Discontinuation Rate of Doxepin in Insomnia Patients / 정신신체의학

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.

Impact of drug therapy on brachioradial pruritus

Abstract: Few studies have described therapeutic options in brachioradial pruritus. We describe a cross-sectional study of brachioradial pruritus patients treated in an outpatient unit. We reviewed medical records and interviewed brachioradial pruritus patients without indication for decompressive surgery, in order to access the perceptions of intensity of pruritus prior to treatment and response to therapy. We found that antidepressants and anticonvulsants were the most frequently prescribed drugs. Best reductions in pruritus were associated with its highest intensities prior to treatment, and with longer periods of therapy.

Trichotillomania: a case report with clinical and dermatoscopic differential diagnosis with alopecia areata

ABSTRACT Trichotillomania is a psychodermatologic disorder characterized by uncontrollable urge to pull one's own hair. Differential diagnoses include the most common forms of alopecia such as alopecia areata. It is usually associated with depression and obsessive-compulsive disorder. Trichotillomania treatment standardization is a gap in the medical literature. Recent studies demonstrated the efficacy of N-acetylcysteine (a glutamate modulator) for the treatment of the disease. We report the clinical case of a 12-year-old female patient who received the initial diagnosis of alopecia areata, but presented with clinical and dermoscopic features of trichotillomania. She was treated with the combination of psychotropic drugs and N-acetylcysteine with good clinical response. Due to the chronic and recurring nature of trichotillomania, more studies need to be conducted for the establishment of a formal treatment algorithm.

Psychotropics in different causes of itch: systematic review with controlled studies

Abstract Among the wide range of symptoms neglected or resistant to conventional treatments in clinical practice, itch is emerging gradually as a theme to be studied. Itch complaints and the negative effects in the quality of life are observed in several medical fields. Although the partially obscure pathophysiology, some researchers decided to check and test the use of psychotropic drugs in resistant itch to conventional topical treatments and antihistamines. The objective of this study was to evaluate scientific evidence in psychotropic use in the treatment of itch of various causes. This is a systematic review of scientific literature. The following databases were used: PubMed, Web of Science, Scopus and Scielo. Randomized controlled trials that should focus on treatment with psychotropic drugs of pruritus of various causes were the inclusion criteria. All articles were analyzed by the authors, and the consensus was reached in cases of disagreement. Fifteen articles were included after analysis and selection in databases, with the majority of clinical trials focusing on psychopharmacological treatment of itch on account of chronic kidney disease. Clinical trials with psychotropic drugs mostly indicated significant improvement in the itching. In most trials of chronic kidney disease as basal disease for itch, greater effectiveness was observed with the use of psychotropic drugs compared with placebo or other antipruritic. However, the small amount of controlled trials conducted precludes the generalization that psychiatric drugs are effective for itch of various causes.

Evaluation of itching sensation in chronic urticaria

Itching is the main symptom in urticaria and can cause a lot of suffering in chronic urticaria. To measure the itch threshold in patients with chronic urticaria before and after treatment and compare them with healthy control. The study was conducted at the department of dermatology, medical city teaching hospital Baghdad in the period from December 2009 to July 2010. A total of 30 patients with chronic urticaria [patients group] and 25 healthy individuals [control group], were included in the study. The age of patients ranged between 21years and 48 years with a mean of 30.96 years +/- 6.09 years [standard deviation]. In control group the age ranged between 20 years and 45 years with a mean of 31.40 years +/- 8.39 years [standard deviation]. Regarding gender, in the patients group 19 were females and 11 were males. While in the control group 14 were females and 11 were males. Electrical skin itch threshold was measured by square wave DC electrical stimulator at 13 points on the skin surface in patients and compared to the healthy controls. Doxepin was given to patients for 2 weeks, the itch threshold was then measured again. The severity of urticaria was also assessed before and after treatment. Patients with chronic urticaria had significantly lower threshold than the control subjects .The lowest threshold recorded in patients group was [1.292 +/- 0.399] volts in the left cheek, while in control group the lowest electrical cutaneous threshold was recorded in the chin [1.89 +/- 0.490] volts then left cheek [1.910 +/- 0.478]. The P-value was significance in all skin spots. The electrical cutaneous threshold increased after treatment in all spots tested after treatment. The increase was statistically significant in all tested the skin spots except in the back of the neck and xyphoid point. The total score decreased from 10.8 before treatment with doxepin to 1.5 after treatment. The individual parameters also decreased significantly after treatment. There were no significant side effects except drowsiness which improved after a few days even with continuation of treatment. Electrical skin itch threshold seems to be a simple test that aids in measuring the severity of itching in urticaria and may be used in the evaluation of drugs used for the alleviation of itching in urticaria and other skin diseases.

Determination of doxepin in whole blood by SPE-LC-MS/MS / 法医学杂志

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.

[Doxepin is more effective than nortriptyline and placebo for the treatment of diarrhea-predominant irritable bowel syndrome: a randomized triple-blind placebo-controlled trial]

The current treatment of IBS is often unsatisfactory and frustrating. Several controlled trials have demonstrated benefits of tricyclic antidepressants for irritable bowel syndrome, especially when pain is a prominent symptom but the efficacy of antidepressants in irritable bowel syndrome is controversial. The aim of this study was to compare the effect of doxepin and nortriptyline on diarrhea-predominant irritable bowel syndrome. Seventy-five patients with IBS according to Rome III criteria were treated for two months. The patients were randomly assigned to one of three groups treated with doxepin, nortriptyline or placebo. Subjects were assessed clinically one month and two months after treatment. The symptoms and adverse effects of the drugs were recorded in the questionnaire. The total score was considered as the number of the symptoms for each patient, which ranged between zero and six. Improvements in abdominal pain and bloating in the doxepin group were significantly higher than the nortriptyline or the placebo groups [P=0.001 and P=0.012, respectively]. However, improvement in diarrhea in patients on nortriptyline was significantly higher than the other groups [P=0.018]. The average improvement of symptoms in the patients after two months of treatment in doxepin, nortriptyline and placebo groups, respectively were 2.56, 2 and 0.6 [P<0.05]. Both doxepin and nortriptyline are effective for the treatment of diarrhea-predominant irritable bowel syndrome in a period of two months but doxepin seems to be more efficacious than nortriptyline in this regard. However, larger comparative trials are suggested

[ efficacy of Fluoxetin and Doxepin in treatment of irritable bowel syndrome]

This study compares the efficacy of Fluoxetine [serotonin-selective reuptake inhibitors-SSRI] with Doxepin [tricyclic antidepressants -TCAs-antihistaminic] in treatment of irritable bowel syndrome [IBS]. This randomized clinical trial recruited 200 patients who had referred to Kermanshah Imam Reza hospital during the period 2006-7. All the patients had been diagnosed with IBS bases on Rome II criteria of IBS and were randomized into two groups. The patients were then received treatment with anti-depresants Fluoxetine [20mg/day] in one group and Doxepin [20mg/day] in the other group for 12 weeks. In order to compare the quantitative variables, we used Leven and t-test. Chi-2 test was used for qualitative variables. There was no statistically significant difference between mean age in Fluoxetine [37 +/- 98 years] and Doxipin group [37 +/- 02 years]. The number of males in Fluoxitine and Doxipin groups was 40 and 42 respectively, which indicated no difference. Doxipin proved more effective on bloating, decreasing stool consistency, need for urgency and incomplete evaluation than Fluoxetine. On the other hand, the effect of Fluoxetin on abdominal pain and increasing of defecation was greater than Doxipin [p<0.05]. The figure for positive response to improvement of 50% was 67% and 52% for Doxipin and Fluoxetine groups respectively [p<0.022]. Our results indicated higher efficacy of Doxipin, the new TCA generation, in reducing most symptoms in patients with IBS, making it the recommended anti-depressant in treating IBS with no constipation

Low dose doxepin for treatment of pruritus in patients on hemodialysis

Pruritus is one of the frequent discomforting complications in patients with end-stage renal disease. We prospectively evaluated the effectiveness of doxepin, an H1-receptor antagonist of histamine, in patients with pruritus resistant to conventional treatment. A randomized controlled trial with a crossover design was performed on 24 patients in whom other etiologic factors of pruritus had been ruled out. They were assigned into 2 groups and received either placebo or oral doxepin, 10 mg, twice a day for 1 week. After a 1-week washout period, the 2 groups were treated conversely. Subjective outcome was determined by asking the patients described their pruritis as completely improved, relatively improved, or remained unchanged/worsened. Complete resolution of pruritus was reported in 14 patients [58.3%] with doxepin and 2 [8.3%] with placebo [P < .001]. Relative improvement was observed in 7 [29.2%] and 4 [16.7%], respectively. Overall, the improving effect of doxepin on pruritus was seen in 87.5% of the patients. Twelve patients [50.0%] complained of drowsiness that alleviated in all cases after 2 days in average. One patient refused to continue the treatment due to its sedative effect. We suggest that doxepin, a tricyclic antidepressant with anti-H1 receptor effect, can help improve pruritus resistant to antihistamines in end-stage renal disease patients who undergo hemodialysis. A low dose of doxepin is safe while effective and its main adverse effect, drowsiness, is temporary and can be easily tolerated by the patients

[Comparison between therapeutic effects of doxepine and hydroxyzine on resistant pruritic lesions due to sulfur mustard]

Chronic pruritus is one of the major complaints in chemically-injured patients. It may cause many psychological problems and consequently, decrease the patient's quality of life. The aim of this study is to compare the safety and efficacy of Doxepin and Hydroxyzine in treatment of chronic pruritus due to Sulfur Mustard. This randomized, double-blind clinical trial was carried out in Baqiyatallah hospital on 50 chemically-injured patients for a period of 4 weeks. Patients randomly divided into 2 groups, first group [mean age of 42.3 +/- 5.4 years old] received Doxepin capsules [10 mg/day] and the second group [mean age of 41.1 +/- 6.2 years old] received Hydroxyzine capsules [25 mg/day]. Pruritus score was measured by a standard questionnaire and Visual Analogue Scale [VAS]. The mean before and after-treatment puritus scores of Hydroxyzine, were 34.6 +/- 3.4 and 25.9 +/- 3.1, respectively [P<0.001] and those of Doxepin were 33.8 +/- 4.4 and 24.5 +/- 4.1, respectively [P<0.001]. Both drugs decreased pruritus, similarly [P = 0.245]. 18 patients in the hydroxyzine-received group and 11 patients in the Doxepin-received group were complaining from sedation as a side-effect [P=0.035]. Both drugs are of significant effectiveness in decreasing pruritus. However, considering its fewer side effects, Doxepin seems to be more useful in these conditions

Analysis of 37 drugs in whole blood by HPLC after solid phase extraction / 法医学杂志

OBJECTIVE@#To develop a specific, sensitive, reproducible SPE-HPLC method for the determination of 37 drugs in whole blood.@*METHODS@#With the doxapram as internal standard, Oasis column was used to extract drugs from whole blood. Two kinds of mobile phases were used in this study. Separations were achieved by a LiChrospher 100 RP-C18 (250 mm x 4.0 mm x 5 microm) column kept at 50 degrees C, the DAD detector was set at 230 nm and 250 nm.@*RESULTS@#The limit of detection were 1-30 ng/mL. The method showed excellent linearity and the linear correlation coefficient was > or =0.997 98. The relative standard deviation for between-day and within-day assay were <10%.@*CONCLUSION@#The method is effective, simple, reliable and has been used in real cases.

Effects of Antidepressants on Sleep / 대한정신약물학회지

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.

The Antipruritic Effect of 5% Doxepin Cream on Korean Patients with Eczematous Dermatitis / 대한피부과학회지

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.

Allergic Contact Dermatitis with Doxepin Hydrochloride Cream / 대한피부과학회지

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.

The Antipruritic Effect of Topical Doxepin Cream in Patients with Atopic Dermatitis / 대한피부과학회지

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.

Cefaléias do tipo tensional / Tensionðtype headaches

O termo cefaléia do tipo tensional (CTT) define as cefaléias primárias anteriormente denominadas de cefaléias tensionais, cefaléias de contração muscular, psicogênicas, psicomiogênicas, de estresse, essencial e de tensão. Essas denominações revelavam-se ambíguas e controversas incluindo simultaneamente aspectos clínicos e propostas de fisiopatologia, não sendo universalmente aceitas e dificultando a realização de estudos aceitos pela comunidade científica. Com a classificação internacional de cefaléias de 1988, as cefaléias do tipo tensional puderam ser melhor definidas e hoje, com a classificação de 2003, seus critérios diagnósticos estão mais claros e próximos da realidade observada na apresentação desses pacientes. As CTTs constituem-se no tipo mais prevalente de cefaléias primárias. Os seus mecanismos são controversos e sua fisiopatologia complexa e pouco esclarecida parecendo envolver processos centrais de disfunção antinocieptiva e periféricos de comprometimento muscular. Apresenta-se nas formas episódicas freqüentes e infrequentes, crônica e provável. O seu tratamento divide-se em preventivo e agudo. O tratamento preventivo inclui o uso de antidepressivos tricíclicos associados ou não ao uso de relaxantes musculares de ação central. O tratamento das crises utiliza analgésicos e/ ou antiinflamatórios não esteróides e/ ou cafeína e/ ou relaxantes musculares e deve ser limitado a duas vezes por semana uma vez que essa dor pode transformar-se em cefaléia crônica diária. Abordagens acessórias como terapia cognitivo-comportamental, técnicas de relaxamento, biofeedback e a melhora geral das condições de vida também são preconizadas. Há importante associação, na forma crônica, com distúrbios emocionais e do sono e o prognóstico é bom quando o paciente é corretamente tratado

Treatment of refractory irritable bowel syndrome with subclinical dosage of antidepressants / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effect of antidepressant on irritable bowel syndrome (IBS).</p><p><b>METHODS</b>A 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.</p><p><b>RESULTS</b>All 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).</p><p><b>CONCLUSIONS</b>Treatment of refractory IBS with subclinical dosage antidepressant is rational and effective, However a further study on its mechanisms is suggested.</p>