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Retrospective analysis of a random sample of adult patients with CUA from 2001-2009.
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Additional well-designed research is needed on prevention and management approaches for OM.
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The N-demethylation of both isomers was inhibited most prominently by tranylcypromine (CYP2C19) to more than 50%. Furafylline (CYP1A2) and sulfaphenazole (CYP2C9) inhibited the N-demethylation to a lesser extent while quinidine (CYP2D6) or troleandomycine (CYP3A4) had no effect. Rh-CYP2C19, -CYP1A2, and -CYP2C9 were able to N-demethylate cis- and trans-doxepin. Only traces of trans-desmethyldoxepin were detectable when CYP3A4 was used. The maximum velocity in the cis- and transdoxepin N-demethylation was significantly (P < 0.05) lower in microsomes with low CYP2C19 activity (345 +/- 44 and 508 +/- 75 pmol/min/ mg protein, respectively) compared to those with high CYP2C19 activity (779 +/- 132 and 1,189 +/- 134 pmollmin/mg).
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A retrospective analysis of Iowa City Department of Veteran's Affairs prescription records from March 1, 1995, to March 1, 1998, was performed. Antidepressants prescribed only by psychiatrists were included. Concomitant use was defined as trazodone prescribed on the same date or up to 42 days after the fill date of the primary antidepressant.
In a 10-week, multicenter, randomized, double-blind, placebo-controlled study in the United States, the efficacy and tolerability of dothiepin and doxepin (both administered as a 150-mg nightly dose) were compared in 579 outpatients with major depression.
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The binding of doxepin hydrochloride (DH) to bovine serum albumin (BSA) was investigated by spectroscopic (fluorescence, UV-vis absorption and circular dichroism) techniques. The binding parameters have been evaluated by fluorescence quenching method. The thermodynamic parameters, Delta H major, Delta S major, and Delta G major calculated at different temperatures indicated that the hydrogen bond and hydrophobic forces played a major role in the interaction of DH with BSA. Based on the Förster's theory of non-radiation energy transfer, the binding average distance, r between the donor (BSA) and acceptor (DH) was evaluated and found to be 2.7 nm. Spectral results observed showed that the binding of DH to BSA induced conformational changes in BSA. The effect of common ions on the binding of DH to BSA was also examined.
The effects of tricyclic antidepressants; imipramine and doxepin, and of new antidepressants; mianserin, danitracen, trazodone, viloxazine and zimelidine, on seizures kindled from the rabbit amygdala were examined. Behavioral and bioelectrical seizures were kindled by a repeated daily stimulation of unilateral amygdala with a low intensity electric current (120 microamperemeter, 1 msec, 50Hz). The following parameters of kindled seizures were analyzed: 1-intensity of behavioral seizures according to a 6-point scale, 2-duration of behavioral seizures, 3-duration of bioelectrical (EEG) seizure activity. Only imipramine inhibited all parameters of kindled seizures. Doxepin, mianserin, danitracen and trazodone affected only two parameters. Zimelidine did not induce any changes of kindled seizure, and viloxazine prolonged duration of the bioelectrical seizure activity. It is likely that inhibition of seizures kindled from the rabbit amygdala is due to noradrenaline stimulating or serotonin inhibiting properties of the drugs, but independent of the antidepressive activity.
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There was one trial of the monoamine oxidase inhibitor moclobemide, and one of the atypical antidepressant venlafaxine. Neither of these detected a significant long-term benefit. There were five trials of selective serotonin reuptake inhibitors; three of fluoxetine, one of sertraline and one of paroxetine. None of these detected significant effects, and there was no evidence of a significant benefit when results were pooled. There were 24 trials of bupropion and six trials of nortriptyline. When used as the sole pharmacotherapy, bupropion (19 trials, OR 2.06, 95% confidence intervals [CI] 1.77 to 2.40) and nortriptyline (four trials, OR 2.79, 95% CI 1.70 to 4.59) both doubled the odds of cessation. In one trial the combination of bupropion and nicotine patch produced slightly higher quit rates than patch alone, but this was not replicated in a second study. Two trials of extended therapy with bupropion to prevent relapse after initial cessation did not show a significant long-term benefit. There is a risk of about 1 in 1000 of seizures associated with bupropion use. Concerns that bupropion may increase suicide risk are currently unproven.
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Eosinophilic folliculitis (EF) comprises classic eosinophilic pustular folliculitis (EPF), human immunodeficiency virus (HIV)-related EF, and infantile EPF subtypes. A fourth proposed subtype describes EF associated with hematologic malignancy. Recently, EF has occurred after bone marrow or stem cell transplantation (SCT).
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The aim of this project was to develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral mucositis (OM) in cancer patients.
Existing data suggest that amitriptyline, doxepin, mianserin, viloxazine and imipramine impair the performance of skilled psychomotor tasks. The degree of impairment, as well as the degree of interaction with alcohol, is closely related to the sedative potency of the drug. the adverse effects on psychomotor skills are, however, mainly limited to the first 10 days of treatment. In contrast, nortriptyline, clomipramine, desipramine, protriptyline, nomifensine and zimeldine have much less marked effects on skilled performance. Despite its being a relatively new antidepressant, the effects of zimeldine on psychomotor skills have already been extensively investigated. It has been shown to be without stimulant or sedative effects, and there does not appear to be any additive effect between zimeldine and ethanol. The lack of detrimental effects on skills related to such tasks as driving, makes zimeldine suitable for use in out-patient populations.
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A sodium exchanged smectite clay mineral (Mt) was used as geo-sorbent for the adsorption of tramadol and doxepin: two pharmaceutical products (PPs) defined as emerging pollutants due to their presence at significant concentration in numerous water compartments. The adsorption isotherms for both the temperatures of 20 and 40°C and the derived data determined through the fitting procedure by using Langmuir, Freundlich and Dubinin-Radushkevich equation models explicitly pointed out that the sorption of both tramadol and doxepin is mainly driven by electrostatic interaction. The studied PPs are intercalated in a monolayer arrangement within the interlayer space through a cation exchange in stoichiometric proportion with the Na(+) cations leading to adsorbed PPs amounts that match the cation exchange capacity (CEC) of Mt. Due to their hydrophobic character, additional doxepin molecules could be adsorbed by weak molecular interaction driving to an increase of the adsorbed amount beyond the CEC at low temperature (20°C). The confinement of PPs within the interlayer space of Mt confirms the use of clay minerals as potential material for the wastewater treatment as well as it drives to an amorphous or glassy state, which can find echo in biopharmaceutical applications for a controlled release of PPs.
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Factors contributing to subjective fatigue in people with idiopathic Parkinson's disease (PD) are not well known. This makes it difficult to manage fatigue effectively in PD.
The affinity constant for doxepin obtained from inhibition of histamine-induced contraction of guinea-pig intestinal smooth muscle at 30 degrees C was 2.6 +/- 0.18 X 10(10)M-1. The slope of a Schild plot was not significantly different from unity. The affinity constant of doxepin did not vary markedly with temperature. At 37 degrees C it was 3.75 +/- 0.02 X 10(10)M-1 and at 25 degrees C 2.1 X 10(10)M-1. Doxepin was a competitive inhibitor of [3H]-mepyramine binding to guinea-pig cerebellar homogenates. The affinity constant derived for doxepin at 30 degrees C was 1.12 +/- 0.45 X 10(10)M-1. Hill coefficients for curves of doxepin or mepyramine inhibition of [3H]-mepyramine binding in guinea-pig cerebellum, cerebral cortex and hippocampus did not differ significantly from unity. The mean affinity of mepyramine for histamine H1-receptors in rat brain homogenates at 30 degrees C was 3.5 X 10(8)M-1. Hill coefficients for curves of doxepin or mepyramine inhibition of [3H]-mepyramine binding to homogenates of rat cerebral cortex or rat whole brain were near unity. These studies provide no evidence that doxepin binds preferentially to a sub-class of histamine H1-receptors in rat brain.
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The effects of mianserin, trazodone, amoxapine, maprotiline, and doxepin were assessed in punishment and pentylenetetrazol drug discrimination paradigms. These two procedures are used to identify antianxiety activity in rats. In the punishment procedure, misanserin produced an inverse dose-related increase in punished responding. The magnitude of the increase in punished responding with mianserin was comparable to that observed with the anxiolytic, buspirone. This effect was not observed with any of the other antidepressants tested. None of the antidepressants were found to be active in antagonizing the discriminative stimulus effects of pentylenetetrazol. In fact, at high doses there was a suggestion that the antidepressants may generalize to the pentylenetetrazol discriminative stimulus. Therefore, several antidepressants with purported clinical antianxiety activity, were not active in two procedures that detect antianxiety activity in rats.
We retrospectively analysed pharmacokinetic therapeutic drug-monitoring data in 114 psychiatric patients (79 females, 35 males) treated with doxepine for a period of 22-306 days, mostly due to major depression. The data were analysed using the computer program NONMEM. For both, doxepine and its metabolite desmethyldoxepine, a one-compartment model was chosen. Pharmacokinetic parameters clearance (CL/F) and volume of distribution (V/F) of doxepine and desmethyldoxepine were modelled in terms of both random and fixed effects.
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Pharmacokinetics of trans (E)- and cis (Z)-doxepin and N-desmethyldoxepin were analyzed after a single dose of 75 mg doxepin in 11 ultrafast metabolizers (UM), 11 extensive metabolizers (EM) and 3 poor metabolizers (PM), identified by genotyping for CYP2D6 alleles *2, *3, *4, *5, *6, *9, *10, *35, *41 and specific analyses to characterize gene duplication. Platelet serotonin concentrations were measured by HPLC.
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The fatal toxicity index (FTI) is the absolute number of fatal poisonings caused by a particular drug divided by its consumption figure. Consequently, it is a useful measure in evaluating toxicity of the drug and its relevance in fatal poisonings. In this study, we assessed the FTI of medicinal drugs in 3 years (2005, 2009, and 2013) in Finland. As the measure of drug consumption, we used the number of defined daily doses (DDD) per population in each year. There were 70 medicinal drugs in Finland for which the mean FTI expressed as the number of deaths per million DDD over the three study years was higher or equal to 0.1. The Anatomical Therapeutic Chemical (ATC) classification system was used for the classification of the active ingredients of medicinal drugs according to the organ or system which they act on. Of these 70 drugs, 55 drugs (78.6 %) acted on the nervous system (denoted by ATC code N), 11 (15.7 %) on the cardiovascular system (C), three (4.3 %) on the alimentary tract and metabolism (A), and one (1.4 %) on the musculoskeletal system (M). The nervous system drugs consisted of 20 psycholeptics, (ATC code N05), 20 psychoanaleptics (N06), eight analgesics (N02), six antiepileptics (N03), and one other nervous system drug (N07). The highest individual FTIs were associated with the opioids methadone, dextropropoxyphene, oxycodone, tramadol, and morphine; the antipsychotics levomepromazine and chlorprothixene; and the antidepressants doxepin, amitriptyline, trimipramine, and bupropion. Buprenorphine was not included in the study, because most of the fatal buprenorphine poisonings were due to smuggled tablets. A clearly increasing trend in FTI was observed with pregabalin and possibly with bupropion, both drugs emerging as abused substances.
The outpatient pharmacy database of the Henry Ford Hospital, Health Alliance Plan (HAP) was searched from 1/1/98 to 6/30/99 for mentions of the 10 most frequently used drugs for the treatment of insomnia listed in the National Disease and Therapeutic Index for 1987-1996. The 10 drugs were alprazolam, amitriptyline, clonazepam, doxepin, flurazepam, lorazepam, temazepam, trazodone, triazolam, and zolpidem. These were classified by their indication as antidepressant, anxiolytic, or hypnotic and the three indication groupings were compared on patient and prescription characteristics.
Detailed histopathologic nerve toxicity evaluations are justified to determine whether N -propyl amitriptyline has potential as a more sensory-selective local anesthetic at lower concentrations or as a predominantly sensory-selective neurolytic agent at higher concentrations.
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In adults with primary insomnia, doxepin 1 mg, 3 mg, and 6 mg was well-tolerated and produced improvement in objective and subjective sleep maintenance and duration endpoints that persisted into the final hour of the night. The side-effect profile was comparable to placebo, with no reported anticholinergic effects, no memory impairment, and no significant hangover/next-day residual effects. These data demonstrate that doxepin 1 mg, 3 mg, and 6 mg is efficacious in improving the sleep of patients with chronic primary insomnia.
Antidepressants belong to a variety of chemical and pharmacologic classes. Most require therapeutic drug monitoring, at least in certain circumstances, such as unexplained inefficacy or suspected toxicity. Several types of chromatographic methods have generally been used. This paper presents a fully automated, sensitive, and specific method for the therapeutic drug monitoring of 13 antidepressants of all classes (amoxapine, amitriptyline, citalopram, clomipramine, dothiepin, doxepin, fluoxetine, imipramine, maprotiline, mianserin, paroxetine, sertraline, trimipramine) and some of their respective active metabolites (nortriptyline, monodesmethylcitalopram, desmethylclomipramine, desipramine, norfluoxetine, desmethylmianserin, N-desmethylsertraline), based on the innovative turbulent-flow liquid chromatography (TFC) technology, coupled to tandem-mass spectrometry (MS/MS). The antidepressants were divided in two groups depending on their chromatographic properties, so that two injections would be necessary to screen all compounds (which is infrequent for therapeutic drug monitoring). Calibration curves ranged from 10 to 500 ng/mL. No significant memory effect was observed after the injection of a blank serum sample spiked at 500 ng/mL. The intra-assay and inter-assay precision CVs ranged from 0.4% to 12% and from 1% to 16%, respectively. The method was further validated by blindly analyzing Heathcontrol-Therapeutic Drugs Scheme samples (Cardiff Bioanalytical Services Ltd.) containing several antidepressants.
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Doxepin is a tricyclic antidepressant that is widely prescribed for the treatment of mild depression. In this study, hair samples collected from a patient receiving 25 mg of doxepin daily were analyzed. Doxepin was administered to the patient for 4 months (June 15 to October 15, 1996). Five hair samples were collected: 1 and 3 months after doxepin therapy began and 1, 3, and 5 months after drug therapy ended. Solid-phase extraction was employed to isolate doxepin and its major metabolite desmethyldoxepin from the hair matrix, and gas chromatography-mass spectrometry (GC-MS) was used for quantitation of both drugs. Six-point standard curves (0.25-20 ng/mg) were prepared for both compounds with an internal standard (doxepin-d3). The standard curves for doxepin and desmethyldoxepin were linear over the range reported and had correlation coefficients of 0.984 and 0.985, respectively. The limit of quantitation for both analytes was 0.25 ng/mg of hair. In addition, the replicate analysis of control hair preparations was performed at two levels (2 ng/mg and 15 ng/mg) to determine intra- and interday variability. Doxepin and desmethyldoxepin were not detected in the patient's sample collected 1 month after doxepin therapy began. The samples collected 3 months after doxepin therapy began and 5 months after drug therapy was terminated had detectable amounts of doxepin and desmethyldoxepin. The highest concentrations of doxepin (mean, 0.59 ng/mg) and desmethyldoxepin (mean, 0.40 ng/mg) were found 5 months after doxepin therapy began, which was also 1 month after the patient had stopped using the drug. Five months after doxepin therapy was terminated, the drug and its metabolite were still present in the patient's hair. The concentration of doxepin in hair was always significantly higher than the concentration of desmethyldoxepin.
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Only RCTs of therapeutic agents used in the prevention and treatment of people with atopic eczema of any age were considered for inclusion. Only studies where a physician diagnosed atopic eczema or atopic dermatitis were included.
The antipsychotics haloperidol, clozapine, ziprasidone, and the antidepressants amitriptyline, doxepin, trimipramine, citalopram, mirtazapine, as well as the anticonvulsive drug tiagabine reversibly reduced the steady-state pHi by up to 0.35 pH-units in concentrations of 5-50 microM. In contrast, venlafaxine, the anticonvulsants carbamazepine, clonazepam, gabapentin, lamotrigine, zonisamide, and the mood stabilizer lithium had no effect on neuronal pHi.