The purpose of this guideline is to establish clinical practice recommendations for the pharmacologic treatment of chronic insomnia in adults, when such treatment is clinically indicated. Unlike ...previous meta-analyses, which focused on broad classes of drugs, this guideline focuses on individual drugs commonly used to treat insomnia. It includes drugs that are FDA-approved for the treatment of insomnia, as well as several drugs commonly used to treat insomnia without an FDA indication for this condition. This guideline should be used in conjunction with other AASM guidelines on the evaluation and treatment of chronic insomnia in adults.
The American Academy of Sleep Medicine commissioned a task force of four experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence. The task force developed recommendations and assigned strengths based on the quality of evidence, the balance of benefits and harms, and patient values and preferences. Literature reviews are provided for those pharmacologic agents for which sufficient evidence was available to establish recommendations. The AASM Board of Directors approved the final recommendations.
The following recommendations are intended as a guideline for clinicians in choosing a specific pharmacological agent for treatment of chronic insomnia in adults, when such treatment is indicated. Under GRADE, a STRONG recommendation is one that clinicians should, under most circumstances, follow. A WEAK recommendation reflects a lower degree of certainty in the outcome and appropriateness of the patient-care strategy for all patients, but should not be construed as an indication of ineffectiveness. GRADE recommendation strengths do not refer to the magnitude of treatment effects in a particular patient, but rather, to the strength of evidence in published data. Downgrading the quality of evidence for these treatments is predictable in GRADE, due to the funding source for most pharmacological clinical trials and the attendant risk of publication bias; the relatively small number of eligible trials for each individual agent; and the observed heterogeneity in the data. The ultimate judgment regarding propriety of any specific care must be made by the clinician in light of the individual circumstances presented by the patient, available diagnostic tools, accessible treatment options, and resources. We suggest that clinicians use suvorexant as a treatment for sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use eszopiclone as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use zaleplon as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use zolpidem as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use triazolam as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use temazepam as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use ramelteon as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use doxepin as a treatment for sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use trazodone as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use tiagabine as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use diphenhydramine as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use melatonin as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use tryptophan as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use valerian as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK).
A large number of processes are involved in the chain from emissions of aerosol precursor gases and primary particles to impacts on cloud radiative forcing. Those processes are manifest in a number ...of relationships that can be expressed as factors dlnX/dlnY driving aerosol effects on cloud radiative forcing. These factors include the relationships between cloud condensation nuclei (CCN) concentration and emissions, droplet number and CCN concentration, cloud fraction and droplet number, cloud optical depth and droplet number, and cloud radiative forcing and cloud optical depth. The relationship between cloud optical depth and droplet number can be further decomposed into the sum of two terms involving the relationship of droplet effective radius and cloud liquid water path with droplet number. These relationships can be constrained using observations of recent spatial and temporal variability of these quantities. However, we are most interested in the radiative forcing since the preindustrial era. Because few relevant measurements are available from that era, relationships from recent variability have been assumed to be applicable to the preindustrial to present-day change. Our analysis of Aerosol Comparisons between Observations and Models (AeroCom) model simulations suggests that estimates of relationships from recent variability are poor constraints on relationships from anthropogenic change for some terms, with even the sign of some relationships differing in many regions. Proxies connecting recent spatial/temporal variability to anthropogenic change, or sustained measurements in regions where emissions have changed, are needed to constrain estimates of anthropogenic aerosol impacts on cloud radiative forcing.
Abstract
Advances in understanding the neurochemistry of sleep and waking have stimulated new pharmacological directions in the treatment of insomnia. While the sedation of historic insomnia ...medications was discovered serendipitously, now compounds can be developed for specific molecular targets with known sleep-related actions. Numerous investigational compounds, including some entirely novel approaches, are being evaluated currently as possible insomnia treatments. In recent years the US Federal Drug Administration (FDA) has approved medications with new pharmacodynamic and pharmacokinetic properties thereby extending the options for personalized pharmacotherapy. The FDA is reviewing new applications for innovative sleep-promoting medications currently, including suvorexant and tasimelteon. Presently the FDA-approved insomnia treatment medications include benzodiazepine receptor agonists available in immediate-release, extended-release, and alternative delivery oral absorption formulations; a melatonin receptor agonist; and a histamine receptor antagonist. Clinical indications include insomnia associated with difficulty with sleep onset, sleep maintenance, and middle-of-the-night awakenings. Alternative approaches to treating insomnia have included prescription medications employed on an off-label basis for insomnia, over-the-counter sleep aids, and assorted unregulated substances marketed to enhance sleep.
Much of the uncertainty in estimates of the anthropogenic forcing of climate change comes from uncertainties in the instantaneous effect of aerosols on cloud albedo, known as the Twomey effect or the ...radiative forcing from aerosol–cloud interactions (RFaci), a component of the total or effective radiative forcing. Because aerosols serving as cloud condensation nuclei can have a strong influence on the cloud droplet number concentration (Nd
), previous studies have used the sensitivity of the Nd
to aerosol properties as a constraint on the strength of the RFaci. However, recent studies have suggested that relationships between aerosol and cloud properties in the present-day climate may not be suitable for determining the sensitivity of the Nd
to anthropogenic aerosol perturbations. Using an ensemble of global aerosol–climate models, this study demonstrates how joint histograms between Nd
and aerosol properties can account for many of the issues raised by previous studies. It shows that if the anthropogenic contribution to the aerosol is known, the RFaci can be diagnosed to within 20% of its actual value. The accuracy of different aerosol proxies for diagnosing the RFaci is investigated, confirming that using the aerosol optical depth significantly underestimates the strength of the aerosol–cloud interactions in satellite data.
Background
Obstructive sleep apnea (OSA) and depression may coexist in the same patient. This article aims to review the link between OSA and comorbid depression and critically evaluate the results ...of studies that assessed the correlation between OSA and depression, the impact of OSA treatment on comorbid depression, and the impact of comorbid depression on continuous positive airway pressure (CPAP) adherence.
Methods
An integrative review was conducted on English language studies and reports that assessed the relationship between OSA and depression. Studies were identified by searching PubMed, Web of Science and Google Scholar databases, and reference lists of included studies.
Results
Generally, cross-sectional studies show a higher prevalence of depression among OSA patients with both community and sleep disorder clinic samples. Nevertheless, the relationship between OSA and depression is complicated by the fact that the disorders have overlapping symptoms. Longitudinal studies demonstrate an increased risk of developing depression among people with OSA, as well as an association between OSA severity and the likelihood of developing depression. On the other hand, studies assessing the impact of CPAP therapy on depression among OSA patients report conflicting results. Therefore, it is essential to consider how the disorders affect one another and to understand the clinical consequences of treating each disorder in isolation.
Conclusion
Depression is prevalent among patients with OSA both in the community and in sleep disorder clinics. Clinicians in general should be aware of this significant association and should aim to treat both disorders.
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.
We introduce and evaluate aerosol simulations with the global aerosol–climate model ECHAM6.3–HAM2.3, which is the aerosol component of the fully coupled aerosol–chemistry–climate model ECHAM–HAMMOZ. ...Both the host atmospheric climate model ECHAM6.3 and the aerosol model HAM2.3 were updated from previous versions. The updated version of the HAM aerosol model contains improved parameterizations of aerosol processes such as cloud activation, as well as updated emission fields for anthropogenic aerosol species and modifications in the online computation of sea salt and mineral dust aerosol emissions. Aerosol results from nudged and free-running simulations for the 10-year period 2003 to 2012 are compared to various measurements of aerosol properties. While there are regional deviations between the model and observations, the model performs well overall in terms of aerosol optical thickness, but may underestimate coarse-mode aerosol concentrations to some extent so that the modeled particles are smaller than indicated by the observations. Sulfate aerosol measurements in the US and Europe are reproduced well by the model, while carbonaceous aerosol species are biased low. Both mineral dust and sea salt aerosol concentrations are improved compared to previous versions of ECHAM–HAM. The evaluation of the simulated aerosol distributions serves as a basis for the suitability of the model for simulating aerosol–climate interactions in a changing climate.
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