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Advanced Biomedical Research 2021Peripheral neurotoxicity is a common side effect of many anticancer chemotherapy drugs, including paclitaxel. Peripheral neurotoxicity may present as changes in sensory...
BACKGROUND
Peripheral neurotoxicity is a common side effect of many anticancer chemotherapy drugs, including paclitaxel. Peripheral neurotoxicity may present as changes in sensory function and mild paresthesia that, in turn, can lead to alleviation of the prescribed dose of the medication. The aim of this study was to evaluate the effectiveness of acute and chronic doxepin administration on development and expression of neuropathic pain during the treatment of cancer with paclitaxel.
MATERIALS AND METHODS
Neuropathic pain was induced in mice by paclitaxel (2 mg/kg, intraperitoneally [i.p.,] once daily from day 1 to day 5) that caused mechanical and cold allodynia. Doxepin was administrated every day from day 6 to 10 (10 and 15 mg/kg i.p.). Mechanical and cold allodynia was evaluated on day 11 of the experiment in both the test and the control group.
RESULTS
Daily administration of doxepin (2.5, 5, and 10 mg/kg i.p.) from day 1 to 5 significantly inhibited the development of cold and mechanical allodynia. As well doxepin administration (5 and 10 mg/kg i.p.) from the 6 day, to 10 day significantly inhibited cold and mechanical allodynia expression. To address the concerns associated with the effectiveness of chemotherapy agents on the tumor, we evaluated paclitaxel cytotoxicity effect in combination with doxepin. Our observations indicate that doxepin even at high concentrations (1 and 10 μg/ml) does not interfere with the cytotoxic effect of paclitaxel (0.05 μg/ml).
CONCLUSIONS
These results indicate that doxepin, when administered during chemotherapy, can prevent the development and expression of paclitaxel-induced neuropathic pain.
PubMed: 35071111
DOI: 10.4103/abr.abr_245_20 -
Trauma Surgery & Acute Care Open 2021Pruritus is a common and often distressing complication after a burn injury. The purpose of this review is to explore the efficacy of drugs classically used to treat...
OBJECTIVES
Pruritus is a common and often distressing complication after a burn injury. The purpose of this review is to explore the efficacy of drugs classically used to treat neuropathic pain in the management of pruritus after burn injury.
METHODS
A systematic literature search of medical databases was conducted to find studies investigating drugs listed in the National Institute for Health and Care Excellence (NICE) guideline (CG173, "neuropathic pain in adults") for the management of pruritus after burn injury in patients of any age. Controlled studies were stratified by the drug class studied and their risk of bias before conducting meta-analysis. A narrative review of case series or observational studies was presented. Severity of pruritus at any time point, with all quantitative and qualitative measures, was included.
RESULTS
Fifteen studies were included in the final analysis, 10 investigated the use of gabapentinoids, 4 studied doxepin, and 1 local anesthetic agents. Meta-analysis of three randomized controlled trials (RCTs) demonstrated that the use of gabapentinoids was associated with an improvement in mean VAS (Visual Analog Scale) 0-10 scores of 2.96 (95% confidence interval (95% CI) 1.20 to 4.73, p<0.001) when compared with placebo or antihistamine. A meta-analysis of four RCTs investigating topical doxepin showed an improvement in mean VAS scores of 1.82 (95% CI 0.55 to 3.09, p<0.001). However, when excluding two studies found to be at high risk of bias, no such improvement was found (-0.32, 95% CI -1.64 to -0.99, p=0.83).
CONCLUSION
This study suggests that gabapentinoids are beneficial in the management of burn-related pruritus. There is a lack of evidence to suggest that doxepin is an effective treatment. Topical local anesthetic agents may be safe and beneficial, but studies are scarce.
LEVEL OF EVIDENCE
Systematic review, level II.
PubMed: 34722931
DOI: 10.1136/tsaco-2021-000810 -
Journal of Chromatography. B,... Oct 2021Conductive vial electromembrane extraction (EME) with prototype equipment was applied for the first time to extract lipophilic basic drugs from serum. With this...
Conductive vial electromembrane extraction (EME) with prototype equipment was applied for the first time to extract lipophilic basic drugs from serum. With this equipment, traditional platinum electrodes were replaced with sample and acceptor vials made from a conductive polymer, making the electrodes fully integrated and disposable. EME was combined with UHPLC-MS/MS, and a method to determine selected psychoactive drugs (alimemazine, amitriptyline, atomoxetine, clomipramine, doxepin, duloxetine, fluvoxamine, levomepromazine, nortriptyline and trimipramine) and metabolites (desmethyl clomipramine and desmethyl doxepin) in serum was developed, optimized, and validated. Extractions were carried out with 50 V for 15 min from serum samples (100 µL) diluted 1:3 with formic acid (0.1% v/v), using 2-nitrophenyl octyl ether as the supported liquid membrane (SLM), and formic acid (0.1% v/v, 300 µL) as acceptor phase. Using conductive vial EME, the extraction of lipophilic drugs reached exhaustive or near-exhaustive conditions, with recoveries in the range 75-117%. The method demonstrated excellent accuracy and precision, with bias within ± 6%, and intra- and inter-day CVs ranging 0.9 - 6% and 2 - 6%, respectively. In addition, acceptor phases were completely free of glycerophosphocholines. EME-UHPLC-MS/MS was successfully applied in determination of psychoactive drugs in 30 patient samples, and the results were in agreement with the current hospital routine method at St. Olav University Hospital (Trondheim, Norway). Obtaining comparable results to well-established routine methods is highly important for future implementation of EME into routine laboratories. These results thus serve as motivation for further advancing the EME technology. Until now, EME has been carried out with laboratory-build equipment, and the introduction of commercially available standardized equipment is expected to have a positive impact on future research activity.
Topics: Chromatography, High Pressure Liquid; Electrochemical Techniques; Humans; Limit of Detection; Linear Models; Psychotropic Drugs; Reproducibility of Results; Tandem Mass Spectrometry
PubMed: 34624684
DOI: 10.1016/j.jchromb.2021.122926 -
Current Neuropharmacology 2022In contrast to that of other monoamine neurotransmitters, the association of the histaminergic system with neuropsychiatric disorders is not well documented. In the last... (Review)
Review
In contrast to that of other monoamine neurotransmitters, the association of the histaminergic system with neuropsychiatric disorders is not well documented. In the last two decades, several clinical studies involved in the development of drugs targeting the histaminergic system have been reported. These include the H3R-antagonist/inverse agonist, pitolisant, used for the treatment of excessive sleepiness in narcolepsy, and the H1R antagonist, doxepin, used to alleviate symptoms of insomnia. The current review summarizes reports from animal models, including genetic and neuroimaging studies, as well as human brain samples and cerebrospinal fluid measurements from clinical trials, on the possible role of the histaminergic system in neuropsychiatric disorders. These studies will potentially pave the way for novel histamine-related therapeutic strategies.
Topics: Animals; Brain; Histamine; Piperidines; Receptors, Histamine
PubMed: 34521328
DOI: 10.2174/1570159X19666210909144930 -
Systematic Reviews Aug 2021Major depressive disorder is a common psychiatric disorder causing great burden on patients and societies. Tricyclic antidepressants are frequently used worldwide to...
Tricyclic antidepressants versus 'active placebo', placebo or no intervention for adults with major depressive disorder: a protocol for a systematic review with meta-analysis and Trial Sequential Analysis.
BACKGROUND
Major depressive disorder is a common psychiatric disorder causing great burden on patients and societies. Tricyclic antidepressants are frequently used worldwide to treat patients with major depressive disorder. It has repeatedly been shown that tricyclic antidepressants reduce depressive symptoms with a statistically significant effect, but the effect is small and of questionable clinical importance. Moreover, the beneficial and harmful effects of all types of tricyclic antidepressants have not previously been systematically assessed. Therefore, we aim to investigate the beneficial and harmful effects of tricyclic antidepressants versus 'active placebo', placebo or no intervention for adults with major depressive disorder.
METHODS
This is a protocol for a systematic review with meta-analysis that will be reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols, bias will be assessed with the Cochrane Risk of Bias tool-version 2, our eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, Trial Sequential Analysis will be conducted to control random errors and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. To identify relevant trials, we will search both for published and unpublished trials in major medical databases and trial registers, such as CENTRAL, MEDLINE, EMBASE and ClinicalTrials.gov from their inception to 12 May 2021. Clinical study reports will be applied for from regulatory authorities and pharmaceutical companies. Two review authors will independently screen the results from the literature searches, extract data and perform risk of bias assessment. We will include any published or unpublished randomised clinical trial comparing tricyclic antidepressants with 'active placebo', placebo or no intervention for adults with major depressive disorder. The following interventions will be assessed: amineptine, amitriptyline, amoxapine, butriptyline, cianopramine, clomipramine, desipramine, demexiptiline, dibenzepin, dosulepin, dothiepin, doxepin, imipramine, iprindole, lofepramine, maprotiline, melitracen, metapramine, nortriptyline, noxiptiline, opipramol, protriptyline, tianeptine, trimipramine and quinupramine. Primary outcomes will be depressive symptoms, serious adverse events and quality of life. Secondary outcomes will be suicide or suicide-attempts and non-serious adverse events. If feasible, we will assess the intervention effects using random-effects and fixed-effect meta-analyses.
DISCUSSION
Tricyclic antidepressants are recommended by clinical guidelines and frequently used worldwide in the treatment of major depressive disorder. There is a need for a thorough systematic review to provide the necessary background for weighing the benefits against the harms. This review will ultimately inform best practice in the treatment of major depressive disorder.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021226161 .
Topics: Adult; Antidepressive Agents, Tricyclic; Depressive Disorder, Major; Humans; Meta-Analysis as Topic; Quality of Life; Review Literature as Topic
PubMed: 34389045
DOI: 10.1186/s13643-021-01789-0 -
Narrative review of the management of oral mucositis during chemoradiation for head and neck cancer.Annals of Translational Medicine May 2021Oral mucositis (OM) can be a significant problem for patients undergoing radiation or chemoradiation for head and neck cancer. In modern clinical trials, grade 3-4 OM... (Review)
Review
Oral mucositis (OM) can be a significant problem for patients undergoing radiation or chemoradiation for head and neck cancer. In modern clinical trials, grade 3-4 OM can be seen in over 40% of patients and can cause a significant impact on their quality of life (QOL). Despite this fact, strategies for the prevention and treatment of OM vary widely, with options including both lifestyle modifications and pharmaceuticals. Here we evaluate and summarize the current clinical interventions for the management of radiation-induced OM. The majority of the current evidence focuses on reducing OM related pain. These agents are detailed over multiple clinical trials including treatment modalities such as: GC4419, doxepin mouthwash, diphenhydramine-lidocaine-antacid (DLA) mouthwash, gabapentin, and methadone. While several strategies have been employed to prevent radiation-induced OM, there is currently no strong evidence for the routine use of these agents in the clinic. After summarization of these treatments, we offer practical guidance for the treatment of OM in the clinic. We recommend a multiagent approach of pharmacological and non-pharmacological treatments including oral rinses, home humidification, escalating doses of gabapentin, doxepin or DLA mouthwash, over the counter analgesics, and lastly methadone. These interventions are tailored to address the expected increase of severity of symptoms during the course of head and neck radiotherapy.
PubMed: 34164550
DOI: 10.21037/atm-20-3931 -
BMC Oral Health Jun 2021Knowing the International Classification of Orofacial Pain helps pain specialists to differentiate types of orofacial pain. It is important to select the best treatment...
Knowing the International Classification of Orofacial Pain helps pain specialists to differentiate types of orofacial pain. It is important to select the best treatment or intervention for the patients based on the diagnosis. As part of our study, we reviewed the article published in BMC Oral Health, titled "Clinical characteristics and associated factors of trigeminal neuralgia: Experience from Addis Ababa, Ethiopia" by Ayele et al. (Ethiopia BMC Oral Health 20(1):7, 2020). For patients suffering from Classical Trigeminal Neuralgia taking a suitable dose of Carbamazepine or Gasser Ganglion radiofrequency could be helpful. Patients complaining Trigeminal neuralgia who had a history of a dental extraction in the painful region should be categorized in other group as Complex Regional Pain Syndrome type 1, who need larger dose of carbamazepine with anticonvulsant or tricyclic agent drugs (e.g. pregabalin or doxepin) or intervention (PPG radiofrequency).
Topics: Carbamazepine; Ethiopia; Humans; Pain; Tooth Extraction; Trigeminal Neuralgia
PubMed: 34098927
DOI: 10.1186/s12903-021-01645-6 -
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 -
Systematic Reviews May 2021Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide. Antidepressants are frequently used to treat major...
Beneficial and harmful effects of antidepressants versus placebo, 'active placebo', or no intervention for adults with major depressive disorder: a protocol for a systematic review of published and unpublished data with meta-analyses and trial sequential analyses.
BACKGROUND
Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide. Antidepressants are frequently used to treat major depressive disorder. It has been shown repeatedly that antidepressants seem to reduce depressive symptoms with a statistically significant effect, but the clinical importance of the effect sizes seems questionable. Both beneficial and harmful effects of antidepressants have not previously been sufficiently assessed. The main objective of this review will be to evaluate the beneficial and harmful effects of antidepressants versus placebo, 'active placebo', or no intervention for adults with major depressive disorder.
METHODS/DESIGN
A systematic review with meta-analysis will be reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), bias will be assessed with the Cochrane Risk of Bias tool-version 2 (ROB2), our eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, Trial Sequential Analysis will be conducted to control for random errors, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. To identify relevant trials, we will search both for published and unpublished trials in major medical databases from their inception to the present. Clinical study reports will be obtained from regulatory authorities and pharmaceutical companies. Two review authors will independently screen the results of the literature searches, extract data, and perform risk of bias assessment. We will include any published or unpublished randomised clinical trial comparing one or more antidepressants with placebo, 'active placebo', or no intervention for adults with major depressive disorder. The following active agents will be included: agomelatine, amineptine, amitriptyline, bupropion, butriptyline, cianopramine, citalopram, clomipramine, dapoxetine, demexiptiline, desipramine, desvenlafaxine, dibenzepin, dosulepin, dothiepin, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, iprindole, levomilnacipran, lofepramine, maprotiline, melitracen, metapramine, milnacipran, mirtazapine, nefazodone, nortriptyline, noxiptiline, opipramol, paroxetine, protriptyline, quinupramine, reboxetine, sertraline, trazodone, tianeptine, trimipramine, venlafaxine, vilazodone, and vortioxetine. Primary outcomes will be depressive symptoms, serious adverse events, and quality of life. Secondary outcomes will be suicide or suicide attempt, suicidal ideation, and non-serious adverse events.
DISCUSSION
As antidepressants are commonly used to treat major depressive disorder in adults, a systematic review evaluating their beneficial and harmful effects is urgently needed. This review will inform best practice in treatment and clinical research of this highly prevalent and burdensome disorder.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020220279.
Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Humans; Meta-Analysis as Topic; Quality of Life; Systematic Reviews as Topic; Vortioxetine
PubMed: 34034811
DOI: 10.1186/s13643-021-01705-6 -
Journal of Veterinary Internal Medicine Jul 2021Laryngeal paralysis commonly affects older Labrador retrievers. Currently, dogs with severe disease require surgical intervention, most commonly arytenoid...
BACKGROUND
Laryngeal paralysis commonly affects older Labrador retrievers. Currently, dogs with severe disease require surgical intervention, most commonly arytenoid lateralization. Anecdotally, doxepin has been proposed to help dogs with laryngeal paralysis.
HYPOTHESIS
Doxepin will improve quality of life measures assessed by owners of Labrador retrievers with laryngeal paralysis not requiring emergency surgery.
ANIMALS
Twenty-two Labrador retrievers with laryngeal paralysis.
METHODS
Dogs were randomized to receive doxepin (3-5 mg/kg q12h PO) or placebo for 28 days. Owners completed quality-of-life assessments before and after completing the study. Data were compared between groups using Rank-Sum tests or Fisher's exact tests.
RESULTS
The 2 groups of dogs did not differ at baseline except for owner-perceived degree of ataxia (owners of dogs receiving doxepin considered them more ataxic than owners of dogs receiving placebo). After 28 days, owner-assessed quality of life measures did not differ between dogs receiving doxepin or placebo (dogs worsening: doxepin = 2, placebo = 1; dogs unchanged: doxepin = 6, placebo = 7; dogs improved: doxepin = 4, placebo = 2; P = .84). Dogs receiving placebo had a greater improvement in client-assessed overall health than dogs receiving doxepin (mean ranks: doxepin = 4.36, placebo = 6.64; P = .04). The study was terminated at this interim analysis.
CONCLUSIONS AND CLINICAL IMPORTANCE
Doxepin did not appear to improve any measures of owner-assessed quality of life in Labrador retrievers with laryngeal paralysis.
Topics: Animals; Dog Diseases; Dogs; Doxepin; Newfoundland and Labrador; Quality of Life; Vocal Cord Paralysis
PubMed: 33998727
DOI: 10.1111/jvim.16162