PROPOFOL is a short-acting, intravenous agent used extensively in anesthesia and intensive care medicine to provide dose-dependent sedation and hypnosis. It is characterized by a short onset, a short duration of action, low toxicity, ability to control sedation, and ease of administration. Thus, it quickly found general acceptance after its introduction into the market in the mid 1980s. The abuse potential of propofol has not completely been defined, but there are anecdotal case reports in the literature about abuse of and dependency on propofol. 1–4We report a case of a 25-yr-old man with attention deficit hyperactive disorder (ADHD) who experienced propofol dependency and, under remarkable circumstances, succeeded in providing himself with this drug on a regular basis.
An otherwise healthy, 25-yr-old man presented to the neurology and psychiatry clinic because he was thought to have ADHD. Urged by his wife, he also reported regular usage of a white milky substance called propofol. At the age of 8 yr, he was given methylphenhydate (ritalin) for 1 yr because of his hyperactive behavior and attention deficits at school. After his parents stopped his ritalin administration for fear of long-term side effects, his symptoms of hyperactivity worsened, but he managed to graduate from high school, and studied to be an accountant in his father's company. At the age of 21 yr, he started to experience tension headaches, which were treated with propofol injections by an anesthesiologist. He had several appointments with this anesthesiologist for propofol treatment. From this time on, he started to inject himself with this drug. Before, he had occasionally self-administered benzodiazepines and morphine, and sometimes, he consumed marijuana. He obtained prescriptions for propofol from various veterinarians whom he told that he was a tropical fish enthusiast and he needed propofol to anesthetize his fish. He had three or four “propofol sessions” per week, lasting 1–2 h. He would inject 5 ml propofol, 1%, in an antecubital vein, fall into a deep, relaxing sleep for approximately 5–10 min, wake up, and inject another 5 ml of the drug, using up to 60–100 ml propofol, 1%, which he had drawn up in 20-ml syringes, per “session.” After he accidentally injected an overdose of this drug, he was found by his wife, unconscious and cyanotic. After a stay of several days in a hospital for clinical observation, he was convinced to attend an in-hospital drug rehabilitation program. There, he did not show any withdrawal symptoms, but after 7 days, he refused to participate in therapy anymore and left the hospital.
Because of its pharmacokinetic and pharmacodynamic features (ultrashort action, potent respiratory depressant), propofol seems not to be the substance of choice for drug abuse. However, reports about sexual disinhibition, reports about pleasant and euphoric feelings during recovery from propofol anesthesia and sedation since the beginning of its use in clinical practice, and several case reports of propofol abuse, the first one in 1992, 1shed some light on the abuse potential of this drug. Three cases were reported of young men with some connection to a hospital, such as being employed as theater technicians, who were stopped by the police for dangerous driving and were found to be injecting themselves with propofol while driving. 2An anesthesiologist experienced an uncontrollable compulsion toward this drug such that he could not abstain from injecting propofol despite the fact that he already had revealed his drug problem to his psychiatrist and the head of his department. 3He reported his previous benzodiazepine and opioid (fentanyl) use rather than admitting his regular propofol injections. In 1997, a case of propofol abuse was published about a general practitioner who injected the substance repeatedly up to more than 100 times a day because the drug effect lasted not more than 5–10 min. 4After injections, mild euphoria and a feeling of relaxation were followed by heavy sedation and loss of consciousness. An intense craving made it impossible to stop taking the drug. Like the anesthesiologist in the earlier case report, he relapsed twice despite psychiatric help. Thus, both individuals fulfilled the criteria of substance dependence, which are as follows: compulsion or craving; loss of control over the amount of the frequency of the drug used; and continued use of the substance despite adverse physical, psychological, social, or occupational consequences. 5Remarkably, none of these individuals experienced signs of withdrawal.
The patient described herein came in contact with propofol when receiving treatment for his tension headaches. Propofol in subanesthetic doses was novel, but was used increasingly to treat migraine and other headaches. 6
Recently, a clinical study in healthy volunteers assessed the rewarding effects and thus abuse potential of this drug. 7The authors of this study concluded that use of propofol may be rewarding (reinforcing) in some people without history of drug abuse and asked for further abuse liability testing.
Why more of these millions of patients who were exposed to propofol do not develop dependency remains a matter of speculation. First, it could be hypothesized that the majority of patients anesthetized with this drug are unaware of which drug was used for this purpose. Thus, a major prerequisite for addiction is missing: knowing what to look for. Second, this case report, as well as the others, suggests that some psychiatric pathology or previous drug abuse was involved. The first reported propofol abuser had alcoholism 1; the second was a stressed anesthesiologist 3who had experimented before with other drugs, such as marjiuana, cocaine, and other chemicals; the third was a general practitioner 2who had depression; and the current patient met the criteria for ADHD and had some other drug abuse experience as well.
Patients with ADHD are said to have an increased risk for development of psychoactive substance use disorders. 8However, even assuming that this patient had ADHD, he is not necessarily prone to dependency on such an “exotic” drug as propofol.
In conjunction with the aforementioned case reports, this case is highly troublesome for two reasons 1: for more than 15 yr, this drug has been widely used in clinical practice, and because of its unique pharmacologic qualities and its excellent safety record, it was administered to millions of patients. Now, there is evidence emerging that this drug might have addictive properties that we did not consider. 2The complete lack of withdrawal phenomena might prevent a potential victim from recognizing this addiction, and might prevent the careworkers involved from understanding and interpreting the problem as addiction, because with other substances the presence of withdrawal symptoms serves as a warning signal and increases readiness to intervene.
In summary, this is the first reported case of a layperson who became highly dependent on propofol. Because of its sole use in anesthesia and intensive care, access to this drug is restricted, and knowledge of what this agent is used for, in any sense, is limited to anesthesiologists, intensivists, and, unfortunately, to persons who detect its unforeseen effects by chance. The potential danger is highlighted, and we believe it is time for thorough abuse liability testing.
The authors thank Dr. Kursh Ahmed, M.B.B.S. (London), F.R.C.A. (Consultant Anaesthetist and Lead Clinician for Day Surgery, Pinderfields General Hospital, Wakefield, West Yorkshire, United Kingdom), for his helpful advice in the preparation of this manuscript.