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Current Topics in Behavioral... 2022Although histamine plays a major role in animal models of stress-related disorders, human neuroimaging data are sparse. Histamine H1 receptors in the human brain were... (Review)
Review
Although histamine plays a major role in animal models of stress-related disorders, human neuroimaging data are sparse. Histamine H1 receptors in the human brain were first imaged by Professor Kazuhiko Yanai in 1992 by using C-doxepin, a potent ligand of H1 receptors, and positron emission tomography (PET). Subsequent work revealed that H1 receptors are reduced in the prefrontal and anterior cingulate cortices in patients with major depressive disorders. A sex difference in H1 receptor binding in the brain has also been found, with women exhibiting more abundant H1 receptor binding than men. Moreover, female patients with anorexia nervosa show higher H1 receptor binding in the amygdala and lentiform nucleus. These studies also found an inverse correlation of depression scores with H1 receptor binding. Histamine is considered to play a major role in the pathophysiology of irritable bowel syndrome (IBS), a representative disorder of brain-gut interactions. Along these lines, hypnotic suggestion dramatically changes the waveforms of viscerosensory cerebral evoked potentials in response to electrical rectal stimulation and these changes are modified by the administration of H1 antagonist. The direction of the H1 antagonist-induced changes in the viscerosensory cerebral evoked potentials differs between IBS patients and healthy controls. Thus, histamine likely plays an important role in stress-related disorders. Further histamine brain imaging studies of humans are warranted.
Topics: Animals; Brain; Depressive Disorder, Major; Doxepin; Female; Histamine; Humans; Hypnotics and Sedatives; Irritable Bowel Syndrome; Ligands; Male; Neuroimaging; Receptors, Histamine H1; Tomography, X-Ray Computed
PubMed: 35156186
DOI: 10.1007/7854_2021_262 -
Current Pain and Headache Reports Mar 2017Topical therapeutic approaches in localized neuropathic pain (LNP) syndromes are increasingly used by both specialists and general practitioners, with a potentially... (Review)
Review
PURPOSE OF REVIEW
Topical therapeutic approaches in localized neuropathic pain (LNP) syndromes are increasingly used by both specialists and general practitioners, with a potentially promising effect on pain reduction. In this narrative review, we describe the available compounds for topical use in LNP syndromes and address their potential efficacy according to the literature.
RECENT FINDINGS
Local anaesthetics (e.g., lidocaine, bupivacaine and mepivacaine), as well as general anaesthetic agents (e.g., ketamine), muscle relaxants (e.g., baclofen), capsaicin, anti-inflammatory drugs (e.g., diclofenac), salicylates, antidepressants (e.g., amitriptyline and doxepin), α2 adrenergic agents (e.g., clonidine), or even a combination of them have been tested in various applications for the treatment of LNP. Few of them have reached a sufficient level of evidence to support systematic use as treatment options. Relatively few systemic side effects or drug-drug interactions and satisfactory efficacy seem to be the benefits of topical treatments. More well-organized and tailored studies are necessary for the further conceptualization of topical treatments for LNP.
Topics: Administration, Topical; Analgesics; Anesthetics, Local; Humans; Neuralgia; Pain Management
PubMed: 28271334
DOI: 10.1007/s11916-017-0615-y -
Indian Dermatology Online Journal 2020Psychodermatological (PD) conditions encountered in dermatologic practice include primary psychiatric conditions such as delusions of parasitosis or secondary... (Review)
Review
Psychodermatological (PD) conditions encountered in dermatologic practice include primary psychiatric conditions such as delusions of parasitosis or secondary psychiatric conditions such as anxiety and depression due to dermatologic disease. The psychotropics include antipsychotic agents, anti-anxiety agents, antidepressants, and miscellaneous drugs such as anti convulsants. Anti psychotics are further divided into first-generation and second-generation drugs. Currently, second-generation drugs e.g., risperidone are preferred over first-generation drugs e.g., pimozide in delusional infestation owing to the side effect profile of the latter. Anti-anxiety agents include benzodiazepines used in acute anxiety and buspirone in chronic anxiety disorders. They are frequently prescribed along with antidepressants. Although dependence and necessity of tapering is a problem with benzodiazepines, delayed onset of action is a feature of buspirone. The commonly used antidepressants in dermatology include selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), selective serotonin norepinephrine reuptake inhibitors (venlafaxine, desvenlefaxine, and duloxetine), norepinephrine dopamine reuptake inhibitors (bupropion), tricyclic antidepressants (doxepin, amitriptyline, imipramine, and clomipramine), and tetracyclic antidepressants (mirtazapine). Miscellaneous drugs include anticonvulsants such as gabapentin and pregabalin, naltrexone, and N-acetyl cysteine. The principles of PD treatment are first establish the psychiatric diagnosis, followed by initiating drug treatment. The choice of drugs is dependent on multiple factors such as side-effect profile, drug interactions, and co-morbid conditions. Usually, drugs are started at a low dose and gradually increased. A literature search was done in Pubmed, Google Scholar, and Medline databases, and articles on treatment were analyzed.
PubMed: 32695685
DOI: 10.4103/idoj.IDOJ_330_19 -
Current Problems in Dermatology 2016Psoriasis is a common chronic inflammatory skin disease observed in about 1-3% of the general population. About 60-90% of patients with psoriasis suffer from itching.... (Review)
Review
Psoriasis is a common chronic inflammatory skin disease observed in about 1-3% of the general population. About 60-90% of patients with psoriasis suffer from itching. Interestingly, in the past itch was not considered as an important symptom of psoriasis. Despite the high frequency of itch in psoriasis, the pathogenesis of this symptom is still not fully elucidated. Although most studies indicate neurogenic inflammation and the role of neuropeptides, other mediators may be important as well. The majority of psoriatic patients consider itch as the most bothersome symptom of the disease as it significantly alters daily functioning and psychosocial well-being. Patients with itch showed greater impairment of their health-related quality of life compared to those without itch, and the intensity of itch correlated with the degree of quality-of-life reduction. However, treatment options for itch in psoriasis are limited. Therapy of itch in patients with psoriasis should be directed toward the resolution of skin lesions, as disease remission usually is linked with itch relief. Recent studies have clearly pointed to an important role of apremilast and biologic agents in itch intensity reduction in subjects suffering from psoriasis. Other treatment modalities include antihistamines, especially with a sedative effect, narrowband ultraviolet B, and antidepressants (doxepin, mirtazapine, paroxetine). Support by family members and/or health professionals may also be of importance in helping psoriatic subjects cope with itch.
Topics: Adaptation, Psychological; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Doxepin; Histamine Antagonists; Humans; Mianserin; Mirtazapine; Paroxetine; Pruritus; Psoriasis; Social Support; Thalidomide; Ultraviolet Therapy
PubMed: 27578078
DOI: 10.1159/000446050 -
Neurological Research and Practice Mar 2021Insomnia is defined as difficulties of initiating and maintaining sleep, early awakening and poor subjective sleep quality despite adequate opportunity and circumstances...
Insomnia is defined as difficulties of initiating and maintaining sleep, early awakening and poor subjective sleep quality despite adequate opportunity and circumstances for sleep with impairment of daytime performance. These components of insomnia - namely persistent sleep difficulties despite of adequate sleep opportunity resulting in daytime dysfunction - appear secondary or co-morbid to neurological diseases. Comorbid insomnia originates from neurodegenerative, inflammatory, traumatic or ischemic changes in sleep regulating brainstem and hypothalamic nuclei with consecutive changes of neurotransmitters. Symptoms of neurological disorders (i.e motor deficits), co-morbidities (i.e. pain, depression, anxiety) and some disease-specific pharmaceuticals may cause insomnia and/or other sleep problems.This guideline focuses on insomnias in headaches, neurodegenerative movement disorders, multiple sclerosis, traumatic brain injury, epilepsies, stroke, neuromuscular disease and dementia.The most important new recommendations are: Cognitive behavioral therapy (CBTi) is recommended to treat acute and chronic insomnia in headache patients. Insomnia is one of the most frequent sleep complaints in neurodegenerative movement disorders. Patients may benefit from CBTi, antidepressants (trazodone, doxepin), melatonin and gaba-agonists. Insomnia is a frequent precursor of MS symptoms by up to 10 years. CBTi is recommended in patients with MS, traumatic brain injury and. Melatonin may improve insomnia symptoms in children with epilepsies. Patients with insomnia after stroke can be treated with benzodiazepine receptor agonists and sedating antidepressants. For patients with dementia suffering from insomnia trazodone, light therapy and physical exercise are recommended.
PubMed: 33691803
DOI: 10.1186/s42466-021-00106-3 -
Pharmacology & Therapeutics Oct 2017We previously reported on brain H receptor occupancy measurements of antihistamines in human brain using [C]doxepin and positron emission tomography (PET). We proposed... (Review)
Review
We previously reported on brain H receptor occupancy measurements of antihistamines in human brain using [C]doxepin and positron emission tomography (PET). We proposed the use of brain H receptor occupancy to classify antihistamines objectively into three categories of sedating, less-sedating, and non-sedating antihistamines according to their sedative effects. Non-sedating antihistamines are recommended for the treatment of allergies such as pollinosis and atopic dermatitis because of their low penetration into the central nervous system. Physicians and pharmacists are responsible for fully educating patients about the risks of sedating antihistamines from pharmacological points of view. If a sedating antihistamine must be prescribed, its sedative effects should be thoroughly considered before choosing the drug. Non-sedating antihistamines should be preferentially used whenever possible as most antihistamines are equally efficacious, while adverse effects of sedating antihistamines can be serious. This review summarizes the pharmacological properties of clinically useful non-sedating antihistamines from the perspective of histamine function in the CNS.
Topics: ATP Binding Cassette Transporter, Subfamily B; Animals; Brain; Gene Expression; Genes, MDR; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Positron-Emission Tomography
PubMed: 28457804
DOI: 10.1016/j.pharmthera.2017.04.004 -
European Neuropsychopharmacology : the... Mar 2018Pruritus is a concomitant symptom of various underlying disorders viz. dermatological, systemic and psychiatric disorders that provoke the person to scratch the skin.... (Review)
Review
Pruritus is a concomitant symptom of various underlying disorders viz. dermatological, systemic and psychiatric disorders that provoke the person to scratch the skin. Many natural as well as, antipruritic therapies are usually practiced in the treatment of pruritus including general preventive measures, topical therapies such as cooling agents, antihistamines, anesthetics, capsaicin, corticosteroids, immunomodulators and; systemic therapies including administration of antihistamines, opioid antagonists/agonists, antiepileptic drugs/neuroleptics (e.g., gabapentin and pregabalin), antidepressants (e.g., doxepin, amitriptyline, paroxetine, fluvoxamine, sertraline, escitalopram and mirtazapine) (Patel and Yosipovitch, 2010; Reich et al., 2011; Martín and Padilla, 2015; Eskeland et al., 2016). Topical therapies are the mainstay of treatment of delicate and localized pruritus while other systemic drug therapies are used to treat stern and generalized pruritus. The reported antipruritic activity of some antidepressant drugs has intrigued this review to focus on the types of pruritus, pruritus mechanism, the antipruritic mechanism of antidepressants and to comprehend the role of antidepressants in the management of pruritus.
Topics: Animals; Antidepressive Agents; Antipruritics; Humans; Pruritus
PubMed: 29456150
DOI: 10.1016/j.euroneuro.2018.01.007 -
The Journal of Dermatological Treatment Feb 2022Doxepin, a tricyclic antidepressant, is the most efficacious antipruritic available to dermatologists; however its use is often suboptimal because of significant... (Review)
Review
Doxepin, a tricyclic antidepressant, is the most efficacious antipruritic available to dermatologists; however its use is often suboptimal because of significant interindividual variability in doxepin plasma levels and clinical response between patients taking the same dose. As result, the Food and Drug Administration approves a maximum dose of 300 mg of doxepin per day and a 10 mg per cc liquid doxepin concentrate. These allow patients to significantly increase or decrease their dose, due to either a lack of clinical efficacy or side effects at typical dermatologic doses (often 10-25 mg per day). This review initially discusses the unique advantages of doxepin in dermatology. Then, it explores internal and external reasons why doxepin plasma levels and clinical response vary so significantly between patients, including genetic polymorphisms, drug interactions, comorbidities, sex, and ethnicity. Blood level monitoring is introduced, a tool dermatologists can use to optimize doxepin dosing in patients responding subtherapeutically to typical dermatologic doses. Without blood level monitoring, patients initially unresponsive to treatment could be labeled treatment failures when in fact they may be cases of inadequate dosing. Blood level monitoring allows for safe dose adjustments in these individuals to maximize patients' chances of achieving therapeutic success with this agent.
Topics: Dermatology; Doxepin; Genotype; Humans; Treatment Failure; Treatment Outcome
PubMed: 32347140
DOI: 10.1080/09546634.2020.1762841 -
Cureus Aug 2023Public health efforts to reduce the opioid overdose epidemic and treat opioid use disorder (OUD) have met with challenges associated with current non-standardized... (Review)
Review
Public health efforts to reduce the opioid overdose epidemic and treat opioid use disorder (OUD) have met with challenges associated with current non-standardized approaches to managing opioid withdrawal symptoms, such as itching, jitteriness, anxiety, depression, craving, vomiting, diarrhea, insomnia, and anorexia. These symptoms pose substantial obstacles to the safe initiation of medications for OUD, maintenance of long-term sobriety, and prevention of relapse. In clinical practice, multiple medications (polypharmacy) are prescribed to manage these withdrawal symptoms, including ondansetron and promethazine for vomiting and nausea, loperamide and Lomotil for diarrhea, hydroxyzine and doxepin for pruritus, benzodiazepines, the Z-drugs, and melatonin for insomnia, and benzos, tricyclic antidepressants (TCAs), and various serotonergic agents for anxiety. This polypharmacy is associated with an increased risk of adverse drug-drug interactions and adverse drug events, increased medical costs, and increased odds of medication non-adherence and relapse. We propose an alternative single medication, mirtazapine, a noradrenergic and specific serotonergic receptor antagonist, that can be used for myriad symptoms of opioid withdrawal. Case series, clinical studies, and clinical trials have shown mirtazapine to be effective for treating nausea and vomiting resulting from multiple etiologies, including hyperemesis gravidarum and chemotherapy-induced emesis. Other evidence supports the salutary effects of mirtazapine on itching and craving. Research findings support mirtazapine's beneficial effects on diarrhea and anxiety, a consequence of its modulating effects on serotonergic receptors mediating mood and gastrointestinal symptoms. There is also evidence supporting its efficacy as a potent and non-addictive sleep aid, which presents itself as a solution for insomnia associated with opioid withdrawal. The current review presents evidence from extant literature supporting mirtazapine as a one-drug strategy to treat the variety of symptoms of opioid withdrawal. This one-drug strategy has much potential to decrease polypharmacy, adverse drug events, relapse, and healthcare cost and increase the likelihood of prolonged sobriety and better quality of life for people living with OUD.
PubMed: 37736438
DOI: 10.7759/cureus.43821 -
Sleep Medicine Reviews Feb 2015Doxepin, 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... (Review)
Review
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.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Doxepin; Drug Therapy, Combination; Female; Humans; Indenes; Male; Middle Aged; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Treatment Outcome; United States; United States Food and Drug Administration; Young Adult
PubMed: 25047681
DOI: 10.1016/j.smrv.2014.06.001