Impairment related to blood drug concentrations of zopiclone and zolpidem compared to alcohol in apprehended drivers

Gustavsen, Ingebjørg; Al-Sammurraie, Muhammad; Mørland, Jörg; Bramness, Jørgen G.

doi:10.1016/j.aap.2009.01.011

Cited by 69 publications

(33 citation statements)

References 29 publications

(34 reference statements)

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“…31 In Norway, a study found higher rates of zopiclone then zolpidem in drivers, reflecting the prescribing bias of the physicians in that country. 8 It is important to note that no study has prospectively studied the propensity for any hypnotic sedative to trigger a parasomnia.…”

Section: Legal Case 4 April 2009mentioning

confidence: 99%

“…6 There are also reports of a high frequency of blood levels of hypnotic sedatives in drivers apprehended for driving under the infl uence (DUI). [7][8][9] An advisory letter was sent and change in package insert information occurred on March 14, 2007, alerting physicians and the public to the possibility of complex behaviors with all hypnotic sedatives.…”

Section: S C I E N T I F I C I N V E S T I G a T I O N Smentioning

confidence: 99%

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Zolpidem Ingestion, Automatisms, and Sleep Driving: A Clinical and Legal Case Series

Poceta

2011

Journal of Clinical Sleep Medicine

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study Objectives: To describe zolpidem-associated complex behaviors, including both daytime automatisms and sleeprelated parasomnias. Methods: A case series of eight clinical patients and six legal defendants is presented. Patients presented to the author after an episode of confusion, amnesia, or somnambulism. Legal defendants were being prosecuted for driving under the infl uence, and the author reviewed the cases as expert witness for the defense. Potential predisposing factors including comorbidities, social situation, physician instruction, concomitant medications, and patterns of medication management were considered. Results: Patients and defendants exhibited abnormal behavior characterized by poor motor control and confusion. Although remaining apparently interactive with the environment, all reported amnesia for 3 to 5 hours. In some cases, the episodes began during daytime wakefulness because of accidental or purposeful ingestion of the zolpidem and are considered automatisms. Other cases began after ingestion of zolpidem at the time of going to bed and are considered parasomnias. Risk factors for both wake and sleep-related automatic complex behaviors include the concomitant ingestion of other sedating drugs, a higher dose of zolpidem, a history of parasomnia, ingestion at times other than bedtime or when sleep is unlikely, poor management of pill bottles, and living alone. In addition, similar size and shape of two medications contributed to accidental ingestion in at least one case. Conclusions s C i e n T i F i C i n V e s T i g a T i O n sT he ingestion of zolpidem and other hypnotic sedative medications for the treatment of insomnia has been associated with sleepwalking and other complex behaviors including sleep eating and sleep driving.1-5 When ingested during the daytime, hypnotic sedatives impair cognition, memory, and motor performance. 6 There are also reports of a high frequency of blood levels of hypnotic sedatives in drivers apprehended for driving under the infl uence (DUI).7-9 An advisory letter was sent and change in package insert information occurred on March 14, 2007, alerting physicians and the public to the possibility of complex behaviors with all hypnotic sedatives.According to the prescribing information for Ambien and Ambien CR, zolpidem is an imidazopyridine chemical class agent available in the US since 1992. It is chemically unrelated to benzodiazepine and barbiturate hypnotic sedatives. Zolpidem in vitro binds the BZ1 receptor of the GABA(A) complex with high affi nity ratio for the alpha1/alpha5 subunits. Mean peak concentrations were 59 (range 29 to 113) after ingestion of the 5 mg tablet and 121 (range 58 to 272) after ingestion of the 10 mg tablet (ng/mL). Time to maximum concentration was 1.6 h for both doses (but 2.2 h if taken with food) with a half-life of approximately 2.6 h (range 1.4 to 4.5) The zolpidem extended release formulation 12.5 mg tablets produced a maximum concentration of 134 (69 to 197) at 1.5 hours. Co-administration with fl uoxetine increased ha...

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Section: Legal Case 4 April 2009mentioning

confidence: 99%

Section: S C I E N T I F I C I N V E S T I G a T I O N Smentioning

confidence: 99%

Zolpidem Ingestion, Automatisms, and Sleep Driving: A Clinical and Legal Case Series

Poceta

2011

Journal of Clinical Sleep Medicine

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“…Prescription drugs (opioids and benzodiazepines) were found more frequently than illegal drugs. Use of such drugs, even within the prescribed dosage regimen may increase the risk of accidents in traffic, and correspondingly at the workplace (14,15). Higher risks at elevated dosage are expected, and use of prescription drugs in combination with illegal drugs can be indicative of non-prescribed use.…”

Section: Discussionmentioning

confidence: 99%

Results of workplace drug testing in Norway

Lund¹,

Bogstrand²,

Christophersen³

2011

Nor J Epidemiol

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Workplace drug testing is less common in Norway than in many other countries. During the period from 2000-2006, 13469 urine or blood samples from employees in the offshore industry, shipping companies and aviation industry were submitted to the Norwegian Institute of Public Health for drug testing. The samples were analysed for benzodiazepines, illicit drugs, muscle relaxants with sedating properties, opioids and z-hypnotics. In total, 2.9% of the samples were positive for one or more substances. During the study period the prevalence decreased for morphine (from 1.9% to 1.1%) and increased for amphetamine (from 0.04% to 0.6%), clonazepam (from 0% to 0.1%), methamphetamine (from 0.04% to 0.6%), nitrazepam (from 0% to 0.4%) and oxazepam (from 0.5% to 1.3%) (p<0.05). There was no significant change in prevalence for the other substances included in the analytical programme. Illicit drugs were significantly associated with lower age (OR: 0.93, p<0.05). This study found low prevalence of drugs among employees in companies with workplace drug testing programmes in Norway.

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“…Concerns have been raised that the tight controls in these studies may underestimate real-life adverse effects of MOTN use owing to patient non-compliance regarding hypnotic dosages and timing of doses. 17,18 For instance, studies of blood levels among drivers stopped for driving under the influence (DUI) in the United States, 19 Norway, 20 and Sweden 21 have found higher-than-expected blood levels of various hypnotic drugs, suggesting that hypnotic misuse involving escalated dosages and/ or improper timing of doses may be associated with impaired driving. 22 This is consistent with other evidence that high proportions of insomniacs self-medicate.…”

Section: Brief Summarymentioning

confidence: 99%

Middle-of-the-Night Hypnotic Use in a Large National Health Plan

Roth

Berglund²,

Shahly³

et al. 2013

Journal of Clinical Sleep Medicine

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that are approved for nocturnal awakenings and/or prolonged wake time after nocturnal awakenings, all but one stipulate bedtime administration with middle-of-the-night use being explicitly disapproved to minimize risk of residual sedation. In other words, such bedtime hypnotics are designed to be preventative treatments for possible nocturnal awakenings rather than active treatments administered after nocturnal awakenings occur. The single hypnotic accepted by the FDA for as-needed MOTN Study Objectives: Although diffi culty maintaining sleep (DMS) is the most common nighttime insomnia symptom among US adults, many FDA-approved hypnotics have indications only for sleep onset, stipulating bedtime administration to offset residual sedation. Given the well-known self-medication tendencies of insomniacs, concern arises that maintenance insomniacs might be prone to self-administer their prescribed hypnotics middle-of-the-night (MOTN) after nocturnal awakenings, despite little effi cacy-safety data supporting such use. However, no US data characterize the actual population prevalence or correlates of MOTN hypnotic use. Methods: Telephone interviews assessed patterns of prescription hypnotic use in a national sample of 1,927 commercial health plan members (ages 18-64) receiving prescription hypnotics within 12 months of study. The Brief Insomnia Questionnaire assessed insomnia symptoms. Results: 20.2% of respondents reported MOTN hypnotic use, including 9.0% who sometimes used twice-per-night (once at bedtime plus once MOTN) and another 11.2% who sometimes used MOTN, but never twice-per-night. The remaining 79.8% used exclusively at bedtime. Among exclusive MOTN users, only 14.0% used MOTN on the advice of their physician (52.6% of those seen by sleep medicine specialists and 42.6% by psychiatrists vs. 5.2% to 13.6% seen by other physicians). MOTN use predictors included DMS being the most bothersome sleep problem, long duration of hypnotic use, and low frequency of DMS. Conclusions: One-fi fth of patients with prescription hypnotics used MOTN, only a minority on advice from their physicians. Since signifi cant next-day cognitive and psychomotor impairment is documented with off-label MOTN hypnotic use, prescribing physicians should question patients about unsupervised MOTN dosing. Keywords: Insomnia, sleep maintenance, hypnotics, middleof-the-night, dosing, medication adherence, prevalence Citation: Roth T; Berglund P; Shahly V; Shillington AC; Stephenson JJ; Kessler RC. Middle-of-the-night hypnotic use in a large national health plan. J Clin Sleep Med 2013;9(7):661-668.http://dx.doi.org/10.5664/jcsm.2832 S C I E N T I F I C I N V E S T I G A T I O N SI nsomnia is the most common nighttime sleep problem, and sleep maintenance insomnia the most common insomnia symptom both in the general population 1 and among adults with clinical insomnia. 2 An estimated one-fourth of all noninstitutionalized US civilians and two-thirds of US insomniacs report frequent sleep maintenance problems involving nocturnal awakenings and/or p...

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Impairment related to blood drug concentrations of zopiclone and zolpidem compared to alcohol in apprehended drivers

Cited by 69 publications

References 29 publications

Zolpidem Ingestion, Automatisms, and Sleep Driving: A Clinical and Legal Case Series

Zolpidem Ingestion, Automatisms, and Sleep Driving: A Clinical and Legal Case Series

Results of workplace drug testing in Norway

Middle-of-the-Night Hypnotic Use in a Large National Health Plan

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