility time of animals in this behavioral test. The obtained results were not affected by the increased locomotor activity of the tested subjects. In conclusion, our findings suggest that Yacon tuber extract is promising as an alternative mood-improving product since it possesses an antidepressant potential and it can acts synergistically with conventional antidepressant drugs. Full article
(This article belongs to the Special Issue Novel Pharmacological Approaches to the Treatment of Depression)
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10 pages, 632 KiB  
Article
The Relationship between the Concentration of Magnesium and the Presence of Depressive Symptoms and Selected Metabolic Disorders among Men over 50 Years of Age
by Iwona Rotter, Adrian Wiatrak, Aleksandra Rył, Katarzyna Kotfis, Olimpia Sipak-Szmigiel, Magdalena Ptak, Natalia Tomska and Aleksandra Szylińska
Life 2021, 11(3), 196; https://0-doi-org.brum.beds.ac.uk/10.3390/life11030196 - 03 Mar 2021
Viewed by 1549
Abstract
Background: changes in the concentration of magnesium influence numerous processes in the body, such as hormone and lipid metabolism, nerve conduction, a number of biochemical pathways in the brain, and metabolic cycles. As a result, changes in magnesium concentration may contribute to the [...] Read more.
Background: changes in the concentration of magnesium influence numerous processes in the body, such as hormone and lipid metabolism, nerve conduction, a number of biochemical pathways in the brain, and metabolic cycles. As a result, changes in magnesium concentration may contribute to the emergence of such pathologies as depressive and metabolic disorders, including hypertension, diabetes, and dyslipidemia. Methods: blood samples were taken from 342 men whose mean age was 61.66 ± 6.38 years. The concentrations of magnesium, lipid parameters, and glucose were determined using the spectrophotometric method. Anthropometric measurements were performed to determine each participant’s body mass index (BMI). Additionally, all participants completed two questionnaires: the Beck Depression Inventory and the author’s questionnaire. Results: abnormal levels of magnesium were found in 78 people. The analysis showed that these subjects more often suffered from metabolic disorders such as diabetes mellitus (p < 0.001), hypertension (p < 0.001), and depressive symptoms (p = 0.002) than participants with normal magnesium levels. Conclusion: our research showed that there is a relationship between abnormal levels of magnesium and the presence of self-reported conditions, such as diabetes, hypertension, and depressive symptoms among aging men. These findings may contribute to the improvement of the diagnosis and treatment of patients with these conditions. Full article
(This article belongs to the Special Issue Novel Pharmacological Approaches to the Treatment of Depression)
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Review

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31 pages, 554 KiB  
Review
Novel Pharmacological Approaches to the Treatment of Depression
by Elias Elias, Ariel Y. Zhang and Melissa T. Manners
Life 2022, 12(2), 196; https://0-doi-org.brum.beds.ac.uk/10.3390/life12020196 - 28 Jan 2022
Cited by 24 | Viewed by 7049
Abstract
Major depressive disorder is one of the most prevalent mental health disorders. Monoamine-based antidepressants were the first drugs developed to treat major depressive disorder. More recently, ketamine and other analogues were introduced as fast-acting antidepressants. Unfortunately, currently available therapeutics are inadequate; lack of [...] Read more.
Major depressive disorder is one of the most prevalent mental health disorders. Monoamine-based antidepressants were the first drugs developed to treat major depressive disorder. More recently, ketamine and other analogues were introduced as fast-acting antidepressants. Unfortunately, currently available therapeutics are inadequate; lack of efficacy, adverse effects, and risks leave patients with limited treatment options. Efforts are now focused on understanding the etiology of depression and identifying novel targets for pharmacological treatment. In this review, we discuss promising novel pharmacological targets for the treatment of major depressive disorder. Targeting receptors including N-methyl-D-aspartate receptors, peroxisome proliferator-activated receptors, G-protein-coupled receptor 39, metabotropic glutamate receptors, galanin and opioid receptors has potential antidepressant effects. Compounds targeting biological processes: inflammation, the hypothalamic-pituitary-adrenal axis, the cholesterol biosynthesis pathway, and gut microbiota have also shown therapeutic potential. Additionally, natural products including plants, herbs, and fatty acids improved depressive symptoms and behaviors. In this review, a brief history of clinically available antidepressants will be provided, with a primary focus on novel pharmaceutical approaches with promising antidepressant effects in preclinical and clinical studies. Full article
(This article belongs to the Special Issue Novel Pharmacological Approaches to the Treatment of Depression)
21 pages, 422 KiB  
Review
Gut Hormones as Potential Therapeutic Targets or Biomarkers of Response in Depression: The Case of Motilin
by Ravi Philip Rajkumar
Life 2021, 11(9), 892; https://0-doi-org.brum.beds.ac.uk/10.3390/life11090892 - 29 Aug 2021
Cited by 7 | Viewed by 2924
Abstract
Recent research has identified the gut–brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut hormones as potential treatments or predictors of response in depression is examined, with specific reference to the [...] Read more.
Recent research has identified the gut–brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut hormones as potential treatments or predictors of response in depression is examined, with specific reference to the peptide hormone motilin. This possibility is explored through two methods: (1) a conceptual review of the possible links between motilin and depression, including evidence from animal and human research as well as clinical trials, based on a literature search of three scientific databases, and (2) an analysis of the relationship between a functional polymorphism (rs2281820) of the motilin (MLN) gene and cross-national variations in the prevalence of depression based on allele frequency data after correction for potential confounders. It was observed that (1) there are several plausible mechanisms, including interactions with diet, monoamine, and neuroendocrine pathways, to suggest that motilin may be relevant to the pathophysiology and treatment of depression, and (2) there was a significant correlation between rs2281820 allele frequencies and the prevalence of depression after correcting for multiple confounding factors. These results suggest that further evaluation of the utility of motilin and related gut peptides as markers of antidepressant response is required and that these molecular pathways represent potential future mechanisms for antidepressant drug development. Full article
(This article belongs to the Special Issue Novel Pharmacological Approaches to the Treatment of Depression)
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19 pages, 320 KiB  
Review
Targeting Metabolic Dysfunction for the Treatment of Mood Disorders: Review of the Evidence
by Brett D. M. Jones, Salman Farooqui, Stefan Kloiber, Muhammad Omair Husain, Benoit H. Mulsant and Muhammad Ishrat Husain
Life 2021, 11(8), 819; https://0-doi-org.brum.beds.ac.uk/10.3390/life11080819 - 11 Aug 2021
Cited by 13 | Viewed by 3552
Abstract
Major depressive disorder (MDD) and bipolar disorder (BD) are often chronic with many patients not responding to available treatments. As these mood disorders are frequently associated with metabolic dysfunction, there has been increased interest in novel treatments that would target metabolic pathways. The [...] Read more.
Major depressive disorder (MDD) and bipolar disorder (BD) are often chronic with many patients not responding to available treatments. As these mood disorders are frequently associated with metabolic dysfunction, there has been increased interest in novel treatments that would target metabolic pathways. The objectives of this scoping review were to synthesize evidence on the impact on mood symptoms of lipid lowering agents and anti-diabetics drugs, while also reviewing current knowledge on the association between mood disorders and dyslipidemia or hyperglycemia. We propose that metabolic dysfunction is prevalent in both MDD and BD and it may contribute to the development of these disorders through a variety of pathophysiological processes including inflammation, brain structural changes, hormonal alterations, neurotransmitter disruptions, alteration on brain cholesterol, central insulin resistance, and changes in gut microbiota. Current evidence is conflicting on the use of statins, polyunsaturated fatty acids, thiazolidinediones, glucagon-like peptide agonists, metformin, or insulin for the treatment of MDD and BD. Given the paucity of high-quality randomized controlled trials, additional studies are needed before any of these medications can be repurposed in routine clinical practice. Future trials need to enrich patient recruitment, include evaluations of mechanism of action, and explore differential effects on specific symptom domains such as anhedonia, suicidality, and cognition. Full article
(This article belongs to the Special Issue Novel Pharmacological Approaches to the Treatment of Depression)
19 pages, 377 KiB  
Review
Zebrafish as an Animal Model for Testing Agents with Antidepressant Potential
by Joanna Lachowicz, Karolina Niedziałek, Ewelina Rostkowska, Aleksandra Szopa, Katarzyna Świąder, Jarosław Szponar and Anna Serefko
Life 2021, 11(8), 792; https://0-doi-org.brum.beds.ac.uk/10.3390/life11080792 - 05 Aug 2021
Cited by 18 | Viewed by 5346
Abstract
Depression is a serious mental disease that, according to statistics, affects 320 million people worldwide. Additionally, a current situation related to the COVID-19 pandemic has led to a significant deterioration of mental health in people around the world. So far, rodents have been [...] Read more.
Depression is a serious mental disease that, according to statistics, affects 320 million people worldwide. Additionally, a current situation related to the COVID-19 pandemic has led to a significant deterioration of mental health in people around the world. So far, rodents have been treated as basic animal models used in studies on this disease, but in recent years, Danio rerio has emerged as a new organism that might serve well in preclinical experiments. Zebrafish have a lot of advantages, such as a quick reproductive cycle, transparent body during the early developmental stages, high genetic and physiological homology to humans, and low costs of maintenance. Here, we discuss the potential of the zebrafish model to be used in behavioral studies focused on testing agents with antidepressant potential. Full article
(This article belongs to the Special Issue Novel Pharmacological Approaches to the Treatment of Depression)
35 pages, 2096 KiB  
Review
Drug Repurposing for the Management of Depression: Where Do We Stand Currently?
by Hosna Mohammad Sadeghi, Ida Adeli, Taraneh Mousavi, Marzieh Daniali, Shekoufeh Nikfar and Mohammad Abdollahi
Life 2021, 11(8), 774; https://0-doi-org.brum.beds.ac.uk/10.3390/life11080774 - 30 Jul 2021
Cited by 12 | Viewed by 4774
Abstract
A slow rate of new drug discovery and higher costs of new drug development attracted the attention of scientists and physicians for the repurposing and repositioning of old medications. Experimental studies and off-label use of drugs have helped drive data for further studies [...] Read more.
A slow rate of new drug discovery and higher costs of new drug development attracted the attention of scientists and physicians for the repurposing and repositioning of old medications. Experimental studies and off-label use of drugs have helped drive data for further studies of approving these medications. A deeper understanding of the pathogenesis of depression encourages novel discoveries through drug repurposing and drug repositioning to treat depression. In addition to reducing neurotransmitters like epinephrine and serotonin, other mechanisms such as inflammation, insufficient blood supply, and neurotoxicants are now considered as the possible involved mechanisms. Considering the mentioned mechanisms has resulted in repurposed medications to treat treatment-resistant depression (TRD) as alternative approaches. This review aims to discuss the available treatments and their progress way during repositioning. Neurotransmitters’ antagonists, atypical antipsychotics, and CNS stimulants have been studied for the repurposing aims. However, they need proper studies in terms of formulation, matching with regulatory standards, and efficacy. Full article
(This article belongs to the Special Issue Novel Pharmacological Approaches to the Treatment of Depression)
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17 pages, 1220 KiB  
Review
Ketamine Alters Functional Plasticity of Astroglia: An Implication for Antidepressant Effect
by Matjaž Stenovec
Life 2021, 11(6), 573; https://0-doi-org.brum.beds.ac.uk/10.3390/life11060573 - 17 Jun 2021
Cited by 9 | Viewed by 2869
Abstract
Ketamine, a non-competitive N–methyl–d–aspartate receptor (NMDAR) antagonist, exerts a rapid, potent and long-lasting antidepressant effect, although the cellular and molecular mechanisms of this action are yet to be clarified. In addition to targeting neuronal NMDARs fundamental for synaptic transmission, ketamine [...] Read more.
Ketamine, a non-competitive N–methyl–d–aspartate receptor (NMDAR) antagonist, exerts a rapid, potent and long-lasting antidepressant effect, although the cellular and molecular mechanisms of this action are yet to be clarified. In addition to targeting neuronal NMDARs fundamental for synaptic transmission, ketamine also affects the function of astrocytes, the key homeostatic cells of the central nervous system that contribute to pathophysiology of major depressive disorder. Here, I review studies revealing that (sub)anesthetic doses of ketamine elevate intracellular cAMP concentration ([cAMP]i) in astrocytes, attenuate stimulus-evoked astrocyte calcium signaling, which regulates exocytotic secretion of gliosignaling molecules, and stabilize the vesicle fusion pore in a narrow configuration, possibly hindering cargo discharge or vesicle recycling. Next, I discuss how ketamine affects astrocyte capacity to control extracellular K+ by reducing vesicular delivery of the inward rectifying potassium channel (Kir4.1) to the plasmalemma that reduces the surface density of Kir4.1. Modified astroglial K+ buffering impacts upon neuronal firing pattern as demonstrated in lateral habenula in a rat model of depression. Finally, I highlight the discovery that ketamine rapidly redistributes cholesterol in the astrocyte plasmalemma, which may alter the flux of cholesterol to neurons. This structural modification may further modulate a host of processes that synergistically contribute to ketamine’s rapid antidepressant action. Full article
(This article belongs to the Special Issue Novel Pharmacological Approaches to the Treatment of Depression)
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Other

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15 pages, 930 KiB  
Systematic Review
The Potential Role of Serotonergic Hallucinogens in Depression Treatment
by Dominika Psiuk, Emilia Nowak, Krystian Cholewa, Urszula Łopuszańska and Marzena Samardakiewicz
Life 2021, 11(8), 765; https://0-doi-org.brum.beds.ac.uk/10.3390/life11080765 - 29 Jul 2021
Cited by 5 | Viewed by 7382
Abstract
Due to an increasing number of depression diagnoses and limited effective treatments, researchers continue to explore novel therapeutic strategies for this disorder. Recently, interest has revolved around the use of serotonergic psychedelics to reduce the symptoms of depression. In this systematic review, we [...] Read more.
Due to an increasing number of depression diagnoses and limited effective treatments, researchers continue to explore novel therapeutic strategies for this disorder. Recently, interest has revolved around the use of serotonergic psychedelics to reduce the symptoms of depression. In this systematic review, we summarize the currently available knowledge on the safety and efficacy of psychedelic substances for the treatment of depression. A literature search of the PubMed/MEDLINE database identified 14 clinical trials from the last 10 years that examined the use of psilocybin, MDMA, DMT, or LSD for the treatment of depression symptoms. Some psychedelics, especially psilocybin, demonstrated an ability to reduce depressive symptoms as measured by several psychological scales, which was often sustained for months after the last psychedelic session. Moreover, one study revealed that psilocybin has comparable efficacy to escitalopram in the treatment of depression. None of the studies reported any serious adverse events associated with psychedelic administration. The reviewed studies suggest that psychedelics have great potential in depression therapy and, after addressing and overcoming the current study limitations, may be used as a novel method of treating depression in the future. Full article
(This article belongs to the Special Issue Novel Pharmacological Approaches to the Treatment of Depression)
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7 pages, 236 KiB  
Case Report
Pharmacogenetic-Guided Antidepressant Selection as an Opportunity for Interprofessional Collaboration: A Case Report
by Céline K. Stäuble, Markus L. Lampert, Thorsten Mikoteit, Martin Hatzinger, Kurt E. Hersberger and Henriette E. Meyer zu Schwabedissen
Life 2021, 11(7), 673; https://0-doi-org.brum.beds.ac.uk/10.3390/life11070673 - 09 Jul 2021
Cited by 6 | Viewed by 2358
Abstract
In the herein reported case of a 42-year-old woman diagnosed with anxiety and depression, a long history of antidepressant ineffectiveness and adverse drug reactions was decisive for an in-depth medication review including pharmacogenetic panel testing. In detail, treatment attempts with paroxetine and escitalopram [...] Read more.
In the herein reported case of a 42-year-old woman diagnosed with anxiety and depression, a long history of antidepressant ineffectiveness and adverse drug reactions was decisive for an in-depth medication review including pharmacogenetic panel testing. In detail, treatment attempts with paroxetine and escitalopram were ineffective and discontinued due to subjective gastrointestinal intolerance. Due to the worsening of the depression after the failed treatment attempts, admission to our clinic became necessary. Herein, owing to the collaboration of psychiatrists with clinical pharmacists, individualized incorporation of pharmacogenetic data into the process of antidepressant selection was enabled. We identified vortioxetine as a suitable therapeutic, namely for being most likely pharmacokinetically unaffected as predicted by pharmacogenetic panel testing and taking into account the current comedication, as well as for its favorable action profile. Herein, our collaborative effort proved to be successful and resulted in the patient’s depression remission and clinic discharge with the interprofessionally selected pharmacotherapy. This exemplary case not only highlights the potential benefits and challenges of pre-emptive pharmacogenetic testing in antidepressant prescription, but also proposes an approach on how to put pharmacogenetics into practice. Full article
(This article belongs to the Special Issue Novel Pharmacological Approaches to the Treatment of Depression)
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