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Fifteen healthy male volunteers (age range, 20-35 years) were divided into 3 subgroups and were studied following single oral administration of cetirizine at 10 mg (n = 5) and 20 mg (n = 5) or hydroxyzine at 30 mg (n = 5) using PET with 11C-doxepin. Each subject was scanned also following the administration of placebo. Binding potential and H(1)RO values were calculated in the prefrontal and anterior cingulate cortices. Subjective sleepiness was also measured, and the correlation to H(1)RO was examined for each antihistamine.
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Our results demonstrate a low affinity of fluvoxamine and a very high affinity of mirtazapine for the human brain H₁R in vivo. This study provides a basis for investigating the efficacy of new-generation antidepressants in central histamine systems.
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The bioavailability of mirtazapine is approximately 50%. Peak plasma concentrations are reached within 2.2 to 3.1 hours after single oral doses of 15 to 75mg and are dose-dependent. Mirtazapine is extensively metabolised in the liver; up to 85% of the drug is eliminated in the urine (up to 4% as unchanged drug) and the remaining 15% is eliminated in the faeces. The mean elimination half-life of mirtazapine is approximately 22 hours, making it suitable for once-daily administration.
A 46-year-old woman's antidepressant therapy was changed from doxepin to desipramine because of sedative side effects. Within ten days of initiation of desipramine, a pruritic, morbilliform rash developed. The rash extended despite attempts to continue therapy with a tartrazine-free desipramine as well as antihistamines and prednisone. The rash promptly improved when desipramine was discontinued. Classic drug eruptions are quite uncommon with tricyclic antidepressants. Tartrazine, a common additive in the food and drug industry, is implicated in a number of hypersensitivity reactions. Our report presents an apparent case of desipramine-induced drug rash independent of tartrazine, and discusses the nonassociation of tartrazine.
A total of 194 studies were found that were eligible for inclusion in our analysis. Of these, 177 focused on the treatment of MDD and 17 on the treatment of dysthymic disorder. We found that antidepressant therapy was significantly more effective than placebo in dysthymic disorder (risk ratio = 1.75; 95% CI, 1.49-2.04; P < .0001), while placebo response rates in dysthymic disorder trials were significantly lower compared to MDD trials (29.9% vs 37.9%, respectively; P = .042). Meta-regression suggested a statistically significant difference in the risk ratio of responding to antidepressants versus placebo when comparing studies either on dysthymic disorder or on MDD, suggesting a greater risk ratio for response in favor of antidepressant therapy versus placebo in patients with dysthymic disorder versus MDD (coefficient of -0.113; P = .007).
We conducted a cross-sectional analysis using insurance claims. We included patients with 1 outpatient claim with an International Classification of Diseases, 9(th)Edition, Clinical Modification (ICD-9-CM) code for idiopathic, other specified, or unspecified urticaria (ICD-9-CM 708.1, 708.8, or 708.9) and either (1) another of these claims 6 or more weeks later; (2) a claim for angioedema (ICD-9-CM 995.1) 6 or more weeks from the urticaria diagnosis; or (3) overlapping claims for 2 prescription medications commonly used for CIU.
The combined application of RTX and antidepressants produced a markedly prolonged nociceptive peripheral nerve block in rat sciatic nerves compared with either agent alone. However, the 2-drug regimen also elicited prolonged blockade of the motor function, although disproportionately less compared with the nociceptive modality, suggesting the existence of nontransient receptor potential vanilloid type 1-mediated mechanisms. The mechanisms through which RTX affects nociceptive signal transduction/transmission have yet to be fully elucidated.
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A universal gas chromatographic method for the determination of the most commonly used antidepressant drugs in 1 ml of serum is described. Prior to extraction the samples were washed with hexane at acid pH. After the hexane wash the drugs were extracted into hexane at pH approximately 10, and subsequently reextracted from the hexane into a 1% solution of formic acid in methanol. The methanolic phase was evaporated, the residue dissolved in isopropanol and analysed by gas chromatography with nitrogen detection on a 3% OV-225 column. Recoveries for amitriptyline, nortriptyline, clomipramine, desmethylclomipramine, doxepin, desmethyldoxepin, imipramine, desipramine, maprotiline, protriptyline, trimipramine and desmethyl-trimipramine were found to be 80% or higher. Limits of detection were found to be 5-10 ng/ml for teritary amines and 10-20 ng/ml for secondary amines. Interferences from some common basic drugs were investigated as well as interferences between different antidepressant drugs. Gas chromatographic data are given for 28 drugs and metabolites.
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Pruritus is one of the frustrating skin manifestations of advanced renal failure. Many options have been used for the management of uremic pruritus (UP) such as pregabalin. There are some studies that reported beneficial effects of pregabalin in reducing UP; however, most of them did not have a comparator arm. Therefore, we designed this study to compare antipruritic effects of pregabalin with doxepin in the management of pruritus in hemodialysis patients.
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Chronic treatment with doxepin (10 mg/kg) significantly reduced the secretion of corticosterone due to 5 min exposure to swim stress. Acute administration of doxepin evoked no effect. Pre-application of AM251 (1 mg/kg) abolished the ability of doxepin to reduce corticosterone secretion. Chronic administration of doxepin (10 mg/kg) led to a significant elevation of the endocannabinoids in the examined brain regions.
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During therapeutic use of doxepin, we have often observed unexpectedly low doxepin plasma concentrations in patients on moderate dosages, e.g. 100 to 200mg daily. While non-compliance seemed the most likely explanation, we present the data for 6 patients in whom we considered non-compliance unlikely. The data can be explained by hypothesizing that in some patients, there is not a linear dosage-plasma concentration relationship and that on a steady dosage, plasma concentrations are not always maintained. If these phenomena can be more carefully documented they may assume clinical importance; indeed for 2 of the patients studied the falling plasma concentrations on a steady dosage were associated with a recurrence of depression.
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Psychotropic medications are an important treatment approach to mental health disorders; such disorders are common in the elderly population. Elderly patients are more likely to experience adverse effects from these agents than their younger counterparts due to age-related changes in pharmacodynamic and pharmacokinetic parameters. Because of these factors, inappropriate use of psychotropic medications in elderly patients has become a focus of concern. In general an agent is considered inappropriate if the risk associated with its use exceeds its benefit. Implicit and explicit criteria for inappropriate use of medications in the elderly have been created and include psychotropic agents. These criteria vary in their make-up but the explicit criteria tend to agree that amitriptyline, doxepin, and benzodiazepines that have long half-lives are not appropriate. Although explicit inappropriate medication criteria have been in existence since 1991, elderly patients continue to receive inappropriate psychotropic medications. A wide array of factors may be responsible for this practice. Provider-related causes include deficits in knowledge, confusion due to the lack of a consensus on the inappropriate psychotropic criteria, difficulties in addressing an inappropriate medication started by a previous provider, multiple prescribers and pharmacies involved in the care of a patient, negative perceptions regarding aging, and cost issues. Patients may contribute to the problem by demanding an inappropriate medication. Finally, the healthcare setting may inadvertently contribute to inappropriate prescribing by such policies as restrictive formularies or lack of reimbursement for pharmacists' clinical services. Successful approaches to optimising prescribing have been either educational or administrative. Educational approaches (e.g. one-on-one sessions, academic detailing) seek to influence decision making, while administrative approaches attempt to enforce policies to curtail the undesired practice. The US Omnibus Budget Reconciliation Act of 1987, which improved psychotropic medication use in long-term care, is an excellent example of administrative intervention. More research specifically focused on the causes of inappropriate psychotropic medication use and methods to avoid this practice is needed before targeted recommendations can be made.
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Male rats were divided randomly into three groups: Control, doxepin 1 mg/kg, and doxepin 5 mg/kg. Rats received an i.p injection of doxepin for 21 days. Then the hippocampi were dissected for the measurement of the expression of BDNF, TNF-α, MAPK14, and AKT1 genes.
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Parenteral slow release formulations of doxepin in lipid vehicles were prepared in the form of suspensions of doxepin hydrochloride, doxepin pamoate and of poly D,L-lactid and poly D,L-lactid-co-glycolide microspheres containing doxepin hydrochloride. The drug particles or the drug containing microspheres were suspended in the vehicles isopropylmyristate or Miglyol. The dissolution rate of the different doxepin formulations was investigated in two flow through cells, a membrane and a non-membrane system, using either plain buffer or human plasma containing buffer as dissolution media, in order to study the influence of dissolution conditions on dissolution rates. An attempt was made to obtain biorelevant dissolution data. In the membrane system a linear relationship between time and percent drug dissolved during the period of investigation was found. Drug release was very slow and incomplete, especially when buffer was used as dissolution medium. Dissolution data from the nonmembrane system were fitted to monoexponential and biexponential models, respectively. Significant differences were found using different modes of formulation positioning and using the two dissolution media. The most rapid release rates were found when the formulations were spread on glass carriers and plasma was used as dissolution medium. It is suggested that this dissolution procedure has physiological relevance.
To evaluate the efficacy and safety of doxepin (DXP) 3 mg and 6 mg in adults diagnosed with primary insomnia.
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The primary purpose of this article is to review critically the literature about use of antidepressants during lactation. Strategies for the clinical management of depressed breast-feeding mothers are also suggested.
Only polysomnographic, parallel-group, randomized controlled drug trials were included; eligibility was determined by two independent authors.
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The primary treatment of urticaria involves identification and discontinuation of the offending agent. Addition of an antihistaminic agent may then be necessary to control pruritus. Because of variable response rates between patients, several alternative agents may need to be tried before the most effective regimen is found. Based on the studies reviewed here, it appears that low-dose doxepin (10 mg po tid) is a potentially effective and well-tolerated alternative in patients who do not respond to conventional antihistamines. This success may be in part due to the more potent H1- and H2-blocking properties associated with doxepin. Data regarding the topical use of doxepin are less convincing; however, the drug appears to have some clinical use for the short-term treatment of pruritus. Doxepin cream does not appear to be as effective as systemic therapy, and adverse effects (including sedation) and drug interactions are still problematic. Topical use may be best suited to conditions involving intact skin that do not require application to large areas of the body, thereby reducing systemic absorption and adverse effects.
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Selective serotonin reuptake inhibitor antidepressants should not be combined with monoamine oxidase inhibitor antidepressants because of the risk of serotonin syndrome.
A simplified and reliable fully automated production of (11) C-doxepin for clinical use was developed, allowing the synthesis of the tracer with high yield using a cGMP-compliant module and procedure. The success of this approach could make the PET tracer (11) C-doxepin more accessible for clinical studies.
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Atopic dermatitis is associated with severe pruritus for which effective topical treatment is lacking. As a potent H1 and H2 antagonist, the antipruritic effect of topical doxepin was first demonstrated in histamine-induced itch in nonatopic volunteers.
In a prospective 2-year follow-up study, 32 patients with panic disorder alone and 20 with panic disorder and concomitant depression were investigated. After controlled treatment with either imipramine or doxepin, patients received naturalistic treatment with antidepressants, benzodiazepines, and supportive psychotherapy. They were evaluated for anxiety, depression, and social disability at least every 3 months during the follow-up period. The data showed fluctuation of symptoms in both groups and a less favorable outcome for the patients with comorbid conditions. However, the overall outcome was better than that reported in other studies and indicates that panic disorder is quite responsive to appropriate treatment.
In this review, we discuss the management of chronic orofacial pain (COFP) patients with insomnia. Diagnostic work-up and follow-up routines of COFP patients should include assessment of sleep problems. Management is based on a multidisciplinary approach, addressing the factors that modulate the pain experience as well as insomnia and including both non-pharmacological and pharmacological modalities. Parallel to treatment, patients should receive therapy for comorbid medical and psychiatric disorders, and possible substance abuse that may be that may trigger or worsen the COFP and/or their insomnia. Insomnia treatment should begin with non-pharmacological therapy, to minimize potential side effects, drug interactions, and risk of substance abuse associated with pharmacological therapy. Behavioral therapies for insomnia include the following: sleep hygiene, cognitive behavioral therapy for insomnia, multicomponent behavioral therapy or brief behavioral therapy for insomnia, relaxation strategies, stimulus control, and sleep restriction. Approved U.S. Food and Drug Administration medications to treat insomnia include the following: benzodiazepines (estazolam, flurazepam, temazepam, triazolam, and quazepam), non-benzodiazepine hypnotics (eszopiclone, zaleplon, zolpidem), the melatonin receptor agonist ramelteon, the antidepressant doxepin, and the orexin receptor antagonist suvorexant. Chronic orofacial pain can greatly improve following treatment of the underlying insomnia, and therefore, re-evaluation of COFP is advised after 1 month of treatment.
The therapy of neuropathic pain may include the use of co-analgesics, such as antidepressants, however, their desired analgesic effect is associated with significant side effects. An alternative approach to this is their local administration which has been proposed, but there is little data regarding their local co-administration with morphine and the nature of the interaction between morphine and either doxepin or venlafaxine, two antidepressant drugs that have been recently used in neuropathic pain therapies.
The author reviews available data on tricyclic antidepressant (TCA) use in medically ill geriatric patients and data from controlled trials performed with physically healthy but depressed geriatric patients. Although these data point to the conclusion that medical illness appears to limit the use of TCAs in elderly patients, such agents as nortriptyline, desipramine, and doxepin can be used effectively. Guidelines are suggested to assist the clinician when confronted with this often complex and challenging patient population.
A close correlation exists between positron emission tomography (PET)-determined histamine H1 -receptor occupancy (H1 RO) and the incidence of sedation. Antihistamines with H1 RO <20% are classified as non-sedating. The objective was to compare the H1 RO of bilastine, a second generation antihistamine, with that of hydroxyzine.
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Old male Wistar rats were used in this study. Doxepin was administered intraperitoneally (1, 5 and 10 mg/kg) for 21 days. Passive avoidance learning test was used for evaluation of learning and memory. Rats received foot electrical shock on fifteen day, and step through latencies were evaluated one week after the electrical shock in retention phase.
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We considered randomized trials comparing anxiolytic or antidepressant drugs to placebo or an alternative therapeutic control for smoking cessation. We excluded trials with less than 6 months follow-up.
The study population included 297 patients with demographics showing 69% female, 71% Caucasian, a mean age of 52.94 (SD: 12.42), and an average 403 days of follow-up. The MPR for the total study population was 0.87 with 78% of the population having an MPR of ≥ 80% and 22% having an MPR of less than 80%. While there was no significant difference in MPR by different pharmaceutical classes, there were significant differences in the MPR by specific agents (p = 0.02), with nortriptyline having the lowest MPR of 0.79 and doxepin, fluoxetine, mirtazapine, and venlafaxine all having MPR over 0.90. There was also a trend toward a difference in MPR between Caucasians versus non-Caucasians, p = 0.055.