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At least 19 recordsLinked to original sources

Doxepin incorporated into a dermatologic cream: an assessment of both doxepin antipruritic action and doxepin action as an inhibitor of papules, in allergen and histamine-caused pruritus.

"Doxederm", a 5% doxepin hydrochloride ("doxepin") cream, has been used for assessments on patients' response to histamine and allergens by means of a prick test. Parameters selected papule diameters, and pruritus intensity. Doxederm was applied: (a) immediately before tests, (b) 10 minutes after tests, and (c) 72 hours before tests. All test reactions have been compared to similar tests that had been performed with a placebo cream. Tests yielded the following findings: (1) a remarkable remission of pruritus when doxederm was applied according to above mentioned (a), (b), and (c) schedules; (2) no inhibition of papule size --should either antigens or histamine be administered, could be observed when doxederm was applied immediately before tests or 10 minutes after tests had been performed (p > 0.10 vs placebo); (3) an evident remission of papules when doxederm had been applied 72 hours before tests were performed. No difference, however, could be detected with patientś forearms placebo cream had been applied whereon (difference among previously observed papules, and papules observed 72 after doxederm application: p > 0.005. Difference between doxederm and placebo: p > 0.10). Pursuant to the above mentioned observations, it can be suggested that doxederm evidences a highly siwft response on pruritus. Doxederm local effect, however, does not alter histaminic responses. Responses, however, are likely to be altered after a doxederm percutaneous absorption.

Administration, Topical↗

Relief of pruritus in patients with atopic dermatitis after treatment with topical doxepin cream. The Doxepin Study Group.

BACKGROUND: 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. OBJECTIVE: The current study was undertaken to compare the efficacy and safety of topical 5% doxepin cream in relieving pruritus associated with atopic dermatitis. METHODS: A total of 270 patients with atopic dermatitis who had daily moderate to severe pruritus for at least 1 week were enrolled in the double-blind, vehicle-controlled, multicenter study. Treatment was randomly assigned: 5% doxepin cream or vehicle cream was applied twice on the day of the baseline visit and four times daily for the remainder of the 7-day trial. RESULTS: Relief of pruritus was achieved in 85% of doxepin-treated patients and 57% of vehicle-treated patients by day 7; a majority of these positive responses occurred during the first 24 hours. Pruritus severity scores demonstrated significantly greater improvement with topical doxepin at each study visit (p < 0.01). Visual analogue scales for pruritus severity and pruritus relief showed similar improvement in the doxepin-treated group. At each of three visits, the physician's global evaluation for relief of pruritus also showed significant improvement in the doxepin treatment group (p < 0.01). The physician's global evaluations of eczema significantly favored topical doxepin on day 7 (p < 0.01). Nineteen patients withdrew from the study because of adverse effects (doxepin, n = 16; vehicle, n = 3). The most commonly reported were localized stinging or burning (doxepin group, n = 39; vehicle group, n = 34) and drowsiness (doxepin group, n = 37; vehicle group, n = 3), all of which decreased in frequency and severity over time. CONCLUSION: Topical doxepin is effective in reducing pruritus in patients with atopic dermatitis. It has an apparent short-term low risk of major side effects or sensitization.

Administration, Cutaneous↗

Doxepin-cimetidine interaction: increased doxepin bioavailability during cimetidine treatment.

The influence of concurrent cimetidine administration on the disposition of doxepin was evaluated in 10 healthy volunteers. Each subject ingested 100 mg of doxepin on two different occasions, once while otherwise drug free and once while receiving cimetidine, 300 mg every 6 hours. Doxepin absorptive parameters--time to peak doxepin plasma concentration (2.3, control, vs. 2.4 hours during cimetidine co-administration) and peak concentration achieved (43.3. vs. 55.5 ng/ml)--were not changed during cimetidine administration. Likewise, doxepin elimination half-life was similar in the control state (12.5 hours) and during cimetidine administration (13.2 hours). However, doxepin area under the plasma concentration-time curve (AUC) was increased during concurrent cimetidine administration (533 vs. 695 ng/ml . hour; p less than 0.05), resulting in a trend toward decreased doxepin oral clearance (4404 vs. 3278 ml/min; 0.05 less than p less than 0.1). Relative bioavailability during concurrent cimetidine treatment was 123% of that during the control trial. Desmethyldoxepin AUC was no different between trials (478, control, vs. 433 ng/ml . hour during cimetidine ingestion). Plasma protein binding of doxepin was similar between trials (percent unbound; 10.5, control, vs. 11.2%) and therefore did not influence calculated AUC. These data indicate that doxepin relative bioavailability is increased during concurrent cimetidine administration and suggest that doxepin hepatic extraction is impaired by cimetidine after oral administration. During chronic doxepin therapy, addition of cimetidine to a therapeutic regimen may result in increased doxepin plasma concentration.

Absorption↗

The antipruritic effect of 5% doxepin cream in patients with eczematous dermatitis. Doxepin Study Group.

BACKGROUND AND DESIGN: Eczematous dermatitis is commonly characterized by intense pruritus. Current treatment modalities for this condition, regardless of its cause, are primarily directed at blunting the cutaneous inflammatory response and thereby providing relief of pruritus. To expand on our previous findings in atopic dermatitis, the present multicenter double-blind trial was conducted to evaluate the safety and antipruritic efficacy of 5% doxepin hydrochloride cream in patients with lichen simplex chronicus (n = 136), nummular eczema (n = 87), or contact dermatitis (n = 86). A total of 309 patients with moderate to severe pruritus were randomly assigned to apply either doxepin cream (n = 154) or vehicle cream (n = 155) to eczematous areas four times per day for a period of 7 days. Efficacy was assessed using a pruritus severity rating scale, a Physician's Global Evaluation for pruritus relief, and a Visual Analogue Scale for pruritus relief. RESULTS: Twenty-four hours after initiation of treatment, and continuing throughout the remainder of the study, patients treated with doxepin cream experienced significantly greater pruritus relief than did vehicle-treated patients as determined by all efficacy parameters (P < .002). Sixty percent of doxepin-treated patients experienced pruritus relief within 24 hours. The response rate increased to 84% by conclusion of the study. As judged by significant changes (P < or = .05) occurring in at least one assessment of efficacy, doxepin cream provided pruritus relief in all forms of eczematous dermatitis that were examined. The study medication was well tolerated. The two most common adverse effects, stinging at the site of application and drowsiness, were usually transient and mild to moderate in severity. CONCLUSION: Topical application of doxepin provides significant antipruritic activity with a favorable safety profile, suggesting a role for doxepin cream in the symptomatic treatment of pruritus associated with eczematous dermatitis.

Administration, Cutaneous↗

Comparison of cinnarizine, cyproheptadine, doxepin, and hydroxyzine in treatment of idiopathic cold urticaria: usefulness of doxepin.

Randomized double-blind trials using doxepin and several conventional antihistamines were carried out for treatment of patients with idiopathic cold urticaria. In the first double-blind trial, eight of nine patients preferred doxepin (10 mg three times daily) to cinnarizine (10 mg three times daily). In the second double-blind trial, the results of ice cube tests suppressing the effect of cyproheptadine (4 mg three times daily), doxepin (10 mg three times daily), and hydroxyzine (10 mg three times daily) did not statistically differ. However, doxepin was subjectively the most effective and it had fewer side effects than other treatments that were compared. Doxepin effectively suppressed the wheal and itching responses and shortened the duration of the wheal response in the ice cube test in all patients with cold urticaria who were studied.

Adolescent↗

Cis- and trans-isomers of doxepin and desmethyldoxepin in the plasma of depressed patients treated with doxepin.

Plasma levels of doxepin and desmethyldoxepin were measured in split samples of 20 depressed patients treated with doxepin by using a conventional extraction and gas chromatography method on a packed column (method 1) and derivation of secondary amine and gas chromatography on a capillary column, allowing the separation and simultaneous quantitation of the cis- and trans-isomers of the two compounds (method 2). We have found that significantly higher levels of desmethyldoxepin and of total drug are detected in plasma when the two isomers are separated and measured by method 2. We concluded that the plasma levels of doxepin reported in most previous studies were underestimated since the cis- and trans-isomers were not separated and included in the total drug concentration. Because the activity of the two isomers is different and their proportion varies in individual patients, we suggest that in future studies correlating plasma levels and the clinical effects of doxepin, both the cis- and the trans-isomers of doxepin and desmethyldoxepin be determined.

Chromatography, Gas↗

Plasma levels of the cis- and trans-isomers of doxepin and desmethyldoxepin after administration of doxepin to patients.

In depressed patients treated with doxepin (Sinequan), a 15:85% mixture of cis- and trans-isomers, plasma levels of the cis- and trans-forms of doxepin and desmethyldoxepin were measured using a GLC-method with a capillary column and a nitrogen detector. A gradual increase of the concentration of the products in the plasma is seen in the first days of administration. There is a remarkable variation from patient to patient in the steady-state concentrations of trans-doxepin and of cis- and trans-desmethyldoxepin. cis-Doxepin levels are always very low. It is suggested that for studies of correlation between plasma levels and therapeutic and toxic effects of doxepin, the isomers of the parent compound and its metabolite should be measured separately.

Doxepin↗

A controlled comparison of doxepin h.s. and doxepin q.i.d.

A controlled double-blind study of 40 depressed psychiatric outpatients who received doxepin either q.i.d. or h.s. showed that doxepin may be administered h.s. without loss of efficacy or increase in side effects. The patients who received doxepin h.s. felt significantly better rested in the morning than the patients who received doxepin in divided doses.

Adult↗

Doxepin in the treatment of duodenal ulcer. A double-blind clinical study comparing doxepin and placebo.

In the double-blind study of 51 patients with duodenal ulcer the effect of doxepin and placebo was evaluated. Complete healing of the ulcer was found in 19 of 23 patients after 4 weeks of treatment with 50 mg doxepin (83%) and in 14 of 27 patients given placebo (52%) (p less than 0.05). Two patients in the placebo group developed complications necessitating surgical intervention. No serious side effects were registered in the doxepin group.

Adult↗

Detection of doxepin and its major metabolite desmethyldoxepin in hair following drug therapy.

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.

Adult↗