Long-term Use Of Hypnotics Research Articles

Factors associated with the long-term use of benzodiazepine receptor agonists as hypnotics among patients with major depressive disorder and comorbid insomnia

BackgroundPatients with major depressive disorder (MDD) and comorbid insomnia are often co-prescribed benzodiazepines (BZDs) or Z-drugs as hypnotics with antidepressants to manage persistent insomnia. However, factors associated with their long-term use remain unclear among MDD patients. MethodsWe retrospectively analyzed data from 351 MDD patients who started antidepressants with co-prescribed hypnotics (BZDs/Z-drugs) and investigated the prevalence of and factors associated with their long-term use at 12 months. We conducted logistic regression analyses of their long-term use, and compared insomnia severities between the continued and discontinued groups of hypnotics in 32 patients whose insomnia severities had been longitudinally assessed. Results66.1% of patients had continued hypnotics for 12 months. Multiple logistic regression analysis revealed that the diazepam-equivalent dose of hypnotics at the start of the combined treatment (>5 mg), the presence of chronic insomnia prior to MDD, and hospitalization correlated with their long-term use (all p < 0.01). We also found the relationship between the insufficient amelioration of insomnia severities and their long-term use. However, confidence in these results is tempered by various factors, including the dependence on hypnotics, the patient's attitude about hypnotic treatment, and the exclusion of subjects treated with other drugs such as sedative antidepressants or antipsychotics. ConclusionsThese clinical indicators may facilitate the selection of treatment strategies for MDD with comorbid insomnia. To avoid the long-term use of hypnotics, their dose at the start of the combined treatment needs to be adequate (≤5 mg) and alternative treatments to BZDs/Z-drugs are required for refractory insomnia.

Prevalence of medication-related problems in complex chronic patients and opportunities for improvement

ObjectiveTo estimate the prevalence of medication-related problems in patients treated in continuous care units and to identify the therapeutic areas in which these problems were more concentrated. MethodObservational descriptive prospective study. Review of clinical histories and outpatient treatment by a hospital pharmacist. Communicating medication-related problems detected to the responsible doctor. Analysis of the therapeutic areas in which the problems were most concentrated. Results85 patients were reviewed, and 368 potential medication-related problems were identified. The areas with the most prevalent medication-related problems were the long-term use of hypnotics, sub-optimal analgesia, optimizable antidepressant treatment, statins in patients older than 75 years in primary prevention and in those with high-intensity doses in secondary prevention, patients with heart failure without angiotensin-converting enzyme inhibitors, and proton-pump inhibitors without indication. ConclusionsTraining interventions should be implemented and computer assistance should be developed to help avoid the most prevalent medication-related problems.

Orexin dual receptor antagonists, zolpidem, zopiclone, eszopiclone, and cognitive research: A comprehensive dose-response meta-analysis.

About one-third of adults have trouble sleeping, ranging from occasional difficulty to chronic insomnia, along with difficulty maintaining sleep. Many studies reported that the long-term use of hypnotics can cause brain dysfunction and damage cognition. The objective of the study is to evaluate whether low, medium, and high doses of orexin dual receptor antagonists (DORA), zopiclone (ZOP), eszopiclone (ESZ), and zolpidem (ZST) can impair cognition. From the beginning through September 20, 2022, PubMed, Embase, Scopus, the Cochrane Library, and Google Scholar were searched. Randomized controlled trials (RCTs) assessing the therapeutic effects of DORA, eszopiclone, and zopiclone for sleep and cognitive function were included. The primary outcomes were indices related to the cognitive profile, including memory, alertness, execution and control function, and attention and orientation. The secondary outcomes were indices related to sleep and adverse events. The standard mean difference (SMD) was generated for continuous variables. Certain data were captured from figures by GetData 2.26 and analyzed using RStudio 4.2. Finally, a total of 8,702 subjects were included in 29 studies. Compared with the placebo, the DSST (Digit Symbol Substitution Test) scores of low, medium, and high doses of DORA were SMD = 0.77; 95% CI: 0.33-1.20; SMD = 1.58; 95% CI: 1.11-2.05; and SMD = 0.85; 95% CI: 0.33-1.36, respectively. The DSST scores of zolpidem at low, medium, and high doses were SMD = -0.39; 95% CI: 0.85-0.07; SMD = -0.88, 95% CI: -2.34-0.58; and SMD = -0.12, 95% CI: -0.85-0.60, respectively. Zopiclone's DSST scale score was SMD = -0.18; 95% CI: -0.54-0.18. In addition, the total sleep time (TST) of low, medium, and high doses of DORA was SMD = 0.28, 95% CI: -0.15-0.70; SMD = 1.36, 95% CI: 0.87-1.86; and SMD = 2.59, 95% CI: 1.89-3.30, respectively. The TST of zolpidem with low, medium, and high doses was SMD = 1.01, 95% CI: 0.18-1.83; SMD = 1.94, 95% CI: 0.46-3.43; and SMD = 1.71, 95% CI: 0.86-2.56, respectively. The TST of low, medium, and high doses of eszopiclone was relatively SMD = 2.03, 95% CI: -0.21-4.27; SMD = 2.38, 95% CI: 1.35-3.42; and SMD = 1.71, 95% CI: 0.60-2.82. Zopiclone's TST was SMD = 2.47, 95% CI: 1.36-3.58. We recommend DORA as the best intervention for insomnia because it is highly effective in inducing and maintaining sleep without impairing cognition. Although zolpidem has a more pronounced effect on maintaining sleep, it is best to reduce its use because of its side effects. Eszopiclone and zopiclone improved sleep quality, but their safety in cognition remains to be verified.

Predicting Hypnotic Use among Insomnia Patients with the Theory of Planned Behavior and Craving.

While long-term hypnotic use is very common in clinical practice, the associated factors have been understudied. This study aims to explore the cognitive factors that might influence the long-term use of hypnotics based on the theory of planned behavior (TPB), and examines the moderating effect of craving between cognitive intention and actual hypnotic-use behavior at follow-up. A total of 139 insomnia patients completed a self-constructed TPB questionnaire to measure their attitude, subjective norm, perceived behavioral control, and behavioral intention of hypnotic use, as well as the Hypnotic-Use Urge Scale (HUS) to measure their craving for hypnotics. They were then contacted through phone approximately three months later to assess their hypnotic use. Hierarchical regression showed that perceived behavioral control was the most significant determinant for behavioral intention of hypnotic use. Behavioral intention, in turn, can predict the frequency of hypnotic use after three months. However, this association was moderated by hypnotic craving. The association was lower among the participants with higher cravings for hypnotic use. The findings suggest that the patients’ beliefs about their control over sleep and daily life situations, and their craving for hypnotics should be taken into consideration in the management of hypnotic use.

Management of chronic insomnia using hypnotics: a friend or a foe?

Epidemiological studies suggest that 10-15% adults meet the present criteria for the diagnosis of insomnia disorder; however, there may be geographical variations. Untreated insomnia disorders have a number of adverse health consequences in addition to economic burden caused by it. Available guidelines mention that CBT-I should be preferred over hypnotics. However, several patients of chronic insomnia are not candidate for CBT-I and for them, hypnotics are the only answer. This paper reviews the literature to answer following questions: What is the current understanding regarding place of hypnotics for in management of insomnia disorder? How many patients misuse or abuse hypnotics, especially benzodiazepines, as commonly believed? Do we have data from human studies regarding low-dose benzodiazepine dependence? What does hypnotics produce-withdrawal insomnia, rebound insomnia or end of dose phenomenon? Are adverse effects of benzodiazepines worse than other psychotropic medications? Is prescription of hypnotics more troublesome than untreated insomnia disorder? Available literature suggests that there is an unreasonable negative bias attached to the use of hypnotics. Only a sub-set of patients who are prescribed hypnotics, meet the criteria for "dependence" in long term. Other patients either discontinue it (as insomnia remits) or change to occasional use (since insomnia may be relapsing remitting disorder), or continue using it in low dose (since insomnia reappears as hypnotics are discontinued, similar to increase in blood sugar after hypoglycemics are discontinued). Meta-analysis shows that adverse effects of hypnotics are comparable to that of other psychotropic medications. Considering the consequences and risks associated with untreated insomnia disorder, even long-term use of hypnotics is justified, however with the careful watch that patients are not increasing the dose. This approach is especially important in geographical areas where trained CBT-I therapists are not available.

The psychological symptom burden in partners of pancreatic cancer patients: a population-based cohort study.

Pancreatic cancer (PC) has high morbidity and mortality and is stressful for patients and their partners. We investigated the psychological symptom burden in partners of PC patients. We followed 5774 partners of PC patients diagnosed from 2000 to 2016 up for first redeemed prescriptions of antidepressants or hospital admission, anxiolytics, and hypnotics as proxies for clinical depression, anxiety, and insomnia and compared them with 59,099 partners of cancer-free spouses. Data were analysed using Cox regression and multistate Markov models. The cumulative incidence proportion of first depression was higher in partners of PC patients compared to comparisons. The highest adjusted HR of first depression was seen the first year after diagnosis (HR 3.2 (95% CI: 2.9; 3.7)). Educational level, chronic morbidity, and bereavement status were associated with an increased risk of first depression. There was a significantly higher first acute use (1 prescription only) of both anxiolytics and hypnotics and chronic use (3+ prescriptions) of hypnotics in partners of PC patients than in comparisons. Being a partner to a PC patient carries a substantial psychological symptom burden and increases the risk for first depression and anxiolytic use and long-term use of hypnotics. Attention should be given to the psychological symptom burden of partners of PC patients, as this may pose a barrier for the optimal informal care and support of the PC patient, as well as a risk for non-optimal management of symptoms in the partner.

Pharmacological Management of Insomnia.

Insomnia is a highly prevalent condition associated with significant morbidity, reduction in quality of life, and increase in healthcare costs, and is a risk factor for multiple physical and mental disorders. The primary treatment modality is cognitive behavioral therapy for insomnia (CBT-I) but this is associated with difficulties with access and higher cost as well as poor response in some patients. Therefore, pharmacotherapy for insomnia is common and hypnotic agents are among the most frequently prescribed medications in the United States. Older medications for insomnia are limited by their side effect burden and narrow therapeutic window. Newer hypnotics, on the other hand, have been shown to have a better safety profile and longer term efficacy. While some studies have shown that long-term hypnotic use is associated with adverse outcomes, the current evidence is equivocal. The decision to treat chronic insomnia disorder with long-term hypnotics should be individualized and balance the potential risks of continuing hypnotic medication use with the risks of untreated persistent insomnia and associated functional limitations. This clinical review discusses the currently available medication options to treat insomnia, their mechanisms of action, dosing, and side effect profiles. This review also provides guidance on long-term management of hypnotics and the use of these medications in the elderly, those with medical comorbidities, and other special populations.

Reconsidering Benzodiazepines and Z-Drug Prescriptions: Responsible Prescribing and Deprescribing

Benzodiazepines and sedative-hypnotic (Z-drugs), collectively termed hypnotic drugs, bind to γ-aminobutyric acid receptors, the primary inhibitory neurotransmitters in the brain. Hypnotic drugs are among the most prescribed medications worldwide, with primary care providers leading this prescribing trend, primarily for the management of insomnia and anxiety. There is no evidence to support the use of long-term hypnotics, and evidence regarding the risks associated with long-term use of hypnotics is growing. However, it is not too late to reverse this hazardous prescribing trend and incorporate responsible hypnotic prescribing and describing practices

Long-term use of hypnotics: Analysis of trends and risk factors

ObjectivePatients with chronic insomnia are prone to long-term use of hypnotics. Reported risk factors include aging, female sex, and comorbid psychiatric disorders. However, most previous studies have been cross-sectional cohort studies. MethodWe conducted a retrospective cohort study using medical service payment data for 330,000 people to determine the duration of prescription of hypnotics and the risk factors for long-term use. We followed up 3981 patients (2382 M, 1599 F, age 40.3 ± 12.4 years) who were prescribed hypnotics for the first time between April 2005 and March 2008. ResultsOf these 3981 patients, 59.6% were prescribed hypnotics for only 1 month, 11.3% were prescribed hypnotics for 2 consecutive months, and 10.1% of patients continued receiving prescriptions for the entire 12-month observation period. In multiple logistic time-dependent Cox analyses, use of antidepressants, mean dose of hypnotics, and advanced age were significantly associated with long-term use of hypnotics (p < 0.01). In an analysis of the association between long-term use of hypnotics and prescribed dosage, high monthly dose, advanced age, and department of first visit were significantly associated with long-term use (p < 0.01). ConclusionThese clinical indicators may be effective for early identification of patients with insomnia who are at high risk of developing physical dependence on hypnotics.

Current Clinical Practice for the Use of Hypnotics to Manage Primary Insomnia in Adults in a Tertiary Hospital in Saudi Arabia: An Audit Study.

Despite the risks associated with hypnotics and their recent increased use in Saudi Arabia, there are no specific national guidelines for using these medicines to treat insomnia nor are there any data on how these medicines are currently prescribed. There is the potential, however, that some physicians might be adhering to the United States guidelines. The current audit study was aimed to assess the current practice in treating insomnia with hypnotics in Saudi Arabia, and to evaluate its agreement with the US guidelines. The audit was conducted using data collected between April 2012 and March 2017 at King Fahad Central Hospital (KFCH; Jazan), of patients who were either prescribed benzodiazepines (BZDs) or Z-drugs or diagnosed with insomnia. The audit criteria followed two US guidelines for the management of insomnia in adults. Data included documented diagnosis, use of CBT-I (Cognitive Behavioral Therapy for Insomnia), use of BZDs and Z-drugs including treatment regimen, and whether physicians prescribed anti-histamines for insomnia. The data were analyzed using STATA 14 after transcription to a MS XL file. Of the 504 records reviewed, 379 patients (75%) were prescribed BZDs or Z-drugs; only 182 (48%) of them had clearly documented indications for their use. Three hundred and seven patients (60%) were diagnosed with insomnia; none of them received CBT-I as initial treatment. No patients on long-term use of hypnotics were reviewed by their physicians after they began using the medication. More than 43% of patients were prescribed anti-histamines for insomnia. No records met all (or even six) of the seven criteria. KFCH physicians do not follow US guidelines. Therefore, the Ministry of Health (MOH) should improve its administrative systems including documentation, and instead of using international guidelines that are seldom followed, physicians should be trained in prescribing hypnotics and national guidelines need to be developed.

Development and psychometric evaluation of the Hypnotic-Use Urge Scale

Hypnotic dependence is a major concern for long-term hypnotic use, but is not consistently reported in empirical studies. The inconsistent findings may be in part due to individual differences in the psychological processes of hypnotic use. To further the understanding of this issue, the current study developed the Hypnotic-Use Urge Scale (HUS) to measure the urge to take hypnotics at bedtime. Insomnia patients with a history of hypnotic use (n = 202; mean age = 46.4 years) were included in the study. Participant’s agreement with 37 statements regarding anticipation, desire, and feelings about hypnotic use at bedtime was rated using Likert-type scales. An exploratory factor analysis identified 20 statements to be included as items of the HUS, which were categorized into three subscales: Factor 1—anticipated effects of hypnotic use; Factor 2—compelling desire to use hypnotics; and Factor 3—preoccupation and pleasurable feelings from hypnotic use. The total scale and subscales demonstrated good internal consistency and test–retest reliability. The scale scores correlated significantly with the frequency of hypnotic use. Intriguingly, although Factor 1 accounted for the highest portion of the total variance, Factor 2 was identified to be the best predictor for the frequency of hypnotic use. The results support the use of the HUS as a valid and reliable measure to assess the urge to use hypnotic at bedtime. It could be used to measure the psychological processes associated with hypnotic dependence in both research and clinical settings.

Mélatonine : aspects physiologiques et pharmacologiques en relation avec le sommeil, intérêt d’une forme galénique à libération prolongée (Circadin®) dans l’insomnie

Melatonin is a hormone secreted by the pineal gland. It displays a very marked nycthohemeral rhythm, which is entrained to the light dark cycle. The secretion spreads over 8–10 hours, with a maximum around 3–4 a.m. Melatonin plays the role of an endogenous synchronizer which regulates circadian rhythms, especially the sleep/wake and temperature rhythms. Acute melatonin administration reduces sleep latency, increases theta/alpha power and spindle activity (soporific activity). Fast-release melatonin preparations showed inconstant effects in insomnia. Melatonin displays a short blood half-life, a fast turn over and undergoes a high first-pass hepatic metabolism. More than 80% is excreted exclusively in the urine as 6-sulfatoxymelatonin. The individual's capacity to produce the endogenous hormone, the decline in circadian clock output and the increase in complaints of poor sleep quality at older age led to develop a prolonged-release melatonin preparation to mimic the endogenous secretion in patients. This reviews provides data on physiological and pharmacological melatonin effects related to sleep and summarizes trials published about Circadin® efficacy and tolerance in insomnia. Preliminary therapeutic data on other indications are given. The main clinically relevant benefits are improvements in sleep quality and latency, next-day morning alertness and quality of life. The response develops over several days. An oral 2-mg dose once daily, for 3 months, is generally well tolerated with no rebound, withdrawal or ‘hangover’ effects and no safety concerns on concomitant therapy with antihypertensive, antidiabetic, lipid-lowering or anti-inflammatory drugs. Untoward effects of hypnotics on cognition, memory, postural stability and sleep structure are not seen with Circadin®. Given as a first-line prescription, with 13 weeks’ posology and the lack of rebound effects, Circadin® has the potential to improve quality of life in insomnia patients aged 55 years and older and avoid long-term use of hypnotics.

Qualitative Study of Long-Term Sedative-Hypnotic use Patterns

Hypnotics are the most common choice of treatment for insomnia. Clinically, high proportion of hypnotic users is long-term user. However, studies showed disagreements over the effectiveness and safety of long-term use of hypnotics. Adopting the methods of the grounded theory, this research has conducted a series of in-depth interviews in order to understand the psychological experience and to construct a behavioral theory of the long-term hypnotics users. Twenty-two long-term users of hypnotics have been interviewed with well-trained interviewer. This research has found that long-term hypnotic users could be divided into three pattern groups: “transitional modality”, “contradictory control”, and “inertia balance”. It is anticipated that this research will shed lights on the treatment of long-term hypnotics medication for the clinical practitioners and provide a foundation for the future studies on the relationship between the relevant variables of the medication patterns and the prognosis.

Factors associated with long-term use of hypnotics among patients with chronic insomnia.

This study investigated factors associated with long-term use of benzodiazepines (BZDs) or benzodiazepine receptor agonists (BzRAs) as hypnotics in patients with chronic insomnia. Consecutive patients (n = 140) with chronic insomnia were enrolled in this study (68 men and 72 women; mean age, 53.8±10.8 years). All patients filled out a self-assessment questionnaire asking clinical descriptive variables at the baseline of the treatment period; patients received the usual dose of a single type of BZD or BzRA. The Pittsburgh Sleep Quality Index (PSQI) and the Zung Self-Rating Depression Scale were self-assessed at the baseline, and the former was re-evaluated at the time of cessation of medication or at the end of the 6-month treatment period. The PSQI included the following sub-items: evaluating sleep quality (C1), sleep latency (C2), sleep duration (C3), habitual sleep efficiency (C4), frequency of sleep disturbance (C5), use of sleeping medication (C6), and daytime dysfunction (C7). Among the patients, 54.6% needed to continue hypnotics for a 6-month treatment period. Logistic regression analysis revealed that, among descriptive variables, only the PSQI score appeared as a significant factor associated with long-term use {odds ratio (OR) = 2.8, 95% confidence interval (CI) = 2.0–4.0}. The receiver operating curve (ROC) analysis identified that the cut-off PSQI total score at the baseline for predicting long-term use was estimated at 13.5 points (area under the curve = 0.86, 95% CI = 0.8–0.92). Among the sub-items of PSQI, the increases in C1: (OR = 8.4, 95% CI = 2.4–30.0), C3: (OR = 3.6, 95% CI = 1.1–11.5), C4: (OR = 11.1, 95% CI = 3.6–33.9), and C6: (OR = 3.4, 95% CI = 1.9–6.2) scores were associated with long-term use. This study revealed that a high PSQI score at the baseline, particularly in the sub-items relating to sleep maintenance disturbance, is predictive of long-term hypnotic treatment. Our results imply the limitation of the effectiveness of hypnotic treatment alone for chronic insomnia.

Novel Developments in the Pharmacological Management of Insomnia

Advances in the basic science of sleep/wake neurophysiology are driving the exploration of new pharmacologic approaches with continued improvement in efficacy and safety.

Effects of pregabalin on patients with hypnotic dependent insomnia

Introduction Long-term use of hypnotics runs the risk of dependency, and the patient usually experiences difficulties in withdrawal or discontinuing treatment. It has been reported that pregabalin has a positive effect on both sleep and withdrawing from hypnotics. The objective of this study was to investigate the efficacy of pregabalin on sleep in patients with hypnotic dependent insomnia. Materials and methods This is a prospective, open-label, single arm, and interventional study. We enrolled patients with hypnotic dependent insomnia who were 18 older. The starting dosage of Pregabalin was 75 mg/day and was increased up to as much as 300 mg/day, depending on the individual patients condition, while tapering off hypnotics. After four weeks of titration, the final dosage amount was maintained for at least another 4 weeks. Sleep and clinical variables were evaluated by using the Pittsburgh Sleep Quality Index (PSQI), Epworth sleepiness scale (ESS), Insomnia Severity Index (ISI), the hospital depression and anxiety scale (HADS), in addition to the polysomnography (PSG) at baseline and after treatment. A paired t-test was used for analyzing the effect of pregabalin using SPSS 18.0 program. Results We enrolled 40 patients whose mean age was 52.33 ± 8.39, 28 were women (70.0%). Twenty-one (52.5%) were successful in withdrawing from hypnotics. The duration of withdrawing from hypnotics was 42.19 ± 16.08 days (range: 27.00–84.00). The mean pregabalin dose was 121.43 ± 69.05 mg/day (range: 75.00–300.00). The results using pregabalin showed a significant improvement with the total score of the PSQI (15.05 ± 2.11, 8.90 ± 3.08, p 0.001), insomnia severity index (20.95 ± 4.32, 9.62 ± 4.41, p 0.001), BDI-2 (7.95 ± 4.20, 5.67 ± 3.69, p = 0.013) and HAS (7.24 ± 4.90, 4.67 ± 3.92, p = 0.002). The main adverse effects of pregabalin were nausea and dizziness. Conclusion Our results showed pregabalin is effective in allowing patients with hypnotic dependent insomnia to withdraw from hypnotics, with a success rate of more than half, and the quality of sleep improved in the group as a whole. Acknowledgements This work was supported by a research promoting grant from Pfizer, Korea.

Risk of Dementia in Patients with Insomnia and Long-term Use of Hypnotics: A Population-based Retrospective Cohort Study

BackgroundHypnotics have been reported to be associated with dementia. However, the relationship between insomnia, hypnotics and dementia is still controversial. We sought to examine the risk of dementia in patients with long-term insomnia and the contribution of hypnotics.MethodsData was collected from Taiwan’s Longitudinal Health Insurance Database. The study cohort comprised all patients aged 50 years or older with a first diagnosis of insomnia from 2002 to 2007. The comparison cohort consisted of randomly selected patients matched by age and gender. Each patient was individually tracked for 3 years from their insomnia index date to identify whether the patient had a first diagnosis of dementia. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsWe identified 5693 subjects with long-term insomnia and 28,465 individuals without. After adjusting for hypertension, diabetes mellitus, hyperlipidemia, and stroke, those with long-term insomnia had significantly higher risks of dementia (HR, 2.34; 95% CI, 1.92–2.85). Patients with long-term insomnia and aged 50 to 65 years had a higher increased risk of dementia (HR, 5.22; 95% CI, 2.62–10.41) than those older than 65 years (HR, 2.33; 95% CI, 1.90–2.88). The use of hypnotics with a longer half-life and at a higher prescribed dose predicted a greater increased risk of dementia.ConclusionsPatients with long-term use of hypnotics have more than a 2-fold increased risk of dementia, especially those aged 50 to 65 years. In addition, the dosage and half-lives of the hypnotics used should be considered, because greater exposure to these medications leads to a higher risk of developing dementia.

Prolonged-release formulation of melatonin (Circadin) for the treatment of insomnia

Introduction: Insomnia is common among the elderly. The use of hypnotic drugs in elderly patients is frequently criticized owing to dependency, cognitive impairments, falls and withdrawal effects. The production of melatonin, a physiological sleep and circadian rhythm regulator, declines with age. Prolonged-release melatonin (Circadin®), designed to mimic the endogenous pattern of melatonin production, is licensed for insomnia in patients aged ≥ 55 years.Areas covered: This review summarizes published studies on Circadin's efficacy and safety (Summary of Product Characteristics and Medline search on ‘Circadin' and ‘insomnia').Expert opinion: The main significant and clinically relevant benefits are improvements in sleep quality and latency, next-day morning alertness and quality of life. The responses may develop over several days. An oral 2-mg dose once daily, for 3 months, has generally been well tolerated with no rebound, withdrawal or ‘hangover' effects and no safety concerns on concomitant therapy with antihypertensive, antidiabetic, lipid-lowering or anti-inflammatory drugs. Untoward effects of hypnotics on cognition, memory, postural stability and sleep structure are not seen with Circadin. Given as a first-line prescription, with 13 weeks' posology and the lack of rebound effects, Circadin has the potential to improve quality of life in insomnia patients aged 55 years and older and avoid long-term use of hypnotics.

The Effect of Non-Pharmacological Treatment for Psychophysiological Insomnia on Cardiovascular Autonomic Regulation Assessed Using Heart Rate Variability

Insomnia is defined as difficulty initiating or maintaining sleep, waking up too early, or experiencing non-restorative sleep. Several studies have shown that insomnia is associated with various medical conditions, including hypertension, diabetes, and congestive heart failure.1,2 Furthermore, both insomnia and short sleep duration are associated with increased risk of cardiovascular complications and high mortality rates.3,4 Studies have examined the relationship between insomnia and the risk of cardiovascular complications by measuring heart rate variability (HRV),5-7 which is a non-invasive method for assessing cardiovascular risk.8 This research showed altered cardiac autonomic regulation, as measured using HRV, in patients with psychophysiological insomnia. Although chronic sleep disturbance may increase the risk of serious health problems, whether improving insomnia will improve health is debatable.9 One recent study found that treating insomnia with hypnotics or non-pharmacological treatment improved patients’ quality of life (QOL).10-13 However, other studies have reported hypnotics decreased the physical aspects of QOL.11 Furthermore, long-term use of hypnotics is associated with various adverse events and, potentially, dependency. Non-pharmacological therapy is a first-line treatment for primary insomnia,14 and it comprises behavioral, cognitive, and educational components. Most studies have reported that nonReceived: February 4, 2011 Revised: March 24, 2011 Accepted: April 1, 2011

Digest

AbstractDepression and anxietyDepression‐related insomniaLong‐term use of hypnotics is frowned on but US investigators have found that a modified‐release formulation of zolpidem has sustained benefits in patients with depression‐related insomnia (J Clin Psychiatry 2011;doi:10.4088/ JCP.09m05571gry). Compared with placebo over eight weeks in individuals taking concomitant escitalopram, zolpidem 12.5mg nightly improved total sleep time, sleep quality and measures of functioning the next day, and reduced sleep onset latency and number of awakenings. It had no effect on scores of depression or quality of life. Some individuals continued treatment for a further 16 weeks, with similar results.Home‐based careService models can also influence the outcome of treatment: in an Austrian study, 60 elderly people with major depression were randomised to receive conventional outpatient management or home‐based care (Br J Psychiatry 2010;197:463‐7). After three and 12 months, home‐based care was associated with fewer symptoms of depression, better global functioning and higher quality of life scores. Those receiving home‐based care had fewer admissions and less time in inpatient care, resulting in lower total costs.SSRIs and strokeSSRIs increase the risk of gastrointestinal bleeding but, surprisingly, there is little evidence about the risk of stroke during treatment. A case‐control study, using the UK General Practice Research Database, identified 365 195 patients who had been prescribed an SSRI or a tricyclic antidepressant (TCA) between 1992 and 2006 (Br J Clin Pharmacol 2011;71:116‐20). Within this cohort, there were 357 cases of stroke, who were matched with 1631 controls. Neither SSRIs nor TCAs were significantly associated with an increased risk of stroke and there was no evidence that a history of cerebrovascular events altered this risk.Depression and HIVPeople with HIV infection who have depression are less likely to take antiretroviral therapy. Treatment with an antidepressant should therefore improve out‐comes but, US investigators say, estimates of this potential benefit have proved unreliable (Arch Gen Psychiatry 2010;67:1282‐90). Monitoring 158 people who were homeless or living in shelters over the five years to 2007, they estimated that antidepressant therapy increased the odds of taking anti‐retroviral therapy nearly four‐fold, increased adherence by 25 per cent and doubled the odds of self‐reported complete adherence. These changes were associated with doubling the odds of achieving viral suppression.Discontinuing benzodiazepinesWhat is the long‐term success rate of discontinuing benzodiazepines? Researchers from The Netherlands report that 59 per cent of patients who received a stepped‐care intervention programme remained abstinent 10 years later (Family Practice 2010; doi:10.1093/ fampra/cmq113). Abstinence at 21 months predicted long‐term success. Those who relapsed tended to use lower doses of benzodiazepines than before the intervention.Psilocybin for anxietyThe search for novel anxiolytics has been a long one. Psilocybin, the serotonergic hallucinogen in magic mushrooms, is the latest candidate (Arch Gen Psychiatry 2011;68:71‐8). In 12 adults with advanced cancer and anxiety, psilocybin 0.2mg per kg significantly reduced anxiety scores at one and three months; there was also a trend for improved mood though this was not consistently significant. No adverse effects were reported. Copyright © 2011 Wiley Interface Ltd