The Experts below are selected from a list of 1731 Experts worldwide ranked by ideXlab platform
Robert L Owens - One of the best experts on this subject based on the ideXlab platform.
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Trazodone effects on obstructive sleep apnea and non rem arousal threshold
Annals of the American Thoracic Society, 2015Co-Authors: Erik Smales, Bradley A Edwards, Pam Deyoung, David G Mcsharry, Andrew Wellman, Adrian Velasquez, Robert L OwensAbstract:Rationale: A low respiratory arousal threshold is a physiological trait involved in obstructive sleep apnea (OSA) pathogenesis. Trazodone may increase arousal threshold without compromising upper airway muscles, which should improve OSA.Objectives: We aimed to examine how Trazodone alters OSA severity and arousal threshold. We hypothesized that Trazodone would increase the arousal threshold and improve the apnea/hypopnea index (AHI) in selected patients with OSA.Methods: Subjects were studied on two separate nights in a randomized crossover design. Fifteen unselected subjects with OSA (AHI ≥ 10/h) underwent a standard polysomnogram plus an epiglottic catheter to measure the arousal threshold. Subjects were studied after receiving Trazodone (100 mg) and placebo, with 1 week between conditions. The arousal threshold was calculated as the nadir pressure before electrocortical arousal from approximately 20 spontaneous respiratory events selected randomly.Measurements and Main Results: Compared with placebo, t...
Andrea Fagiolini - One of the best experts on this subject based on the ideXlab platform.
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a randomized double blind study comparing the efficacy and safety of Trazodone once a day and venlafaxine extended release for the treatment of patients with major depressive disorder
International Clinical Psychopharmacology, 2020Co-Authors: Andrea Fagiolini, Umberto Albert, Laura Ferrando, Erik Herman, Cosmina Muntean, Eva Palova, Agnese Cattaneo, Alessandro Comandini, Giorgio Di Dato, Giorgio Di LoretoAbstract:This double-blind, randomized study evaluated the efficacy and safety of Trazodone OAD (once-a-day) in comparison with venlafaxine XR (extended-release) in 324 patients (166 Trazodone and 158 venlafaxine) with major depressive disorder (MDD). The primary efficacy endpoint was the mean change from baseline in the 17-item Hamilton Depression Rating Scale (HAM-D) at week 8. Both treatments were effective in reducing the HAM-D-17 total score at week 8 vs. baseline (intent-to-treat: Trazodone -12.9, venlafaxine -14.7; per protocol: Trazodone -15.4, venlafaxine -16.4). Patients in the venlafaxine group achieved better results after 8 weeks, whereas the Trazodone group achieved a statistically significant reduction in HAM-D-17 following only 7 days of treatment. The most frequent adverse events (AEs) were dizziness and somnolence in the Trazodone group, and nausea and headache in the venlafaxine group. Most AEs were mild-to-moderate in severity. This study confirmed that both venlafaxine XR and Trazodone OAD may represent a valid treatment option for patients with MDD.
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clinical effectiveness of parenteral Trazodone for the management of psychomotor activation in patients with bipolar disorder
Neuro endocrinology letters, 2018Co-Authors: Martina Ballerio, Alessandro Cuomo, Pierluigi Politi, Calogero Crapanzano, Enzo Emanuele, Arianna Goracci, Andrea FagioliniAbstract:OBJECTIVES Trazodone is a multifunctional triazolopyridine drug with antidepressant, anxiolytic, sedative, and hypnotic properties. The current retrospective study was designed to investigate the effectiveness of Trazodone for reducing acute psychomotor activation (PA) in patients with bipolar disorder (BD). We specifically reasoned that a parenteral route of administration could offer potential advantages in this clinical setting. METHODS We assessed the effectiveness and safety of parenteral Trazodone in a retrospective study conducted in 64 inpatients with BD and acute PA. The effectiveness assessment was the Clinical Global Impression Scale - Severity Of Illness (CGI-S) rated before the administration of parenteral Trazodone (baseline) and at the end of treatment. A post-treatment reduction in CGI-S score ≥ 20% compared with baseline was considered as the primary outcome measure. RESULTS Administration of parenteral Trazodone was associated with significant improvements in CGI-S scores from baseline (5.4 ± 0.9) to the end of the study (4.2 ± 1.0; p < 0.001, Wilcoxon matched-pairs signed-ranks test). A total of 34 patients (53.1%) showed a post-treatment reduction in CGI-S score ≥ 20% compared to baseline. Multivariable binary logistic regression analysis using a forward selection procedure identified treatment duration (in days) as the only independent predictor of post-treatment reduction in CGI-S score ≥ 20% (odds ratio: 1.28; 95% confidence interval: 1.02-1.60, p <0.05). Adverse effects occurred in 13 (20.3%) patients. CONCLUSIONS Parenteral Trazodone is well-tolerated and effective in 53.1% of patients with BP and acute PA. Treatment duration was identified as an independent predictor of response in our sample.
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off label Trazodone prescription evidence benefits and risks
Current Pharmaceutical Design, 2015Co-Authors: Letizia Bossini, Anna Coluccia, I Casolaro, Jim Benbow, Giovanni Amodeo, Riccardo De Giorgi, Andrea FagioliniAbstract:Although Trazodone is approved and marketed in most countries worldwide for the sole treatment of Major Depressive Disorder, the use for this medication is very common for many other conditions, such as primary or secondary insomnia, Generalised Anxiety Disorder, Panic Disorder, Post-Traumatic Stress Disorder and Obsessive- Compulsive Disorder. Other, not officially approved, uses of Trazodone include: the treatment of bulimia, benzodiazepine and/or alcohol dependence or abuse, fibromyalgia, degenerative diseases of the central nervous system such as dementia and other organic disorders, schizophrenia, chronic pain, and diabetic neuropathy. In addition, due to its 5HT2A receptor antagonistic action, Trazodone may be used to prevent the occurrence of initial and long-term side effects of SSRI, such as anxiety, insomnia and sexual dysfunction. Despite the favorable clinical experience and the encouraging results from the studies that have tested the efficacy of Trazodone for some of its off-label indications, it is paramount that large, randomized and controlled clinical trials be conducted in the near future to evaluate which of the many off-label indications are supported by a strong scientific evidence.
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Rediscovering Trazodone for the Treatment of Major Depressive Disorder
CNS Drugs, 2012Co-Authors: Andrea Fagiolini, Alessandro Comandini, Mario Catena Dell’osso, Siegfried KasperAbstract:Trazodone is a triazolopyridine derivative that belongs to the class of serotonin receptor antagonists and reuptake inhibitors (SARIs). The drug is approved and marketed in several countries worldwide for the treatment of major depressive disorder (MDD) in adult patients. In clinical studies, Trazodone has demonstrated comparable antidepressant activity to other drug classes, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and serotonin–noradrenaline (norepinephrine) reuptake inhibitors (SNRIs). Moreover, the SARI action of Trazodone may overcome the tolerability issues that are often associated with second-generation antidepressants such as SSRIs (i.e. insomnia, anxiety and sexual dysfunction). Recent focus has been placed on the development of a new prolonged-release once-a-day formulation of Trazodone (TzCOAD), which may provide improved tolerability over the conventional immediate-release formulation of Trazodone. Clinical studies have led to the recent approval in the USA of TzCOAD (as Oleptro™; Angelini Labopharm LLC, Princeton, NJ, USA), which may see resurgence of interest in the drug for the management of patients with MDD. Although Trazodone is approved for the treatment of depression, evidence supports the use of low-dose Trazodone as an off-label hypnotic for the treatment of sleep disorders in patients with MDD. The most common adverse effects reported with Trazodone are drowsiness (somnolence/sedation), headache, dizziness and dry mouth. Other events reported, albeit with low incidence, include orthostatic hypotension (particularly in elderly patients or those with heart disease), minimal anticholinergic activity, corrected QT interval prolongation and torsade de pointes, cardiac arrhythmias, and rare occurrences of priapism and suicidal ideation. Overall, Trazodone is an effective and well tolerated antidepressant (SARI) with an important role in the current treatment of MDD both as monotherapy and as part of a combination strategy. Trazodone is effective in controlling a wide range of symptoms of depression, while avoiding the negative effects on sleep seen with SSRI antidepressants. The recently approved prolonged-release formulation should provide further optimization of this antidepressant and may be useful for enabling an appropriate therapeutic dose to be administered with improved patient compliance.
David J Greenblatt - One of the best experts on this subject based on the ideXlab platform.
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short term clarithromycin administration impairs clearance and enhances pharmacodynamic effects of Trazodone but not of zolpidem
Clinical Pharmacology & Therapeutics, 2009Co-Authors: Dora Farkas, Laurie P Volak, Jerold S Harmatz, L L Von Moltke, Michael H Court, David J GreenblattAbstract:The kinetic and dynamic interactions of 5 mg zolpidem and 50 mg Trazodone with 500 mg clarithromycin (4 doses given over 32 h) were investigated in a 5-way double crossover study with 10 healthy volunteers. The five treatment conditions were: placebo + placebo; zolpidem + placebo; zolpidem + clarithromycin; Trazodone + placebo; and Trazodone + clarithromycin. Coadministration of clarithromycin increased Trazodone area under the curve, prolonged elimination half-life, increased peak plasma concentration (Cmax), and reduced oral clearance. In contrast, clarithromycin had no significant effect on any kinetic parameter for zolpidem. Clarithromycin did not potentiate sedation caused by zolpidem. However, clarithromycin coadministered with Trazodone significantly increased self- and observer-rated sedation and ratings of feeling “spacey.” Thus, short-term clarithromycin coadministration significantly impairs Trazodone clearance, elevates plasma concentrations, and enhances sedative effects. However, clarithromycin has no significant kinetic or dynamic interaction with zolpidem. Clinical Pharmacology & Therapeutics (2009); 85, 6, 644–650 doi:10.1038/clpt.2008.293
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short term exposure to low dose ritonavir impairs clearance and enhances adverse effects of Trazodone
The Journal of Clinical Pharmacology, 2003Co-Authors: David J Greenblatt, Jerold S Harmatz, L L Von Moltke, Steven M Fogelman, Gengsheng Chen, Jennifer A Graf, Polyxane Mertzanis, Susan Byron, Kerry E Culm, Brian W GrandaAbstract:Antiretroviral agents may participate in drug interactions that influence the efficacy and toxicity of other antiretrovirals, as well as pharmacologic treatments of coincident or complicating diseases. The viral protease inhibitor, ritonavir, may cause drug interactions by inhibiting the activity of cytochrome P450-3A (CYP3A) isoforms. In a single-dose, blinded, four-way crossover study, 10 healthy volunteer subjects received 50 mg of Trazodone hydrochloride or matching placebo concurrent with low-dose ritonavir (four doses of 200 mg each) or with placebo. Compared to the control condition, ritonavir significantly reduced apparent oral clearance of Trazodone (155 +/- 23 vs. 75 +/- 12 ml/min, p < 0.001), prolonged elimination half-life (6.7 +/- 0.7 vs. 14.9 +/- 3.9 h, p < 0.05), and increased peak plasma concentrations (842 +/- 64 vs. 1125 +/- 111 ng/ml, p < 0.05) (mean +/- SE). Coadministration of Trazodone with ritonavir increased sedation, fatigue, and performance impairment compared to Trazodone plus placebo; differences reached significance only for the digitsymbol substitution test. Three subjects experienced nausea, dizziness, or hypotension when Trazodone was given with ritonavir; 1 of these subjects also experienced syncope. Thus short-term low-dose administration of ritonavir impairs oral clearance of Trazodone and increases the occurrence of adverse reactions. The findings are consistent with impairment of CYP3A-mediated Trazodone metabolism by ritonavir.
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Trazodone and valproate in patients discontinuing long term benzodiazepine therapy effects on withdrawal symptoms and taper outcome
Psychopharmacology, 1999Co-Authors: Karl Rickels, Edward Schweizer, Garcia F Espana, George D Case, Nicholas Demartinis, David J GreenblattAbstract:Recent uncontrolled research suggested that Trazodone and sodium valproate may be helpful in benzodiazepine (BZ) discontinuation. We therefore undertook a double-blind study to assess whether Trazodone and valproate, as compared to placebo, would attenuate withdrawal and facilitate discontinuation in BZ-dependent patients with a minimum of 1 year daily BZ use. Seventy-eight patients, taking a mean dose of 19 ± 17 mg/day of diazepam (or its equivalent), were stabilized for several weeks on their BZ (16 diazepam, 25 lorazepam, 37 alprazolam) and then for 1–2 weeks, pretreated with Trazodone, sodium valproate or placebo before being tapered at 25% per week. All treatments were continued for 5 weeks post-taper. BZ-free status was assessed after 5 and 12 weeks post-taper. Neither Trazodone nor valproate had any significant effect on withdrawal severity. Peak physician withdrawal checklist change from baseline to peak severity was 16.4 for Trazodone, 18.04 sodium valproate and 18.24 placebo (F = 0.10; NS). Taper success rates were significantly effected by both active agents at the 5-week, but not 12-week, assessment. At 5 weeks post-taper, 79% of sodium valproate and 67% of Trazodone, but only 31% of placebo patients were BZ-free (χ2 = 7.34; df 2; P < 0.03). Major adverse events for Trazodone were sedation and dry mouth, and for valproate, diarrhea, nausea and headaches.
S Stahl - One of the best experts on this subject based on the ideXlab platform.
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early response to Trazodone once a day in major depressive disorder review of the clinical data and putative mechanism for faster onset of action
Cns Spectrums, 2021Co-Authors: Umberto Albert, Pallavi Lamba, S StahlAbstract:Background Most antidepressants have a delayed onset of action and must be administered for several weeks to generate therapeutic effects. Trazodone is a serotonin antagonist and reuptake inhibitor approved for the treatment of major depressive disorder. The once-a-day (OAD) formulation of Trazodone has an improved tolerability profile compared to its conventional formulations. In this study, we systematically reviewed the evidence available for the antidepressant efficacy and early improvement in depressive symptoms with Trazodone OAD treatment. Method We conducted a PubMed database search for randomized controlled trials published from 2005 to 2020. Results Two studies, a placebo-controlled and an active-comparator (venlafaxine extended-release or XR) study were found. Both the studies demonstrated that Trazodone exhibits antidepressant activity at a starting dose of 150 mg/day and results in statistically significant greater reduction in Hamilton Depression Rating Scale (HAM-D17) scores within 1 week of starting treatment compared to placebo or venlafaxine XR (P < .05). Trazodone also resulted in significant early improvement in the HAM-D17 sleep disturbance factor compared to placebo or venlafaxine XR at day 7 (P < .05). This clinical effect is supported by in vitro proprietary data for the affinity of Trazodone for different target receptors. Activity at these receptors may underlie Trazodone’s fast antidepressant action. Conclusions Trazodone, if properly dosed, can be an effective antidepressant with early onset of action and good tolerability. Future studies designed to specifically evaluate onset and timing of improvement of depressive symptoms remain necessary to confirm and extend these results.
Andrew Wellman - One of the best experts on this subject based on the ideXlab platform.
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Trazodone effects on obstructive sleep apnea and non rem arousal threshold
Annals of the American Thoracic Society, 2015Co-Authors: Erik Smales, Bradley A Edwards, Pam Deyoung, David G Mcsharry, Andrew Wellman, Adrian Velasquez, Robert L OwensAbstract:Rationale: A low respiratory arousal threshold is a physiological trait involved in obstructive sleep apnea (OSA) pathogenesis. Trazodone may increase arousal threshold without compromising upper airway muscles, which should improve OSA.Objectives: We aimed to examine how Trazodone alters OSA severity and arousal threshold. We hypothesized that Trazodone would increase the arousal threshold and improve the apnea/hypopnea index (AHI) in selected patients with OSA.Methods: Subjects were studied on two separate nights in a randomized crossover design. Fifteen unselected subjects with OSA (AHI ≥ 10/h) underwent a standard polysomnogram plus an epiglottic catheter to measure the arousal threshold. Subjects were studied after receiving Trazodone (100 mg) and placebo, with 1 week between conditions. The arousal threshold was calculated as the nadir pressure before electrocortical arousal from approximately 20 spontaneous respiratory events selected randomly.Measurements and Main Results: Compared with placebo, t...
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Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold
Sleep, 2014Co-Authors: Danny J Eckert, Andrew Wellman, Atul Malhotra, David P WhiteAbstract:Study Objectives: The effect of common sedatives on upper airway physiology and breathing during sleep in obstructive sleep apnea (OSA) has been minimally studied. Conceptually, certain sedatives may worsen OSA in some patients. However, sleep and breathing could improve with certain sedatives in patients with OSA with a low respiratory arousal threshold. This study aimed to test the hypothesis that Trazodone increases the respiratory arousal threshold in patients with OSA and a low arousal threshold. Secondary aims were to examine the effects of Trazodone on upper airway dilator muscle activity, upper airway collapsibility, and breathing during sleep. Design: Patients were studied on 4 separate nights according to a within-subjects cross-over design. Setting: Sleep physiology laboratory. Patients: Seven patients with OSA and a low respiratory arousal threshold. Interventions: In-laboratory polysomnograms were obtained at baseline and after 100 mg of Trazodone was administered, followed by detailed overnight physiology experiments under the same conditions. During physiology studies, continuous positive airway pressure was transiently lowered to measure arousal threshold (negative epiglottic pressure prior to arousal), dilator muscle activity (genioglossus and tensor palatini), and upper airway collapsibility (Pcrit). Measurements and Results: Trazodone increased the respiratory arousal threshold by 32 ± 6% (-11.5 ± 1.4 versus -15.3 ± 2.2 cmH2O, P < 0.01) but did not alter the apnea-hypopnea index (39 ± 12 versus 39 ± 11 events/h sleep, P = 0.94). Dilator muscle activity and Pcrit also did not systematically change with Trazodone. Conclusions: Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold without major impairment in dilator muscle activity or upper airway collapsibility. However, the magnitude of change in arousal threshold was insufficient to overcome the compromised upper airway anatomy in these patients.
