Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their complex association. Their interaction may be conceptualized and classified into 3 groups: pruritic diseases with psychiatric sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. Management of chronic pruritus is directed at treating the underlying causes and adopting a multidisciplinary approach to address the dermatologic, somatosensory, cognitive, and emotional aspects. Pharmcotherapeutic agents that are useful for chronic pruritus with comorbid depression and/or anxiety comprise selective serotonin reuptake inhibitors, mirtazapine, tricyclic antidepressants (amitriptyline and doxepin), and anticonvulsants (gabapentin, pregabalin); the role of neurokinin receptor-1 antagonists awaits verification. Antipsychotics are required for treating itch and formication associated with schizophrenia and delusion of parasitosis (including Morgellons disease).
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Although the manufacturer of the polyclonal fluorescence polarization immunoassay (FPIA) for tricyclic antidepressants (TCA) only recommends its use in the diagnosis of overdose, the assay is nevertheless widely used in therapeutic drug monitoring. Using plasma samples from 337 patients taking one of eight different tricyclic antidepressants, the authors investigated the performance of the TDx assay procedure for eight different TCAs by comparison to specific high-performance liquid chromatography (HPLC) assay methods. The regression correlation between the TDx assay value and that for active tricyclic measured by HPLC was poor (r2 < 0.9) for amitriptyline, clomipramine, dothiepin, and doxepin. The regression line for amitriptyline also had a significant positive y-axis intercept. Moreover, the TDx method overestimated the concentration of active drug to an extent that varied considerably between different TCAs and within the usual therapeutic range for a single TCA. The authors conclude that the TDx assay is probably satisfactory for routine TDM of desipramine, imipramine, nortriptyline, and trimipramine. However, it significantly overestimates therapeutic concentrations of amitriptyline, clomipramine, dothiepin, and doxepin. The use of TDx and HPLC assay methods by different laboratories for sequential therapeutic drug monitoring of TCAs in the same patient may confuse physicians and confound dose adjustment and patient management. Although their study shows that the TDx assay can give satisfactory therapeutic drug monitoring results for some drugs, the authors conclude that its use should be restricted to the evaluation of overdose as recommended by the manufacturer.
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We searched the Cochrane Schizophrenia Group Trials Register (March 2007), inspected references of all identified studies for further trials, contacted relevant pharmaceutical companies, drug approval agencies and authors of trials.
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After some positive results with prostaglandin inhibitors, we undertook a study in which we randomly placed patients on four different forms of therapy for their pruritus. The therapies included hydroxyzine with or without doxepin at night, pentoxifylline, indomethacin and topical moisturization with medium-strength topical steroids. All patients were evaluated for both subjective relief as well as side effects.
The present analysis provides further evidence that the current use of SSRIs is associated with a slightly decreased risk for AMI.
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We considered randomized trials comparing antidepressant drugs to placebo or an alternative therapeutic control for smoking cessation. For the meta-analysis, we excluded trials with less than six months follow-up.
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Five weeks of nightly administration of DXP 3 mg and 6 mg to adults with chronic primary insomnia resulted in significant and sustained improvements in sleep maintenance and early morning awakenings (with the exception of SE in the final quarter of the night on N29 for 3 mg [P=0.0691]). These sleep improvements were not accompanied by next-day residual effects or followed by rebound insomnia or withdrawal effects upon discontinuation. These findings confirm the unique profile of sleep maintenance efficacy and safety of DXP observed in prior studies.
Our 10 subjects' mean age was 35.8 +/- 3.179 years. Histamine wheal response was suppressed starting on minute 90 and the wheal width were back to >/= 7 mm(2 )on minute 270. Significant histamine reactivity difference between genders (P = 0.201) and atopic status (P = 1.000), which could be a source of bias in histamine STR, was not found among our subjects.
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A variety of antidepressants of different chemical classes were tested for their in vivo and in vitro activity at 5-HT1C receptors in the brain. Conventional tricyclic antidepressants (imipramine, desipramine, maprotiline, clomipramine, trimipramine, amitriptyline, nortriptyline, doxepin, amoxapine) as well as mianserin and trazodone were found to display high to low nanomolar affinity for 5-HT1C receptors. Antidepressants of other chemical classes and with other mechanisms of action (affecting amine uptake systems: fluoxetine, citalopram, sertraline, fluvoxamine, nomifensine, amineptine; or monoamine oxidase inhibitors: moclobemide, iproniazid) had negligible affinities (micromolar range) for 5-HT1C receptors, except fluoxetine. When tested in an in vivo rat model thought to reveal functional agonistic or antagonistic properties at 5-HT1C receptors, all antidepressants displaying high affinity for this receptor type (except clomipramine and trimipramine) were antagonists at 5-HT1C receptors. Antidepressants with a lower affinity for 5-HT1C receptors (except nomifensine) were inactive in this functional in vivo model. Taken together, these results suggest that antagonism at brain 5-HT1C receptors is a component of the antiserotonergic properties of a number of established antidepressants. In addition, the study confirmed that 5-HT1A receptors functionally interact with 5-HT1C receptors, which suggests that some degree of activity at 5-HT1A receptors may also be an important property for antidepressant activity.
The effect of combined treatment with doxepin and ethanol was tested in mice, rats and rabbits. Doxepin was given in a single dose (5 or 10 mg/kg) or chronically (10 mg/kg/d for 21 days). Doxepin did not affect ethanol toxicity and ethanol-induced impairment of rota-rod performance, but potentiated ethanol-induced hypothermia (only acutely) and prolonged ethanol-induced sleep in mice. Given acutely it potentiated the inhibitory effect of ethanol on locomotor activity in mice, while given chronically it counteracted the ethanol-induced sedation. Doxepin did not interfere with ethanol-induced EEG effects in rabbits, and prevented the development of tolerance to hypothermic, but not to hypnotic effects of ethanol in rats. In general, the interference of doxepin with ethanol was more pronounced after single doses of the drug than after chronic treatment.
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Only four large, randomized, double-blind, placebo-controlled clinical trials with definitive conclusions (grade A) support the use of topical antihistaminic agents, specifically topical doxepin, for relief of pruritus. Of seven grade B trials, four supported the efficacy of topical antihistamines while three refute their use in relieving pruritus. One grade B trial was inconclusive. All remaining trials (grade C) lacked placebo controls or randomization, or contained fewer than 20 patients in each treatment group.
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There was one trial each of moclobemide, sertraline and venlafaxine, two of fluoxetine, five of nortriptyline, and twenty trials of bupropion. In the bupropion trials, 18 had a placebo arm, two of which tested long-term use to prevent relapse. Nine of the bupropion trials have been published in full. Nortriptyline (five trials, OR 2.80, 95% CI 1.81 - 4.32) and bupropion (16 trials, OR 1.97, 95% CI 1.67 - 2.34) both increased 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 have failed to detect a long-term benefit.
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The objectives of this medicolegal case report are the following: 1) to present details of a chronic pain patient (CPP) who was placed on chronic opioid analgesic therapy (COAT), and subsequently overdosed on multiple drugs, some of which were not prescribed by his COAT physician; 2) to present both the plaintiff's and defendant's (the COAT prescriber) expert witnesses' opinions as to the allegation that COAT prescribing was the cause of death; and 3) based on these opinions, to develop some recommendations on how pain physicians can utilize the use of Controlled Substances Model Guidelines in order to protect the patient and themselves from such an occurrence.
To evaluate the efficacy and safety of doxepin 1, 3, and 6 mg in insomnia patients.
The findings from this study suggest the effective therapeutic approaches for itch. The major limitations are that there are small numbers of available RCTs and methodological differences across studies.
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Based on MR1 values, 10 patients were classified as EM (extensive metabolizers) and 1 patient as PM (poor metabolizer). During the study, after doxepin treatment, none of patients has changed phenotype status. However, MR2 values were statistically significantly higher than MR1.
This retrospective study reports on the clinical presentation of equine atopic skin disease and evaluates response to treatment with allergen-specific immunotherapy (ASIT) based on intradermal testing and/or serum testing. Computerized medical records from January 1991 to December 2008 yielded 54 horses included in the study. Presenting clinical signs (CS) included urticaria (n=28), pruritus (n=8) or both (n=18). Forty-one of 54 horses received ASIT, and response to ASIT (n=32) was evaluated via telephone survey. Eighty-four per cent (n=27) of owners reported that ASIT reduced their horse's CS; 59% (n=19) were able to manage CS by ASIT alone. Three horses (9%) were managed with ASIT in combination with doxepin and discontinued use of corticosteroids. There was no statistical significance between type of test performed and reported success of ASIT (χ(2) analysis, P=0.53). Ninety-three per cent (n=30) of owners reported use of antipruritic medications prior to starting ASIT; 57% (n=17) of these owners reported discontinuing those medications due to success of ASIT. Adverse effects were limited to swelling at the injection site, seen in 16% (n=5). Seventy-five per cent (n=24) of owners elected to discontinue ASIT after 6 months to 8 years (mean 2.2 years): 15 due to resolution of CS, six due to persistent CS, two because the horse was sold, and one due to cost. Ten owners reported no recurrence of CS after discontinuing ASIT; five had recurrence within a median of 2 years of discontinuing ASIT (range 1-12 years). Allergen-specific immunotherapy is a safe and effective way to manage equine atopic skin disease.
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A 50-year-old woman developed rhabdomyolysis and myoglobinuric renal impairment after an oral dose of 250 mg nitrazepam and 1,250 mg doxepin. Serum creatinine increased from 70 mumol/l to 472 mumol/l in two days. Serum creatine phosphokinase reached a maximal level of 391 mu kat/l (reference range less than 2.5 mu kat/l) on the third day and serum myoglobin was maximally 910 nmol/l (reference range less than 4.5 nmol/l) on the fourth day after the overdose. Passive and active movements of the knees and ankles became increasingly restricted, but the patient felt no muscle pain. Diuresis decreased to 20-22 ml/hour in spite of repetitive doses of furosemide, but was enforced to greater than 100 ml/hour by vigorous infusion of saline. Haemodialysis was avoided on this regimen. It is suggested that in patients intoxicated with nitrazepam and/or doxepin, rhabdomyolysis should be suspected when a rapidly increasing serum concentration of creatinine is found, even in the absence of muscle pain.
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A total of 19 women with detrusor overactivity and associated symptoms completed a double-blind placebo-controlled crossover study of doxepin. All patients had previously failed to respond to conventional pharmacotherapy. Doxepin was given at bedtime in a single 50 mg. dose for the first 2 weeks and, if needed, the dose was increased with 25 mg. in the morning for the last week of the 3-week treatment period, which was followed by 2 weeks of washout before crossover. The preference for doxepin to placebo was statistically significant (p less than 0.01). Doxepin caused a significant decrease in the nighttime micturition frequency and the nighttime incontinence episodes (p less than 0.05). Urine loss at the standardized 1-hour pad weighing test decreased significantly during treatment with doxepin although statistical significance (p equals 0.07) was not obtained. Cystometric parameters (first sensation and maximum cystometric capacity) improved significantly during treatment with doxepin (p less than 0.06 and less than 0.04, respectively). Side effects were frequent but mild. Suggestions for use of this tricyclic antidepressant in women with detrusor overactivity and possible mechanisms of action are discussed.
The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of mirtazapine are reviewed. Mirtazapine is a new anti-depressant that blocks presynaptic alpha 2-adrenergic receptors and postsynaptic serotonin type 2 and type 3 receptors. Mirtazapine has FDA-approved labeling for treatment of depression. Limited data suggest it may also have beneficial anxiolytic and sedative effects. The drug is rapidly and completely absorbed after oral administration. It is biotransformed by hepatic demethylation and is suitable for once-daily doses. In several clinical trials, patients receiving mirtazapine showed significantly greater improvement as measured by scores on the Hamilton Rating Scale for Depression (HAM-D) compared with patients receiving placebo. Mirtazapine has been shown to be equally efficacious as amitriptyline, clomipramine, and doxepin as assessed by scores on the HAM-D or other depression rating scales. Mirtazapine is well tolerated. The most commonly reported adverse effects associated with mirtazapine are somnolence, increased appetite, weight gain, and dizziness. Few drug-drug interactions have been reported. The recommended starting dosage is 15 mg/day administered in a single dose at bedtime. Mirtazapine seems to be an effective, well-tolerated antidepressant and may be effective for treating comorbid anxiety disorders.
We analysed 136 Caucasian depressed inpatients treated with amitriptyline, citalopram, clomipramine, doxepin, fluvoxamine, mirtazapine, paroxetine, sertraline and venlafaxine, who underwent weekly plasma concentration measurements, assessment of the severity of illness and side effects during their stay in the hospital. Patients were genotyped with respect to CYP2C9 alleles *1 and *2, the CYP2C19 alleles *1, *2 and *3 and the CYP2D6 alleles *1 to *9 and CYP2D6 gene duplication.
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In this work, three-phase liquid-phase microextraction (LPME) based on a supported liquid membrane (SLM) sustained in the wall of a hollow fiber was investigated with special focus on optimization of the experimental procedures in terms of recovery and repeatability. Recovery data for doxepin, amitriptyline, clomipramine, and mianserin were in the range of 67.8-79.8%. Within-day repeatability data for the four basic drugs were in the range of 4.1-7.7%. No single factor was found to be responsible for these variations, and the variability was caused by several factors related to the LPME extractions as well as to the final HPLC determination. Although the volume of the SLM varied within 0.4-3.1% RSD depending on the preparation procedure, and the volume of the acceptor solution varied within 4.8% RSD, both recoveries and repeatability were found to be relative insensitive to these variations. Thus, the handling of microliters of liquid in LPME was not a very critical factor, and the preparation of the SLM was accomplished in several different ways with comparable performance. Reuse of hollow fibers was found to suffer from matrix effects due to built-up of analytes in the SLM, whereas washing of the hollow fibers in acetone was beneficial in terms of recovery, especially for the extraction of the most hydrophobic substances. Several of the organic solvents used in the literature as SLM suffered from poor long-term stability, but silicone oil AR 20 (polyphenylmethylsiloxane), 2-nitrophenyl octyl ether (NPOE), and dodecyl acetate (DDA) all extracted with unaltered performance even after 60 days of storage at room temperature.
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Phantom pain phenomenon is a poorly understood but relatively common sequela of limb amputation that may result in significant psychological and physical morbidity. In this review, proposed pathoneurophysiological mechanisms for the development of phantom pain are reviewed as well as psychological mechanisms that may be involved. The authors recommend an integrated approach to management of chronic phantom pain that takes into consideration the multiple factors that may contribute to its etiology.
The central effect of olopatadine (((Z)-11-[3-dimethylamino)propylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic acid hydrochloride, CAS 140462-76-6, KW-4679) was studied in comparison with those of ketotifen and doxepin using spontaneous EEG and EEG spectral powers in conscious rats. Both ketotifen (20 mg/kg p.o.) and doxepin (20 mg/kg p.o.) caused drowsy patterns in spontaneous EEG characterized by slow waves of high amplitude at the frontal cortex, occipital cortex and amygdala, and by disappearance of the regularity in theta waves recorded from the hippocampus. In EEG spectral powers, both drugs caused a significant increase in the power densities of the delta band recorded from the frontal cortex, occipital cortex and amygdala. On the contrary, no visible changes were elicited by the treatment with olopatadine (20 mg/kg p.o.) in both spontaneous EEG and EEG spectral powers recorded from the frontal cortex, occipital cortex, hippocampus and amygdala. These results indicate that olopatadine provides no remarkable effect on the central nervous system.
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A 36-year-old white woman with a 20-year history of cutaneous, respiratory, and cardiovascular symptoms triggered by physical activity and by exposure to either heat or cold was evaluated. A routine evaluation for the cause of her condition was positive only for certain physical factors. Cutaneous testing for dermatographism, ice-cube challenge, and exposure to ultraviolet A and ultraviolet B light were negative. A methacholine skin test was positive. Sitting in a cold room (4 degrees C) induced micropapular wheals on exposed areas similar to those classically associated with cholinergic urticaria. Placing both feet in warm water (44 degrees C) induced similar but more intense cutaneous lesions at sites not exposed to heat, light headedness, and severe asthma. Exercise for 10 minutes caused confluent and punctate urticarial lesions. Simultaneous measurement of plasma histamine during cold and heat challenges revealed increases paralleling the course of symptoms. Repeat challenge with cold, heat, and exercise after beginning treatment with both H1 and H2 histamine antagonists resulted in marked reduction in symptoms; however, significant rises in plasma histamines were still noted.
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Peripheral anticholinergic activity of single acute doses of three tricyclic antidepressants (amitriptyline 50 mg, desipramine 50 mg, doxepin 100 mg) and placebo was assessed by several physiologic measures in normal male volunteers. Amitriptyline and doxepin produced similar significant depressions in salivary flow and finger sweating compared to placebo, while desipramine produced no change. Supine and standing blood pressures and standing pulse yielded significant differences among the drugs. Measures in at least three areas (salivation, perspiration, and pulse-blood pressure) offer a simple and reliable battery of tests for the peripheral autonomic effects of tricyclic antidepressants.
Although allergic contact dermatitis to topical preparations of doxepin has been published, systemic contact dermatitis from oral doxepin is more of a theoretical consideration and is rarely reported. We report a case of a patient with contact allergy to doxepin hydrochloride 5% cream who developed a systemic contact dermatitis to oral doxepin.
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The fit of the model to the concentration-time data was significantly improved when V/F was expressed as a function of weight ( P<0.05) and CL/F as a function of age ( P<0.05). Co-medication that inhibits P(450) isoenzymes lowered CL/F of doxepine by 15%.