Many insomnia medications with high specificity have become available recently. They provide a window into the clinical effects of modulating specific brain systems and establish a new guiding principal for conceptualizing insomnia medications: "mechanism matters." A new paradigm for insomnia therapy in which specific drugs are selected to target the specific type of sleep difficulty for each patient includes administering specific treatments for patients with insomnia comorbid with particular psychiatric disorders. This article reviews insomnia medications and discusses the implications for optimizing the treatment of insomnia occurring comorbid with psychiatric conditions.

There is growing experimental evidence that the relationship between psychiatric disorders and sleep is complex and includes bidirectional causation. This article provides the evidence that supports this point of view, reviewing data on sleep disturbances seen in patients with psychiatric disorders as well as data on the impact of sleep disturbances on psychiatric conditions. Although much has been learned about the psychiatric disorders-sleep relationship, additional research is needed to better understand the relationship. Such work promises to improve comprehension of these phenomena and lead to better treatment for the many patients with sleep disorders and psychiatric disorders.

Alterations in sleep are extremely common in patients with neuropsychiatric illness. In addition, sleep disorders such as insomnia, obstructive sleep apnea, rapid eye movement sleep behavior disorder, and circadian rhythm disorders commonly occur at a rate greater than the general population in neuropsychiatric conditions. Historically, sleep problems have been viewed as symptoms of associated neuropsychiatric disorders. However, there is increasing evidence suggesting a complex inter-relationship with possible bidirectional causality. The inter-relatedness of these conditions represents an opportunity for understanding mechanisms and improving clinical treatment. To the extent that sleep problems affect neuropsychiatric conditions, it may be possible to address sleep problems and have a positive impact on the course of neuropsychiatric illnesses. Further, some treatments for sleep disorders have direct effects on neuropsychiatric illnesses that may be unrelated to their effects on sleep disorders. Similarly, neuropsychiatric conditions and their treatments can affect sleep and sleep disorders. This article reviews available evidence on the effects of therapies for sleep disorders on neuropsychiatric conditions and also secondarily considers the impacts of therapies for neuropsychiatric conditions on sleep. Primary goals of this review are to identify gaps in current research, to determine the extent to which the cross-therapeutic effects of these treatments help to elucidate therapeutic or pathological mechanisms, and to assist clinicians in optimizing therapeutic choice in patients with sleep disorders and neuropsychiatric conditions.

Kappa-opioid receptor (KOR) antagonists are currently being considered for the treatment of a variety of neuropsychiatric conditions, including depressive, anxiety, and substance abuse disorders. A general ability to mitigate the effects of stress, which can trigger or exacerbate these conditions, may explain their putative efficacy across such a broad array of conditions. The discovery of their potentially therapeutic effects evolved from preclinical research designed to characterize the molecular mechanisms by which experience causes neuroadaptations in the nucleus accumbens (NAc), a key element of brain reward circuitry. This research established that exposure to drugs of abuse or stress increases the activity of the transcription factor CREB (cAMP response element binding protein) in the NAc, which leads to elevated expression of the opioid peptide dynorphin that in turn causes core signs of depressive- and anxiety-related disorders. Disruption of KORs-the endogenous receptors for dynorphin-produces antidepressant- and anxiolytic-like actions in screening procedures that identify standard drugs of these classes, and reduces stress effects in tests used to study addiction and stress-related disorders. Although interest in this target is high, prototypical KOR antagonists have extraordinarily persistent pharmacodynamic effects that complicate clinical trials. The development of shorter acting KOR antagonists together with more rapid designs for clinical trials may soon provide insight on whether these drugs are efficacious as would be predicted by preclinical work. If successful, KOR antagonists would represent a unique example in psychiatry where the therapeutic mechanism of a drug class is understood before it is shown to be efficacious in humans.

A number of medications are available for treating patients with insomnia. These medications include agents approved as insomnia therapies by the U.S. Food and Drug Administration (FDA), agents approved by the FDA for another condition that are used "off-label" to treat insomnia, and agents available "over-the-counter" that are taken by individuals with insomnia. These agents differ in their properties, their safety and efficacy when used for different insomnia patient subtypes, and the available data on their efficacy and safety in these subtypes. As a result, optimizing the medication treatment of insomnia for a given patient requires that the clinician select an agent for use which has characteristics that make it most likely to effectively and safely address the type of sleep difficulty experienced by that individual. This article is intended to assist clinicians and researchers in carrying out this optimization. It begins by reviewing the basic characteristics of the medications used to treat insomnia. This is followed by a review of the fundamental ways that individuals with insomnia may differ and affect the choice of medication therapy. This review includes discussions that illustrate how to best choose a medication based on the characteristics of the available medications, the key differences among insomnia patients, and the available research literature. Lastly, we discuss future directions for the optimizing pharmacologic management of insomnia. It is hoped that the treatment tailoring methods discussed herein serve as a means of improving the clinical management of insomnia and, thus, improve the lives of the many patients who suffer from this common and impairing condition.

Study objectives

Insomnia, which is very common in patients with chronic low back pain (LBP), has long been viewed as a pain symptom that did not merit specific treatment. Recent data suggest that adding insomnia therapy to pain-targeted treatment should improve outcome; however, this has not been empirically tested in LBP or in any pain condition treated with a standardized pain medication regimen. We sought to test the hypothesis that adding insomnia therapy to pain-targeted treatment might improve sleep and pain in LBP.

Design

Double-blind, placebo-controlled, parallel-group, 1-mo trial.

Setting

Duke University Medical Center Outpatient Sleep Clinic.

Patients

Fifty-two adult volunteers with LBP of at least 3 mo duration who met diagnostic criteria for insomnia (mean age: 42.5 y; 63% females).

Interventions

Subjects were randomized to eszopiclone (ESZ) 3 mg plus naproxen 500 mg BID or matching placebo plus naproxen 500 mg twice a day.

Measurements and results

ESZ SIGNIFICANTLY IMPROVED TOTAL SLEEP TIME (MEAN INCREASE: ESZ, 95 min; placebo, 9 min) (primary outcome) and nearly all sleep measures as well as visual analog scale pain (mean decrease: ESZ, 17 mm; placebo, 2 mm) (primary pain outcome), and depression (mean Hamilton Depression Rating Scale improvement ESZ, 3.8; placebo, 0.4) compared with placebo. Changes in pain ratings were significantly correlated with changes in sleep.

Conclusions

The addition of insomnia-specific therapy to a standardized naproxen pain regimen significantly improves sleep, pain, and depression in patients with chronic low back pain (LBP). The findings indicate the importance of administering both sleep and pain-directed therapies to patients with LBP in clinical practice and provide strong evidence that improving sleep disturbance may improve pain.

Trial registration

clinicaltrials.gov identifier: NCT00365976.

Purpose

Pulse oximetry is the current standard for detecting drops in arterial blood oxygen saturation (SpO₂) associated with obstructive sleep apnea and hypopnea events in polysomnographic (PSG) testing. However, cellular energy monitoring (CE monitoring), a measure related to cellular hypoxia in the skin, is likely to be more responsive to inadequate breathing during sleep because during hypoxic challenge, such as occurs during apneic events, regulatory mechanisms restrict blood flow to the skin to preferentially maintain SpO₂ for more vital organs. We carried out initial proof of concept testing to determine if CE monitoring has promise for being more responsive to hypoxic challenge occurring during sleep-disordered breathing (SDB) than pulse oximetry.

Methods

We assessed both CE monitoring and pulse oximetry in a series of conditions which affect oxygen supply: (1) breathing nitrogen or 100% oxygen, (2) physical exertion, and (3) studying a night of sleep in an individual known to be a loud snorer. We also present the results of a preliminary study comparing CE monitoring to pulse oximetry in eight individuals undergoing standard clinical overnight polysomnography for suspected SDB.

Results

CE monitoring is responsive to changes in cellular oxygen supply to the skin and detects hypoxia during SDB events that is not detected by pulse oximetry.

Conclusion

CE monitoring is a promising tool for identifying pathology at the mild end of the SDB spectrum.

Insomnia poses significant challenges to public health. It is a common condition associated with marked impairment in function and quality of life, psychiatric and physical morbidity, and accidents. As such, it is important that effective treatment is provided in clinical practice. To this end, this paper reviews critical aspects of the assessment of insomnia and the available treatment options. These options include both non-medication treatments, most notably cognitive behavioral therapy for insomnia, and a variety of pharmacologic therapies such as benzodiazepines, "z-drugs", melatonin receptor agonists, selective histamine H1 antagonists, orexin antagonists, antidepressants, antipsychotics, anticonvulsants, and non-selective antihistamines. A review of the available research indicates that rigorous double-blind, randomized, controlled trials are lacking for some of the most commonly administered insomnia therapies. However, there are an array of interventions which have been demonstrated to have therapeutic effects in insomnia in trials with the above features, and whose risk/benefit profiles have been well characterized. These interventions can form the basis for systematic, evidence-based treatment of insomnia in clinical practice. We review this evidence base and highlight areas where more studies are needed, with the aim of providing a resource for improving the clinical management of the many patients with insomnia.

Among obese pregnant women, 15%-20% have obstructive sleep apnea (OSA) and this prevalence increases along with body mass index and in the presence of other comorbidities. Prepregnancy obesity and pregnancy-related weight gain are certainly risk factors for sleep-disordered breathing in pregnancy, but certain physiologic changes of pregnancy may also increase a woman's risk of developing or worsening OSA. While it has been shown that untreated OSA in postmenopausal women is associated with a range of cardiovascular, pulmonary, and metabolic comorbidities, a body of literature is emerging that suggests OSA may also have serious implications for the health of mothers and fetuses during and after pregnancy. In this review, we discuss the following: pregnancy as a vulnerable period for the development or worsening of OSA; the associations between OSA and maternal and fetal outcomes; the current screening modalities for OSA in pregnancy; and current recommendations regarding peripartum management of OSA.

Sleep is essential to cognitive function and health in humans, yet the ultimate reasons for sleep-i.e. 'why' sleep evolved-remain mysterious. We integrate findings from human sleep studies, the ethnographic record, and the ecology and evolution of mammalia