Pharmacotherapy For Insomnia Research Articles

Pros and cons of pharmacotherapy in insomnia

The consultation of personnel in relation to sleep disorders in Korea increased by 1.6 times between 2008 and 2012, and the related days of clinical practice increased by nearly 12 times during the same period. Among the sleep disorders, the most common diagnosis is insomnia, which is most commonly treated with medication. Medication is not only easy to access, but also effective immediately. However, the beneficial effect of hypnotic medication on sleep disorder for an extended period of time may be trivial. Tolerance is another barrier to treating chronic insomnia. In addition, such adverse effects as psychomotor slowing, memory loss, forgetfulness, and decreased sense of balance can heighten the risk of motor vehicle accidents and falling-related injuries. Recently, there have been reports about the association between the chronic use of sleeping pills and cancer mortality and dementia incidence. However, there are still many limitations to understanding whether it is the chronic use of hypnotics, or coexisting mental and physical illness, which increases the risk. Nevertheless, it is worthwhile to pay special attention to the abovementioned risks when using hypnotics and to consider alternative treatment options like cognitive behavioral therapy for insomnia.

Pharmacotherapy in Insomnia

Insomnia is one of the most prevalent sleep disorders. Patients with insomnia tend to have altered quality of life, impaired daytime functioning and increased risk of road traffic accidents. Insomnia is commonly associated with chronic medical conditions and psychiatric illness like depression and anxiety. However, it is now being recognized as an independent disorder. All patients of Insomnia should receive therapy for any medical illness, psychiatric disorders, substance abuse or sleep disorders that might precipitate insomnia. In this review, we discuss the current pharmacotherapeutic options for treatment of insomnia. Research for newer therapeutics for insomnia is often complicated by multifactorial etiology. of insomnia. Understanding the molecular and receptor mechanisms involved in promoting sleep may provide further approaches tothe development of newer drugs.

Chronic Insomnia, Pharmacotherapy and the Cognitive Behavioral Approaches

Insomnia is a common complaint of patients presenting to primary care physician and sleep medicine experts. Approximately 10-20% of the general population worldwide has reported symptoms of chronic insomnia of which 25% have primary insomnia. Insomnia is more prevalent among females and the elderly subjects (over 65 years). Pharmacotherapy for insomnia is mainly focused on hypnotics such as benzodiazepine receptor agonists (BzRAs), antihistamine drugs, tricyclic antidepressants like doxepin, and a melatonin receptor agonist (ramelteon). However, these very often used medications are shown to have potential untoward effects outweighing their benefits in many instances. Once the underlying disorder affecting sleep is appropriately addressed, cognitive behavioral therapy, singly or combined with drug therapy, is demonstrated to be amongst the most efficacious treatment strategies in some cases with refractory insomnia.

Cognitive-behavior treatment of insomnia

Beside pharmacotherapy, cognitive-behavior therapy is an important approach to treating people with problem of insomnia. Cognitive-behavior therapy of insomnia is multicomponent treatment with some nonspecific components (like hygiene of sleeping) and some specific components directed to dysfunctional behavior and way of thinking, like sleep education, stimulus control, sleep restriction, relaxation training, and cognitive therapy. The advantage of this therapy vs. pharmacotherapy of insomnia is that there are no problems of addiction, tolerance, side effects etc. The results of clinical trials suggest that the cognitive- behavior therapy leads to better quality of sleeping of most people with problem of insomnia, but insufficient number of educated cognitive-behavior therapists limits the much wider use of cognitive-behavior therapy in the treatment of insomnia.

Pharmacotherapeutic options for treatment of insomnia

Insomnia is a functionally debilitating condition characterized by repeated difficulty with sleep initiation, maintenance, or quality of sleep despite adequate opportunity. If left untreated, it can lead to increased risk of depression, poor memory, reduced concentration, poor work performance, and poor general health. Although gamma-aminobutyric acid (GABA) ergic system remains the primary target for current insomnia treatments, still over-the-counter (OTC) drugs with a different mechanism of action are in use for insomnia. OTC drugs target only one of the parallel arousing systems and may improve mild insomnia for a short period. They are not likely to improve symptoms over long-term and thus are not the ideal agents. Studies evaluating the efficacy and outcomes of sedative hypnotic drugs beyond 1 year are limited. Currently, there are no Food and Drug Administration approved pharmacotherapies for insomnia in the pediatric population. Increased understanding of complex neuronal networks involved in sleep and wake has led to the development of new drugs for insomnia that target a diverse range of receptors. Potential agents under investigations are targeting mechanisms and pathways including histamine (H 1 ) receptor, melatonin, and orexin receptors. This review describes the pharmacotherapy of insomnia and the drugs under development for the treatment of insomnia.

Current and Emerging Pharmacotherapies in the Management of Insomnia in Adults

This review primarily focuses on the pharmacotherapy for insomnia, including current and emerging pharmacotherapy for insomnia. Currently, there are 10 FDA-approved drugs for the treatment of insomnia. The mainstay treatments are benzodiazepine receptor agonists, which are now available in controlled release formulation to support sleep maintenance. Melatonin receptor agonists are usually used for sleep initiation insomnia. Doxepin an antidepressant is approved for treatment of insomnia. Anticonvulsants and antipsychotics are used ‘off-label’ to treat insomnia, despite limited data to support its use. 5-HT2A serotonin receptor inverse agonists and orexin receptor antagonists are in Phase II and III clinical trials for insomnia with different mechanisms of action. When treating insomnia patients, it is important to individualize treatment by considering various comorbid conditions. Further research is needed to evaluate the efficacy and safety of newly emerging medications, as well as medications that are frequently used without established clinical evidence.

OP.06 The psychological management of sleep problems

Insomnia disorder is the most common of all sleep disorders, affecting night time sleep pattern and quality and having daytime consequences. There is growing evidence that insomnia is implicated in...

Pharmacotherapy of Insomnia with Ramelteon: Safety, Efficacy and Clinical Applications

Ramelteon is a tricyclic synthetic analog of melatonin that acts specifically on MT1 and MT2 melatonin receptors. Ramelteon is the first melatonin receptor agonist approved by the Food and Drug Administration (FDA) for the treatment of insomnia characterized by sleep onset difficulties. Ramelteon is both a chronobiotic and a hypnotic that has been shown to promote sleep initiation and maintenance in various preclinical and in clinical trials. The efficacy and safety of ramelteon in patients with chronic insomnia was initially confirmed in short-term placebo-controlled trials. These showed little evidence of next-day residual effects, withdrawal symptoms or rebound insomnia. Other studies indicated that ramelteon lacked abuse potential and had a minimal risk of producing dependence or adverse effects on cognitive or psychomotor performance. A 6-month placebo-controlled international study and a 1-year open-label study in the USA demonstrated that ramelteon was effective and well tolerated. Other potential off-label uses of ramelteon include circadian rhythm sleep disorders such as shift-work and jet lag. At the present time the drug should be cautiously prescribed for short-term treatment only.

Wake up to insomnia: future approaches to the management of insomnia

Wake up to insomnia: future approaches to the management of insomnia

Insomnia: clinical experience with zolpidem (sanval)

The paper describes the present view of the problem of insomnia and gives a classification of sleep disorders and basic methods for their drug and non-drug therapy. Emphasis is placed on the role of the objective sleep study - polysomnography. The use of the current hypnotics belonging to a three Zs group and the minimization of administration of benzodiazepines are most important in pharmacotherapy for insomnia. The results of a clinical polysomnographic study of the effect of Zolpidem (Sanval) in patients with insomnia are presented. The subjective evaluation of the beneficial effect of a 10-day course of Sanval is confirmed by the objective studies of the sleep pattern undergoing positive changes in the most important indicators, such as the process of falling asleep, the time of intrasleep awakenings, and the duration of Δ-sleep. The high safety and good tolerability of Sanval permit the latter to be assessed as an effective agent for the treatment of insomnia.

Use of pharmacotherapy for insomnia in child psychiatry practice: A national survey

ObjectiveTo examine clinical practice patterns regarding non-prescription and prescription medication use for insomnia by child and adolescent psychiatrists. MethodsSurvey mailed to 6018 members of the American Academy of Child and Adolescent Psychiatry. ResultsThe final sample (N=1273) reported that insomnia was a major problem in almost a third of their school-aged and adolescent patients and endorsed using medication to treat the insomnia in at least a quarter of these patients. Overall, 96% of respondents recommended at least one of the listed prescription medications in a typical month, and 88% recommended an over-the-counter medication. Alpha agonists were the most commonly prescribed insomnia medication for ADHD (81%), significantly higher than in MR/DD (67%), mood (40%), or anxiety disorders (31%). Trazodone was the most commonly prescribed insomnia medication for children with mood (78%) and anxiety disorders (72%). Antidepressants as a class were also commonly used for children in these diagnostic groups. Atypical antipsychotics, anticonvulsants, and short-acting hypnotics were also more likely to be used in children with mood disorders. Melatonin was recommended by more than one-third of respondents. Mitigation of the effects of sleep disruption on daytime functioning was endorsed as an important rationale for the use of sleep medication; concerns about side effects and the lack of empirical support regarding efficacy were cited as significant barriers to their use. ConclusionsInsomnia is a significant clinical problem in children treated by child psychiatrists for a variety of behavioral, neurodevelopmental, and psychiatric conditions. Management with a broad array of psychotropic medications is common and indicates a highly variable clinical approach to insomnia in this pediatric population.

The Effect of Sleep Medications on Cognitive Recovery From Traumatic Brain Injury

To summarize the literature on the available pharmacotherapy for insomnia and the adverse cognitive effects of those options in persons with traumatic brain injury (TBI). Ovid/MEDLINE databases were searched by using the following key words: "brain injury," "sleep initiation and maintenance disorders," "hypnotics and sedatives," "benzodiazepines," "trazodone," and "neuronal plasticity." The reviewed literature consistently reported that benzodiazepines and atypical gamma-aminobutyric acid (GABA) agonists result in cognitive impairment when plasma levels are at their peak. Evidence of residual effects on cognition was reported for benzodiazepines but was seen less often in atypical GABA agonists. However, evidence has also been presented that GABA agonists have adverse effects on neuroplasticity, raising concerns about their use in patients recovering from TBI. Use of benzodiazepines in TBI has been discouraged and some authors also advocate caution in prescribing atypical GABA agonists. Alternate treatments including trazodone and a newer class of agents, melatonin agonists, are highlighted, along with the limited data available addressing the use of these medications in TBI. Finally, suggestions are offered for further research, especially on topic related to neural plasticity and functional recovery.

The Pharmacologic Management of Insomnia in Patients with HIV

Insomnia is common in human immunodeficiency virus (HIV) seropositive populations. Some studies have estimated as many as 70% of HIV patients experience insomnia at some point during their illness. Insomnia has been linked to reduced quality of life as well as treatment non-adherence in these patients. However, there has been very limited research on the treatment of insomnia in this setting. Lacking treatment trials, we carried out a review of the available literature relevant to the pharmacologic treatment of insomnia in HIV seropositive individuals in order to provide guidance for the clinical management of this complex population. A systematic MEDLINE search was performed using as search terms each of the FDA approved or commonly prescribed insomnia medications and "insomnia and HIV." In addition, we reviewed the published literature on HIV therapies and common comorbid conditions and their interactions with insomnia therapies. We found 4 primary factors affecting the pharmacotherapy of insomnia in individuals with HIV: (1) medications used to treat HIV; (2) antibiotics used to treat opportunistic infections; (3) the HIV infection itself; and (4) conditions frequently associated with HIV infection. The means by which these factors affect the expected risk-benefit profile of insomnia therapies is discussed, and recommendations are made for choosing medications in patients encountered in clinical practice.

Pharmakotherapie der primären Insomnie - Über die Wirksamkeit, Sicherheit und Effektivität verschiedener Therapieoptionen

Die Wirksamkeit, Sicherheit und Effektivität der pharmakologischen Therapie insomnischer Beschwerden wurde in den letzten 20 Jahren vielerseits diskutiert. Im vorliegenden Artikel werden auf der Basis publizierter Metaanalysen die verschiedenen Behandlungsoptionen bestehend aus Benzodiazepin-Rezeptor-Agonisten, sedierenden Antidepressiva, Melatonin und alternativen Pharmakotherapien sowie kognitiv-verhaltenstherapeutischen Interventionen dargestellt und verglichen. Bis auf wenige Ausnahmen liegen bisher keine Langzeitstudien vor. Als gesichert scheint, dass die Benzodiazepin-Rezeptor-Agonisten in der Kurzzeitbehandlung der Insomnie zweifellos effektiv sind und sedierende Antidepressiva mittlerweile einen festen Platz in der Behandlung der chronischen Form einnehmen. Trotzdem sind weiterhin Langzeituntersuchungen notwendig, um zu belegen, dass diese pharmakologischen Substanzen langfristig effektiv und gut verträglich sind.

Pharmacotherapy of insomnia

Insomnia is the most common sleep disorder in the industrialized world. A variety of precipitating events have been identified, but when it becomes a persistent problem, maladaptive patterns become established, thereby, perpetuating the sleep disturbance. Individuals with insomnia have impaired next-day functioning, which impacts their quality of life and places them at increased risk of motor vehicle accidents. Insomnia is commonly associated with chronic medical conditions, as well as an increased incidence of mental disorders. Despite considerable scientific advances in both the understanding and treatment, insomnia continues to be inadequately identified and treated, with < 15% of those with severe insomnia receiving appropriate treatment. The mainstay of treatment for insomnia is cognitive-behavioral therapy, along with judicious use of hypnotic agents.

The influence of co-morbidities on prescribing pharmacotherapy for insomnia: evidence from US national outpatient data 1995–2004

SummaryObjective: Patients with insomnia are likely to have other co-morbidities that could affect pharmacotherapeutic choices. This study examined the prevalence and impact of co-morbidities on the pharmacological treatment of insomnia.Study design: A retrospective data analysis of the National Ambulatory Medical Care Survey from 1995 to 2004, comprising patients with a diagnosis of insomnia, was conducted. Multivariate logistic regression models were used to predict the impact of co-morbidities on pharmacotherapy for insomnia.Results: A total of 5,487 unweighted patient visits with insomnia were identified, representing 161.4 million patients in the US. Approximately 38% of these patients had at least one co-morbid condition. Patients with mental co-morbidities, especially anxiety, had decreased likelihood of receiving pharmacotherapy for insomnia.Conclusions: Mental co-morbidities such as episodic mood disorder, anxiety and depression are prevalent in patients with insomnia. However, many co-morbid patients do not receive pharmacological therapy specific for insomnia.

Long-Term Pharmacotherapy in the Management of Chronic Insomnia

Chronic insomnia is common among primary care patients and often necessitates long-term management. The available treatment options for the clinical care of such patients are limited. Medication management is the most common therapy for this condition; however, this practice was hindered until recently by clinical guidelines that discouraged the prescription of the medications approved by the Food and Drug Administration for longer than 4 weeks. Further, few research studies have been conducted on the longer-term medication management of insomnia that might allow clinicians to assess the expected risks and benefits of longer-term therapy. Recent research, however, indicates that longer-term treatment with some agents may be safe and effective. This article reviews these studies and discusses them in the context of the diagnostic steps to consider when deciding whether to initiate or continue pharmacotherapy for insomnia.

Combined therapeutics for insomnia: Should our first approach be behavioral or pharmacological?

Despite the interest in combining therapeutics many issues remain to be resolved regarding the combination of behavioral treatment and pharmacotherapy for insomnia. Studies examining the relative advantages of cognitive behavioral therapy (CBT) and pharmacotherapy have found that improvements may be achieved more quickly with drug treatment but are more sustained with CBT. Combining modes of treatment is not necessarily superior to monotherapy because long-term effects can vary between patients. Various modes of combination are possible, with one or other type of treatment being started or discontinued depending on the phase of treatment and the patient's response. Which treatment to initiate first, or whether to run treatments concurrently, depends on factors such as the nature of the insomnia, treatment history, comorbid conditions, acceptability of treatment to the patient, and treatment cost or availability. Issues of dosage, treatment duration or whether treatment should be given continuously or intermittently will have an effect on how these treatment types can be integrated to provide the best outcome for the patient. A detailed look at the efficacy of behavioral and pharmacological therapies with regard to different outcome measures gives some indication of how these different types of treatment may act in a complementary fashion; observations that may be exploited in the integration of behavioral with pharmacological approaches in clinical practice.

The Use of Pharmacotherapy in the Treatment of Pediatric Insomnia in Primary Care: Rational Approaches. A Consensus Meeting Summary

To formulate a rational approach to the pharmacologic treatment of pediatric insomnia, and to develop clinical guidelines regarding indications, target populations, and parameters for the use of these medications, especially by community-based pediatricians. A multidisciplinary task force developed under the auspices of the American Academy of Sleep Medicine, which included experts in pediatric sleep medicine, psychiatry, pharmacology, neurology, and general pediatrics. Review of existing data regarding current use of over-the-counter and prescription medications for pediatric insomnia in the primary care practice setting, and of empirical data on the pharmacology, safety, efficacy, and tolerability of medications commonly used for the treatment of pediatric insomnia. Group consensus definition of pediatric insomnia and clinical guidelines; working group recommendations regarding special populations and future directions. Use of medications for pediatric insomnia should be diagnostically driven, and should be implemented in conjunction with empirically-based behavioral treatment strategies and adequate sleep hygiene. Specific target populations include children with neurodevelopmental disorders, pervasive developmental disorders, chronic medical conditions, and psychiatric disorders. Additional research, including clinical trials, is critically needed to provide an evidence-based approach to the use of these medications in clinical practice.

Sleep Experts Wake Up to Value Of CBT for Insomnia

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessSleep Experts Wake Up to Value Of CBT for InsomniaJim RosackJim RosackSearch for more papers by this authorPublished Online:3 Dec 2004https://doi.org/10.1176/pn.39.23.00390032aResearchers at Harvard Medical School have shown that patients with chronic sleep-onset insomnia see greater improvement from a course of cognitive-behavioral therapy (CBT) than they do from the market-leading hypnotic medication zolpidem (Ambien).The study, reported in the September 27 Archives of Internal Medicine, was a randomized controlled trial involving 63 adults with chronic sleep-onset insomnia. The research was funded by grants from the National Institutes of Health and National Institute on Drug Abuse.Patients were randomly assigned to CBT, pharmacotherapy (with zolpidem), a combination of CBT and zolpidem, or placebo. Those in the CBT group received five 30-minute sessions over six weeks. The patients were given daily exercises to teach them to “recognize, challenge, and change stress-inducing thoughts,” according to the study's lead author, Gregg Jacobs, Ph.D., an assistant professor of psychiatry at Harvard and a researcher at the Harvard-affiliated Sleep Disorders Center at Beth Israel Deaconess Medical Center.Patients were taught techniques such as delaying time of going to bed or getting up to read if they were unable to fall asleep within about 20 minutes of going to bed, Jacobs said in a press release.Those assigned to receive zolpidem started with 10 mg a night for the first 28 nights (four weeks) of the eight-week treatment period. For the following seven days (week 5), they received 5 mg a night, and then 5 mg every other night for an additional week (week 6). No medication was taken during the final two weeks.Patients randomly assigned to receive placebo followed the same protocol as the medication group without any CBT or “sham therapy.”Jacobs was surprised at what he and his team found.“Sleeping pills are the most frequent treatment for insomnia, yet CBT techniques clearly were more successful in helping the majority of study participants to become normal sleepers. The pills were found to be only moderately effective compared with CBT, and lost their effectiveness soon after they were discontinued.”All patients kept sleep diaries for 14 days before treatment began, for 14 days at mid-treatment (weeks 3 and 4), and for 14 days after treatment ceased (the end of the protocol). In addition, patients underwent three nights of home-based “nightcap” recordings before and after treatment. The“ nightcap monitor” is a two-channel sleep monitor that measures sleep-onset latency as well as other measures of sleep by using eyelid- and head-movement sensors attached to a small, battery-operated recorder placed under the bed pillow.The CBT and the combination groups showed the greatest changes in sleep-onset latency at mid-treatment, with both groups showing a 44 percent reduction in the amount of time it took to fall asleep at bed time. Those taking zolpidem showed only a 29 percent reduction, and those on placebo had only a 10 percent reduction in sleep latency. By the end of week 8, the CBT and combined treatment group each yielded a 52 percent reduction in sleep onset. These significant improvements were maintained for the follow-up period of 18 months, whereas improvements seen in the zolpidem group were not maintained over the long term. In fact, Jacob pointed out, “by the end of the eight-week treatment phase, insomnia returned to baseline levels and did not differ from [those of] the placebo group.”Intriguingly, no significant differences emerged among the groups in terms of total sleep time, though each group exhibited some increase.“Our results suggest CBT should now be considered the first-line treatment for insomnia, which is experienced on a nightly basis by one-third of the nation's adult population,” Jacobs concluded.An abstract of “Cognitive-Behavior Therapy and Pharmacotherapy for Insomnia” is posted online at<http://archinte.ama-assn.org/cgi/content/abstract/164/17/1888>.▪ Arch Intern Med 2004 164 1888 ISSUES NewArchived