Zolpidem

Zolpidem increased cancer risk in patients with sleep disorder: A 3-year follow-up study

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  Abstract

Background: Zolpidem has been increasingly used in patients with sleep disorder due to its minimal respiratory depressor effects and short half-life. Materials and Methods: Recent case reports indicate that zolpidem usage may be associated with increased cancer mortality. This study aimed to determine the impact of zolpidem usage on the risk of incident cancer events in sleep disorder patients over a 3-year follow-up. Of the 6924 subjects diagnosed with sleep disorder in 2004, 1728 had used zolpidem. A Cox proportional hazard model was performed to estimate 3-year cancer event-free survival rates for patients using zolpidem and those not using it, after adjusting for confounding and risk factors. Results: At the end of follow-up, 56 patients had incident cancers, 26 (1.5%) who used zolpidem, and 30 (0.6%) who did not. After adjustments for gender, age, comorbidities, and other medications, patients using zolpidem had a 1.75 times (95% confidence interval [CI], 1.02–3) greater risk of cancer events than those not using zolpidem during the 3-year follow-up. Greater mean daily dose and longer use were associated with increased risk. Among patients with sleep disorder, mean daily dose >10 mg and length of drug use >2 months was associated with 3.74 times greater risk (95% CI, 1.42–9.83; P = 0.008) of incident cancer events. Conclusions: In this study, zolpidem use increased cancer events risk in sleep disorder patients. Risks and benefits of chronic zolpidem usage should be explained to sleep disorder patients, and long-term use should be monitored.

Keywords: Cancer, hazard ratios, mean daily dose, sleep disorder, zolpidem

 

How to cite this article:
Lin SC, Su YC, Huang YS, Lee CC. Zolpidem increased cancer risk in patients with sleep disorder: A 3-year follow-up study. J Med Sci 2016;36:68-74

 

How to cite this URL:
Lin SC, Su YC, Huang YS, Lee CC. Zolpidem increased cancer risk in patients with sleep disorder: A 3-year follow-up study. J Med Sci [serial online] 2016 [cited 2018 Dec 15];36:68-74. Available from: http://www.jmedscindmc.com/text.asp?2016/36/2/68/181522

 

  Introduction Top

The clinical use of sedatives or hypnotics has increased gradually so that a 53% growth in prescriptions over 5 years was reported in 2006.[1] Some 6–10% of US adults have used hypnotics, and the percentage is higher in Europe.[2] The most commonly prescribed medications are benzodiazepines, nonbenzodiazepines, gamma-aminobutyric acid (GABA) agonists, melatonin receptor agonists, sedating antidepressants, antihistamines, and wake-promoting drugs.[3] However, the potential side effects of hypnotics, such as cancer risk, may be overlooked.

Zolpidem, an imidazopyridine in use since 1980, has been increasingly used in patients with sleep disorder due to its very few respiratory depressor effects and short half-life of 2.5 h.[4],[5] Of the 8607 patients who reported side effects of zolpidem on the eHealthMe website, which continuously monitor drug adverse effects, 71 (i.e. 0.82%) reported incident cancer.[6] Previous studies reported an association of hypnotics and cancer death.[7],[8],[9] However, in these studies, neither the specific hypnotic drug nor the quantity was provided. Furthermore, zolpidem was not included in these series. Recently, Kripke et al. conducted a matched cohort study and found that taking hypnotics, either zolpidem or temazepam, was associated with increased cancer risk in rural US patients.[10] The main limitation of this study was its stratification of hypnotic drug dosage in three equivalent groups to validate the dose-response relationship; however, such stratification is not practical in terms of clinical use.

The critical dosage and length of use at which zolpidem will affect the development of incident cancer events in patients with sleep disorder have not clearly explored. The goals of the current study are (1) to determine the relative risk of incident cancer events associated with zolpidem use in sleep disorder patients using a population-based dataset and (2) to provide the critical dosage and length of zolpidem usage associated with increased cancer risk.

  Materials and Methods Top

Ethics statement

This study was initiated after approval by the Institutional Review Board of Buddhist Dalin Tzu Chi General Hospital, Taiwan. Since all identifying personal information was stripped from the secondary files before analysis, the review board waived the requirement for written informed consent from the patients involved.

Database

The National Health Insurance Program, which provides compulsory universal health insurance, was implemented in Taiwan in 1995. It enrolls up to 99% of the Taiwanese population and contracts with 97% of all medical providers. The resulting database contains comprehensive information on insured subjects including dates of clinical visits, diagnostic codes, details of prescriptions, and expenditure amounts. This study used the Longitudinal Health Insurance Dataset for 2004–2006 released by the Taiwan Nation Health Research Institute. The patients studied did not differ statistically significantly from the general population in age, gender, or health care costs, as reported by the Taiwan National Health Research Institute (www. nhri.org.tw).

Study population

All patient records in the dataset between January 1, 2002, and December 31, 2002, with sleep disorder diagnostic codes (International Classification of Diseases, 9th revision-Clinical Modification [ICD-9-CM] 780.5x) from an urban area were included in the study.[11],[12] Excluded were those with any type of cancer (ICD-9-CM codes 140-208) diagnosed before or during the index ambulatory visit.

Identification of study cohort

A total of 6924 sleep disorder patients were identified. Each patient was tracked for 3 years from his or her index ambulatory visit in 2002 to identify outcomes, including any type of incident cancer (ICD-9-CM 140-208). To maximize case ascertainment, only patients verified by also being in cancer and catastrophic illness patient database were included in the study. These patients were then linked to the administrative data for the period 2002–2004 to calculate cancer disease-free survival time, with cases censored for patients who withdrew coverage from the National Health Insurance Program or were still robust without defined events at the end of follow-up.

Definition of exposure and covariate adjustment

The main exposure of interest was zolpidem. The dosage, date of prescription, supply days, and a total number of pills dispensed were obtained from the outpatient pharmacy prescription database. The mean daily dose was estimated by dividing the cumulative number of pills prescribed by the follow-up time from the date of initiating zolpidem treatment to the date of incident cancer, date of stopping medicine, or end of this follow-up study. The defined daily dose (DDD) was 10 mg for zolpidem. Other medications included in analysis were antihypertensives (i.e. propranolol, terazosin, doxazosin, prazosin, atenolol, furosemide, nifedipine, verapamil, diltiazem, isosorbide dinitrate, lisinopril, amitriptyline, chlorpromazine, or prochlorperazine), psychotropic agents (i.e. diazepam, alprazolam, or haloperidol), oral hypoglycemic agents, and insulin. Information on patients’ age, gender, comorbidities, and monthly income level as a proxy of socioeconomic status (SES) were collected. The comorbidities for each patient was based on the modified Charlson comorbidity index score, a widely used measure for risk adjustment in administrative claims data sets.[13]

Statistical analysis

The SAS statistical package, version 9.2 (SAS Institute, Inc., Cary, NC), and SPSS version 15 (SPSS Inc., Chicago, IL, USA) were used for data analysis. Pearson’s Chi-square test was used for categorical variables, demographic characteristics (age group and gender), comorbidities, and medications.

The 3-year cancer event-free survival rate was estimated using the Kaplan–Meier method. The cumulative risk of incident cancer event was estimated as a function of time from initial treatment. A Cox proportional hazard regression model was used to calculate the risk of cancer event in sleep disorder patients who used zolpidem versus those who did not, after adjustments for age, gender, comorbidities, SES and other medication usage. A P < 0.05 was considered statistically significant in the regression models.

  Results Top

The distribution of demographic characteristics for the two cohorts is shown in [Table 1]. Those taking zolpidem were significantly older and more likely to be female than those who did not take it. They were also more likely to have more comorbidities, low SES, and more frequently used antiglycemic drugs, psychotropic agents, and antihypertensive medications.

Table 1: Baseline characteristics (n=6924)

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At the end of follow-up, 56 patients had incident cancers, 26 (1.5%) in those using zolpidem, and 30 (0.6%) in those not using it. Patients using zolpidem had an increased risk of cancer events. [Table 2] shows the types of cancer events for the two cohorts stratified by gender. Increased mean daily dose and longer use were associated with increased cumulative risk of cancer events [Figure 1] and [Figure 2]. After adjustments for gender, age, comorbidities, and other medications, patients using zolpidem had a 1.75-times (95% CI, 1.02–3.02) higher risk of cancer events than those who did not use zolpidem during the 3-year follow-up period. [Figure 3] shows the combined effect of mean daily dose and length of zolpidem use on increased cancer risk. [Table 3] shows the adjusted ratios of cancer incidence with zolpidem usage after adjusting for gender, comorbidities, and other medications. Mean daily dose >1 DDD and usage >2 months was associated with 3.74 times (95% CI, 1.42–9.83; P = 0.008) higher risk of incident cancer events in a Cox regression model.

Table 2: Incident tumors in individuals with zolpidem usage and those without by stratification for gender

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Figure 1: Effect of zolpidem dose on cancer risk

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Figure 2: Effect of zolpidem duration on cancer risk

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Figure 3: Combined effect of zolpidem dose and duration on cancer risk

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Table 3: Adjusted hazard ratios for zolpidem in patients with sleep disturbance

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  Discussion Top

Our data showed that zolpidem usage was associated with increased incident cancer risk in patients with sleep disorder. Zolpidem usage >1 DDD for a period >2 months incurred a 3.7-fold higher risk of cancer events. Although zolpidem, the newer nonbenzodiazepine, has been shown to be safe and effective in patients with insomnia,[14] its chronic usage should be carefully restricted and monitored.

Our results suggest that zolpidem usage for more than 2 months increases cancer risk significantly in patients with sleep disorder. Comparing with previous studies, this series further provided a critical period (>2 months) and mean daily dose (>1 DDD) for elevated risk of incident cancer for clinical physicians and the general population.

Due to its short half-life and selective Type I GABAA receptor agonist, zolpidem is a widely used, standard treatment for patients with sleep disorder or insomnia.[3],[15] Of the 8607 patients who reported side effects with zolpidem use on the eHealthMe website, which continuously monitors drug adverse effects, 71 (i.e., 0.82%) reported an incident cancer.[6] In our study, 1.5% persons with zolpidem usage developed incident cancer within 3 years. Zolpidem use was associated with a 1.8-times higher risk of cancer events after adjusting for other medications and confounding factors. Our findings are consistent with Iqbal et al. that zolpidem usage was associated with a 1.13-times higher risk of cancer (95% CI, 1.09–1.17).[16] Higher doses and longer use were positively associated with cancer risk. This series revealed that a mean daily dose >1 DDD and drug usage >2 months was associated with 3.7 times risk (95% CI, 1.4–10) of incident cancer events in patients with sleep disorder.

The exact relationship between zolpidem and infection events remains unknown although several mechanisms are plausible. Benzodiazepines have been found to affect polymorphonuclear cell chemotaxis and phagocytosis.[17] Benzodiazepines in general suppress the immune response through peripheral and central benzodiazepine receptors.[18] The impairment of macrophage spreading could be attributed to the anti-inflammatory effect of the peripheral benzodiazepine receptor on blood cells through inhibition of the release of pro-inflammatory cytokines such as interleukin-6 and interleukin-13.[19] An uncontrolled small case series described carcinogenicity following the prescription of zopiclone or eszopiclone to HIV Type 1 infected individuals.[20] Eszopiclone and zolpidem use have been reported associated with increased risk of infection, raising the speculation that hypnotics impair immune surveillance.[21] A suppression of immune function may partly explain the increased risk of incident cancers. Sparse data on the new hypnotics (eszopiclone, zaleplon, zolpidem, and ramelteon) suggest an increased risk of cancer, which is supported by studies demonstrating a carcinogenic effect in rodents.[22]

Furthermore, hypnotics such as zolpidem can increase the incidence of sleep apnea and may suppress the respiratory drive. Zolpidem increased the apnea index and provoked greater oxygen desaturation than flurazepam and placebo in a controlled, double–blind, cross-over study. Such that 20 mg zolpidem failed to overcome the existing contraindications to administration of hypnotic drugs in patients with heavy snoring and obstructive sleep apnea syndrome.[23] Sleep apnea induced by medication may in turn induce early apoptosis of large granular lymphocytes which further compromises immunity and reduces immune surveillance.[24]

A greater incidence of depression with zolpidem use has been reported.[25] A decrease in the number of natural killer T-cells has also been reported in patients with major depressive disorder.[26] Depressed immunity to varicella zoster in older adults with major depressive disorder has been observed.[27] Compromised immunity may contribute to tumor formation.

Benzodiazepines can decrease lower esophageal sphincter tone, independently of the awareness or drowsiness of patients.[28] Zolpidem reduced the arousal response to nocturnal acid exposure and increased the duration of each esophageal acid reflux event.[29] Gastroesophageal reflux can lead to chronic sinusitis, recurrent croup, and laryngitis.[30] A recent meta-analysis reported an increased risk of infection with zolpidem use.[21] Infection may result from increased gastroesophageal regurgitation or from zolpidem usage and subsequent increased cancer development.[31] However, the exact relationship between zolpidem and cancer event remains unknown, and further research is needed to explore the possible mechanism.

This study has several limitations. First, the diagnosis of sleep disorder, incident cancer, and any other comorbid conditions are completely dependent on accurate recording of ICD-9-CM codes. However, the cancer events were further verified by their appearance in the registry for cancer and catastrophic illness patient database. Furthermore, the National Health Insurance Bureau of Taiwan randomly reviews charts and interviews patients to verify diagnosis accuracy. Hospitals with outlier charges or practice may undergo an audit, with subsequent heavy penalties for malpractice or discrepancies. Second, the database did not include detailed information on body mass index, smoking, or alcohol drinking. Further studies linking administrative data and primary surveys of health behaviors are warranted. Third, we did not control for depression, anxiety, and other emotional factors, which may have influenced these results. Fourth, the number of cases was small, warranting caution in interpreting the data. Finally, associations derived from epidemiological studies do not prove causality. It is hard to discern the correlation between the zolpidem usage and the sleep disorder in time sequence. We cannot exclude the possibility that zolpidem usage is a marker for other risk factors or cancer-related illness and acts a confounder in its association with cancer.

In summary, this study found that zolpidem use was associated with increased risk of cancer events in sleep disorder patients. For patients with sleep disorder who chronically use zolpidem, the likelihood of developing cancer events within 3 years is 1.7 times that of those who do not use zolpidem. Risks and benefits of chronic zolpidem usage should be explained to sleep disorder patients. Cognitive-behavioral therapy for patients with chronic insomnia may be more beneficial than use of hypnotics.[32]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

  References Top

 

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Pharmacologic Treatment of Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

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Background: Pharmacologic interventions are often prescribed for insomnia disorder.

Purpose: To assess the benefits, harms, and comparative effectiveness of pharmacologic treatments for adults with insomnia disorder.

Data Sources: Several electronic databases (2004-September 2015), reference lists, and U.S. Food and Drug Administration (FDA) documents.

Study Selection: 35 randomized, controlled trials of at least 4 weeks’ duration that evaluated pharmacotherapies available in the United States and that reported global or sleep outcomes; 11 long-term observational studies that reported harm information; FDA review data for nonbenzodiazepine hypnotics and orexin receptor antagonists; and product labels for all agents.

Data Extraction: Data extraction by single investigator confirmed by a second reviewer; dual-investigator assessment of risk of bias; consensus determination of strength of evidence.

Data Synthesis: Eszopiclone, zolpidem, and suvorexant improved short-term global and sleep outcomes compared with placebo, although absolute effect sizes were small (low- to moderate-strength evidence). Evidence for benzodiazepine hypnotics, melatonin agonists, and antidepressants, and for most pharmacologic interventions in older adults, was insufficient or low strength. Evidence was also insufficient to compare efficacy within or across pharmacotherapy classes or versus behavioral therapy. Harms evidence reported in trials was judged insufficient or low strength; observational studies suggested that use of hypnotics for insomnia was associated with increased risk for dementia, fractures, and major injury. The FDA documents reported that most pharmacotherapies had risks for cognitive and behavioral changes, including driving impairment, and other adverse effects, and they advised dose reduction in women and in older adults.

Limitations: Most trials were small and short term and enrolled individuals meeting stringent criteria. Minimum important differences in outcomes were often not established or reported. Data were scant for many treatments.

Conclusion: Eszopiclone, zolpidem, and suvorexant may improve short-term global and sleep outcomes for adults with insomnia disorder, but the comparative effectiveness and long-term efficacy of pharmacotherapies for insomnia are not known. Pharmacotherapies for insomnia may cause cognitive and behavioral changes and may be associated with infrequent but serious harms.

Zolpidem and Driving Impairment — Identifying Persons at Risk.

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Zolpidem (Ambien, Sanofi) is the most widely used prescription drug for insomnia and one of the most commonly used drugs in the United States. Treatment of insomnia, which has important effects on patients’ quality of life, may also have larger public health benefits. In its 2006 report, the Institute of Medicine (IOM) Committee on Sleep Medicine and Research concluded that sleep deprivation and sleep disorders represent an unaddressed public health problem that has substantial health consequences and leads to high health care costs.1 The IOM noted that one of every five serious injuries from driving accidents can be attributed to driver sleepiness. Numerous sleep drugs are available for treating insomnia and are also used to reduce next-day somnolence. But it is widely recognized that these drugs themselves can sometimes contribute to next-day somnolence, depending on such factors as drug dose, dosage form, and individual patient characteristics.

The treatment of insomnia may focus on two distinct problems: falling asleep and remaining asleep; drugs that treat insomnia may be directed at one or both of these problems. For patients whose main problem is falling asleep, shorter-acting drugs can be effective without conferring a risk of sedation the following morning. When the problem is staying asleep during the night (sleep maintenance), longer-acting drugs — drugs with longer half-lives or controlled-release formulations — are generally used. Some patients can also take a very small dose of a sleep drug (e.g., zolpidem is available at a dose of 1.75 to 3.5 mg) or a very short-acting drug (e.g., zaleplon) if they wake up in the middle of the night and have difficulty falling back asleep.

Zolpidem was initially approved, in 1992, in an immediate-release formulation (Ambien) for insomnia characterized by difficulty in falling asleep. At the time of its approval, there was concern regarding morning impairment, even after a 7-to-8-hour period of sleep, particularly with regard to activities requiring full alertness, such as driving a motor vehicle. There was also some recognition that people’s risk of impairment could vary, and the drug label advised that “the dose of Ambien should be individualized.” Although the recommended adult dose was 10 mg, the recommended dose for the elderly (who had higher levels of the drug in their blood the next morning) and for patients with hepatic impairment (who metabolized the drug more slowly) was 5 mg. Individual differences became more apparent as new dosage forms of zolpidem were developed to address sleep maintenance and middle-of-the-night waking.

In 2005, a modified-release formulation of zolpidem (Ambien CR, Sanofi) was approved for insomnia characterized by difficulty falling asleep, difficulty staying asleep, or both; it came in a 12.5-mg dose. In 2011, a sublingual, lower-dose tablet (Intermezzo, Purdue) was approved for difficulty falling back to sleep after a middle-of-the-night awakening. Intermezzo was labeled so as to provide doses of zolpidem that differed for men and women (3.5 mg for men and 1.75 mg for women), since new data revealed a difference between men and women in morning blood drug levels.

The review and approval of Intermezzo was particularly informative, because a study was conducted to assess the relationship between blood zolpidem levels and driving impairment. The study assessed patients 3 hours after taking the drug (the label instructs patients to take the product at least 4 hours before morning awakening) and revealed significant impairment in driving ability in patients whose blood concentration of zolpidem was above 50 ng per milliliter. Such impairment is thought to increase the risk of a motor vehicle accident.

Recognition of a threshold blood level that would lead to concern about driving allowed assessment of other dosage forms of zolpidem in order to determine what doses would pose a risk of morning driving impairment. In some patients — particularly women, who clear zolpidem more slowly than men — blood levels the morning after taking the recommended bedtime doses could be considerably higher than 50 ng per milliliter. Reanalysis of data from studies of immediate-release zolpidem products showed that 8 hours (i.e., a typical period of sleep) after taking 10 mg of an immediate-release zolpidem product, 15% of women and 3% of men still had blood zolpidem levels of 50 ng per milliliter or higher; when a modified-release higher-dose (12.5 mg) product was taken, the percentages were much higher — 33% of women and 25% of men. These findings, consistent with the sex difference observed with the sublingual low-dose product (Intermezzo), prompted the Food and Drug Administration (FDA) earlier this year to revise the dosing recommendations for the labels of zolpidem-containing products to lower doses, particularly for women.2,3

Manufacturers of zolpidem-containing products, such as Ambien, Ambien CR, Edluar, and Zolpimist, must now make dosage recommendations that differ for women and men, to decrease the likelihood that women will have blood levels of the drug after they wake up that will impair their driving ability. Accordingly, the recommended dose of zolpidem for women has been reduced from 10 mg to 5 mg for immediate-release products (Ambien, Edluar, and Zolpimist) and from 12.5 mg to 6.25 mg for modified-release products (e.g., Ambien CR). Although labeling will also suggest that the lower doses should be considered for men, the stronger recommendation for reduced dosage in women underscores the clear sex-associated differences in zolpidem pharmacokinetics observed in studies.

The FDA has also pointed out that the risk of impairment with modified-release formulations of zolpidem (Ambien CR and generics) is greater than the risk with immediate-release formulations.2 Accordingly, the agency announced in May 2013 that patients who take modified-release formulations, either 6.25 mg or 12.5 mg, even if they then sleep for the required 8-hour period, should refrain, for the day subsequent to using the drug, from driving or engaging in any activity that requires full alertness.3 This recommendation reflects not only the higher zolpidem content in the modified-release formulation but also the ability of the modified-release design to prolong the period of drug exposure.

Although the evaluation of driving impairment caused by prescription drugs is not new, quantitative analyses of the relationships among drug dose, blood levels, and driving impairment, as illustrated in the approval of Intermezzo and the associated review of zolpidem products, are likely to be of growing interest (and perhaps debate). It is clear that performance on a driving test cannot be directly and quantitatively translated to driving risk, but similar data about effects on performance have been used to set standards for blood alcohol levels, and the tests of performance have considerable face validity. Certainly, these data are far more informative than reports of motor vehicle accidents, in which the relation to drug dose, the time between zolpidem ingestion and the accident, and the use of ethanol or other drugs is generally uncertain. The FDA has asked the makers of insomnia drugs to submit all available data addressing the risk of residual impairment after prescribed use, and the agency is currently analyzing these data.

It could be asked why the FDA did not leave the recommended doses unchanged and continue to warn patients to watch for driving impairment. A variety of new data have shown that people affected by impairment after taking zolpidem frequently do not recognize their impaired state; patient self-perception is not an adequate gauge for impairment. Among patients whose sleep needs are satisfied with the use of the lower doses, unnecessary risk can be avoided, and as the labels point out, patients whose symptoms do not respond to the lower doses can be given the higher doses. The sex-specific labeling revisions reflect an evidence-based approach to risk management and dose individualization.

Source: NEJM

 

Zolpidem-Related Emergency Department Visits Triple over 5 Years.

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The number of emergency department visits related to the insomnia drug zolpidem (e.g., Ambien) more than tripled in the U.S. from 2005 to 2010, according to a report from the Substance Abuse and Mental Health Services Administration.

Overall, the number rose from 6111 to 19,487. Females were especially at risk, accounting for over two thirds of visits in 2010. (In January 2013, the FDA halved the recommended dose of zolpidem in women, noting that women process the drug more slowly than men.) One third of visits involved adults aged 65 and older.
The report concludes: “Physicians and pharmacists can emphasize the importance of using zolpidem safely and only for short-term problems with insomnia. This may be especially crucial for older adults, for whom insomnia is a common complaint and who often take other prescription medications that may interact with zolpidem.”

Sleeping pills could actually IMPROVE your memory, claims controversial new research.

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  • Researchers claim that the zolpidem in some sleeping pills enhances the brain’s ability to build-up memories
  • They say the findings could help in the development of treatments for Alzheimer’s and dementia
  • Contradicts previous research which found the drug may actually CAUSE memory loss

 

 

 

Taking sleeping tablets could help improve your memory, according to controversial new research.

 

A team of researchers claim to have discovered the mechanism that enables the brain to build-up memories – and say they found that a commonly prescribed sleeping tablet containing zolpidem enhances this process.

 

They hope the discovery could lead to new sleep therapies that could improve memory for ageing adults and those with dementia, Alzheimer’s and schizophrenia.

 

The findings contradict a wealth of previous research that has suggested that sleeping pills can have devastating effects on health, including memory.

 

The new research claims to have demonstrated, for the first time, the critical role that sleep spindles play in consolidating memory in the hippocampus.

 

Sleep spindles are bursts of brain activity that last for a second or less during sleep.

 

Earlier research found a link between sleep spindles and the consolidation of memories that depend on the hippocampus, the part of the brain that is involved in memory forming, organising, and storing.

 

The research team say they showed that the drugs could significantly improve that process, far more than sleep alone.

 

Lead author of the study, Dr Sara Mednick, a psychologist from the University of California Riverside, said: ‘We found that a very common sleep drug can be used to increase memory.

 

‘This is the first study to show you can manipulate sleep to improve memory.

 

‘It suggests sleep drugs could be a powerful tool to tailor sleep to particular memory disorders.’

 

But previous research has suggested that sleeping pills taken by more than a million Britons significantly increase the risk of dementia.

 

Pensioners who used benzodiazepines – which include temazepam and diazepam – are 50 per cent more likely to succumb to the devastating illness, a Harvard University study found.

 

They work by changing the way messages are transmitted to the brain, which induces a calming effect but scientists believe that at the same time they may be interfering with chemicals in the brain known as neurotransmitters, which may be causing dementia.

 

The new study tested normal sleepers, who were given varying doses of sleeping pills and placebos, allowing several days between doses to allow the drugs to leave their bodies.

 

Researchers monitored their sleep, measured sleepiness and mood after napping, and used several tests to evaluate their memory.

 

They found that zolpidem significantly increased the density of sleep spindles and improved verbal memory consolidation.

 

Dr Mednick said: ‘Zolpidem enhanced sleep spindles in healthy adults producing exceptional memory performance beyond that seen with sleep alone or sleep with the comparison drug.

 

‘The results set the stage for targeted treatment of memory impairments as well as the possibility of exceptional memory improvement above that of a normal sleep period.’

 

Dr Mednick also hopes to study the impact of zolpidem on older adults who experience poor memory because individuals with Alzheimer’s, dementia and schizophrenia are known experience decreases in sleep spindles.

 

Dr Mednick, who began studying sleep in the early 2000s, says sleep is a very new field of research and its importance is generally not taught in medical schools.

 

‘We know very little about it,’ she said.

 

‘We do know that it affects behaviour, and we know that sleep is integral to a lot of disorders with memory problems.

 

‘We need to integrate sleep into medical diagnoses and treatment strategies. This research opens up a lot of possibilities.’

 

Source: http://www.dailymail.co.uk

 

 

 

Zolpidem Use Among Inpatients Associated with Higher Rate of Falls .

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Inpatients who were given zolpidem were six times more likely to fall than patients who were prescribed the drug but didn’t take it, according to a cohort study in the Journal of Hospital Medicine.

Researchers assessed zolpidem prescriptions among all non-ICU, non-pregnant inpatients at the Mayo Clinic in 2010. After adjusting for factors such as delirium and insomnia, patients who were administered zolpidem had a higher rate of falls than those who did not take zolpidem (3.04 vs. 0.71 falls per 100 patients). The authors estimate for every 55 patients treated with zolpidem, one additional fall could be expected to occur.

They note that at their institution, order sets have been changed to discourage use of zolpidem, and they recommend that other hospitals follow suit.

Source:Journal of Hospital Medicine

Psychotropic Drug Use Associated with Increased Risk for Car Crashes .

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Antidepressants, benzodiazepines, and so-called “Z-drugs” such as zolpidem (Ambien) and zaleplon (Sonata) are associated with increased risk for motor vehicle accidents, according to a case-control study in the British Journal of Clinical Pharmacology.

Using registry and claims data from Taiwan, researchers assessed use of psychotropic drugs among 5200 people who were drivers during motor vehicle accidents and 31,000 matched controls who were not in accidents.

Relative to nonusers, the risk for motor vehicle accidents was higher among patients who had taken the following classes of drugs within the previous month: antidepressants (adjusted odds ratio, 1.73), benzodiazepines (1.56), and Z-drugs (1.42), but not antipsychotics. Even relatively low doses of antidepressants and benzodiazepines conferred increased risks.

The authors conclude that clinicians should “choose safer, alternative treatments and advise patients not to drive, especially while taking medications, to minimize the risk of causing [traffic accidents] under the influence of psychotropic medications.”

Source: British Journal of Clinical Pharmacology