Doxepin hydrochloride cream with potent H1 and H2 blocker activity is a tricyclic antidepressant, which is structurally similar to phenothiazines, and also known to be a contact sensitizer and photosensitizer. We report a case of allergic contact dermatitis due to doxepin hydrochloride cream in a 75-year-old-man, who developed facial edema and eczema at the application sites (face, neck and upper trunk) within several hours of application of doxepin hydrochloride cream. Clinicians should be aware of the possibility of allergic contact dermatitis to doxepin cream, if the condition worsens with use of this medication.
Dermatitis, Allergic Contact* ; Dermatitis, Contact ; Doxepin* ; Eczema ; Edema ; Neck ; Phenothiazines

BACKGROUND: Optimal use of tricyclic antidepressants (TCAs) requires serum monitoring to determine if the appropriate therapeutic range has been attained and to assess possible side effects. This study was to evaluate the resolution capacity of the following four mobile phases which were previously reported; mobile phase I (methanol, acetonitrile and 5 mmol/L Na2HPO4: 41/15/44 by volume), II (methanol, acetonitrile and 5 mmol/L Na2HPO4,: 15/60/25 by volume), III (acetonitrile and 2-propanol: 95/5 by volume) and IV (methanol and n-butylamine: 99.5/0.5 by volume). METHODS: Amitriptyline (AT), nortriptyline (NT), imipramine (IMI) and doxepin (DOX) were used for the selection of appropriate mobile phase in high performance liquid chromatographic (HPLC) determination. TCAs were extracted from serum with hexane, isoamyl alcohol (99:1). The drug was re-extracted into 0.1 N HCl and an aliquot was injected into the HPLC. The analytical column was C-18 reversed phase column (3.9 mm x 30 cm; Waters, USA) with the flow rate of 1.5 mL/min. The UV detector signal was monitored at 254 nm. RESULTS: Mobile phase I disclosed 9.8-15.8 retention time (min), 5.1-8.8 capacity ratio and 1.0-2.2 resolution factors for the above four TCAs. Precision studies using this mobile phase demonstrated a coefficient variation of 2.4-4.7% in the concentration range of 500-125 ng/mL. Analytical recovery of AT and IMI was 85-90% at a concentration of 125 ng/mL and 250 ng/mL. CONCLUSIONS: Mobile phase I provided a reliable and excellent resolution of TCAs in the use of HPLC with the C-18 reversed phase column and UV absorbance detector.
2-Propanol ; Amitriptyline ; Antidepressive Agents, Tricyclic* ; Chromatography, High Pressure Liquid ; Doxepin ; Imipramine ; Nortriptyline

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 has been demonstrated in eczematous dermatitis. OBJECTIVE: We evaluated the efficacy and safety of topical 5% doxepin cream in relieving pruritus associated with atopic dermatitis. METHODS: A total of 44 patients with atopic dermatitis, who had moderate to severe daily pruritus for at least 1 week, were enrolled in the double-blind, vehicle-controlled study. Randomly assigned 5% doxepin cream or vehicle cream was applied four times daily for 7 days trial. RESULTS: Relief of pruritus was achieved in 85% of doxepin-treated patients and 57% of vehicle-treated patients by day 7. At each study visit, the physician's global evaluation for relief of pruritus showed significant improvement in the doxepin treatment group (p < 0.01). Visual analogue scales for pruritus severity and pruritus relief showed similar improvements in the doxepin-treated group. The most common adverse effects reported included localized erythema, xerosis (doxepin group, n=5; vehicle group, n=3) and drowsiness (doxepin group, n=2; vehicle group, n=0). CONCLUSION: Topical doxepin is effective in reducing pruritus in patients with atopic dermatitis. It has apparently a short-term low risk of major side effects or sensitization.
Dermatitis, Atopic* ; Doxepin* ; Eczema ; Erythema ; Humans ; Pruritus ; Sleep Stages ; Weights and Measures

BACKGROUND: Eczematous dermatitis is associated with severe pruritus, but there are only a few effective treatment modalities. Preliminary studies suggest that topical application of doxepin cream is effective in the treatment of eczematous dermatitis. OBJECTIVE: This study was undertaken to evaluate the efficacy and safety of topical 5% doxepin cream in reducing ruritus associated with eczematous dermatitis in Korea. METHODS: A total of 62 patients with eczematous dermatitis, who daily experienced severe pruritus for at least 1 week, were enrolled in the study. Five percent doxepin cream was applied twice a day on the baseline visit, and four times daily for up to 7 days. We evaluated pruritus scores using visual analog scales, which consisted of a 100-mm horizontal line labeled "no itch" and "worst itch imaginable" at opposite ends. RESULTS: Pruritus scores evaluated by patients revealed significantly-better improvement on each visit day. Furthermore, there was a significant decrease in the pruritus scores and erythema evaluated by physicians on each visit day. Furthermore, the most common adverse effects were a stinging sensation and aggravation of erythema at the site of application. CONCLUSION: Five percent doxepin cream is safe and effective in reducing pruritus in patients with eczematous dermatitis.
Bites and Stings ; Doxepin* ; Eczema* ; Erythema ; Humans ; Korea ; Pruritus ; Sensation ; Visual Analog Scale

Solar urticaria is an uncommon disorder characterized by pruritus, erythema and whealing occurring minutes after exposure to sunlight or artificial radiation, and generally resolves in a few hours. A 46-year-old woman presented with a 2-year history of pruritus and whealing, which occurred immediately after exposure to sunlight. Phototesting elicited urticarial reactions in the UVA and visible sepectra. The results of passive and reverse passive transfer studies were all negative. The patient was treated with cetirizine, doxepin and prednisolone. After 2 months of the treatment, the symptoms did not appear.
Cetirizine ; Doxepin ; Erythema ; Female ; Humans ; Middle Aged ; Prednisolone ; Pruritus ; Sunlight ; Urticaria*

PURPOSE: To compare the inhibitory effects of various tricyclic antidepressants (TCAs) on contractile response of the rat vas deferens to electrical stimulation of hypogastric nerve. MATERIALS AND METHODS: A total of forty Spraque Dawley rats (weight 300-350gm) were divided into 8 groups (n=5 in each): doxepine, amitriptyline, trimipramine, desipramine, imipramine, clomipramine, protriptyline, and prazosin treated groups. Before (baseline pressure) and 20 minutes after intravenous injection of each agent (0.1-, 1-, 10-, and 20-fold of therapeutic doses for human in each agent), the hypogastric nerves, iden tified under operative microscope, were electrically stimulated with rectangular pulses of 0.5 mseconds duration, 10 Hz, and 10 V for 10 seconds. Dose of drug administered was gradually increased in order of 0.1- to 20-fold dose. RESULTS: All drugs tested in this study caused dose-dependent inhibition of the rat intravasal pressure induced by the electrical stimulation of hypogastric nerve. Inhibitory potency of each drug was doxepine (88.5% and 96.5% at 10- and 20-fold dose)> OR = amitriptyline (76.8% and 91.8%)>clomipramine (66.7% and 74.4%)> OR =imipramine (48.2% and 67.0%)=prazosin (45.6% and 63.5%)=trimipramine (52.7% and 65.4%)> OR =desi pramine (45.3% and 49.0%)> protriptyline (18.9% and 19.9%). CONCLUSIONS: Inhibitory effects of TCAs on contractile response of the rat vas deferens to electrical stimulation of hypogastric nerve would increase in proportion to their potency of alpha1-adrenoceptor blocking actions.
Amitriptyline ; Animals ; Antidepressive Agents, Tricyclic* ; Clomipramine ; Desipramine ; Doxepin ; Electric Stimulation* ; Humans ; Imipramine ; Injections, Intravenous ; Prazosin ; Protriptyline ; Rats* ; Trimipramine ; Vas Deferens*

OBJECTIVES: We aimed to investigate the discontinuation rate and reasons of doxepin base prescription pattern in insomnia outpatients of psychiatry department of a university hospital. METHODS: 534 patients prescribed doxepin were screened. 201 patients were included and reviewed for their medical records retrospectively. The discontinuation rate and reasons of doxepin after 2 months of prescription were investigated. Patients were divided into three groups according to the prescription patterns. The initial group, prescribed doxepin as the first hypnotic, the add-on group, prescribed doxepin while maintaining existing hypnotics, and the switching group, prescribed doxepin after discontinuation of existing hypnotics. RESULTS: The discontinuation rate after 2 months of prescription of doxepin was 56.2%. There were significant differences in the discontinuation rate among three groups. The initial group had the highest while the add-on group had the lowest (p=0.018). In reasons for discontinuation of doxepin among three groups, lack of efficacy (p < 0.001) and adverse events (p < 0.001) were significantly higher in the add-on group. In the initial group, patient's refusal (p=0.022) and unknown or loss to follow up (p < 0.001) were significantly higher. CONCLUSIONS: The results of this study suggested that add-on is superior than switching method and gradual reduction of existing hypnotics is necessary to maintain doxepin treatment and prevent adverse events. Additional large scale prospective studies are needed to evaluate various factors and risks of discontinuation of doxepin.
Doxepin ; Follow-Up Studies ; Humans ; Hypnotics and Sedatives ; Medical Records ; Methods ; Outpatients ; Prescriptions ; Prospective Studies ; Retrospective Studies ; Sleep Initiation and Maintenance Disorders

The diverse effects of antidepressants on sleep are mediated by their agonistic or antagonistic properties on specific neurotransmitters: the catecholamine, serotonergic, cholinergic, and histaminergic neurotransmitter systems, which also regulate the timing and cycling of sleep. Therefore, antidepressants can have both class- and compound-specific effects on sleep/wake dynamics, sleep stages, and on motor control during sleep. For these reasons, the sedating or wake-promoting effects of these medications are important factors influencing specific drug selection. As these sleep-related effects may in turn influence both medication compliance as well as the course of the disease state itself, it is important for clinicians to understand and predict the possible effects of antidepressants on sleep. Some antidepressants, such as amitriptyline, doxepine, trazodone, and mirtazapine, possess sedating properties and improve sleep continuity via alpha-1 adrenoceptors and histamine H1 receptor blockade, combined with 5HT(2A/2C) receptor blockade. Other antidepressants, such as SSRI, SNRI and MAOIs, worsen sleep and may cause insomnia, an effect which may be linked to facilitation of 5HT(2A/2C) receptors. The majority of antidepressants are REM (rapid eye movement) suppressants, though some, such as nefazodone, bupropion, and mirtazapine, lack REM-suppressing effects. On the other hand, the effects of antidepressants on slow wave sleep (SWS) are much less consistent than their effects on REM sleep. Available data suggest that antidepressants, including some TCAs, and trazodone, increase SWS, possibly as a function of their 5-HT(2A/2C) receptor antagonism. In contrast, antidepressants lacking 5-HT(2A/2C) receptor antagonist effects, including SSRIs, SNRIs and MAOIs, may produce no change or even decrease in SWS. Knowledge of the effects of antidepressants on sleep will be helpful in estimating the sleep disturbance caused by these compounds, and can thus help in the selection of appropriate compound for individual patients.
Amitriptyline ; Antidepressive Agents* ; Bupropion ; Doxepin ; Hand ; Humans ; Medication Adherence ; Neurotransmitter Agents ; Receptors, Adrenergic ; Receptors, Histamine H1 ; Sleep Initiation and Maintenance Disorders ; Sleep Stages ; Sleep, REM ; Trazodone

OBJECTIVETo investigate the effect of antidepressant on irritable bowel syndrome (IBS).

METHODSA self-control and follow-up study on subclinical dosage of antidepressants therapy (fluoxetine 10 mg/d, paroxetine 10 mg/d or doxepin 45 mg/d) for 9-12 wks in 46 patients with refractory IBS symptoms according to Rome II criteria was performed, the clinical outcomes were evaluated by scales changes of symptom-related-anxiety, severity index of symptom, and quality of life specific of IBS, as well as general psychiatric health by SCL-90 during treatment and follow-up periods.

RESULTSAll 46 cases completed therapy and first follow-up unit (12 wks after treatment) (FFU), at the end of FFU, clinical symptoms in all patients were improved (P < 0.01). Comparison of the scores of symptom-related-anxiety, index of symptom, and quality of life specific of IBS at the end of FFU with that at basal level, indexes of the severity (3.4 +/- 1.5 vs 1.8 +/- 0.84) and frequency (3.8 +/- 1.60 vs 2.0 +/- 0.76) of symptoms were subsided significantly (P < 0.01, respectively); the scores of symptom-anxiety questionnaire including body anxiety (16.04 +/- 1.65 vs 10.83 +/- 1.64, P < 0.001), cognitive anxiety (18.78 +/- 2.12 vs 11.17 +/- 1.89, P < 0.001), fear (15.80 +/- 1.76 vs 10.78 +/- 1.85, P < 0.001) and avoiding (15.47 +/- 1.53 vs 10.16 +/- 1.59, P < 0.001) were also subsided significantly. In the meantime, IBS-QoL improved significantly (P < 0.05), dysphoria, body image, interference with activity, health worry, social reaction and overall scores were improved significantly (P < 0.01, respectively). The status of general psychiatric health was also improved significantly (P < 0.01).

CONCLUSIONSTreatment of refractory IBS with subclinical dosage antidepressant is rational and effective, However a further study on its mechanisms is suggested.

Adult ; Antidepressive Agents ; administration & dosage ; Doxepin ; administration & dosage ; Female ; Fluoxetine ; administration & dosage ; Follow-Up Studies ; Humans ; Irritable Bowel Syndrome ; drug therapy ; Male ; Middle Aged ; Paroxetine ; administration & dosage ; Quality of Life

OBJECTIVE: To develop a method of SPE-LC-MS/MS for the determination of doxepin in whole blood. METHODS: After solid phase extraction, the samples were identified by LC-MS/MS. Positive ion electrospray ionization mode and multiple reaction monitoring (MRM) mode was selected. Amitriptyline was used as internal standard. The m/z of doxepin: 280-->107, 280-->235 and 280-->220. The m/z of amitriptyline: 278-->233. The retaining time of doxepin and amitriptyline were 15.15 and 16.94 min, respectively. RESULTS: The calibration curve was linear among the concentration of doxepin range from 0.005 to 1.00 microg/mL. The linear correlation equation was y = 3.2047x + 0.0339, the correlation coefficient was 0.9996. The detection limit of doxepin was 0.001 microg/mL and average recovery rate was 78.0%-82.9%. The relative standard precision for within-day and between-day were less than 2.55% and 5.90%, respectively. CONCLUSION The method is effective, simple, reliable and can be used in the determination of doxepin in whole blood.
Amitriptyline/blood* ; Antidepressive Agents, Tricyclic/poisoning* ; Biomarkers/blood* ; Chromatography, Liquid/methods* ; Doxepin/poisoning* ; Drug Overdose ; Forensic Toxicology ; Humans ; Reproducibility of Results ; Sensitivity and Specificity ; Solid Phase Extraction/methods* ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry/methods*