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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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The effect of fecal microbiota transplantation on psychiatric symptoms among patients with inflammatory bowel disease: an experimental study.
Kilinçarslan, S, Evrensel, A
Actas espanolas de psiquiatria. 2020;(1):1-7
Abstract
INTRODUCTION Over the past decade, evidence that supports the relationship between intestinal microbiota and the brain has been obtained. Ageing, stress, nutrition and medicines can alter the composition of bacteria in the intestinal microbiota. This condition, called dysbiosis, can be repaired through prebiotics, probiotics or fecal microbiota transplantation (FMT). FMT is effective in the treatment of inflammatory bowel diseases (IBD). Information on FMT's use with psychiatric disorders is limited. This study aims to investigate changes in the severity of depression, anxiety and obsession of patients who received FMT for the treatment of inflammatory bowel diseases. METHODS This study was conducted with 10 patients with IBD who underwent FMT between March and September 2017. FMT was performed by an experienced gastroenterologist. The patients completed the Beck Depression Inventory (BDI), Symptom Checklist-90-Revised (SCL-90-R) and Maudsley Obsessive Compulsive Inventory (MOCI) before FMT and again at 1 month after FMT. RESULTS Significant decreases were found in BDI (Z=2.49, p=0.013), SCL-90-R (Z=-2.09, p=0.037) and MOCI (Z=2.08, p=0.037) scores after 1 month of FMT. Although the SCL-90-R anxiety subscale scores decreased, this decrease was not statistically significant (Z=-1.55, p=0.121). CONCLUSIONS The severity of anxiety, depression and obsession in IBD patients decreased after FMT. The decrease in psychiatric symptoms may result from the direct neuropsychiatric effect of FMT (primary effect), but also the improvement of gastrointestinal symptoms (secondary effect). Another possibility is that this result is independent of these two conditions. Therefore, the results of our study are not sufficient to establish a cause-effect relationship. More randomised controlled trials with larger samples from patients with anxiety or depression but without comorbid physical illnesses are needed to generalise these results.
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The effect of an intensive patients' education program on anxiety, depression and patient global assessment in diabetic foot ulcer patients with Wagner grade 1/2: A randomized, controlled study.
Chen, H, Cai, C, Xie, J
Medicine. 2020;(6):e18480
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Abstract
This study aimed to synthetically evaluate the impact of intensive patients' education program (IEP) on anxiety, depression and patient global assessment (PGA) in diabetic foot ulcer (DFU) patients.One hundred eighty DFU patients with Wagner grade 1 and Wagner grade 2 were consecutively recruited in this randomized, controlled study and randomly assigned to IEP group (N = 90) or control group (N = 90) as 1:1 ratio. In the IEP group, patients received the IEP and usual care, and patients in the control group received usual care only. IEP included educating patients and their family members, supervising patients' harmful habits and diets, psychological care for the patients and establishing a patient-physician-nurse WeChat group. Hospital Anxiety and Depression Scale-anxiety/depression (HADS-A/D) and Zung Self-Rating Anxiety/depression Scale (SAS/SDS) were applied to assess anxiety/depression at M0-M3. PGA score was also assessed at M0-M3.For anxiety assessment, IEP group presented decreased HADS-A/SAS scores at M2/M3 and increased HADS-A/SAS score changes (M3-M0) compared to control group. For depression assessment, IEP group displayed reduced HADS-D/SDS scores at M2/M3 and raised SDS score change (M3-M0) compared to control group. Moreover, IEP group exhibited reduced PGA score at M1/M2/M3 and elevated PGA score change (M3-M0) compared to control group. Further subgroup analyses disclosed that IEP reduced HADS-A/SAS/HADS-D/PGA scores at M3 and elevated these score changes (M3-M0) in patients with Wagener grade 2 but not Wagener grade 1.IEP ameliorates anxiety, depression and PGA in DFU patients with Wagner grade 2 but not Wagner grade 1.
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Oral Administration of S-Adenosylmethionine (SAMe) and Lactobacillus Plantarum HEAL9 Improves the Mild-To-Moderate Symptoms of Depression: A Randomized, Double-Blind, Placebo-Controlled Study.
Saccarello, A, Montarsolo, P, Massardo, I, Picciotto, R, Pedemonte, A, Castagnaro, R, Brasesco, PC, Guida, V, Picco, P, Fioravanti, P, et al
The primary care companion for CNS disorders. 2020;(4)
Abstract
OBJECTIVE To assess the effects of the combination of SAMe (S-adenosylmethionine) 200 mg and Lactobacillus plantarum (L. plantarum) HEAL9 1 × 10⁹ CFU for the overall symptomatology of mild-to-moderate depression. METHODS This 6-week randomized, double-blind, placebo-controlled study included subjects aged 18-60 years with mild-to-moderate depression (according to ICD-10 diagnostic criteria) recruited from September 17, 2018, to October 5, 2018. Difference between groups in change from baseline to treatment week 6 on the Zung Self-Rating Depression Scale (Z-SDS) was the primary outcome. Comparisons between groups in change from baseline to treatment week 2 of the Z-SDS and from baseline to treatment weeks 2 and 6 of other scales (related to insomnia, anxiety, irritable bowel syndrome, and health status) were also analyzed. RESULTS Ninety patients were randomized to SAMe plus L. plantarum HEAL9 (n = 46) or placebo (n = 44) groups. A greater reduction for the new combination compared to placebo was seen at treatment week 6 in the Z-SDS total score (P = .0165) and the core depression subdomain (P = .0247). A significant reduction in favor of the combination was shown at treatment week 2 for the Z-SDS total score (P = .0330), the cognitive and anxiety subdomains (P = .0133 and P = .0459, respectively), and the anxiety questionnaire (P = .0345). No treatment-related adverse events occurred. CONCLUSIONS Supplementation of SAMe and L. plantarum HEAL9 in adults with subthreshold or mild-to-moderate symptoms of depression resulted in fast and clinically relevant effects after 2 weeks. The combination was safe and significantly improved symptoms of depression, anxiety, and cognitive and somatic components. The effect of this novel product is independent from the severity of the symptoms unlike traditional antidepressants available on the market that have minimal benefits for subthreshold or mild-to-moderate symptoms. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03932474.
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Metabolically healthy status and BMI in relation to depression: A systematic review of observational studies.
Malmir, H, Mirzababaei, A, Moradi, S, Rezaei, S, Mirzaei, K, Dadfarma, A
Diabetes & metabolic syndrome. 2019;(2):1099-1103
Abstract
AIM: Findings of association between metabolically healthy status and BMI and risk of depression are controversial. This study aimed to assess the relation between metabolically healthy status and BMI and depression. METHODS All published studies up to 25 June 2018 were searched by using the databases of PubMed, ISI Web of Science, SCOPUS and Google Scholar and following key words were used: metabolically AND (healthy OR unhealthy OR benign) AND (overweight OR obes* OR "over weight") AND phenotype AND (depression OR depress* OR "depressive disorder"). RESULTS After screening title and abstract and considering inclusion criteria, 5 studies were found to be included in our study. Metabolically unhealthy obesity was associated with 30%-83% increased risk of depression and metabolically unhealthy non-obesity was associated with 19%-60% increased risk of depression. Metabolically healthy obesity was not associated with the risk of depression in all studies. CONCLUSIONS In conclusion, metabolically health status and BMI are associated with risk of depression. Metabolically unhealthy situation increased risk of depression greater than metabolically healthy status.
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The effect of Hypericum perforatum on postmenopausal symptoms and depression: A randomized controlled trial.
Eatemadnia, A, Ansari, S, Abedi, P, Najar, S
Complementary therapies in medicine. 2019;:109-113
Abstract
OBJECTIVES Hypericum perforatum (St John's wort) is an herbal plant that has antidepressant activity and contains ingredients such as flavonols derivatives, bioflavonoids, proanthocyanidins, xanthones, phloroglucinol, and naphthodianthrones. This study was aimed to test the effect of Hypericum perforatum on hot flashes, menopausal symptoms, and depression in postmenopausal women. DESIGN & SETTING This randomized controlled study was conducted on 80 postmenopausal women aged 45-60 in Izeh, Iran. INTERVENTION Two groups received 270-330 μg of H. perforatum (n = 40) or placebo (n = 40) tablets three times a day for two months. MAIN OUTCOMES Data were collected using a socio-demographic questionnaire, the modified Kupperman index before the intervention and 2, 4, 6 and 8 weeks after intervention. The Hamilton Depression Rating Scale was used to gather data before the intervention and in the 8th week of intervention. The data were analyzed using an independent t-test, chi-square test, and repeated measure test. RESULTS Seventy women completed the study and five women from each group withdrew the study. The frequency and intensity of hot flashes and the score of Kupperman scale significantly decreased in the H. perforatum group compared to the control group (p < 0.001). In addition, the intensity of depression significantly decreased in the H. perforatum group compared to the control group. At the end of the study, 80% of women in the intervention group did not have depression compared to only 5.7% in the control group (p < 0.001). CONCLUSION Treatment with Hypericum perforatum is an efficient way of reducing hot flashes, menopausal symptoms, and depression in postmenopausal women.
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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.