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Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants.
Kadriu, B, Greenwald, M, Henter, ID, Gilbert, JR, Kraus, C, Park, LT, Zarate, CA
The international journal of neuropsychopharmacology. 2021;(1):8-21
Abstract
BACKGROUND The glutamatergic modulator ketamine has created a blueprint for studying novel pharmaceuticals in the field. Recent studies suggest that "classic" serotonergic psychedelics (SPs) may also have antidepressant efficacy. Both ketamine and SPs appear to produce rapid, sustained antidepressant effects after a transient psychoactive period. METHODS This review summarizes areas of overlap between SP and ketamine research and considers the possibility of a common, downstream mechanism of action. The therapeutic relevance of the psychoactive state, overlapping cellular and molecular effects, and overlapping electrophysiological and neuroimaging observations are all reviewed. RESULTS Taken together, the evidence suggests a potentially shared mechanism wherein both ketamine and SPs may engender rapid neuroplastic effects in a glutamatergic activity-dependent manner. It is postulated that, though distinct, both ketamine and SPs appear to produce acute alterations in cortical network activity that may initially produce psychoactive effects and later produce milder, sustained changes in network efficiency associated with therapeutic response. However, despite some commonalities between the psychoactive component of these pharmacologically distinct therapies-such as engagement of the downstream glutamatergic pathway-the connection between psychoactive impact and antidepressant efficacy remains unclear and requires more rigorous research. CONCLUSIONS Rapid-acting antidepressants currently under investigation may share some downstream pharmacological effects, suggesting that their antidepressant effects may come about via related mechanisms. Given the prototypic nature of ketamine research and recent progress in this area, this platform could be used to investigate entirely new classes of antidepressants with rapid and robust actions.
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Ketogenic diet for depression: A potential dietary regimen to maintain euthymia?
Włodarczyk, A, Cubała, WJ, Stawicki, M
Progress in neuro-psychopharmacology & biological psychiatry. 2021;:110257
Abstract
Approximately 30% of patients with major depressive disorder (MDD) present resistance to current pharmacological therapies. There is the possibility that an appropriate nutritional regimen can maintain euthymia. Poor dietary pattern and lack of nutritional knowledge are common among today's population; nutrient-rich foods are being replaced by highly processed foods that lead to a higher risk of developing chronic diseases such as metabolic syndrome, hypercholesterolemia, and diabetes. There is growing evidence of the beneficial role of vitamins and dietary supplements for improving symptoms in a range of affective disorders by regulating the gut microbiome, gut-brain axis, and neurotransmitter levels. Reduced GABA neurotransmission is regularly observed in MDD. Moreover, positive allosteric GABA modulators (i.e benzodiazepines) are widely prescribed to alleviate depression symptoms, but their use needs to be limited, as it can lead to addiction. An alternative option may be the adherence to a ketogenic diet, which consists of low-carbohydrate, moderate-protein, and high-fat intake. It is mainly known for its beneficial role in weight-loss, refractory epilepsy treatment, and balancing glucose levels. A ketogenic diet can also increase GABA levels to aid the mechanism of action of monoaminergic drugs. Thus, it could potentially be used in the treatment for affective disorders due to its potential role in GABA/glutamate balance. While more research is needed before this regimen can be regularly recommended to patients, here we discuss evidence that may encourage physicians to prescribe ketogenic diet as an adjuvant for patients receiving psychotherapy and pharmacology.
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Pharmacotherapy for depression and bipolar disorder during lactation: A framework to aid decision making.
Sprague, J, Wisner, KL, Bogen, DL
Seminars in perinatology. 2020;(3):151224
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Abstract
OBJECTIVE Breastmilk is recommended as the exclusive source of nutrition for infants younger than 6 months due to the numerous health benefits for both infants and mothers. Although many women are prescribed medications during pregnancy and postpartum, limited data are available to assist women in weighing the benefits compared to the risks of peripartum medication use. The goals of this paper are to discuss the importance of breastmilk for the health of both the mother and infant, evaluate the impact of medication use on women's infant feeding choice, describe the transfer of drugs to breastmilk and infants, and provide a framework for clinicians to support evidence-based counseling for women treated for mood disorders. RECOMMENDATIONS We recommend early pregnancy counseling to discuss the benefits and risks of medications during breastfeeding. The Surgeon General's Call to Action (2011) highlights the short and long-term negative health effects of not providing breastmilk. Integrating recommendations from the pediatric and obstetric teams allows patients to make decisions based on evidence and reach their infant feeding goals. Databases containing summaries of research findings and pharmacologic properties of the drug of interest are an essential resource for clinicians.
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Nutraceutical Augmentation Strategies for Depression: A Narrative Review.
Lande, RG
The Journal of the American Osteopathic Association. 2020;(2):100-106
Abstract
CONTEXT Depression is one of the most commonly diagnosed psychiatric disorders, but antidepressant pharmacotherapy often fails to achieve remission, leading health care professionals and researchers to consider various augmentation strategies to improve clinical outcomes. OBJECTIVE To assess the safety, tolerability, and efficacy of nutraceutical augmentation for depression. METHODS Nutraceutical-focused systematic reviews and clinical practice guidelines identified the more commonly studied augmentation strategies for depression. RESULTS S-adenosylmethionine, l-methylfolate, omega-3 fatty acids, and hydroxyvitamin D have sufficient scientific evidence to support their clinical consideration in the stepped care approach to the management of depression. CONCLUSIONS Clinical remission is the goal in the management of depression, and nutraceuticals may be part of an overall treatment approach to achieve that outcome.
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Depression and Treatment with Effective Herbs.
Fathinezhad, Z, Sewell, RDE, Lorigooini, Z, Rafieian-Kopaei, M
Current pharmaceutical design. 2019;(6):738-745
Abstract
Depression is a common psychiatric disease and one of the main causes of disability worldwide. In spite of certain developments in this field, chemical and synthetic drugs used for the treatment of depression disrupt the treatment process due to numerous side effects and high cost. Today, the goal of using a potential method for treating depression involves the use of medicinal and phytochemical plants, which have many therapeutic benefits. Studies have shown that medicinal plants affect the nervous system and exert antidepressant effects in various ways, including synaptic regulation of serotonin, noradrenaline and dopamine, and inflammatory mediators. In this study, depression as well as the factors and mechanisms involved in its development are first addressed, and then medicinal plants effective in the treatment of depression along with their mechanisms of actions are reported.
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Distribution of the anti-inflammatory and anti-depressant compounds: Incensole and incensole acetate in genus Boswellia.
Al-Harrasi, A, Csuk, R, Khan, A, Hussain, J
Phytochemistry. 2019;:28-40
Abstract
Incensole and its acetate have shown anti-inflammatory and anti-depression activities due to their ability to activate ion channels in the brain to alleviate anxiety or depression. The natural occurrence of these two structurally and medicinally fascinating 14-membered diterpenoids was reported mainly from the genus Boswellia. Incensole and incensole acetate were detected in and isolated from both essential oils and resins of frankincense. One total synthesis was reported for incensole. Both incensole and its acetate served as precursors for several synthetic transformations. Given the fact that no specific enzymes were isolated from Boswellia trees, the major sources for incensole and incensole acetate, the biosynthetic pathway of these two compounds was only speculated. Recent studies on incensole and incensole acetate including ours have revealed another secret of the ancient drug. Understanding their mode of action will open a door in modern neurobiology and provides new insights on the mysterious diseases of the nervous system. This review interpretatively discusses the natural existence of incensole and incensole acetate, the variation of their percentages in different Boswellia species and other sources, their synthetic modifications, their biosynthesis and their therapeutic potential.
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New Drug Discovery from Medicinal Plants and Phytoconstituents for Depressive Disorders.
Dereli, FTG, Ilhan, M, Akkol, EK
CNS & neurological disorders drug targets. 2019;(2):92-102
Abstract
BACKGROUND & OBJECTIVE Depression, a risk factor for several serious diseases, is a highly prevalent and life-threatening psychiatric disorder. It can affect the individual's position in life and reduce the living standards. The research on the use of medicinal plants in treating this disease has increased enormously because of the possible low rehabilitation rate and side effects of available synthetic drugs, such as sexual dysfunction, nausea, fatigue, insomnia, hypersomnia, and weight gain. CONCLUSION Therefore, this review aimed to draw attention to the antidepressant effects of culinary herbs and traditional medicinal plants and their active components, thereby promoting their use in the development of more potent antidepressants with improved side effect profile.
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Low high-density lipoprotein and psychopathology: A review.
Douglas, J, Nasrallah, HA
Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists. 2019;(3):209-213
Abstract
BACKGROUND An association between the level of total cholesterol and psychopathology has been the focus of numerous studies. Low total cholesterol has been found to be related to depression, personality disorders, and dissociative disorder. High cholesterol has been associated with schizophrenia, obsessive-compulsive disorder (OCD), panic disorder, generalized anxiety disorder, and posttraumatic stress disorder. However, no reviews of the psychiatric correlates of high-density lipoprotein (HDL) have been published. We reviewed the literature for studies reporting a significant association between low or high levels of HDL and psychopathology. METHODS A search of major databases (PubMed and CINAHL) was conducted using the following keywords: HDL, depression, anxiety, schizophrenia, OCD, and psychiatric disorders. RESULTS Eight studies met our search criteria. Six of the 8 studies reported significantly higher rates of depression, anxiety, suicide attempts, and violent behaviors in participants with low HDL. CONCLUSIONS Overall, a low HDL may not only be associated with risk for cardiac disease, but also with increased risk for serious psychiatric disorders. Further controlled studies are warranted.
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Ten Surprising Facts About Stressful Life Events and Disease Risk.
Cohen, S, Murphy, MLM, Prather, AA
Annual review of psychology. 2019;:577-597
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Abstract
After over 70 years of research on the association between stressful life events and health, it is generally accepted that we have a good understanding of the role of stressors in disease risk. In this review, we highlight that knowledge but also emphasize misunderstandings and weaknesses in this literature with the hope of triggering further theoretical and empirical development. We organize this review in a somewhat provocative manner, with each section focusing on an important issue in the literature where we feel that there has been some misunderstanding of the evidence and its implications. Issues that we address include the definition of a stressful event, characteristics of diseases that are impacted by events, differences in the effects of chronic and acute events, the cumulative effects of events, differences in events across the life course, differences in events for men and women, resilience to events, and methodological challenges in the literature.
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Inflammatory theory of depression.
Gałecki, P, Talarowska, M
Psychiatria polska. 2018;(3):437-447
Abstract
Brain diseases are one of the most socially and economically burdening diseases in Europe. Among all brain diseases, more than 60% of social and economic costs are generated by mental disorders (mainly depressive disorders and anxiety disorders). Recurrent depressive disorders have been a significant civilizational problem in recent times. Among the biological and psychological theories explaining the causes of depression, the hypothesis involving an active inflammatory process taking place in a human organism is becoming increasingly important. The following are considered inflammation markers: inflammatory enzymes (e.g., manganese superoxide dismutase (MnSOD), myeloperoxidase (MPO), inducible nitric oxide synthase), proinflammatory and anti-inflammatory cytokines, and the phenomenon of oxidative stress. Through the kynurenine pathway, these factors lead to a deficit in serotonin and melatonin, which is considered one of the main reasons of depression. We can consider depression to be a chronic cold of the organism, which develops in response to the action of greater or smaller everyday stressors. This paper presents results of recent studies regarding this matter.