| Reference | [1]. JAMA. 2019 Apr 16;321(15):1481-1490. doi: 10.1001/jama.2019.3504.<br />
Effect of Doxepin Mouthwash or Diphenhydramine-Lidocaine-Antacid Mouthwash vs Placebo on Radiotherapy-Related Oral Mucositis Pain: The Alliance A221304 Randomized Clinical Trial.<br />
Sio TT(1), Le-Rademacher JG(2), Leenstra JL(3), Loprinzi CL(4), Rine G(5), Curtis A(6), Singh AK(7), Martenson JA Jr(3), Novotny PJ(2), Tan AD(2), Qin R(2), Ko SJ(8), Reiter PL(9), Miller RC(8)(10).<br />
Author information: (1)Department of Radiation Oncology, Mayo Clinic Hospital, Phoenix, Arizona. (2)Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota. (3)Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. (4)Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota. (5)Wichita National Cancer Institute Community Oncology Research Program, Wichita, Kansas. (6)Southeast Clinical Oncology Research Consortium National Cancer Institute Community Oncology Research Program, Spartanburg, South Carolina. (7)Roswell Park Cancer Institute, Buffalo, New York. (8)Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida. (9)Ohio State University Medical Center, Columbus. (10)Now with the University of Maryland School of Medicine, Baltimore.<br />
Comment in JAMA. 2019 Apr 16;321(15):1459-1461.<br />
IMPORTANCE: Oral mucositis causes substantial morbidity during head and neck radiotherapy. In a randomized study, doxepin mouthwash was shown to reduce oral mucositis-related pain. A common mouthwash comprising diphenhydramine-lidocaine-antacid is also widely used. OBJECTIVE: To evaluate the effect of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash for the treatment of oral mucositis-related pain.<br />
DESIGN, SETTING, AND PARTICIPANTS: A phase 3 randomized trial was conducted from November 1, 2014, to May 16, 2016, at 30 US institutions and included 275 patients who underwent definitive head and neck radiotherapy, had an oral mucositis pain score of 4 points or greater (scale, 0-10), and were followed up for a maximum of 28 days.<br />
INTERVENTIONS: Ninety-two patients were randomized to doxepin mouthwash (25 mg/5 mL water); 91 patients to diphenhydramine-lidocaine-antacid; and 92 patients to placebo.<br />
MAIN OUTCOME AND MEASURES: The primary end point was total oral mucositis pain reduction (defined by the area under the curve and adjusted for baseline pain score) during the 4 hours after a single dose of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash compared with a single dose of placebo. The minimal clinically important difference was a 3.5-point change. The secondary end points included drowsiness, unpleasant taste, and stinging or burning. All scales ranged from 0 (best) to 10 (worst). RESULTS: Among the 275 patients randomized (median age, 61 years; 58 [21%] women), 227 (83%) completed treatment per protocol. Mucositis pain during the first 4 hours decreased by 11.6 points in the doxepin mouthwash group, by 11.7 points in the diphenhydramine-lidocaine-antacid mouthwash group, and by 8.7 points in the placebo group. The between-group difference was 2.9 points (95% CI, 0.2-6.0; P = .02) for doxepin mouthwash vs placebo and 3.0 points (95% CI, 0.1-5.9; P = .004) for diphenhydramine-lidocaine-antacid mouthwash vs placebo. More drowsiness was reported with doxepin mouthwash vs placebo (by 1.5 points [95% CI, 0-4.0]; P = .03), unpleasant taste (by 1.5 points [95% CI, 0-3.0]; P = .002), and stinging or burning (by 4.0 points [95% CI, 2.5-5.0]; P < .001). Maximum grade 3 adverse events for the doxepin mouthwash occurred in 3 patients (4%); diphenhydramine-lidocaine-antacid mouthwash, 3 (4%); and placebo, 2 (2%). Fatigue was reported by 5 patients (6%) in the doxepin mouthwash group and no patients in the diphenhydramine-lidocaine-antacid mouthwash group. CONCLUSIONS AND RELEVANCE: Among patients undergoing head and neck radiotherapy, the use of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash vs placebo significantly reduced oral mucositis pain during the first 4 hours after administration; however, the effect size was less than the minimal clinically important difference. Further research is needed to assess longer-term efficacy and safety for both mouthwashes.<br />
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02229539.<br />
DOI: 10.1001/jama.2019.3504 PMCID: PMC6484809 PMID: 30990550<br />
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[2]. Dermatol Ther. 2019 Jul;32(4):e12993. doi: 10.1111/dth.12993. Epub 2019 Jul 14.<br />
Doxepin in difficult-to-treat chronic urticaria: A retrospective, cross-sectional study from Turkey.<br />
Özkaya E(1), Babuna Kobaner G(1), Yılmaz Z(1), Kutlay A(1).<br />
Author information: (1)Department of Dermatology and Venereology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.<br />
Doxepin is an old tricyclic antidepressant, whose efficacy in chronic urticaria had been well documented until 1990. However, over the past three decades, there has been limited data on its use. We aimed to assess the efficacy and safety of doxepin in the treatment of patients with chronic urticaria who were poorly responsive to antihistamines. In this retrospective, cross-sectional, single-center study from Turkey, data were examined from patients with chronic urticaria who had poor antihistamine responses and received doxepin therapy from 1998 to 2017. Patient data were analyzed with regard to the duration of the disease, age, sex, treatment outcomes using a weekly urticaria activity score (UAS7), and adverse effects of doxepin therapy. A reduction of ≥90% in UAS7 was defined as "complete response," 30-89% as "partial response" and <30% as "no significant response." Thirty-six patients were included in this study. Doxepin was effective in a majority (n = 27, 75%) of the patients with a short onset time. Sixteen patients (44.4%) showed a complete response. Mild sedative and anticholinergic side effects were well tolerated. Doxepin seems to be a reasonable, efficient, and affordable alternative for the treatment of chronic urticaria in patients who respond poorly to antihistamine therapy.<br />
DOI: 10.1111/dth.12993 PMID: 31175673<br />
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[3]. J Clin Psychopharmacol. 2018 Jun;38(3):279-280. doi: 10.1097/JCP.0000000000000874.<br />
Doxepin: Misuse and Abuse.<br />
Spurling B(1), Clark L, Fusick AJ, Whiting WL.<br />
Author information: (1)Department of Psychiatry University of South Florida Morsani College of Medicine Tampa, FL. Psychiatry Consult Service James A. Haley VA Hospital and University of South Florida College of Medicine Tampa, FL [email protected].<br />
DOI: 10.1097/JCP.0000000000000874 PMID: 29620700<br />
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[4]. Sleep Med Rev. 2015 Feb;19:75-83. doi: 10.1016/j.smrv.2014.06.001. Epub 2014 Jun 19.<br />
Doxepin for insomnia: a systematic review of randomized placebo-controlled trials.<br />
Yeung WF(1), Chung KF(2), Yung KP(1), Ng TH(1).<br />
Author information: (1)Department of Psychiatry, University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region. (2)Department of Psychiatry, University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region. Electronic address: [email protected].<br />
Doxepin, a sedating tricyclic drug, at 3 mg and 6 mg doses was recently approved by the U.S. food and drug administration (FDA) for the treatment of insomnia. The objective of this systematic review was to obtain a precise summary of the efficacy and safety of doxepin as a hypnotic. We searched key databases and trial registers up to March 2014 and contacted pharmaceutical companies and the FDA for unpublished data. A total of nine randomized placebo-controlled trials were analyzed. Six studies were on doxepin 1-6 mg/d, two on doxepin 25-300 mg/d, and one on ramelteon 8 mg and doxepin 3 mg combined. All low-dose studies were industry-sponsored. We found that low-dose doxepin had a small to medium effect size against placebo for sleep maintenance and sleep duration but not for sleep initiation at both immediate and short-term posttreatment. There was no significant next-day residual effect with low-dose doxepin. Headache and somnolence were the most common side effects. We concluded that low-dose doxepin for 1-2 nights appeared to be safe and effective in improving sleep. However, a clear conclusion on its short-term benefits and risks as well as withdrawal effects was not possible due to the small number of studies.<br />
DOI: 10.1016/j.smrv.2014.06.001 PMID: 25047681<br />
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[5]. J Clin Sleep Med. 2020 May 15;16(5):743-747. doi: 10.5664/jcsm.8338. Epub 2020 Feb 7.<br />
Doxepin in children and adolescents with symptoms of insomnia: a single-center experience.<br />
Shah YD(1), Stringel V(1), Pavkovic I(1), Kothare SV(1).<br />
Author information: (1)Division of Child Neurology, Department of Pediatrics, Cohen Children's Medical Center, New Hyde Park, New York.<br />
STUDY OBJECTIVES: Pediatric insomnia is a widespread problem and especially difficult to manage in children with neurodevelopmental disorders. There are currently no US Food and Drug Administration-approved medications to use once first-line therapy fails. The objective of this study was to evaluate the efficacy and tolerability of doxepin in pediatric patients. METHODS: This is a retrospective single-center chart review of children and adolescents (2-17 years of age) whose sleep failed to improve with behavioral intervention and melatonin who were then trialed on doxepin. Treatment was initiated at a median starting dose of 2 mg and slowly escalated to a median maintenance dose of 10 mg. Improvement in sleep was recorded using a 4-point Likert scale reported by parents on follow-up visits. RESULTS: A total of 29 patients were included in the analysis. Mean follow-up duration was 6.5 ± 3.5 months. Of 29 patients, 4 (13.8%) patients discontinued doxepin because of lack of efficacy or side effects. Eight (27.6%) patients showed significant improvement of their insomnia, 8 (27.6%) showed moderate improvement, 10 (34.5%) showed mild improvement, and 3 (10.3%) showed minimal to no improvement on treatment with doxepin (P < .05) Only 2 patients (6.9%) experienced adverse effects in the form of behavioral side effects (aggression) and enuresis. CONCLUSIONS: Results of our studies suggest that low-dose doxepin is both effective and well tolerated in pediatric patients with insomnia.<br />
DOI: 10.5664/jcsm.8338 PMCID: PMC7849801 PMID: 32029069
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