Doxepin in children and adolescents with symptoms of insomnia: a single-center experience

Abstract

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.

Pharmacological management of pediatric insomnia

“…Antidepressants are occasionally prescribed for the treatment of pediatric insomnia, given that some have sedative side effects. While the tricyclic antidepressant doxepin has been FDA approved in low doses for the treatment of insomnia in adults, there is no FDA approved antidepressant for pediatric insomnia (Shah et al, 2020). Nonetheless, trazodone is frequently utilized by clinicians for pediatric insomnia when comorbid with mood and anxiety disorders.…”

Novel Pharmacological Approaches to the Treatment of Depression

“…Research on the use of TCAs for chronic migraine [39], insomnia [40,41], alcohol use disorder [42,43], and neuropathic corneal pain has been conducted with indications of therapeutic efficacy, though adverse effects remain a concern.…”

Could Histamine H1 Receptor Antagonists Be Used for Treating COVID-19?

“…An in silico study has found that mizolastine exhibits excellent binding affinities when docked against the SARS-CoV-2 protease M pro crystal structure [ 70 ].Doxepin, a H1 receptor antagonist, could prevent a SARS-CoV-2 spike pseudovirus from entering the ACE2-HEK293T cell with a reduced infection rate of 25.82% [ 71 ]. The antiviral effect of doxepin may rely on its inhibition of the reuptake of serotonin and norepinephrine [ 72 ], which needs to be further explored. Hydroxyzine, diphenhydramine, and azelastine were shown to exert direct antiviral activity on SARS-CoV-2 in a model in which lentivirus pseudotyped with the SARS-CoV-2 surface glycoprotein was used to infect ACE2-expressing HEK293 cells [ 73 ].…”