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The Journal of Clinical Psychiatry 2018A large number of antidepressant drugs are available across the world. All have been compared against placebo, and many have been compared with some but not all other...
A large number of antidepressant drugs are available across the world. All have been compared against placebo, and many have been compared with some but not all other antidepressants. There is therefore little information about a hierarchy of the efficacy and acceptability of these drugs. About 9 years ago, a network meta-analysis attempted to rank the efficacy and acceptability of 12 newer antidepressant drugs in adults with major depressive disorder. Very recently, this network meta-analysis was updated to include 21 antidepressant drugs, most of which were introduced during the 1980s and afterward. The present article explains what meta-analysis and network meta-analysis do, summarizes the important findings of the 21-antidepressant network meta-analysis, and offers comments on the findings. In general, it appears that antidepressant drugs are associated with clinically significant superiority over placebo with regard to response and remission rates; that almost all antidepressants do not differ from placebo with regard to all-cause discontinuation; that escitalopram, mirtazapine, amitriptyline, venlafaxine, and paroxetine are associated with better response rates than certain other antidepressants; that reboxetine, trazodone, and fluoxetine are associated with poorer response rates than certain other antidepressants; that agomelatine, escitalopram, and vortioxetine are associated with lower all-cause discontinuation than certain other antidepressants; and that clomipramine, reboxetine, and duloxetine are associated with higher all-cause discontinuation than certain other antidepressants. Whereas this conclusion is necessarily subjective, escitalopram could be a first choice in the balance of efficacy and acceptability, and reboxetine, the last choice. The strengths and limitations of the network meta-analysis are examined, and some comments on the findings are offered.
Topics: Antidepressive Agents; Depressive Disorder, Major; Health Services Accessibility; Humans; Meta-Analysis as Topic; Network Meta-Analysis; Treatment Outcome
PubMed: 29718600
DOI: 10.4088/JCP.18f12254 -
Cleveland Clinic Journal of Medicine Jan 2022Stopping antidepressants can be challenging due to the high rate of discontinuation symptoms. Patients with antidepressant discontinuation syndrome (ADS) commonly... (Review)
Review
Stopping antidepressants can be challenging due to the high rate of discontinuation symptoms. Patients with antidepressant discontinuation syndrome (ADS) commonly experience insomnia, flu-like symptoms, mood disturbances, dizziness, and paresthesias, but a broad array of adverse effects is possible. Symptoms can last for days to months, and different symptoms have different durations. Patient education, identification of patients most at risk for developing symptoms, and a slow antidepressant taper or cross-taper are important steps in mitigating the risk of ADS and managing patient concerns about ADS. Tapers should be carried out over weeks to months. Discontinuation symptoms should be managed with restarting the prior dose of antidepressant and then tapering even more slowly, with additional symptomatic management as needed.
Topics: Humans; Antidepressive Agents; Paresthesia; Deprescriptions
PubMed: 34983798
DOI: 10.3949/ccjm.89a.21020 -
International Journal of Molecular... Sep 2020This review analyzes the current scientific literature on the role of the Sigma1R chaperone in the pathogenesis of depressive disorders and pharmacodynamics of... (Review)
Review
This review analyzes the current scientific literature on the role of the Sigma1R chaperone in the pathogenesis of depressive disorders and pharmacodynamics of antidepressants. As a result of ligand activation, Sigma1R is capable of intracellular translocation from the endoplasmic reticulum (ER) into the region of nuclear and cellular membranes, where it interacts with resident proteins. This unique property of Sigma1R provides regulation of various receptors, ion channels, enzymes, and transcriptional factors. The current review demonstrates the contribution of the Sigma1R chaperone to the regulation of molecular mechanisms involved in the antidepressant effect.
Topics: Animals; Antidepressive Agents; Depressive Disorder; Humans; Receptors, sigma; Sigma-1 Receptor
PubMed: 32992988
DOI: 10.3390/ijms21197088 -
Expert Opinion on Drug Metabolism &... May 2020: Pregnancy-related physiological changes exert a crucial impact on the pharmacokinetics of antidepressants; however, the current evidence presents inconsistencies. A... (Meta-Analysis)
Meta-Analysis
: Pregnancy-related physiological changes exert a crucial impact on the pharmacokinetics of antidepressants; however, the current evidence presents inconsistencies. A clearer understanding of pregnancy-related effects on antidepressant disposition may facilitate the development of guidelines for appropriate dose adjustments during the course of pregnancy based on therapeutic drug monitoring.: We systematically reviewed studies comparing antidepressant levels in the same individuals during pregnant and non-pregnant states. Using dose-adjusted plasma concentration measurements, we estimated alteration ratios between the 3rd trimester and baseline (before or after pregnancy). Additionally, we performed a meta-analysis for changes in dose-adjusted concentrations to estimate mean differences.: Data for several antidepressants display clear alteration patterns during pregnancy. On the basis of the alteration ratios trimipramine, fluvoxamine, and nortriptyline show a prominent decrease in dose-adjusted levels, especially in the 3rd trimester. Clomipramine, imipramine, citalopram, and paroxetine show smaller decreases in dose-adjusted concentrations in the third trimester. For escitalopram, venlafaxine and fluoxetine, changes are considered negligible. For sertraline, there was a tendency toward increased dose-adjusted concentrations in pregnancy. Available evidence suffers from major limitations and factors affecting pharmacokinetics have been insufficiently addressed. Further research is required to promote knowledge on pregnancy effects on antidepressant pharmacokinetics.
Topics: Antidepressive Agents; Depression; Dose-Response Relationship, Drug; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third
PubMed: 32238008
DOI: 10.1080/17425255.2020.1750598 -
Agri : Agri (Algoloji) Dernegi'nin... Oct 2023Pregabalin (PGB) is used in drug-resistant epilepsy. Also, it has analgesic effects in painful syndromes. Depression and anxiety are commonly seen in epilepsy and...
OBJECTIVES
Pregabalin (PGB) is used in drug-resistant epilepsy. Also, it has analgesic effects in painful syndromes. Depression and anxiety are commonly seen in epilepsy and neuropathic pain patients. PGB is often combined with anxiolytics and antidepressants. We aimed to investigate the antidepressant and anxiolytic effects of PGB and compare its effects with those of antidepressant and anxiolytic drugs and their combined use.
METHODS
Wistar Albino rats were used, and PGB (5, 10, 20, and 40 mg/kg), amitriptylin (AMT), fluoxetine (FLX), ketamine (KET), and diazepam (DZM), as well as combinations of PGB (20 mg/kg) with AMT, FLX, KET, and DZM, were administered. Elevated plus maze, forced swimming, and locomotor activity tests were performed.
RESULTS
In the elevated plus maze, PGB10, 20, 40, AMT, FLX, and DZM increased open arm time. The PGB20+FLX combination increased compared to PGB20. In forced swimming, PGB doses increased immobility time. AMT, FLX, DZM, and KET decreased compared to control and PGB doses. Other combinations of PGB20 reversed immobility time, except FLX. In locomotor activity, PGB20, AMT, KET, and DZM decreased distance.
CONCLUSION
PGB had a depressant effect in all doses and a dose-dependently anxiolytic effect. In combinations of PGB with AMT, KET, and DZM, it reversed their antidepressant effects. We assumed FLX could be preferred instead of AMT in patients using PGB. When PGB is used in combination, drug interactions should be considered. These results are also very remarkable in terms of pharmacoeconomics.
Topics: Rats; Humans; Animals; Anti-Anxiety Agents; Pregabalin; Rats, Wistar; Antidepressive Agents; Fluoxetine; Amitriptyline; Ketamine; Epilepsy
PubMed: 37886867
DOI: 10.14744/agri.2022.98474 -
British Journal of Pharmacology Sep 2022A high proportion of depressed patients fail to respond to antidepressant drug treatment. Treatment-resistant depression (TRD) is a major challenge for the... (Review)
Review
A high proportion of depressed patients fail to respond to antidepressant drug treatment. Treatment-resistant depression (TRD) is a major challenge for the psychopharmacology of mood disorders. Only in the past decade have novel treatments, including deep brain stimulation (DBS) and ketamine, been discovered that provide rapid and sometimes prolonged relief to a high proportion of TRD sufferers. In this review, we consider the current status of TRD from four perspectives: the challenge of developing an appropriate regulatory framework for novel rapidly acting antidepressants; the efficacy of non-pharmacological somatic therapies; the development of an animal model of TRD and its use to understand the neural basis of antidepressant non-response; and the potential for rapid antidepressant action from targets (such as 5-HT receptors) beyond the glutamate receptor. LINKED ARTICLES: This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc.
Topics: Animals; Antidepressive Agents; Depression; Depressive Disorder, Treatment-Resistant; Ketamine
PubMed: 34128229
DOI: 10.1111/bph.15596 -
International Journal of Molecular... May 2023Depression and schizophrenia are two highly prevalent and severely debilitating neuropsychiatric disorders. Both conventional antidepressant and antipsychotic... (Review)
Review
Depression and schizophrenia are two highly prevalent and severely debilitating neuropsychiatric disorders. Both conventional antidepressant and antipsychotic pharmacotherapies are often inefficient clinically, causing multiple side effects and serious patient compliance problems. Collectively, this calls for the development of novel drug targets for treating depressed and schizophrenic patients. Here, we discuss recent translational advances, research tools and approaches, aiming to facilitate innovative drug discovery in this field. Providing a comprehensive overview of current antidepressants and antipsychotic drugs, we also outline potential novel molecular targets for treating depression and schizophrenia. We also critically evaluate multiple translational challenges and summarize various open questions, in order to foster further integrative cross-discipline research into antidepressant and antipsychotic drug development.
Topics: Humans; Antipsychotic Agents; Antidepressive Agents; Schizophrenia
PubMed: 37298431
DOI: 10.3390/ijms24119482 -
British Journal of Clinical Pharmacology Jan 2021Antidepressant prescribing has increased year on year since the introduction of the selective serotonin reuptake inhibitors (SSRIs) in the 1980s. More than 10% of adults... (Review)
Review
Antidepressant prescribing has increased year on year since the introduction of the selective serotonin reuptake inhibitors (SSRIs) in the 1980s. More than 10% of adults in England are now taking antidepressants for depression/anxiety, with a median length of treatment of more than 2 years, but antidepressants can cause side effects and withdrawal symptoms which increase with longer use. Surveys of antidepressant users suggest 30-50% have no evidence-based indication to continue, but coming off antidepressants is often difficult due to fears of relapse, withdrawal symptoms and a lack of psychological treatments to replace maintenance treatment and prevent relapse. GPs should not prescribe antidepressants routinely for mild depressive/anxiety symptoms. Patients starting antidepressants should be advised that they are to be taken for a limited period only, and that there is a risk of withdrawal problems on stopping them. Prescribers should actively review long-term antidepressant use and suggest coming off them slowly to patients who are well. The relationship between SSRI dose and serotonin transporter receptor occupancy suggests that hyperbolic tapering regimes may be helpful for patients with troubling withdrawal symptoms who cannot stop treatment within 4-8 weeks, and tapering strips can allow carefully titrated slower dose reduction over some months. Internet and telephone support to patients wanting to reduce their antidepressants is being trialled in the REDUCE programme. More research is needed to establish the incidence of withdrawal symptoms in representative samples of patients coming off antidepressants, and large randomised controlled trials are needed to test different tapering strategies.
Topics: Adult; Antidepressive Agents; England; Humans; Recurrence; Selective Serotonin Reuptake Inhibitors; Telephone
PubMed: 32656861
DOI: 10.1111/bcp.14475 -
Annual Review of Clinical Psychology May 2021The therapeutic onset of traditional antidepressants is delayed by several weeks and many depressed patients fail to respond to treatment altogether. In contrast,... (Review)
Review
The therapeutic onset of traditional antidepressants is delayed by several weeks and many depressed patients fail to respond to treatment altogether. In contrast, subanesthetic ketamine can rapidly alleviate symptoms of depression within hours of a single administration, even in patients who are considered treatment-resistant. Ketamine is thought to exert these effects by restoring the integrity of neural circuits that are compromised in depression. This hypothesis stems in part from preclinical observations that ketamine can strengthen synaptic connections by increasing glutamate-mediated neurotransmission and promoting rapid neurotrophic factor release. An improved understanding of how ketamine, and other novel rapid-acting antidepressants, give rise to these processes will help foster future therapeutic innovation. Here, we review the history of antidepressant treatment advances that preceded the ketamine discovery, critically examine mechanistic hypotheses for how ketamine may exert its antidepressant effects, and discuss the impact this knowledge has had on ongoing drug discovery efforts.
Topics: Antidepressive Agents; Humans; Ketamine
PubMed: 33561364
DOI: 10.1146/annurev-clinpsy-072120-014126 -
Molecules (Basel, Switzerland) Mar 2020Increasing prevalence and burden of major depressive disorder presents an unavoidable problem for psychiatry. Existing antidepressants exert their effect only after... (Review)
Review
Increasing prevalence and burden of major depressive disorder presents an unavoidable problem for psychiatry. Existing antidepressants exert their effect only after several weeks of continuous treatment. In addition, their serious side effects and ineffectiveness in one-third of patients call for urgent action. Recent advances have given rise to the concept of psychoplastogens. These compounds are capable of fast structural and functional rearrangement of neural networks by targeting mechanisms previously implicated in the development of depression. Furthermore, evidence shows that they exert a potent acute and long-term positive effects, reaching beyond the treatment of psychiatric diseases. Several of them are naturally occurring compounds, such as psilocybin, ,-dimethyltryptamine, and 7,8-dihydroxyflavone. Their pharmacology and effects in animal and human studies were discussed in this article.
Topics: Animals; Antidepressive Agents; Biological Products; Clinical Studies as Topic; Depression; Drug Evaluation, Preclinical; Humans; Structure-Activity Relationship; Treatment Outcome
PubMed: 32150976
DOI: 10.3390/molecules25051172