The Experts below are selected from a list of 15519 Experts worldwide ranked by ideXlab platform
Joe Kossowsky - One of the best experts on this subject based on the ideXlab platform.
-
efficacy and safety of selective serotonin Reuptake Inhibitors serotonin norepinephrine Reuptake Inhibitors and placebo for common psychiatric disorders among children and adolescents a systematic review and meta analysis
JAMA Psychiatry, 2017Co-Authors: Cosima Locher, Helen Koechlin, Sean R Zion, C R Werner, Daniel S Pine, Irving Kirsch, Ronald C Kessler, Joe KossowskyAbstract:Importance Depressive disorders (DDs), anxiety disorders (ADs), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) are common mental disorders in children and adolescents. Objective To examine the relative efficacy and safety of selective serotonin Reuptake Inhibitors (SSRIs), Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), and placebo for the treatment of DD, AD, OCD, and PTSD in children and adolescents. Data Sources PubMed, EMBASE, PsycINFO, Web of Science, and Cochrane Database from inception through August 7, 2016. Study Selection Published and unpublished randomized clinical trials of SSRIs or SNRIs in youths with DD, AD, OCD, or PTSD were included. Trials using other antidepressants (eg, tricyclic antidepressants, monoamine oxidase Inhibitors) were excluded. Data Extraction and Synthesis Effect sizes, calculated as standardized mean differences (Hedges g ) and risk ratios (RRs) for adverse events, were assessed in a random-effects model. Main Outcomes and Measures Primary outcomes, as defined by authors on preintervention and postintervention data, mean change data, and adverse event data, were extracted independently by multiple observers following PRISMA guidelines. Results Thirty-six trials were eligible, including 6778 participants (3484 [51.4%] female; mean [SD] age, 12.9 [5.1] years); 17 studies for DD, 10 for AD, 8 for OCD, and 1 for PTSD. Analysis showed that SSRIs and SNRIs were significantly more beneficial compared with placebo, yielding a small effect size ( g = 0.32; 95% CI, 0.25-0.40; P g = 0.56; 95% CI, 0.40-0.72; P g = 0.20; 95% CI, 0.13-0.27; P g = 1.57; 95% CI, 1.36-1.78; P g = 1.03; 95% CI, 0.84-1.21; P g = 0.71; 95% CI, 0.45-0.97; P P = .01 or RR, 1.49; 95% CI, 1.22-1.82; P P P Conclusions and Relevance Compared with placebo, SSRIs and SNRIs are more beneficial than placebo in children and adolescents; however, the benefit is small and disorder specific, yielding a larger drug-placebo difference for AD than for other conditions. Response to placebo is large, especially in DD. Severe adverse events are significantly more common with SSRIs and SNRIs than placebo.
Kristia Thorlund - One of the best experts on this subject based on the ideXlab platform.
-
comparative efficacy and safety of selective serotonin Reuptake Inhibitors and serotonin norepinephrine Reuptake Inhibitors in older adults a network meta analysis
Journal of the American Geriatrics Society, 2015Co-Authors: Kristia Thorlund, Eric Druyts, Chakrapani Alijepalli, Denis Keohane, Edward J MillsAbstract:Objectives To establish the comparative efficacy and safety of selective serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake Inhibitors in older adults using the network meta-analysis approach. Design Systematic review and network meta-analysis. Participants Individuals aged 60 and older. Measurements Data on partial response (defined as at least 50% reduction in depression score from baseline) and safety (dizziness, vertigo, syncope, falls, loss of consciousness) were extracted. A Bayesian network meta-analysis was performed on the efficacy and safety outcomes, and relative risks (RRs) with 95% credible intervals (CrIs) were produced. Results Fifteen randomized controlled trials were eligible for inclusion in the analysis. Citalopram, escitalopram, paroxetine, duloxetine, venlafaxine, fluoxetine, and sertraline were represented. Reporting on partial response and dizziness was sufficient to conduct a network meta-analysis. Reporting on other outcomes was sparse. For partial response, sertraline (RR = 1.28), paroxetine (RR = 1.48), and duloxetine (RR = 1.62) were significantly better than placebo. The remaining interventions yielded RRs lower than 1.20. For dizziness, duloxetine (RR = 3.18) and venlafaxine (RR = 2.94) were statistically significantly worse than placebo. Compared with placebo, sertraline had the lowest RR for dizziness (1.14) and fluoxetine the second lowest (1.31). Citalopram, escitalopram, and paroxetine all had RRs between 1.4 and 1.7. Conclusion There was clear evidence of the effectiveness of sertraline, paroxetine, and duloxetine. There also appears to be a hierarchy of safety associated with the different antidepressants, although there appears to be a dearth of reporting of safety outcomes.
Michael E. Thase - One of the best experts on this subject based on the ideXlab platform.
-
Vortioxetine: a New Treatment for Major Depressive Disorder.
Expert opinion on pharmacotherapy, 2016Co-Authors: K. Ryan Connolly, Michael E. ThaseAbstract:ABSTRACTIntroduction: Vortioxetine is a structurally novel medication that has recently been approved for treatment of major depressive disorder (MDD). This medication is a serotonin Reuptake inhibitor that also has a number of other potentially relevant effects on serotoninergic receptors, which may differentiate the drug’s effects from those of current first-line antidepressants, such as selective serotonin Reuptake Inhibitors (SSRIs) and serotonin norepinephrine Reuptake Inhibitors (SNRIs).Areas Covered: This article will review the basic clinical pharmacology of vortioxetine, summarize the major clinical trials that were performed prior to approval by the US Food and Drug Administration (FDA), discuss relevant post-marketing studies of this drug, and offer expert commentary on the significance of this new agent in clinical practice. Pre-approval studies were identified as all randomized, placebo-controlled studies of vortioxetine listed on clinicaltrials.gov. Other referenced studies were identified v...
-
comparison of adjunctive use of aripiprazole with bupropion or selective serotonin Reuptake Inhibitors serotonin norepinephrine Reuptake Inhibitors analysis of patients beginning adjunctive treatment in a 52 week open label study
BMC Research Notes, 2014Co-Authors: Anita H. Clayton, Ross A. Baker, John J. Sheehan, Zachary Cain, Robert A. Forbes, S.v. Marler, Ronald N. Marcus, Robert M. Berman, Michael E. ThaseAbstract:Background This post hoc analysis assessed the safety, tolerability and effectiveness of long-term treatment with aripiprazole adjunctive to either bupropion or selective serotonin Reuptake Inhibitors (SSRIs)/serotonin–norepinephrine Reuptake Inhibitors (SNRIs) in patients with major depressive disorder (MDD).
Feng Zhu - One of the best experts on this subject based on the ideXlab platform.
-
what contributes to serotonin norepinephrine Reuptake Inhibitors dual targeting mechanism the key role of transmembrane domain 6 in human serotonin and norepinephrine transporters revealed by molecular dynamics simulation
ACS Chemical Neuroscience, 2018Co-Authors: Weiwei Xue, Guoxun Zheng, Panpan Wang, Fengyuan Yang, Xiaojun Yao, Yu Zong Chen, Feng ZhuAbstract:Dual inhibition of serotonin and norepinephrine transporters (hSERT and hNET) gives greatly improved efficacy and tolerability for treating major depressive disorder (MDD) compared with selective Reuptake Inhibitors. Pioneer studies provided valuable information on structure, function, and pharmacology of drugs targeting both hSERT and hNET (serotonin–norepinephrine Reuptake Inhibitors, SNRIs), and the differential binding mechanism between SNRIs and selective Inhibitors of 5-HT (SSRIs) or NE (sNRIs) to their corresponding targets was expected to be able to facilitate the discovery of a privileged drug-like scaffold with improved efficacy. However, the dual-target mechanism of SNRIs was still elusive, and the binding mode distinguishing SNRIs from SSRIs and sNRIs was also unclear. Herein, an integrated computational strategy was adopted to discover the binding mode shared by all FDA approved SNRIs. The comparative analysis of binding free energy at the per-residue level discovered that residues Phe335, Le...
-
What Contributes to Serotonin–Norepinephrine Reuptake Inhibitors’ Dual-Targeting Mechanism? The Key Role of Transmembrane Domain 6 in Human Serotonin and Norepinephrine Transporters Revealed by Molecular Dynamics Simulation
2018Co-Authors: Weiwei Xue, Guoxun Zheng, Panpan Wang, Fengyuan Yang, Xiaojun Yao, Yu Zong Chen, Feng ZhuAbstract:Dual inhibition of serotonin and norepinephrine transporters (hSERT and hNET) gives greatly improved efficacy and tolerability for treating major depressive disorder (MDD) compared with selective Reuptake Inhibitors. Pioneer studies provided valuable information on structure, function, and pharmacology of drugs targeting both hSERT and hNET (serotonin–norepinephrine Reuptake Inhibitors, SNRIs), and the differential binding mechanism between SNRIs and selective Inhibitors of 5-HT (SSRIs) or NE (sNRIs) to their corresponding targets was expected to be able to facilitate the discovery of a privileged drug-like scaffold with improved efficacy. However, the dual-target mechanism of SNRIs was still elusive, and the binding mode distinguishing SNRIs from SSRIs and sNRIs was also unclear. Herein, an integrated computational strategy was adopted to discover the binding mode shared by all FDA approved SNRIs. The comparative analysis of binding free energy at the per-residue level discovered that residues Phe335, Leu337, Gly338, and Val343 located at the transmembrane domain 6 (TM6) of hSERT (the corresponding residues Phe317, Leu319, Gly320, and Val325 in hNET) were the determinants accounting for SNRIs’ dual-acting inhibition, while residues lining TM3 and 8 (Ile172, Ser438, Thr439, and Leu443 in hSERT; Val148, Ser419, Ser420, and Met424 in hNET) contributed less to the binding of SNRIs than that of SSRIs and sNRIs. Based on these results, the distances between an SNRI’s centroid and the centroids of its two aromatic rings (measuring the depth of rings stretching into hydrophobic pockets) were discovered as the key to the SNRIs’ dual-targeting mechanism. This finding revealed SNRIs’ binding mechanism at an atomistic level, which could be further utilized as structural blueprints for the rational design of privileged drug-like scaffolds treating MDD
Ian Gilron - One of the best experts on this subject based on the ideXlab platform.
-
neuropathic pain principles of diagnosis and treatment
Mayo Clinic proceedings, 2015Co-Authors: Ian Gilron, Ralf Baron, Troels S JensenAbstract:Neuropathic pain is caused by disease or injury of the nervous system and includes various chronic conditions that, together, affect up to 8% of the population. A substantial body of neuropathic pain research points to several important contributory mechanisms including aberrant ectopic activity in nociceptive nerves, peripheral and central sensitization, impaired inhibitory modulation, and pathological activation of microglia. Clinical evaluation of neuropathic pain requires a thorough history and physical examination to identify characteristic signs and symptoms. In many cases, other laboratory investigations and clinical neurophysiological testing may help identify the underlying etiology and guide treatment selection. Available treatments essentially provide only symptomatic relief and may include nonpharmacological, pharmacological, and interventional therapies. Most extensive evidence is available for pharmacological treatment, and currently recommended first-line treatments include antidepressants (tricyclic agents and Serotonin-Norepinephrine Reuptake Inhibitors) and anticonvulsants (gabapentin and pregabalin). Individualized multidisciplinary patient care is facilitated by careful consideration of pain-related disability (eg, depression and occupational dysfunction) as well as patient education; repeat follow-up and strategic referral to appropriate medical/surgical subspecialties; and physical and psychological therapies. In the near future, continued preclinical and clinical research and development are expected to lead to further advancements in the diagnosis and treatment of neuropathic pain.
-
nontricyclic antidepressant analgesics and pain are serotonin norepinephrine Reuptake Inhibitors snris any better
Pain, 2011Co-Authors: Peter C N Watson, Ian Gilron, Jana Sawynok, Mary E LynchAbstract:Almost 50 years of clinical investigation has resulted in a large amount of literature regarding pain and antidepressants, one of the first categories of drugs found effective for chronic noncancer pain (CNCP) by randomized controlled trials (RCTs). These RCTs first examined tricyclic antidepressants (TCAs) based on published observational data and the rationale that their actions potentiated descending pain-inhibitory brainstem mechanisms involving serotonin andnoradrenaline [5]. Attention turned tomore selective antidepressants as they were developed because of limitations in efficacy and concern about adverse effects. These were initially the selective serotonin Reuptake Inhibitors (SSRIs) (fluoxetine and congeners) and the more noradrenergic agents (the tetracyclic antidepressant maprotiline and the TCAs nortriptyline and desipramine, which are themetabolites of amitriptyline and imipramine). The results of these investigationswere generally disappointing regarding any superiority (except for nortriptyline) [54]. Recent pain treatment research has explored the dual serotonin noradrenaline Reuptake inhibitor antidepressants (SNRIs), particularly venlafaxine, duloxetine, and milnacipran. Like the TCA amitriptyline, these have a more balanced effect on both serotonin and noradrenaline Reuptake, but potentially have fewer adverse effects because of fewer receptor interactions. Recent RCTs have been primarily placebocontrolled trials of single agents, and there are few head-to-head trials comparing efficacy and side effects [54]. This reviewwill focus on the SNRIs and RCTs in neuropathic pain (NP) and fibromyalgia (FM). There is a need to address whether these drugs represent an advance in efficacy and safety over older antidepressants and other analgesics. Of importance to the clinician are the following: (1) the clinical meaningfulness of the results of a reportedly positive RCT; (2) how antidepressants compare directly in head-to-head RCTs [54]; and (3) the role of indirect comparisons of SNRIs with each other and with other drugs (older TCAs, gabapentinoids, opioids, cannabinoids) using number needed to treat (NNT) and number needed to harm (NNH) as estimates of efficacy and tolerability [12]. Also critical for the practitioner is an appreciation of how generalizable RCT results are to clinical practice (external validity) [51]
-
Neuropathic pain: a practical guide for the clinician
Canadian Medical Association Journal, 2006Co-Authors: Ian Gilron, C. Peter N. Watson, Catherine M. Cahill, De MoulinAbstract:Neuropathic pain, caused by various central and peripheral nerve disorders, is especially problematic because of its severity, chronicity and resistance to simple analgesics. The condition affects 2%–3% of the population, is costly to the health care system and is personally devastating to the people who experience it. The diagnosis of neuropathic pain is based primarily on history (e.g., underlying disorder and distinct pain qualities) and the findings on physical examination (e.g., pattern of sensory disturbance); however, several tests may sometimes be helpful. Important pathophysiologic mechanisms include sodium-and calcium-channel upregulation, spinal hyperexcitability, descending facilitation and aberrant sympathetic–somatic nervous system interactions. Treatments are generally palliative and include conservative nonpharmacologic therapies, drugs and more invasive interventions (e.g., spinal cord stimulation). Individualizing treatment requires consideration of the functional impact of the neuropathic pain (e.g., depression, disability) as well as ongoing evaluation, patient education, reassurance and specialty referral. We propose a primary care algorithm for treatments with the most favourable risk–benefit profile, including topical lidocaine, gabapentin, pregabalin, tricyclic antidepressants, mixed serotonin–norepinephrine Reuptake Inhibitors, tramadol and opioids. The field of neuropathic pain research and treatment is in the early stages of development, with many unmet goals. In coming years, several advances are expected in the basic and clinical sciences of neuropathic pain, which will provide new and improved therapies for patients who continue to experience this disabling condition.
