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The Journal of Family Practice Jul 2023Insomnia is a distinct disorder that is common, yet underrecognized and undertreated in primary care. Treating insomnia has been shown to improve outcomes, including... (Review)
Review
Insomnia is a distinct disorder that is common, yet underrecognized and undertreated in primary care. Treating insomnia has been shown to improve outcomes, including reduced risk of developing cardiovascular and mental health disorders. Insomnia is influenced by the brain's regulation of sleep and wake, which are mutually exclusive events. Insomnia should be treated as a distinct condition, even when occurring with a comorbid diagnosis such as depression or anxiety. Clinicians should implement a multimodal approach to insomnia management, including nonpharmacologic interventions and pharmacologic therapy (when indicated). Pharmacologic agents that are approved by the US Food and Drug Administration for insomnia include benzodiazepine receptor agonists (zolpidem, eszopiclone, and zaleplon), low-dose doxepin (tricyclic antidepressant), ramelteon (melatonin receptor agonist), and dual orexin receptor agonists (DORAs, daridorexant, lemborexant, and suvorexant). Unlike other pharmacologic agents, DORAs inhibit wakefulness rather than induce sedation. Additionally, these medications have no evidence of rebound insomnia or withdrawal, and little to no abuse potential. Daridorexant is the newest DORA, has an ideal half-life of 8 hours, and has demonstrated continued efficacy over a 12-month period. Selection of pharmacologic agent should be based on the patient's comorbid conditions, treatment goals and preferences, and other clinical characteristics.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Sleep; Zolpidem; Doxepin
PubMed: 37549414
DOI: 10.12788/jfp.0620 -
Lancet (London, England) Jul 2022Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently used worldwide. We aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder.
METHODS
In this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials. We included studies comparing pharmacological treatments or placebo as monotherapy for the treatment of adults (≥18 year) with insomnia disorder. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Primary outcomes were efficacy (ie, quality of sleep measured by any self-rated scale), treatment discontinuation for any reason and due to side-effects specifically, and safety (ie, number of patients with at least one adverse event) both for acute and long-term treatment. We estimated summary standardised mean differences (SMDs) and odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with Open Science Framework, https://doi.org/10.17605/OSF.IO/PU4QJ.
FINDINGS
We included 170 trials (36 interventions and 47 950 participants) in the systematic review and 154 double-blind, randomised controlled trials (30 interventions and 44 089 participants) were eligible for the network meta-analysis. In terms of acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo (SMD range: 0·36-0·83 [CINeMA estimates of certainty: high to moderate]). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27-0·71 [moderate to very low]). Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (OR 0·72 [95% CI 0·52-0·99; moderate], 0·70 [0·51-0·95; moderate] and 0·71 [0·52-0·98; moderate], respectively). Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00 [95% CI 1·28-3·13; very low]; zolpidem: 1·79 [1·25-2·50; moderate]); and zopiclone caused more dropouts than did eszopiclone (OR 1·82 [95% CI 1·01-3·33; low]), daridorexant (3·45 [1·41-8·33; low), and suvorexant (3·13 [1·47-6·67; low]). For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27-2·78 [high to very low]). For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63 [95% CI 0·36-0·90; very low]; lemborexant: 0·41 [0·04-0·78; very low]) and eszopiclone was more effective than ramelteon (0.63 [0·16-1·10; very low]) and zolpidem (0·60 [0·00-1·20; very low]). Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43 [95% CI 0·20-0·93; very low]; zolpidem: 0·43 [0·19-0·95; very low]); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00 [95% CI 1·11-3·70; very low]).
INTERPRETATION
Overall, eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Doxepin, seltorexant, and zaleplon were well tolerated, but data on efficacy and other important outcomes were scarce and do not allow firm conclusions. Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits. These results should serve evidence-based clinical practice.
FUNDING
UK National Institute for Health Research Oxford Health Biomedical Research Centre.
Topics: Adult; Benzodiazepines; Doxepin; Eszopiclone; Humans; Melatonin; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Zolpidem
PubMed: 35843245
DOI: 10.1016/S0140-6736(22)00878-9 -
Acta Dermatovenerologica Alpina,... Sep 2020Chronic inducible urticaria (CIndU) is a common inflammatory skin condition characterized by the recurrence of itchy wheals and/or angioedema that lasts more than 6... (Review)
Review
Chronic inducible urticaria (CIndU) is a common inflammatory skin condition characterized by the recurrence of itchy wheals and/or angioedema that lasts more than 6 weeks and is induced by specific physical or environmental stimuli (cold, heat, exercise, pressure, sunlight, vibration, water, etc.). According to the current international classification, it includes physical urticarias (dermographism, delayed-pressure urticaria, exercise-induced urticaria, cold urticaria, heat urticaria, solar urticaria, and vibratory urticaria) and non-physical urticarias caused by exposure to specific stimuli (cholinergic urticaria, contact urticaria, and aquagenic urticaria). In terms of frequency, more common types of CIndU are dermographism, cholinergic urticaria, and delayed-pressure urticaria. In clinical practice, it is often difficult to define the exact type of CIndU; management thus begins with accurate identification of a possible trigger and its avoidance. The definite diagnosis for CIndU requires obtaining a detailed medical history of a patient with comprehensive information about predisposing factors, physical examination, and provocation testing (challenge tests). It is always necessary to recognize the prophylactic options for all the types and to have access to different therapies (primarily second-generation H1 antihistamines, but also H2 antihistamines, hydroxyzine, doxepin, oral glucocorticoids, omalizumab/anti-IgE therapy, phototherapy, physical desensitization, immunomodulatory agents, etc.) individualized for each patient.
Topics: Chronic Urticaria; Humans
PubMed: 32975301
DOI: No ID Found -
Journal of Clinical Medicine Mar 2023Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects,... (Review)
Review
Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding the safest and most effective way to transition from one medication to another. Thus, we developed evidence-based guidelines to inform clinicians regarding best practices when deprescribing or transitioning between insomnia medications. Five U.S.-based sleep experts reviewed the literature involving insomnia medication deprescribing, tapering, and switching and rated the quality of evidence. They used this evidence to generate recommendations through discussion and consensus. When switching or discontinuing insomnia medications, we recommend benzodiazepine hypnotic drugs be tapered while additional CBT-I is provided. For Z-drugs zolpidem and eszopiclone (and not zaleplon), especially when prescribed at supratherapeutic doses, tapering is recommended with a 1-2-day delay in administration of the next insomnia therapy when applicable. There is no need to taper DORAs, doxepin, and ramelteon. Lastly, off-label antidepressants and antipsychotics used to treat insomnia should be gradually reduced when discontinuing. In general, offering individuals a rationale for deprescribing or switching and involving them in the decision-making process can facilitate the change and enhance treatment success.
PubMed: 37048577
DOI: 10.3390/jcm12072493 -
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 -
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 -
Systematic Reviews Nov 2019This review aimed to assess the existing evidence regarding the clinical effectiveness and safety of pharmacological and non-pharmacological interventions in adults with... (Review)
Review
BACKGROUND
This review aimed to assess the existing evidence regarding the clinical effectiveness and safety of pharmacological and non-pharmacological interventions in adults with insomnia and identify where research or policy development is needed.
METHODS
MEDLINE, Embase, PsycINFO, The Cochrane Library, and PubMed were searched from inception until June 14, 2017, along with relevant gray literature sites. Two reviewers independently screened titles/abstracts and full-text articles, and a single reviewer with an independent verifier completed charting, data abstraction, and quality appraisal.
RESULTS
A total of 64 systematic reviews (35 with meta-analysis) were included after screening 5024 titles and abstracts and 525 full-text articles. Eight of the included reviews were rated as high quality using the Assessment of Multiple Systematic Reviews 2 (AMSTAR2) tool, and over half of the included articles (n = 40) were rated as low or critically low quality. Consistent evidence of effectiveness across multiple outcomes based on more than one high- or moderate quality review with meta-analysis was found for zolpidem, suvorexant, doxepin, melatonin, and cognitive behavioral therapy (CBT), and evidence of effectiveness across multiple outcomes based on one high-quality review with meta-analysis was found for temazepam, triazolam, zopiclone, trazodone, and behavioral interventions. These interventions were mostly evaluated in the short term (< 16 weeks), and there was very little harms data available for the pharmacological interventions making it difficult to evaluate their risk-benefit ratio.
CONCLUSIONS
Assuming non-pharmacological interventions are preferable from a safety perspective CBT can be considered an effective first-line therapy for adults with insomnia followed by other behavioral interventions. Short courses of pharmacological interventions can be supplements to CBT or behavioral therapy; however, no evidence regarding the appropriate duration of pharmacological therapy is available from these reviews.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42017072527.
Topics: Antidepressive Agents; Antipsychotic Agents; Azepines; Benzodiazepines; Cognitive Behavioral Therapy; Comparative Effectiveness Research; Humans; Hypnotics and Sedatives; Melatonin; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Systematic Reviews as Topic; Triazoles; Zolpidem
PubMed: 31730011
DOI: 10.1186/s13643-019-1163-9