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Journal of Clinical Sleep Medicine :... May 2020Pediatric insomnia is a widespread problem and especially difficult to manage in children with neurodevelopmental disorders. There are currently no US Food and Drug...
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.
Topics: Adolescent; Child; Doxepin; Humans; Melatonin; Retrospective Studies; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 32029069
DOI: 10.5664/jcsm.8338 -
Expert Opinion on Pharmacotherapy Jun 2020Chronic insomnia, whether it is primary or in combination with another medical or psychiatric disorder, is a prevalent condition associated with significant morbidity,... (Review)
Review
INTRODUCTION
Chronic insomnia, whether it is primary or in combination with another medical or psychiatric disorder, is a prevalent condition associated with significant morbidity, reduced productivity, increased risk of accidents, and poor quality of life. Pharmacologic and behavioral treatments have equivalent efficacy with each having its own advantages and limitations.
AREAS COVERED
The purpose of this perspective is to delineate the limitations encountered in implementing cognitive behavioral therapy (CBT) and to review the pharmacological treatments designed to target the different phenotypes of insomnia. The discussions address how to choose the optimal medication or combination thereof based on patients' characteristics, available medications, and the presence of comorbid conditions. Selective nonbenzodiazepine sedative 'Z-drug' hypnotics, melatonin receptor agonist-ramelteon, and low-dose doxepin are the agents of choice for treatment of primary and comorbid insomnia.
EXPERT OPINION
A pharmacological intervention should be offered if cognitive behavioral therapy for insomnia is not available or has failed to achieve its goals. Increasing evidence of the significant adverse consequences of long-term benzodiazepines should limit the prescription of these agents to specific conditions. Testing novel dosing regimens with a combination of hypnotic classes augmented with CBT deserve further investigation.
Topics: Cognitive Behavioral Therapy; Humans; Quality of Life; Sleep Initiation and Maintenance Disorders
PubMed: 32202451
DOI: 10.1080/14656566.2020.1743265 -
The Cochrane Database of Systematic... 2000There are two reasons to believe anxiolytics might help in smoking cessation. Anxiety may be a symptom of nicotine withdrawal. Second, smoking appears to be due, in... (Review)
Review
BACKGROUND
There are two reasons to believe anxiolytics might help in smoking cessation. Anxiety may be a symptom of nicotine withdrawal. Second, smoking appears to be due, in part, to deficits in dopamine, serotonin and norepinephrine, all of which are increased by anxiolytics and antidepressants.
OBJECTIVES
The aim of this review is to assess the effectiveness of anxiolytic drugs in aiding long term smoking cessation. The drugs include buspirone; diazepam; doxepin; meprobamate; ondansetron; and the beta-blockers metoprolol, oxprenolol and propanolol.
SEARCH STRATEGY
We searched the Cochrane Tobacco Addiction Group trials register which includes trials indexed in Medline, Embase, SciSearch and PsycLit, and meetings abstracts.
SELECTION CRITERIA
We considered randomized trials comparing anxiolytic drugs to placebo or an alternative therapeutic control for smoking cessation. We excluded trials with less than 6 months follow-up.
DATA COLLECTION AND ANALYSIS
We extracted data in duplicate on the type of study population, the nature of the drug therapy, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed effects model.
MAIN RESULTS
There was one trial each of the anxiolytics diazepam, meprobamate, metoprolol and oxprenolol. There were two trials of the anxiolytic buspirone. None of the trials showed strong evidence of an effect for any of these drugs in helping smokers to quit. However, confidence intervals were wide, and an effect of anxiolytics cannot be ruled out on current evidence.
REVIEWER'S CONCLUSIONS
There is no consistent evidence that anxiolytics aid smoking cessation, but the available evidence does not rule out a possible effect.
Topics: Adrenergic beta-Antagonists; Anti-Anxiety Agents; Humans; Smoking; Smoking Cessation
PubMed: 11034774
DOI: 10.1002/14651858.CD002849 -
Arquivos de Neuro-psiquiatria May 2022Although, insomnia is one of the most common diseases that health professionals face in their practice, it receives little attention in medical training. Diagnosis is...
Although, insomnia is one of the most common diseases that health professionals face in their practice, it receives little attention in medical training. Diagnosis is based on a careful history taking, and physicians must be aware of the diagnostic criteria. Insomnia should not be considered a symptom, but a comorbid condition. Although cognitive behavioral therapy (CBT) has been the mainstay treatment for insomnia for many years, it is usually regarded as a novel therapeutic strategy, both because of scarcity of qualified psychologists and of limited knowledge about insomnia among physicians. GABA receptor acting drugs are being abandoned in the treatment of insomnia because of abuse and dependence potential and accident risk. Two main current therapeutic options with the best scientific evidence are the tricyclic antidepressant, doxepin, and a new melatoninergic receptor agonist, ramelteon. Newer drugs to treat insomnia are in the pipeline. Hypocretine blocking agents will be marketed in the near future.
Topics: Cognitive Behavioral Therapy; Humans; Sleep Initiation and Maintenance Disorders
PubMed: 35976314
DOI: 10.1590/0004-282X-ANP-2022-S124 -
Canadian Pharmacists Journal : CPJ =... Sep 2014Insomnia is one of the most frequent complaints encountered in primary care practice, one that results in significant clinical consequences and cost burden to the public... (Review)
Review
BACKGROUND
Insomnia is one of the most frequent complaints encountered in primary care practice, one that results in significant clinical consequences and cost burden to the public health system. It is more common in elderly adults (≥65 years of age), with frequent complaints regarding sleep maintenance and early morning wakening. Current treatment options have limitations. This review was conducted to evaluate the evidence behind ultra-low-dose doxepin in insomnia and to discuss its potential advantages, its place in therapy and its implications in practice in the treatment of older patients.
METHODS
A systematic literature search was conducted of MEDLINE via Ovid, PubMed and EMBASE using the MeSH and key terms "doxepin," "sleep initiation and maintenance disorders," "insomnia," and "low dose." Only randomized controlled trials comparing 3 mg and/or 6 mg of doxepin to placebo and involving participants diagnosed with primary insomnia were included. Primary outcomes for this review were objective sleep study parameters.
RESULTS
Five studies were identified, 3 of which (n = 571) were conducted in older adults. Doxepin 3 mg and 6 mg significantly reduced waking after sleep onset and increased total sleep time. There was no significant difference between the 2 doses of doxepin. Latency to persistent sleep did not differ significantly compared with placebo for any doses of doxepin. The most frequent adverse events reported were somnolence and headache. Adverse events did not appear to be dose-related, and studies reported the incidence of adverse effects to be comparable to placebo.
CONCLUSION
Doxepin 3 mg and 6 mg significantly improved and sustained sleep maintenance and sleep duration into the last third of the night but did not significantly affect sleep onset. Sleep benefits were achieved without next-day residual or discontinuation effects. Doxepin appears to be well suited for managing insomnia in older people.
PubMed: 25364337
DOI: 10.1177/1715163514543856 -
Repurposing Doxepin to Ameliorate Steatosis and Hyperglycemia by Activating FAM3A Signaling Pathway.Diabetes Jun 2020Mitochondrial protein FAM3A suppresses hepatic gluconeogenesis and lipogenesis. This study aimed to screen drug(s) that activates FAM3A expression and evaluate its...
Mitochondrial protein FAM3A suppresses hepatic gluconeogenesis and lipogenesis. This study aimed to screen drug(s) that activates FAM3A expression and evaluate its effect(s) on hyperglycemia and steatosis. Drug-repurposing methodology predicted that antidepressive drug doxepin was among the drugs that potentially activated FAM3A expression. Doxepin was further validated to stimulate the translocation of transcription factor HNF4α from the cytoplasm into the nucleus, where it promoted FAM3A transcription to enhance ATP synthesis, suppress gluconeogenesis, and reduce lipid deposition in hepatocytes. HNF4α antagonism or FAM3A deficiency blunted doxepin-induced suppression on gluconeogenesis and lipid deposition in hepatocytes. Doxepin administration attenuated hyperglycemia, steatosis, and obesity in obese diabetic mice with upregulated FAM3A expression in liver and brown adipose tissues (BAT). Notably, doxepin failed to correct dysregulated glucose and lipid metabolism in FAM3A-deficient mice fed on high-fat diet. Doxepin's effects on ATP production, Akt activation, gluconeogenesis, and lipogenesis repression were also blunted in FAM3A-deficient mouse livers. In conclusion, FAM3A is a therapeutic target for diabetes and steatosis. Antidepressive drug doxepin activates FAM3A signaling pathways in liver and BAT to improve hyperglycemia and steatosis of obese diabetic mice. Doxepin might be preferentially recommended as an antidepressive drug in potential treatment of patients with diabetes complicated with depression.
Topics: Animals; Antidepressive Agents, Tricyclic; Cytokines; Databases, Pharmaceutical; Doxepin; Drug Repositioning; Fatty Liver; Forkhead Box Protein O1; Gene Expression Regulation; Hep G2 Cells; Hepatocyte Nuclear Factor 4; Hepatocytes; Humans; Hyperglycemia; Male; Mice; Mice, Knockout
PubMed: 32312868
DOI: 10.2337/db19-1038 -
Clinics in Dermatology 2013Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their...
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).
Topics: Adult; Child; Diagnosis, Differential; Humans; Pruritus; Psychophysiologic Disorders; Psychotherapy; Quality of Life; Severity of Illness Index
PubMed: 23245971
DOI: 10.1016/j.clindermatol.2011.11.004 -
Dose-response : a Publication of... 2022Radiation-induced lung injuries (RILI) is one of the serious complications of radiotherapy posed by the damage of alveolar cells and inflammation over-reaction. We aimed...
Radiation-induced lung injuries (RILI) is one of the serious complications of radiotherapy posed by the damage of alveolar cells and inflammation over-reaction. We aimed to investigate the potential protective effects of doxepin on RILI (20 Gy total dose at 3 Gy/min of X-ray irradiation), as well as its underlying mechanism. For animal experiments, such parameters as Immunohistochemistry and hematoxylin and eosin (H&E) staining, WBC (white blood cell), CRP (C-reactive protein), Western blot, and q-PCR were detected. The results indicated that both survival status and weight increase of irradiated rats treated by doxepin (3 mg/kg/day, rat) were higher than those of treated with irradiation alone (Dosing started the day before irradiation). Further, histological examinations showed doxepin could tenuate the radiation injury, as indicated as alveolar inflammatory exudation and there was only mild interstitial inflammation infiltration. Western blotting and q-PCR showed that expression of NF-κβ in X group were higher than that in XMD group. For the first time, we reported doxepin functioned as a radioprotectant candidate, which provide a promising application of doxepin for protecting radiotherapy injuries.
PubMed: 35693872
DOI: 10.1177/15593258221107193 -
Experimental and Therapeutic Medicine Oct 2015Anxiety disorders are frequently comorbid with insomnia, and sleep disturbance in patients with anxiety disorders is the most common complaint. Antidepressants can...
Anxiety disorders are frequently comorbid with insomnia, and sleep disturbance in patients with anxiety disorders is the most common complaint. Antidepressants can affect sleep quality; however, their effect in patients with comorbid insomnia and anxiety disorders is unclear. The aim of the present study was to comprehensively evaluate the dose, treatment duration, treatment efficacy and safety of clinical citalopram and doxepin application in patients with comorbid insomnia and anxiety disorders. It was found that both citalopram (20 mg/day) and low-dose doxepin (12.5 mg/day) significantly improved sleep latency, duration and disturbances, as well as daytime dysfunction and the global Pittsburgh Sleep Quality Index during the 12-week treatment period. Notably, low-dose doxepin significantly improved sleep latency in patients after treatment for 8 and 12 weeks as compared with citalopram. It was further observed that both citalopram and low-dose doxepin improved anxiety. A significant and positive correlation was found between the improvement in the sleep quality and anxiety in the two treatment groups. Citalopram and low-dose doxepin both showed good efficacy and a low adverse reaction rate in the treated patients. These data support a potential application of citalopram and low-dose doxepin in the treatment of patients with comorbid insomnia and anxiety disorders.
PubMed: 26622482
DOI: 10.3892/etm.2015.2686 -
The Journal of Clinical Psychiatry Jun 2021To describe lemborexant for the treatment of insomnia () in adults using number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or... (Randomized Controlled Trial)
Randomized Controlled Trial
Lemborexant for the Treatment of Insomnia: Direct and Indirect Comparisons With Other Hypnotics Using Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed.
To describe lemborexant for the treatment of insomnia () in adults using number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH). Lemborexant data were obtained from two Phase 3 trials conducted 2016-2018. Efficacy was assessed using different categorical definitions for response, and tolerability was assessed by evaluating rates of adverse events (AEs). Direct comparisons were made with zolpidem extended release (ER), and indirect comparisons were made with other hypnotic agents, including suvorexant, doxepin, ramelteon, zolpidem immediate release, eszopiclone, zaleplon, and selected benzodiazepines, using data from published reports and regulatory documents. Lemborexant had a clinically relevant magnitude of therapeutic effect, as evidenced by NNT values versus placebo as robust as 3 (95% CI, 2-3). In general, NNH values for lemborexant versus placebo were ≥ 10, suggesting that lemborexant is relatively tolerable. Somnolence was the most common AE, with NNH estimates of 28 (95% CI, 18-61) and 15 (95% CI, 11-22) for lemborexant 5 mg and 10 mg, respectively. Rates of discontinuation of lemborexant because of an AE were low, and for lemborexant 5 mg the rate was lower than that for placebo. LHH contrasting the statistically significant endpoint efficacy measures versus discontinuation because of an AE ranged from 13 to 54. NNT values for lemborexant were generally more robust than for zolpidem ER for the polysomnography and sleep diary outcomes. In indirect comparisons, NNT data for the other hypnotics demonstrated effect sizes that were generally similar to those for lemborexant. In Phase 3 trials, the benefit-risk ratio for lemborexant is favorable as measured by NNT, NNH, and LHH. ClinicalTrials.gov identifiers: NCT02783729, NCT02952820.
Topics: Acetamides; Adolescent; Adult; Azepines; Benzodiazepines; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Orexin Receptor Antagonists; Pyridines; Pyrimidines; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Triazoles; Young Adult; Zolpidem
PubMed: 34077032
DOI: 10.4088/JCP.20m13795