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Progress in Neuro-psychopharmacology &... Jan 2021Depression is the most common psychiatric illness affecting numerous people world-wide. The currently available antidepressant treatment presents low response and... (Review)
Review
Depression is the most common psychiatric illness affecting numerous people world-wide. The currently available antidepressant treatment presents low response and remission rates. Thus, new effective antidepressants need to be developed or discovered. Aiming to give an overview of novel possible antidepressant drug targets, we summarized the molecular targets of antidepressants and the underlying neurobiology of depression. We have also addressed the multidimensional perspectives on the progress in the psychopharmacological treatment of depression and on the new potential approaches with effective drug discovery.
Topics: Antidepressive Agents; Brain; Depressive Disorder; Drug Discovery; Glutamic Acid; Humans; gamma-Aminobutyric Acid
PubMed: 32682872
DOI: 10.1016/j.pnpbp.2020.110041 -
American Family Physician Aug 2006Antidepressant discontinuation syndrome occurs in approximately 20 percent of patients after abrupt discontinuation of an antidepressant medication that was taken for at... (Review)
Review
Antidepressant discontinuation syndrome occurs in approximately 20 percent of patients after abrupt discontinuation of an antidepressant medication that was taken for at least six weeks. Typical symptoms of antidepressant discontinuation syndrome include flu-like symptoms, insomnia, nausea, imbalance, sensory disturbances, and hyperarousal. These symptoms usually are mild, last one to two weeks, and are rapidly extinguished with reinstitution of antidepressant medication. Antidepressant discontinuation syndrome is more likely with a longer duration of treatment and a shorter half-life of the treatment drug. A high index of suspicion should be maintained for the emergence of discontinuation symptoms, which should prompt close questioning regarding accidental or purposeful self-discontinuation of medication. Before antidepressants are prescribed, patient education should include warnings about the potential problems associated with abrupt discontinuation. Education about this common and likely underrecognized clinical phenomenon will help prevent future episodes and minimize the risk of misdiagnosis.
Topics: Antidepressive Agents; Diagnosis, Differential; Humans; Risk Factors; Substance Withdrawal Syndrome; Syndrome
PubMed: 16913164
DOI: No ID Found -
Psychological Medicine Feb 2023Depression in dementia is common, disabling and causes significant distress to patients and carers. Despite widespread use of antidepressants for depression in dementia,... (Review)
Review
Depression in dementia is common, disabling and causes significant distress to patients and carers. Despite widespread use of antidepressants for depression in dementia, there is no evidence of therapeutic efficacy, and their use is potentially harmful in this patient group. Depression in dementia has poor outcomes and effective treatments are urgently needed. Understanding why antidepressants are ineffective in depression in dementia could provide insight into their mechanism of action and aid identification of new therapeutic targets. In this review we discuss why depression in dementia may be a distinct entity, current theories of how antidepressants work and how these mechanisms of action may be affected by disease processes in dementia. We also consider why clinicians continue to prescribe antidepressants in dementia, and novel approaches to understand and identify effective treatments for patients living with depression and dementia.
Topics: Humans; Antidepressive Agents; Treatment Outcome; Dementia
PubMed: 36621964
DOI: 10.1017/S003329172200397X -
Pharmacology, Biochemistry, and Behavior Mar 2020The robust antidepressant effects of (R,S)-ketamine are among the most important discoveries in mood research over the last half century. Off-label use of... (Review)
Review
The robust antidepressant effects of (R,S)-ketamine are among the most important discoveries in mood research over the last half century. Off-label use of (R,S)-ketamine, which is an equal mixture of (R)-ketamine and (S)-ketamine, has become especially popular in the United States (US) for treatment-resistant depression. On March 5, 2019, the US Food and Drug Administration approved an (S)-ketamine nasal spray for use in treatment-resistant depression, though its use has been limited to certified medical offices or clinics. On December 19, 2019, (S)-ketamine nasal spray was approved for the same indication in Europe. However, despite its potential for benefit, there are several concerns about the efficacy of (S)-ketamine nasal spray. Accumulating evidence from preclinical studies show that (R)-ketamine has greater potency and longer lasting antidepressant effects than (S)-ketamine in animal models of depression, and that (R)-ketamine has fewer detrimental side effects than either (R,S)-ketamine or (S)-ketamine. As such, clinical studies of (R)-ketamine in humans are now underway by Perception Neuroscience Ltd. In this article, we review the brief history of (R,S)-ketamine and its two enantiomers as novel antidepressants. We also discuss the mechanisms of ketamine's antidepressant actions.
Topics: Animals; Antidepressive Agents; Depression; Depressive Disorder, Treatment-Resistant; Humans; Ketamine; Stereoisomerism; Treatment Outcome
PubMed: 32035078
DOI: 10.1016/j.pbb.2020.172870 -
Current Neuropharmacology 2017Ketamine has been reported to exert rapid and sustained antidepressant effects in patients with depression, including patients with treatment-resistant depression.... (Review)
Review
BACKGROUND
Ketamine has been reported to exert rapid and sustained antidepressant effects in patients with depression, including patients with treatment-resistant depression. However, ketamine has several drawbacks such as psychotomimetic/dissociative symptoms, abuse potential and neurotoxicity, all of which prevent its routine use in daily clinical practice.
METHODS
Therefore, development of novel agents with fewer safety and usage concerns for the treatment of depression has been actively investigated. From this standpoint, searching for active substances (stereoisomers and metabolites) and agents acting on the N-methyl-D-aspartate (NMDA) receptor have recently gained much attention.
RESULTS
The first approach includes stereoisomers of ketamine, (R)-ketamine and (S)-ketamine. Although (S)-ketamine has been considered as the active stereoisomer of racemic ketamine, recently, (R)-ketamine has been demonstrated to exert even more prolonged antidepressant effects in animal models than (S)-ketamine. Moreover, ketamine is rapidly metabolized into several metabolites, and some metabolites are speculated as being active substances exerting antidepressant effects. Of such metabolites, one in particular, namely, (2R,6R)-hydroxynorketamine, has been reported to be responsible for the antidepressant effects of ketamine. The second approach includes agents acting on the NMDA receptor, such as glycine site modulators and GluN2B subunit-selective antagonists. These agents have been tested in patients with treatment-resistant depression, and have been found to exhibit rapid antidepressant effects like ketamine.
CONCLUSION
The above approaches may be useful to overcome the drawbacks of ketamine. Elucidation of the mechanisms of action of ketamine may pave the way for the development of antidepressant that are safer, but as potent and rapidly acting as ketamine.
Topics: Animals; Antidepressive Agents; Drug Discovery; Humans; Ketamine
PubMed: 28228087
DOI: 10.2174/1570159X15666170221101054 -
Pharmacological Reports : PR 2013Although depression is a common disorder that is often resistant to pharmacotherapy, its pathophysiology has remained elusive. Since the early 1950s, when the first... (Review)
Review
Although depression is a common disorder that is often resistant to pharmacotherapy, its pathophysiology has remained elusive. Since the early 1950s, when the first antidepressants were introduced, i.e., the non-selective MAO inhibitors and tricyclic drugs, a number of hypotheses describing ethiopathogenesis of depression and antidepressant drug action have been formulated. The Institute of Pharmacology, the Polish Academy of Sciences has performed experimental and clinical research focused on the pathophysiology of depression and the mechanisms of action of antidepressant drugs for over 40 years. Our results from this period have significantly contributed to understanding the complex mechanisms of antidepressant drug actions and new pathways that underpin the pathophysiology of depression. Most of these theories are based on the finding that the chronic administration of antidepressants leads to adaptive changes in pre- and post-synaptic monoaminergic and glutamatergic neurotransmission as well as to alterations in gene transcription and immune-inflammatory and neurotrophic factors, resulting in neuroplastic changes in the brain. Taking into account the functional interdependence of the neuronal, hormonal and immunologic systems, we propose neurodevelopmental and neuroimmune theories for affective disorders. Moreover, commonalities have been documented for the pathomechanisms of depression and neurodegenerative and metabolic disorders as well as drug dependence. The aim of this special issue is to briefly present the major research contributions and the new research directions of the Institute of Pharmacology, the Polish Academy of Sciences with respect to the neurobiology of affective disorders and the mechanisms of action of marketed and new putative antidepressant drugs.
Topics: Animals; Antidepressive Agents; Brain; Depression; Humans; Mood Disorders
PubMed: 24552991
DOI: 10.1016/s1734-1140(13)71504-4 -
Neurochemical Research Oct 2022Crocin is a monomer of Chinese traditional herbs extracted from saffron, relieving depression-like behavior. However, its underlying mechanism of action remains unclear....
Crocin is a monomer of Chinese traditional herbs extracted from saffron, relieving depression-like behavior. However, its underlying mechanism of action remains unclear. Herein, we explored whether crocin's antidepressant effect depended on the mammalian target of the rapamycin (mTOR) signaling pathway. The model of PC12 cells injury was established by corticosterone, the changes in cell survival rate were tested by the CCK-8 method, and the changes in cellular morphology were observed under a fluorescence microscope. The depression model was established by chronic unpredictable mild stress (CUMS), and its antidepressant effect was estimated by open field test (OFT), forced swimming test (FST), and tail suspension test (TST). Western blot was used to monitor the protein expression. The results showed that crocin could effectively improve cell survival rate and cellular synaptic growth, alleviate the depressive behavior of CUMS mice, and promote the expression of BDNF, P-mTOR, P-ERK, and PSD95. However, when rapamycin was pretreated, the antidepressant effects of crocin were inhibited. In summary, crocin plays a significant antidepressant effect. After pretreatment with rapamycin, the anti-depression effect of crocin was significantly inhibited. It is suggested that the mechanism of the anti-depression effect of crocin may be related to the mTOR signaling pathway.
Topics: Animals; Antidepressive Agents; Behavior, Animal; Brain-Derived Neurotrophic Factor; Carotenoids; Disease Models, Animal; Hippocampus; Mammals; Mice; Rats; Signal Transduction; Sirolimus; Stress, Psychological; TOR Serine-Threonine Kinases
PubMed: 35804209
DOI: 10.1007/s11064-022-03668-z -
The Cochrane Database of Systematic... Jan 2006Depression is a relatively common experience in older adults. The syndrome is associated with considerable distress, morbidity and service commitment. Approximately two... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Depression is a relatively common experience in older adults. The syndrome is associated with considerable distress, morbidity and service commitment. Approximately two thirds of patients presenting with severe forms will respond to antidepressant treatment and the last twenty years has witnessed a great increase in the number of these drugs. Older, frail people are particularly vulnerable to side effects.
OBJECTIVES
The aims of this review were to examine the efficacy of antidepressant classes, to compare the withdrawal rates associated with each class and describe the side effect profile of antidepressant drugs for treating depression in patients described as elderly, geriatric, senile or older adults, aged 55 or over.
SEARCH STRATEGY
The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR-Studies) was searched (2003-08-13). Reference lists of relevant papers and previous systematic reviews were hand searched for published reports and citations of unpublished studies.
SELECTION CRITERIA
Only randomised controlled trials were included. Trials had to compare at least two active antidepressant drugs in the treatment of depression.
DATA COLLECTION AND ANALYSIS
Reviewers extracted data independently. In examining efficacy, the reviewers assumed that people who died or dropped out had no improvement. Withdrawal rates irrespective of cause and specifically due to side effects were compared between drug classes. Relative risk (RR) for dichotomous data and weighted mean difference for continuous data were calculated with 95% confidence intervals (CI). Qualitative side effect data were reported in terms of ratios of side effects and percentage of patients experiencing specific side effects.
MAIN RESULTS
A total of 29 trials provided data for inclusion in the review. We were unable to find any differences in efficacy when comparing classes of antidepressants. However, as the trials contained relatively small numbers of patients, these findings may be explained by a type two error. Tricyclic antidepressants (TCAs) compared less favourably with selective serotonin reuptake inhibitors (SSRIs) in terms of numbers of patients withdrawn irrespective of reason (RR: 1.24, CI 1.04, 1.47) and number withdrawn due to side effects (RR: 1.30, CI 1.02, 1.64). Subgroup analyses demonstrated that TCA related antidepressants had similar withdrawal rates to SSRIs irrespective of reason of withdrawal (RR: 1.49, CI 0.74, 2.98) or withdrawal due to side effects (RR: 1.07, CI 0.43, 2.70). The qualitative analysis of side effects showed a small increased profile of gastro-intestinal and neuropsychiatric side effects associated with classical TCAs.
AUTHORS' CONCLUSIONS
Our findings suggest that SSRIs and TCAs are of the same efficacy. However, we have found some evidence suggesting that TCA related antidepressants and classical TCAs may have different side effect profiles and are associated with differing withdrawal rates when compared with SSRIs. The review suggests that classical TCAs are associated with a higher withdrawal rate due to side effect experience, although these results must be interpreted with caution due to the relatively small size of the review and the heterogeneity of the drugs and patient populations.
Topics: Aged; Aged, 80 and over; Antidepressive Agents; Antidepressive Agents, Tricyclic; Depression; Humans; Middle Aged; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Refusal
PubMed: 16437456
DOI: 10.1002/14651858.CD003491.pub2 -
Annual Review of Pharmacology and... Jan 2019For decades, symptoms of depression have been treated primarily with medications that directly target the monoaminergic brain systems, which typically take weeks to... (Review)
Review
For decades, symptoms of depression have been treated primarily with medications that directly target the monoaminergic brain systems, which typically take weeks to exert measurable effects and months to exert remission of symptoms. Low, subanesthetic doses of ( R,S)-ketamine (ketamine) result in the rapid improvement of core depressive symptoms, including mood, anhedonia, and suicidal ideation, occurring within hours following a single administration, with relief from symptoms typically lasting up to a week. The discovery of these actions of ketamine has resulted in a reconceptualization of how depression could be more effectively treated in the future. In this review, we discuss clinical data pertaining to ketamine and other rapid-acting antidepressant drugs, as well as the current state of pharmacological knowledge regarding their mechanism of action. Additionally, we discuss the neurobiological circuits that are engaged by this drug class and that may be targeted by a future generation of medications, for example, hydroxynorketamine; metabotropic glutamate receptor 2/3 antagonists; and N-methyl-d-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and γ-aminobutyric acid receptor modulators.
Topics: Animals; Antidepressive Agents; Brain; Depression; Humans; Ketamine
PubMed: 30296896
DOI: 10.1146/annurev-pharmtox-010617-052811 -
Pharmacological Reports : PR 2013Allergic contact dermatitis is a delayed-type hypersensitivity reaction mediated by hapten-specific T cells. Many cell types, inflammatory mediators and cytokines are... (Review)
Review
Allergic contact dermatitis is a delayed-type hypersensitivity reaction mediated by hapten-specific T cells. Many cell types, inflammatory mediators and cytokines are involved in this reaction. Contact hypersensitivity is a self-limited reaction and can be regulated at different levels. Because it is known that disturbances in the immune system underpin the onset of depression and that antidepressant drugs have immunomodulatory effects, it can be hypothesized that antidepressants may have some efficacy in the treatment of contact hypersensitivity. There are some reports on the effectiveness of antidepressants in the inhibition of cutaneous sensitization in mice, and the aim of this narrative review is to assess the evidence for the effectiveness of antidepressant drugs in reducing the recurrence of contact hypersensitivity reactions.
Topics: Animals; Antidepressive Agents; Dermatitis, Contact; Humans
PubMed: 24553016
DOI: 10.1016/s1734-1140(13)71529-9