1. Introduction
The Z-drug zolpidem (ZLP) is an imidazopyridine hypnotic that is prescribed widely for short-term treatment of sleeping problems (1). It has attained popularity as an alternative to benzodiazepines due to the claims regarding its milder and fewer problematic side effects although they have been refuted in recent studies (2-4). Side effects related to ZLP have been frequently reported. Nausea, dizziness, malaise, hallucination, nightmares, agitation, and headache are some of the most frequently reported adverse effects of ZLP (5). Several systematic descriptive reviews of ZLP dangerous side effects including psychotic types have been undertaken (6, 7). Although ZLP appears to be well tolerated in adults (8), there are so many reports of abuse, dependence, and withdrawal syndrome of ZLP. It merits mentioning that a larger number of these cases had used ZLP more than the prescribed dose and most of these people had a history of substance or drug abuse and/or psychiatric disorders (6, 9).
Further to the extant reports of adverse reactions related to zolpidem use, hereby two cases with zolpidem intoxication effects are presented.
2. Case Presentation
Two 29-year-old single males who were graduated in pharmacy, sharing an apartment in Tehran, without any diagnosed mood disorder or neuropsychiatric disease, went to another pharmacist friend’s house to have dinner together.
Being fully alert and free of any drug at that night, the host declared the following statements:
Case 1: He had been using ZLP often but irregularly throughout the past 2 years. He had not any history of using another drug. He used to use ZLP for his sleeping problems, but in the repercussion of repetitive use, he became interested in the pleasurable and felicific mental encounters of ZLP. He also had a history of an unsuccessful suicide attempt upon taking ZLP. Within the recent 2 years, he had been taking 10-80 mg of ZLP on an irregular basis and he had entirely forgotten the happenings of the nights when he took ZLP.
Case 2: He had only used ZLP for a few times and he did not have any history of continuous use of this drug. He was free of any other medication.
As both cases declared later, they suffered a dramatically gloomy night on 3rd November 2016. Unbeknown to the host, as they arrived at his house, they each took four pills of ZLP 5 mg with a full glass of water. After a few minutes, they were invited to a dining room to have the meal. Case 1 started eating food voraciously and non-stop while opining around music for about 30 minutes. Case 2 had less attention to the food. He just drank a lot of water and talked about a mixture of religious, romantic, and philosophical topics. In the middle of the dinner, the second case started to fancy that several people with deformed faces and winding bodies were gazing through the room window.
The first case demanded some more ZLP tablets. He got prepared for buying ZLP and case 2 decided to accompany him.
The host tried his best to prevent them from going out, but they remained utterly determined. He joined them towards a 24-hour pharmacy in case any unexpected problem occurred. Along the way, both cases 1 and 2 were unable to navigate the pathway to the pharmacy and their balance was impaired. Case 2 said that some people were hiding behind the trees and were watching them. Case 1 entered the pharmacy and bought a full package of ZLP 10 mg with a package of atorvastatin 10 mg tablets. He stated, “I did not want to seem suspicious”.
After returning to the house, case 1 and case 2 attempted to use 60 mg of ZLP apiece. They were advised to go to sleep by the host. After a short time, they fell asleep fast while breathing normally. The host checked their pulse rate and their blood pressure with an automatic sphygmomanometer and they were normal. Both of them reacted to loud voice and had movement on the bed during their sleep. Their pupils started to contract as the host flashed the torch into their eyes.
They woke up easily at eight in the morning after; however, they were feeling dizziness, headache, lightheadedness, and gastrointestinal discomfort.
3. Discussion
Due to the tolerance, dependence, and associated adverse effects, the abuse of benzodiazepines and Z-drugs has become a serious public health problem (10, 11). ZLP as a very commonly prescribed Z-drug has the potential for both medical misuse -when it is taken for the long term without or against medical advice- and recreational use -when is abused to achieve a “high”- (11-13).
There have been reports of some life-threatening complications associated with ZLP overdose, such as suicidal attempts, seizure, and coma (13, 14). There have also been some other reports in which the cases experienced altered mental status (AMS) and as a result, expressed dangerous behaviors (15-17).
AMS as a condition, in which the levels of consciousness and/or cognition are altered, has myriad causes (18). The term is used to describe various disorders of mental functioning that can range from slight confusion to coma (18, 19).
Sleepwalking, as a sleep-related disorder, also known as somnambulism, is a phenomenon of combined sleep and wakefulness (20). It performs activities that are usually performed during a state of full consciousness. These activities can be as benign as sitting up in the bed, walking to a bathroom, and cleaning, or as critical as cooking, driving, rubbery, violent gestures, or even suicide or homicide (21, 22).
Although both cases were responsive to stimuli, the occurred case cannot be identically classified as a serious AMS or simple and benign somnambulism.
By and large, the following points are worth mentioning:
Due to its contribution to abnormal and hazardous behavior, the case should be considered as a potentially dangerous situation in an intoxicated person.
As underlined by FDA (23), it is suggested to use ZLP at the lowest effective dose for the shortest period of time, as necessarily needed.
As observed in these cases and based on the clinical evidence (24), ZLP has a very rapid onset of action. It is highly suggested to administer and use ZLP just before bedtime.
As described in the case presentation section and based on some evidence, ZLP may cause an acute change in eating behavior (25). Due to the altered level of consciousness, to prevent the blockage of the airway during eating, it is highly recommended advising patients to avoid eating or drinking after taking ZLP.
3.1. Conclusions
Since this case was based on personal declarations, further studies are suggested to disclose the true outcomes of the zolpidem-induced altered level of consciousness. On the other hand, dose modification and potentially dangerous consequences of zolpidem intoxication are necessary to be publicized.
