Toxicology data can establish the likely presence or absence of zolpidem at the time of the offense. Ultimay, it is a matter of fact to determine whether a defendant has taken zolpidem (or any other substance). Absent toxicology data, the expert must rely on the statement of the defendant as to whether zolpidem was ingested before the offense. Blood samples have been used to approximate the timing and dosage of the drug, whereas urine samples have been used to corroborate its presence. Toxicologists have used blood 34 and urine 35 samples to introduce evidence of the presence of zolpidem.
Two additional criminal cases were identified, in which defendants appealed for a change of plea, arguing that use of zolpidem near the time of the plea had rendered them incompetent to enter a plea. Three employment-related cases were found in which the use of zolpidem was argued to mitigate civil responsibility. The Lexis-Nexis search returned 28 relevant legal cases. The criminal cases by committing offense included: 7 violent crimes, 10 driving-related incidents, 1 sex offense, and 2 false reports. In these cases, the defendants argued that the use of zolpidem near the time of the offense reduced their criminal liability. The following will summarize key factors that have arisen when courts have evaluated these claims involving zolpidem. Two negligence tort cases were found in which plaintiffs sued Sanofi-Aventis for driving-related damages.
Anterograde amnesia is also frequently reported with zolpidem. 1 Postmarketing studies of zolpidem found the incidence of complex behaviors to be low, occurring in less than one percent of cases, although a recent case series found it higher, at five percent. 16 The incidence of hallucinations with zolpidem is reported to occur in less than one percent of patients. Complex, parasomnia-like behaviors have also been reported, such as driving, talking, eating, and engaging in sex. These include disinhibition (extroversion or aggressiveness that seem out of character), depersonalization, hallucinations, and alterations in mood. 1 Because these behaviors are accompanied by amnesia, it is likely that they are underreported. The FDA's prescribing information for zolpidem lists a variety of abnormal thinking and behavioral changes that can be associated with it and other hypnosedatives.
Discussions with colleagues confirm that many cases have arisen where a history of zolpidem treatment is used as a means to influence criminal or civil liability. Psychiatrists are frequently consulted by attorneys to assess the credibility of these allegations. The sleep-related, complex behaviors associated with zolpidem have been the basis of two legal strategies of interest in the forensic psychiatry arena: the concept of “the pill made me do it ” and the sleepwalking defense.
32 Ms. While intoxicated, she made several crank phone calls to police dispatch that included sexual innuendos and a false report of a fire behind her home. The court ruled that even if her physician had not warned her of the potential side effects of zolpidem, she had voluntarily taken more than the prescribed dose and stayed awake. Kelly had a history of abusing zolpidem and had in fact attempted suicide in the past by overdose of the drug. After work one evening she took several tablets of zolpidem and deliberay remained awake to play video games. The court stated that “the very point of a sleep aid is to fall asleep.” The court also considered that Ms. Kelly was a police officer until her termination after improper conduct. Salt Lake City Civil Service Commission. Forseeability was at issue in the case of Kelly v. She appealed the decision to terminate her employment on the grounds that her behavior was an involuntary result of taking prescribed medication.
Bingham was charged with first-degree murder and attempted murder. State, 30 Mr. Bingham's physician had counseled him on all known effects of his medication. His wife died of the injuries while his stepson survived. In Bingham v. Records were introduced that showed that Mr. At his trial, he raised the defense of involuntary intoxication, arguing that his use of prescription drugs, including zolpidem, created a “distorted thought process.” The jury found him guilty of the lesser charges of voluntary manslaughter and attempted murder. The court of appeals upheld the conviction, finding that Mr. Bingham shot his wife and his stepson during a domestic dispute. Mr. Bingham did not provide sufficient evidence to prove that his intoxication by prescription medications was involuntary.
One night, she took a shower after her dose of zolpidem and went to sleep later than her usual time. Concerned for her safety, she had gotten the axe from the tool shed and placed it on her nightstand. She had no memory of writing the text messages. (This is a composite description.). She woke up with a garden axe on her nightstand with no memory of how it got there. In them, she described to her partner hearing voices from her kitchen and seeing moving images out of the corner of her eye. Later she scrolled through her text messages from the night before and discovered a conversation that she had had with her partner after her shower. A young adult with no prior history of psychiatric illness used zolpidem once a week to fall asleep.
31 Ms. In some cases, the courts will consider what a reasonable person would have done in similar circumstances. Direct warnings include warnings by physicians and labels on prescription bottles. Chaffey took an overdose of 120 alprazolam tablets in a suicide attempt and then drove recklessly while in a delirious state. The trier of fact seeks to determine to what degree the defendant (or plaintiff) could have foreseen the consequences of taking zolpidem. Although the court ruled that she did not intend to drive her car, they found that it was foreseeable that such an ingestion could lead to unpredictable behavior. Chaffey. An often-cited case involving a benzodiazepine is People v. She was convicted of driving while intoxicated.
This case is similar to the one described at the beginning of this article, in which the patient sent text messages reporting hallucinatory experiences after taking zolpidem and not going to sleep. The boyfriend reported that she had a linear conversation with him, although she appeared disinhibited. 14 Le Bon and Neu 24 reported a case of a woman who had a conversation with her boyfriend about their relationship 45 minutes after ingesting 10 mg of zolpidem. These patients typically retain the ability to speak in short, coherent phrases. It is helpful to conceptualize distinct mechanisms to explain these abnormal behaviors. A patient may inadvertently (or intentionally) remain awake after taking zolpidem and begin to experience disinhibition or hallucinations with associated anterograde amnesia. She had no recollection of the conversation the next day.
4 Zolpidem remains a top prescribed medication, with more than 28 million prescriptions written in 2008, ranking as the 16th most prescribed generic medication that year, 5 with gross sales of over $700 million. Zolpidem is an imidazopyridine hypnotic agent that is approved by the U.S. In 2007, Ambien's patent protection expired, and zolpidem became available as a generic medication manufactured by 13 different companies. market since 1992, sold under the trade name Ambien by the French company Sanofi-Aventis. 7. 6 These figures do not include the ongoing sales for Ambien CR (controlled release), which had more than 7 million prescriptions in 2008. Ambien has been widely prescribed, ranking as the ninth most prescribed medication in the United States in 2006, with more than 20 million prescriptions, 2 grossing nearly 2 billion dollars in sales 3 that year alone. 1 It has been on the U.S. Food and Drug Administration (FDA) for the short-term treatment of insomnia in the United States.
NBRAs available in the United States include zolpidem, eszopiclone, and zaleplon. 13 Clinical studies of zolpidem have shown significant impairments in memory and psychomotor performances at one and four hours after ingestion. 8 The selectivity of zolpidem for the α-1 subtype was believed to confer more specific sedative properties along with less memory impairment and less residual daytime sedation, when compared with benzodiazepines. 8, 12 Six different α-receptor subtypes are currently known. 14. These medications bind to the same GABA A receptor complexes as the benzodiazepines, but are more selective to the α-1 receptor subtype. Agonism of the α-1 receptor type is believed to result in sedation and amnesia. Zolpidem is a member of a newer class of hypnosedative drugs known as nonbenzodiazepine receptor agonists (NBRAs). The other receptor types have anxiolytic, anticonvulsant, and muscle relaxant properties.
15. The courts presume that anyone who consumes alcohol or illegal drugs knows or should know the potential to induce unconscious states. Prescription medications, however, can be considered for an involuntary intoxication defense as long as the defendant can show that he was not aware of the potentially adverse effect at the time of ingestion. The defendant must also show that an intoxicating substance caused the behavior and that he did not knowingly consume the substance. In several of the cases reviewed, defendants advanced an argument of reduced or negated criminal liability attributable to involuntary intoxication. This defense does not absolve him of criminal responsibility, but may succeed in negating a specific-intent element of a crime (for example premeditated murder) and reduce the severity of the charges. Alcohol and illegal drugs cannot be used as part of an involuntary intoxication defense. In this legal strategy, the defendant must show that at the time of the accused crime he was in an altered state of mind, such that he was unaware of his actions. If the defendant is able to prove that he was intoxicated, but is unable to prove that the intoxication was involuntary, the defendant may still try to argue a case of voluntary intoxication.
Sleep-related eating behavior has been associated with zolpidem. In most but not all cases, patients were amnestic for the nocturnal eating. 17 In these cases, the patients all had comorbid sleep disorders. 18 Amnesia and the appearance on the next day of a messy kitchen were reported in another case. Weight gain of 50 pounds over a one-year period was described in a separate case of zolpidem-related sleep eating. 19 A theory presented in these cases is that zolpidem may aggravate underlying sleep pathology leading to nocturnal eating. A case series from the Mayo Clinic described five patients who exhibited new-onset or worsening of sleep-related eating after initiation of zolpidem.
Such complex behaviors are more likely to occur early in treatment but can happen at any time, in some reports after an individual has used the medication for as long as two years. Several risk factors have been previously identified for parasomnias including personal or family history of parasomnia, use of alcohol or drugs, sleep deprivation, fever, and personal stress. Concomitant use of other psychotropic medications may also have an additive risk for sleep-related, complex behaviors. 29 In the cases reviewed here, the risk for sleep-related, complex behaviors associated with zolpidem tended to be dose-dependent, with higher doses increasing the risk. The term parasomnia is used to refer to any of several sleep arousal disorders including sleepwalking, night terrors, and restless leg syndrome. 8. In this review, triazolam was the most frequent of the benzodiazepines to be reported to cause complex behavior. 17 A recent review showed that zolpidem accounted for 15 of 17 case reports of sleep-related, complex behaviors within the NBRA class of medications.
14 Another case report described a patient, who, after starting zolpidem, awoke in the middle of the night, walked into his parents' room with a blank stare, and spoke incoherently. The man urinated on the floor and appeared confused. 28 Yang et al. 19 reported on an inpatient who began getting out of bed in the middle of the night after initiation of zolpidem 10 mg. In all of these cases, the behaviors ceased when zolpidem was discontinued. A recent case report described a patient with no previous history of parasomnia who began sleepwalking after she started taking zolpidem. Her husband reported that she spoke incoherently during these episodes.
She had no recollection of the the next day. She was able to input her username and password to log on. Other complex behaviors reported in the medical literature include manipulating objects (e.g., putting gas in a lawnmower), cleaning the house, and engaging in conversations and sex. The, however, contained odd grammar, format, and punctuation. 22 Although sleepwalking has been associated with violence and murder, 23 the present review of the medical literature identified no reports of any such incidents associated specifically with zolpidem. 8 One case report described a patient who wrote an two hours after ingestion of zolpidem.
14. The patient may be able to speak coherently, but act out of character. A second, similar mechanism occurs when the patient falls asleep, but then has an arousal from sleep while still under the influence of zolpidem. The patient may then engage in behaviors and not remember them because of the anterograde amnestic effects.
Her prescribing physician testified that he had warned Ms. Johns of the dangers of driving while taking these medications. Johns had a civil lawsuit pending against him in the same matter. The defense argued that the physician had motive to lie because Ms. The question of warnings by physicians introduces a potential conflict for those who may also be sued by defendants. In People v. Johns, a California case, 33 Ms. Johns was charged with vehicular manslaughter after she hit a pedestrian while under the influence of zolpidem and alprazolam.
The Lexis-Nexis database contains federal district court, appellate, and Supreme Court cases. The database also covers state and appellate level and Supreme Court cases. The search included cases through January 2010. An additional Lexis-Nexis search was performed to explore benzodiazepines for comparison cases using the keywords benzodiazepine, clonazepam, Klonopin, diazepam, Valium, alprazolam, Xanax, triazolam, or Ambien, along with criminal responsibility, voluntary intoxication, involuntary intoxication, negligence, and malpractice. State level district court cases are not included in the database and were not reviewed for this article. A Lexis-Nexis search was conducted using the keyword zolpidem or Ambien, along with involuntary intoxication, voluntary intoxication, criminal responsibility, negligence, and malpractice.
The expert then can testify to what extent the defendant showed evidence of impairment at the time of the offense. The courts look at the record as a whole in determining as a matter of fact whether the person was intoxicated as a result of zolpidem. Defendants using a defense related to zolpidem typically call experts to testify to the propensity of zolpidem to cause abnormal behaviors and amnesia.
To the authors' knowledge, this is the first published review in the forensic psychiatry literature of the legal ramifications of zolpidem use. We examine appellate level cases involving zolpidem, to illustrate how the courts have applied the current scientific knowledge in contemporary cases. We use these examples to formulate recommendations to assist experts who are consulted on such cases. In this article, we review the medical literature that describes the pharmacologic properties specific to zolpidem that are associated with its potential to cause sleep-related, complex behaviors.
Zolpidem is one of 13 hypnosedative medications approved by the FDA for treatment of insomnia, 8 although by far it has been the most prescribed hypnosedative over the past decade. Its popularity is the likely result of aggressive marketing 9 and early reports of low rates of daytime sedation and low abuse potential. 10.
Case law will be explored to determine how the courts have handled the claims surrounding sleep-related, complex behaviors alleged to be caused by zolpidem. To the authors’ knowledge, this is the first review in the forensic literature of the legal ramifications of zolpidem. Zolpidem is a widely prescribed nonbenzodiazepine hypnotic medication available in the United States since 1992. Attention has been drawn recently to its potential to cause sleep-related, complex behaviors such as sleepwalking and sleep driving. In this article, the medical literature will be reviewed to explore the current understanding of zolpidem’s specific psychopharmacology. These automatic behaviors have led to a deluge of legal claims. Finally, a summary of recommendations will be provided for forensic psychiatrists who are asked to be experts in these cases.
20 A case series reviewed the clinical appearance of drivers convicted of driving while under the influence (DUI), with zolpidem found on toxicology analysis. In those drivers using only zolpidem, symptoms included slowed or slurred speech, disorientation, poor coordination, and blacking out. Incidents of sleep driving have been described in association with zolpidem. 21.
This property is similar to that of triazolam, 8 a benzodiazepine that gained notoriety in the early 1990s because of its association with aberrant behaviors, culminating with its removal from European markets and a successful product liability suit in the United States ( Freeman v. Dist. When compared with most hypnosedatives, it has a short half-life, two to three hours. 1 When compared with other hypnosedatives, zolpidem has a high binding affinity for the GABA A receptor. Ct. Zolpidem is rapidly absorbed in the gastrointestinal tract, with onset of action of approximay 30 minutes and average peak concentration at 90 minutes. It is metabolized by hepatic metabolism by CYP 3A4 enzymes. A (Tex. Drug-drug interactions are possible with medications that affect 3A4 enzymes such as ketoconazole. Upjohn Co., No. 1992)). 15.
The search returned dozens of articles. The search included articles through January 2010. Representative articles were selected for review. A PubMed search was conducted using the keyword zolpidem, along with complex behaviors, sleepwalking, driving, eating, parasomnias, memory, forensic, legal, amnesia, violence, and aggression.
However, postmarketing studies and case reports began to show that zolpidem was associated with sleep-related, complex behaviors. This regulation took effect in March 2007 11 and was widely publicized. 8 As these behaviors became recognized, the FDA requested that specific warnings be put on all hypnosedative medications. These included sleep driving, sleep cooking, sleep eating, sleep conversations, and, rarely, sleep sex, generally accompanied by anterograde amnesia for the event.
FDA data indicate that zolpidem does not significantly change sleep architecture, 1 but it has been reported that it decreases REM sleep with a corresponding increase in non-REM sleep time. 26 This increase in total non-REM sleep time may increase the risk of somnambulistic behaviors. 25 Speech is typically incoherent. 25 In a recent study of outpatients with sleep disorders, use of zolpidem was positively correlated with sleepwalking and sleep-related eating. These behaviors appear purposeless to outside observers. Finally, zolpidem may induce or aggravate parasomnias, such as sleepwalking, a distinct phenomenon wherein complex behaviors take place during electroencephalographically verifiable slow-wave sleep (non-REM Stages 3–4). 27.Zolpidem vs clonazepam