Doxepin Group Research Articles

Doxepin is more effective than zolpidem in improving executive function in patients with insomnia disorder.

Patients with primary insomnia were randomly assigned to receive doxepin 6mg/dayorally or zolpidem 5-10mg/day orally. Polysomnography (PSG) and the Pittsburgh Sleep Quality Index (PSQI) were used at baseline and after the 8-week treatment to compare clinical efficacy in the two groups. Safety was assessed using the Treatment Emergent Symptom Scale (TESS). Executive function was evaluated using the Wisconsin sorting card test (WSCT). Of 120 patients enrolled in the study, 60 participants were assignedto each group. A total of 109 participants (53 in the doxepin group and 56 in the zolpidem group) completed the study. After treatment, the wake after sleep onset (WASO) and total sleep time (TST) values in the doxepin group were 80.3 ± 21.4min and 378.9 ± 21.9min, respectively, which were significantly better than those in the zolpidem group (132.9 ± 26.5min and 333.2 ± 24.2min, respectively; (P < 0.05)). The sleep onset latency (SOL) value in the zolpidem group (20.3 ± 4.7min) was significantly better than that in the doxepin group (28.2 ± 5.6min; P < 0.05). The sleep efficiency (SE) in the doxepin group was 77.8 ± 4.2%, which was significantly better than that in the zolpidem group (68.6 ± 5.0%; P < 0.05). The PSQI score of the doxepin group was 6.1 ± 1.1, which was significantly lower than that in the zolpidem group (7.9 ± 1.9; P < 0.05). The treatment adverse eventsin the doxepin group was 23.3%, which was significantly higher than that in the zolpidem group (13.3%; P < 0.05). The WSCT showed a significant improvement in persistent errors (PE), random errors (RE), and categories in the two groups after 8-week treatment, and the improvement in RE and the categories was more obvious in the doxepin group (P < 0.05). Both doxepin and zolpidem were found to be effective in improving sleep quality, but the effects exhibited different patterns. Doxepin improved executive function more effectively than zolpidem in patients with insomnia disorder.

Stigma and Efficacy of Zhizhu Kuanzhong Capsules Versus Doxepin in the Treatment of Refractory Functional Dyspepsia: A Randomized Controlled Trial.

Stigma related with antidepressants is prevalent in patients with functional dyspepsia. It affects medication compliance and efficacy. Herbal medicine acquired a deep-rooted cultural identity in relieving dyspeptic symptoms in Asians. The research was designed to compare the effectiveness of Zhizhu Kuanzhong capsules (ZZKZ) versus doxepin hydrochloride (doxepin) on alleviating stigma and medication nonadherence among patients with refractory FD (rFD). Patients with rFD from February 2021 to February 2022 were randomly allocated to receive either doxepin (n = 56) or ZZKZ (n = 57) combined with omeprazole for 4 weeks. Medication possession ratio (MPR), the disease- and medication-associated stigma were analyzed. The scales were utilized to assess dyspeptic symptoms (Leeds Dyspepsia Questionnaire) and psychological conditions (Generalized Anxiety Disorder Questionnaire and Patient Health Questionnaire). The MPR values for ZZKZ were significantly higher than those for doxepin (P < 0.001). The stigma scores decreased in ZZKZ group while increased in doxepin group compared to baseline after treatment. The proportion of patients showing ZZKZ-associated stigma was significantly lower than doxepin-associated stigma (P < 0.001). The MPR values were negatively correlated with post-treatment stigma scores in both groups (P < 0.001). Dyspeptic symptoms and psychological condition were improved in both groups after treatment, with no significant difference on post-treatment Leeds Dyspepsia Questionnaire, Generalized Anxiety Disorder Questionnaire, or Patient Health Questionnaire scores between 2 groups. ZZKZ is superior to doxepin in alleviating stigma and medication non-adherence, with comparable efficacy in improving dyspeptic symptoms and psychological condition of patients with rFD.

Comparison of gabapentin and doxepin in the management of uremic pruritus: A randomized crossover clinical trial.

Gabapentin and doxepin are well-known treatments of uremic pruritus in hemodialysis patients but no head-to-head studies were conducted to date. The aim of this trial is to compare the efficacy and the tolerability of gabapentin and doxepin in the treatment of uremic pruritus in hemodialysis patients. A single-blind crossover randomized trial was conducted that included hemodialysis patients with uremic pruritus. Patients were randomized to receive 10 mg doxepin daily or 100 mg gabapentin for 4 weeks and the two groups were treated conversely for another 4 weeks after a 4-week washout period. Eighty-five patients were screened for eligibility. Thirty-one met the inclusion criteria and four were excluded. Sixteen patients agreed and signed the consent and two withdrew from the study. VAS scores at baseline were 6.71 and 6.14, and dropped to 0.57 and 2.35 at week 4 in the gabapentin and doxepin groups, respectively. Mean scores of the 5-Domain Itch Scale (5-D) at baseline were 14.71 and 14.64, and dropped to 5.78 and 7.57 at week 4 in the gabapentin and doxepin groups, respectively. Mean scores of the Dermatology Life Quality Index (DLQI) at baseline were 9.6429 and 8.7857, and dropped to 0.71 and 3.35 at week 4 in the gabapentin and doxepin groups, respectively. Reductions in Visual Analog Scale (VAS), 5-D and DLQI were statistically significant (P < .05). No serious side effects were recorded. Limitations of this study include single-blind design, small number of included cases and lack of placebo control. Gabapentin was more effective than doxepin in decreasing uremic pruritus severity and improving quality of life of these patients.

Antidepressant polypharmacy and the potential of pharmacokinetic interactions: Doxepin but not mirtazapine causes clinically relevant changes in venlafaxine metabolism

BackgroundTo uncover pharmacokinetic interactions between venlafaxine and doxepin or mirtazapine in a naturalistic sample. MethodsA therapeutic drug monitoring database containing plasma concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODVEN) was analyzed. We included 1067 of 1594 patients in the analysis. Three study groups were considered; a group of patients under venlafaxine without confounding medications, V0 (n = 905), a group of patients co-medicated with doxepin, VDOX (n = 25) and a second group, co-medicated with mirtazapine, VMIR, n = 137. Plasma concentrations of VEN, ODVEN and the clinically relevant active moiety, sum of venlafaxine and O-desmethylvenlafaxine (ODVEN) (AM), as well as dose-adjusted plasma concentrations (C/D) were compared. ResultsMedian concentrations in the doxepin group showed 57.7% and 194.4% higher values for AM and VEN respectively; these differences were statistically significant (p < 0.001 for AM and p = 0.002 for VEN). Similar differences were detected for C/D concentrations of active moiety and VEN (p < 0.001 and p = 0.001) with higher values also in the doxepin group. The ratios ODVEN/VEN were lower in the doxepin group (p < 0.001). A co-medication with mirtazapine did not cause any changes in venlafaxine metabolism. ConclusionsHigher concentrations for VEN and AM imply an inhibiting effect of doxepin on the metabolism of venlafaxine, although the huge variability of concentrations has to be taken into account. It is recommended to monitor plasma concentrations in combination treatment to avoid problems in safety and efficacy. LimitationsDespite the large size of our study sample, the naturalistic nature of this data may arise some concerns of information bias potentially resulting from non-standardized data recording.

Comparison of pregabalin with doxepin in the management of uremic pruritus: a randomized single blind clinical trial.

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. Seventy-two patients suffering from UP were randomly assigned to receive pregabalin (50 mg every other day) or doxepin (10 mg per day) for 4 weeks. Severity of pruritus and its effect on quality of life were assessed by visual analog scale (VAS), 5-D itch scale and dermatology life quality index (DLQI) at baseline and after 1 week, 2 weeks and 4 weeks of the treatment. Mean scores of the VAS decreased from 7.5± 1.4 and 7.1 ± 1.3 at baseline to 2.1 ± 2.6 and 4.2 ± 2.6 at the end of the study (P < 0.001) in the pregabalin and doxepin groups, respectively. Similarly, pregabalin significantly reduced mean scores of the 5-D itch scale and the DLQI compared to doxepin. The most reported side effect in each group was somnolence which occurred in similar rates in the both groups. Pregabalin was more effective than doxepin in reducing the severity of uremic pruritus and improving the quality of life of patients in this study, so we suggest that clinician can consider pregabalin prior to using antihistamine drugs in the management of severe itch in hemodialysis patients.

Neurotoxicity of intrathecal doxepin in rats

Objective To investigate the neurotoxicity of intrathecal (IT) doxepin in rats.Methods Twenty-four adult male Wistar rats weighing 250-300 g in which intrathecal micro-catheter was successfully implanted without complications were randomly divided into 4 groups ( n =6 each):control group ( group N ) and 3 doxepin groups receiving IT doxepin 40,20 and 10 mmol/L 0.2 μl/g respectively (groups D40,D20,D10 ).In N group normal saline was injected IT instead of doxepin.The animals were killed at 6 h after IT administration.The lumbar segment of the spinal cord was removed for microscopic examination and determination of myelin basic protein (MBP) content in the spinal cord using a double-antibody sandwich (ELISA).Results The severity of neuronal damage and decrease in MBP content in the spinal cord induced by IT doxepin were dose-dependent.Conclusion The neurotoxicity induced by IT doxepin is dose-dependent. Key words: Doxepin; Injections, spinal; Drug toxicity

Comparison of Hydroxyzine and Doxepin in Treatment of Pruritus Due to Sulfur Mustard

To compare the safety and efficacy of doxepin and hydroxyzine in the treatment of chronic pruritus due to exposure to sulfur mustard. In a randomized, double-blind safety and efficacy study, 50 patients with chronic pruritus were given either doxepin 10 mg/d or hydroxyzine 25 mg/d for 4 weeks. Pruritic score was calculated for each patient before treatment and 1 month after. After treatment, the mean pruritic scores +/- SD of the hydroxyzine and doxepin groups were 16.7+/-2.3 and 17.8+/-2.5, respectively. The severity of pruritus was decreased in 80% of patients in the hydroxyzine group and 75% in the doxepin group (P=.786). Eighteen patients in the hydroxyzine group and 14 patients in the doxepin group reported sedation. Both hydroxyzine and doxepin are effective and have equivalent results in controlling the symptoms of patients with chronic pruritus due to exposure to sulfur mustard.

Doxepin in the treatment of primary insomnia — A placebo-controlled, double-blind, polysomnographic study

BACKGROUND Over recent years, the use of antidepressants for the symptomatic treatment of insomnia has grown substantially, but controlled studies are still lacking. Our study is the first investigation to prove objective efficacy and tolerability of low doses of a sedating antidepressant in a randomized, double-blind, and placebo-controlled manner in patients with primary insomnia. METHOD Forty-seven drug-free patients meeting DSM-IV criteria for primary insomnia (mean +/- SD duration of complaints = 11.2+/-9.7 years) received either 25-50 mg of the tricyclic antidepressant doxepin or placebo for 4 weeks followed by 2 weeks of placebo withdrawal. Sleep was measured by polysomnography at baseline and the first night of application, at 4 weeks of treatment and the first to third night of withdrawal, and after 2 weeks of withdrawal. RESULTS In the doxepin-treated patients who completed the study (N = 20, 47.6+/-11.3), medication significantly increased sleep efficiency after acute (night 1, p < or = .001) and subchronic (night 28, p < or = .05) intake compared with the patients who received placebo (N = 20, 47.4+/-16.8 years of age). Latency to sleep onset was not affected since the patients had normal baseline sleep latencies. Investigators found doxepin to cause significantly (p < or = .05) better global improvement at the first day of treatment. Patients rated sleep quality (p < or = .001) and working ability (p < or = .005) to be significantly improved by doxepin during the whole treatment period. Overall rebound in sleep parameters was not observed, but patients with severe rebound insomnia were significantly more frequent in the doxepin group (night 29, p < .01, night 30, p < or = .01; night 31, p < or = .05). No significant group differences in side effects were found, but 2 doxepin-treated patients dropped out of the study due to specific side effects (increased liver enzymes, leukopenia, and thrombopenia). CONCLUSION The results support the effectiveness of low doses of doxepin to improve sleep and working ability in chronic primary insomniacs, although subjective effects were light to moderate, and in some patients, rebound insomnia and specific side effects have to be considered.

Topical doxepin hydrochloride reduces neuropathic pain: a randomized, double-blind, placebo controlled study

Tricyclic antidepressants have a proven efficacy in neuropathic pain but their use is frequently complicated by side-effects. In a randomized, double-blind, placebo controlled study we compared the effect of twice daily application of doxepin hydrochloride 5% and placebo in forty patients with neuropathic pain. Results were obtained from 75% of those enrolled. There was a significant reduction in pain scores (linear visual analogue scores, 0-10) in those treated with topical doxepin hydrochloride when compared to placebo (mean fall in doxepin group 1.18, P < 0.01). minor side-effects were seen in 3 patients. there was no significant difference drowsiness levels in the two groups.We conclude that topical doxepin hydrochloride has an analgesic effect in neuropathic pain and its use is not commonly complicated by side-effects.

Doxepin cream relieves eczema-associated pruritus within 15 minutes and is not accompanied by a risk of rebound upon discontinuation

Doxepin hydrochloride 5% cream has been previously demonstrated to be effective for relief of pruritus associated with atopic dermatitis and lichen simplex chronicus. In these studies, no evaluations prior to 12 h after the first application, or following discontinuation of topical doxepin therapy, were performed. The current study was done to investigate the onset of action of topical 5% doxepin cream and to ascertain whether discontinuance of doxepin therapy is associated with ‘rebound’ worsening of pruritus. A total of 120 patients with atopic dermatitis or lichen simplex chronicus with moderate to severe pruritus were treated with 5% doxepin cream in a single-blind treatment period (days 0 to 7) followed by a double-blind treatment period (days 7 to 14) in which patients were randomized to receive either doxepin or vehicle cream to evaluate the effects of cessation of active therapy. Pruritus evaluations performed 15 min following application of doxepin cream demonstrated significant antipruritic activity compared with baseline as measured by visual analogue scales of pruritus severity (P< 0.001) and pruritus relief (P< 0.001). Of the 120 patients, 75% reported reductions in pruritus severity in just 15 min and 84% reported such reductions by 120 min following doxepin cream application. Decreasing pruritus severity and increasing pruritus relief continued significantly through day 7. A statistically significant (P<0.001) improvement in both the pruritus severity rating and the physician's global evaluation of pruritus relief was present on day 7 and continued to day 14 compared with baseline in both treatment groups. Eczema severity was significantly improved on both days 7 and 14 in all treatment groups compared with baseline (P<0.001), with significant continued improvement in the doxepin group on day 14 compared with day 7 (P=0.011). Adverse experiences were predominantly mild to moderate in severity and decreased throughout the study. Within 15 min of application, topically applied 5% doxepin cream provided significant antipruritic activity in patients with atopic dermatitis and lichen simplex chronicus. After completing a 7-day treatment period, it was possible to replace active treatment with an emollient without a rebound effect being observed.

Doxepin in the Treatment of Duodenal Ulcer

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.

Doxepin sammenlignet med cimetidin i behandlingen av pasienter med endoskopisk påviste duodenalsår

SummaryDoxepin reduces both basal and pentagastrin-stimulated output of gastric acid and pepsin in man. An open study was carried out, therefore, in 43 patients with endo-scopically confirmed duodenal ulcers to compare the effectiveness of doxepin (50 mg at night) or cimetidine (200+200+200+400 mg daily) for 6 weeks. Endoscopic examinations at 3 and 6 weeks were performed blindly. At 3 weeks, 60% of the patients treated with doxepin and 59% of those receiving cimetidine revealed endo-scopically healed ulcers. At 6 weeks, 84% of the patients treated with doxepin and 82 % of those receiving cimetidine were found to have endoscopically healed ulcers. No statistically significant differences in pain relief and assessments of patient well-being were found. Ulcer relapse occurred in 4 patients in the doxepin group and in 6 in the cimetidine group within 3 months. Thus, no significant differences in either healing frequency or pain relief were found in the two groups studied.

Maprotiline and doxepin in the treatment of depression

Maprotiline (Ludiomil) and doxepin were compared in the treatment of depression in a double-blind multicentre trial. Four centres and 95 in- and out-patients took part in the trial. The severity of depression was evaluated with the aid of a visual analogue scale and nine target symptoms. Both maprotiline and doxepin diminished neurotic as well as psychotic depression significantly. The mean time of onset of action was 7.0 days in the maprotiline group and 7.7 days in the doxepin group. No statistically significant differences in antidepressive effect were found between the treatments. Two patients in the maprotiline group and four patients in the doxepin group discontinued the treatment because of unwanted effects, one patient in each group because of lack of efficacy and nine patients due to reasons not related to the treatment.

Psychiatric treatment for nursing home patients: drug, alcohol, and milieu.

Following a four-week control period, 64 nursing home patients receiving doxepin, other psychoactive drugs, or no medication were placed on an alcohol regimen of beer or wine in the ward or in a simulated pub setup. The alcohol produced significant improvement in all groups, especially the doxepin group. However, the pub milieu did not demonstrate a significant superiority over ward milieu. The authors suggest that the pub milieu should be used as a catalyzer, rather than as an independent treatment modality, to facilitate the alcohol therapy.