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Cleveland Clinic Journal of Medicine Apr 2006Adverse effects of antidepressant drugs can decrease compliance and delay recovery. It is therefore crucial to consider potential side effects when choosing an... (Review)
Review
Adverse effects of antidepressant drugs can decrease compliance and delay recovery. It is therefore crucial to consider potential side effects when choosing an antidepressant. Although there is no perfect antidepressant that works quickly and is completely free of adverse reactions, newer antidepressants are safer, better tolerated, and associated with a lower rate of noncompliance.
Topics: Antidepressive Agents; Humans
PubMed: 16610395
DOI: 10.3949/ccjm.73.4.351 -
Cell Mar 2021It is unclear how binding of antidepressant drugs to their targets gives rise to the clinical antidepressant effect. We discovered that the transmembrane domain of...
It is unclear how binding of antidepressant drugs to their targets gives rise to the clinical antidepressant effect. We discovered that the transmembrane domain of tyrosine kinase receptor 2 (TRKB), the brain-derived neurotrophic factor (BDNF) receptor that promotes neuronal plasticity and antidepressant responses, has a cholesterol-sensing function that mediates synaptic effects of cholesterol. We then found that both typical and fast-acting antidepressants directly bind to TRKB, thereby facilitating synaptic localization of TRKB and its activation by BDNF. Extensive computational approaches including atomistic molecular dynamics simulations revealed a binding site at the transmembrane region of TRKB dimers. Mutation of the TRKB antidepressant-binding motif impaired cellular, behavioral, and plasticity-promoting responses to antidepressants in vitro and in vivo. We suggest that binding to TRKB and allosteric facilitation of BDNF signaling is the common mechanism for antidepressant action, which may explain why typical antidepressants act slowly and how molecular effects of antidepressants are translated into clinical mood recovery.
Topics: Animals; Antidepressive Agents; Binding Sites; Brain-Derived Neurotrophic Factor; Cell Line; Cholesterol; Embryo, Mammalian; Fluoxetine; Hippocampus; Humans; Mice; Models, Animal; Molecular Dynamics Simulation; Protein Domains; Rats; Receptor, trkB; Visual Cortex
PubMed: 33606976
DOI: 10.1016/j.cell.2021.01.034 -
Molecular Psychiatry Jun 2022Major depressive disorder (MDD) was previously hypothesized to be a disease of monoamine deficiency in which low levels of monoamines in the synaptic cleft were believed... (Review)
Review
Major depressive disorder (MDD) was previously hypothesized to be a disease of monoamine deficiency in which low levels of monoamines in the synaptic cleft were believed to underlie depressive symptoms. More recently, however, there has been a paradigm shift toward a neuroplasticity hypothesis of depression in which downstream effects of antidepressants, such as increased neurogenesis, contribute to improvements in cognition and mood. This review takes a top-down approach to assess how changes in behavior and hippocampal-dependent circuits may be attributed to abnormalities at the molecular, structural, and synaptic level. We conclude with a discussion of how antidepressant treatments share a common effect in modulating neuroplasticity and consider outstanding questions and future perspectives.
Topics: Adult; Antidepressive Agents; Depression; Depressive Disorder, Major; Hippocampus; Humans; Neuronal Plasticity
PubMed: 35354926
DOI: 10.1038/s41380-022-01520-y -
Annual Review of Pharmacology and... Jan 2019New approaches to the neurobiology of posttraumatic stress disorder (PTSD) are needed to address the reported crisis in PTSD drug development. These new approaches may... (Review)
Review
New approaches to the neurobiology of posttraumatic stress disorder (PTSD) are needed to address the reported crisis in PTSD drug development. These new approaches may require the field to move beyond a narrow fear-based perspective, as fear-based medications have not yet demonstrated compelling efficacy. Antidepressants, particularly recent rapid-acting antidepressants, exert complex effects on brain function and structure that build on novel aspects of the biology of PTSD, including a role for stress-related synaptic dysconnectivity in the neurobiology and treatment of PTSD. Here, we integrate this perspective within a broader framework-in other words, a dual pathology model of ( a) stress-related synaptic loss arising from amino acid-based pathology and ( b) stress-related synaptic gain related to monoamine-based pathology. Then, we summarize the standard and experimental (e.g., ketamine) pharmacotherapeutic options for PTSD and discuss their putative mechanism of action and clinical efficacy.
Topics: Animals; Antidepressive Agents; Brain; Humans; Stress Disorders, Post-Traumatic
PubMed: 30216745
DOI: 10.1146/annurev-pharmtox-010818-021701 -
Deutsches Arzteblatt International May 2019Antidepressants are among the most commonly prescribed drugs worldwide. They are often discontinued, frequently without the knowledge of the prescribing physician. It... (Review)
Review
BACKGROUND
Antidepressants are among the most commonly prescribed drugs worldwide. They are often discontinued, frequently without the knowledge of the prescribing physician. It is, therefore, important for physicians to be aware of the withdrawal and rebound phenomena that may arise, in order to prevent these phenomena, treat them when necessary, and counsel patients appropriately.
METHODS
This review is based on a comprehensive, structured literature search on antidepressant withdrawal phenomena that we carried out in the CENTRAL, PubMed (Medline), and Embase databases. We classified the relevant publications and reports by their methodological quality.
RESULTS
Out of a total of 2287 hits, there were 40 controlled trials, 38 cohort studies and retrospective analyses, and 271 case reports that met the inclusion criteria. Withdrawal manifestations are usually mild and self-limiting; common ones include dizziness, headache, sleep disturbances, and mood swings. More serious or pro- longed manifestations rarely arise. There is an increased risk with MAO inhibitors, tricyclic antidepressants, venlafaxine, and paroxetine; on the other hand, for agome- latine and fluoxetine, abrupt discontinuation seems to be unproblematic. There is also some evidence of rebound phenomena, i.e., of higher relapse rates or especially severe relapses of depression after the discontinuation of an anti- depressant.
CONCLUSION
A robust evidence base now indicates that there can be acute with- drawal phenomena when antidepressants are discontinued. Putative rebound phenomena have not been adequately studied to date. It is recommended that antidepressants should be tapered off over a period of more than four weeks.
Topics: Antidepressive Agents; Fluoxetine; Humans; Paroxetine; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Substance Withdrawal Syndrome
PubMed: 31288917
DOI: 10.3238/arztebl.2019.0355 -
Journal of Midwifery & Women's Health 2013The mainstays of treatment for peripartum depression are psychotherapy and antidepressant medications. More research is needed to understand which treatments are safe,... (Review)
Review
The mainstays of treatment for peripartum depression are psychotherapy and antidepressant medications. More research is needed to understand which treatments are safe, preferable, and effective. Postpartum depression, now termed peripartum depression by the DSM-V, is one of the most common complications in the postpartum period and has potentially significant negative consequences for mothers and their families. This article highlights common clinical challenges in the treatment of peripartum depression and reviews the evidence for currently available treatment options. Psychotherapy is the first-line treatment option for women with mild to moderate peripartum depression. Antidepressant medication in combination with therapy is recommended for women with moderate to severe depression. Although pooled case reports and small controlled studies have demonstrated undetectable infant serum levels and no short-term adverse events in infants of mothers breastfeeding while taking sertraline (Zoloft) and paroxetine (Paxil), further research is needed including larger samples and long-term follow-up of infants exposed to antidepressants via breastfeeding controlling for maternal depression. Pharmacologic treatment recommendations for women who are lactating must include discussion with the patient regarding the benefits of breastfeeding, risks of antidepressant use during lactation, and risks of untreated illness. There is a growing evidence base for nonpharmacologic interventions including repetitive transcranial magnetic stimulation, which may offer an attractive option for women who wish to continue to breastfeed and are concerned about their infants being exposed to medication. Among severe cases of peripartum depression with psychosis, referral to a psychiatrist or psychiatric advanced practice registered nurse is warranted. Suicidal or homicidal ideation with a desire, intent, or plan to harm oneself or anyone else, including the infant, is a psychiatric emergency, and an evaluation by a mental health professional should be conducted immediately. Peripartum depression treatment research is limited by small sample sizes and few controlled studies. Much work is still needed to better understand which treatments women prefer and are the most effective in ameliorating the symptoms and disease burden associated with peripartum depression.
Topics: Antidepressive Agents; Breast Feeding; Depression, Postpartum; Female; Humans; Psychotherapy
PubMed: 24131708
DOI: 10.1111/jmwh.12104 -
Biological Psychiatry Jul 2021Neurotrophic factors, particularly BDNF (brain-derived neurotrophic factor), have been associated with depression and antidepressant drug action. A variety of... (Review)
Review
Neurotrophic factors, particularly BDNF (brain-derived neurotrophic factor), have been associated with depression and antidepressant drug action. A variety of preclinical and clinical studies have implicated impaired BDNF signaling through its receptor TrkB (neurotrophic receptor tyrosine kinase 2) in the pathophysiology of mood disorders, but many of the initial findings have not been fully supported by more recent meta-analyses, and more both basic and clinical research is needed. In contrast, increased expression and signaling of BDNF has been repeatedly implicated in the mechanisms of both typical and rapid-acting antidepressant drugs, and recent findings have started to elucidate the mechanisms through which antidepressants regulate BDNF signaling. BDNF is a critical regulator of various types of neuronal plasticities in the brain, and plasticity has increasingly been connected with antidepressant action. Although some equivocal data exist, the hypothesis of a connection between neurotrophic factors and neuronal plasticity with mood disorders and antidepressant action has recently been further strengthened by converging evidence from a variety of more recent data reviewed here.
Topics: Antidepressive Agents; Brain-Derived Neurotrophic Factor; Depression; Humans; Mood Disorders; Receptor, trkB; Signal Transduction
PubMed: 34053675
DOI: 10.1016/j.biopsych.2021.05.008 -
Advances in Pharmacology (San Diego,... 2021Depression is one of the leading causes of disability worldwide and a major contributor to the global burden of disease, yet the cellular and molecular etiology of...
Depression is one of the leading causes of disability worldwide and a major contributor to the global burden of disease, yet the cellular and molecular etiology of depression remain largely unknown. Major Depressive Disorder (MDD) is associated with a variety of chronic physical inflammatory and autoimmune disorders, and mood disorders may act synergistically with other medical disorders to worsen patient outcomes. Here, we outline the neuroimmune complement, explore the evidence for altered immune system function in MDD, and present some of the potential mechanisms by which immune cells and molecules may drive the onset and course of MDD. These include pro-inflammatory signaling, alterations in the hypothalamic-pituitary-adrenal axis, dysregulation of the serotonergic and noradrenergic neurotransmitter systems, neuroinflammation, and meningeal immune dysfunction. Finally, we discuss the interactions between current antidepressants and the immune system and propose the possibility of immunomodulatory drugs as potential novel antidepressant treatments.
Topics: Antidepressive Agents; Depression; Depressive Disorder, Major; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System
PubMed: 34099111
DOI: 10.1016/bs.apha.2021.03.004 -
International Journal of Molecular... Mar 2023Depression is a mental health disorder that develops as a result of complex psycho-neuro-immuno-endocrinological disturbances. This disease presents with mood... (Review)
Review
Depression is a mental health disorder that develops as a result of complex psycho-neuro-immuno-endocrinological disturbances. This disease presents with mood disturbances, persistent sadness, loss of interest and impaired cognition, which causes distress to the patient and significantly affects the ability to function and have a satisfying family, social and professional life. Depression requires comprehensive management, including pharmacological treatment. Because pharmacotherapy of depression is a long-term process associated with the risk of numerous adverse drug effects, much attention is paid to alternative therapy methods, including phytopharmacotherapy, especially in treating mild or moderate depression. Preclinical studies and previous clinical studies confirm the antidepressant activity of active compounds in plants, such as St. John's wort, saffron crocus, lemon balm and lavender, or less known in European ethnopharmacology, roseroot, ginkgo, Korean ginseng, borage, brahmi, mimosa tree and magnolia bark. The active compounds in these plants exert antidepressive effects in similar mechanisms to those found in synthetic antidepressants. The description of phytopharmacodynamics includes inhibiting monoamine reuptake and monoamine oxidase activity and complex, agonistic or antagonistic effects on multiple central nervous system (CNS) receptors. Moreover, it is noteworthy that the anti-inflammatory effect is also important to the antidepressant activity of the plants mentioned above in light of the hypothesis that immunological disorders of the CNS are a significant pathogenetic factor of depression. This narrative review results from a traditional, non-systematic literature review. It briefly discusses the pathophysiology, symptomatology and treatment of depression, with a particular focus on the role of phytopharmacology in its treatment. It provides the mechanisms of action revealed in experimental studies of active ingredients isolated from herbal antidepressants and presents the results of selected clinical studies confirming their antidepressant effectiveness.
Topics: Humans; Depression; Phytotherapy; Antidepressive Agents; Depressive Disorder; Hypericum
PubMed: 36902200
DOI: 10.3390/ijms24054772 -
Current Psychiatry Reports Aug 2017The aim of this review article was to summarize recent publications on effects of antidepressants on sleep and to show that these effects not only depend on the kind of... (Review)
Review
PURPOSE OF REVIEW
The aim of this review article was to summarize recent publications on effects of antidepressants on sleep and to show that these effects not only depend on the kind of antidepressant drugs but are also related to the dose, the time of drug administration, and the duration of the treatment.
RECENT FINDINGS
Complaints of disrupted sleep are very common in patients suffering from depression, and they are listed among diagnostic criteria for this disorder. Moreover, midnocturnal insomnia is the most frequent residual symptom of depression. Thus, all antidepressants should normalize sleep. However, at least in short-term treatment, many antidepressants with so-called activating effects (e.g. fluoxetine, venlafaxine) may disrupt sleep, while others with sedative properties (e.g., doxepin, mirtazapine, trazodone) rapidly improve sleep, but may cause problems in long-term treatment due to oversedation.For sleep-promoting action, the best effects can frequently be achieved with a very low dose, administered early enough before bedtime and importantly, always as a part of more complex interventions based on the cognitive-behavioral protocol to treat insomnia (CBT-I). For successful treatment of depression, it is necessary to understand the effects of antidepressants on sleep. Each physician should also be aware that some antidepressants may worsen or induce primary sleep disorders like restless legs syndrome, sleep bruxism, REM sleep behavior disorder, nightmares, and sleep apnea, which may result from an antidepressant-induced weight gain.
Topics: Antidepressive Agents; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Sleep; Sleep Wake Disorders; Time Factors
PubMed: 28791566
DOI: 10.1007/s11920-017-0816-4