Buprenorphine Abuse Research Articles

Epidemiology and outcomes of community-onset methicillin-susceptible Staphylococcus aureusbacteraemia in a university hospital in Singapore

BackgroundMethicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia remains a condition associated with considerable morbidity and mortality worldwide. It is a common but little-studied problem outside of Europe and North America.MethodsA single-centre retrospective case series profiling all patients with community onset-MSSA bacteraemia presenting between March 2005 and February 2006 to a tertiary acute-care university hospital in Singapore. In addition to epidemiological and clinical data collection, risk factors for complicated bacteremia and attributable mortality were analysed.ResultsA total of 100 patients met the case definition. Patients were more likely to be male (65%) and below 65 years of age (69%). Seventeen patients were intravenous drug abusers, while 38 had diabetes mellitus. There were 18 cases of endocarditis, with 11 occurring in intravenous buprenorphine abusers. Attributable mortality was 11%, and 46% of patients developed complicated bacteremia. On multivariate analysis, age > 65 years and presence of chronic pulmonary disease were the only significant risk factors for the former, while valvular heart disease was a significant risk factor for the latter.ConclusionMSSA bacteraemia is associated with a significant risk of serious complications in Singapore. Other Asian cities should be alert to the risk factors for adverse outcomes for this important cause of morbidity and mortality.

Use and misuse of buprenorphine in the management of opioid addiction

Buprenorphine was approved in late 2004 for the treatment of opioid abuse and dependence in specially trained and certified physicians' offices. At the time of the approval, there was a regulatory concern that given the anticipated wide exposure there would be unexpectedly high levels of abuse in the high-risk population for which it was intended. To assess its abuse potential, the authors recruited more than 1000 individuals seeking treatment for prescription opioid abuse from 100 stand-alone (i.e., self-pay or insurance) drug abuse treatment programs around the country to determine whether they misused buprenorphine in the past 30 days to get high. The results indicate that there was a time-related increase in the number of subjects who used buprenorphine to get high, reaching 30-35 percent of individuals completing a questionnaire in the second quarter of 2006. At this time, it was equivalent to the misuse of methadone, both of which, however, were considerably lower than hydrocodone and oxycodone. Thereafter, the number of individuals using buprenorphine to get high dropped in a near linear fashion to less than 20 percent of those completing a questionnaire in the second quarter of 2007, significantly lower than that for methadone, oxycodone, and hydrocodone. The most likely interpretation of these data is that the poly-substance-abusing population, for whom buprenorphine is intended, experimented with this medication for its mood-altering effects for a period of time, but presumably because of its lack of euphorogenic properties, its use has now dissipated. Additionally, support for this conclusion is the very rare endorsement of buprenorphine as a primary drug (<3 percent of the total sample). Thus, the results indicate that it is unlikely that buprenorphine abuse will ever reach the epidemic that was feared by some regulatory groups and that its use in opioid detoxification and maintenance should continue.

Concomitant Use of Midazolam and Buprenorphine and its Implications Among Drug Users in Singapore

The aim of this study was to determine the prevalence and characteristics of benzodiazepine (BZD) abuse among intravenous opioid users in Singapore. Eligibility criteria for inclusion in this study were all intravenous buprenorphine abusers, who presented to the Community Addictions Management Programme (CAMP) over a 1-year period from February 2005 to January 2006. One hundred and twenty subjects, who consented to the study, completed an interviewer-administered questionnaire and underwent blood test for blood-borne viral infections. The age of the 120 subjects ranged from 20 to 64 years, with a mean age of 39.0 (SD 8.0) years. The majority of the participants were male (90.0%); 48.3% were Chinese. Ninety-eight (81.7%) patients were using BZDs concomitantly. Midazolam was the most commonly used BZD. Buprenorphine abusers who were concomitantly using BZDs were significantly younger and reported an earlier age of onset of illicit drug abuse as compared to those not using BZDs. Those abusing BZDs were more likely to share syringes (x 2 = 5.8, P = 0.02), and were more likely to be seropositive for hepatitis C virus (x 2 = 4.3, P = 0.04). This study highlights the extreme caution that needs to be exercised in prescribing BZDs to all patients in general and patients with injecting drug use or histories of drug abuse in particular. At a public health level, general practitioners (GPs) who prescribe buprenorphine should have compulsory training which highlights the potential dangers of abuse and concomitant abuse of BZDs.

Subutex®Abuse Presenting to the Emergency Department: A Case Series

IntroductionSubutex®(sublingual buprenorphine hydrochloride) tablets are prescribed to alleviate symptoms of opiate withdrawal in addicts undergoing a cessation programme. Although Subutex®is safe and effective, parenteral abuse is an emerging phenomenon. A variety of complications may present due to the different areas that patients inject themselves.AimWe present a case series of four patients who presented to the emergency department following complications of Subutex®abuse. The complications included deep venous thrombosis, limb ischaemia and epidural abscess with osteomyelitis of the spine.DiscussionSublingual buprenorphine was launched in Singapore in 2002. It is currently the preferred alternative to methadone for treating opiate dependency locally. Despite safeguards, instances of abuse of buprenorphine exist. These medications can be passed or sold to others not on a cessation programme. Two of the 4 patients in this series obtained Subutex®illegally. Parenteral abuse of Subutex®is of grave concern. In Australia and France, between 23–37% of Subutex®users have abused it in this fashion.ConclusionSubutex®abuse is not uncommon in Singapore. Complications especially from parenteral use can occur and may result in serious morbidity. A high index of suspicion among physicians must be maintained in patients with unusual limb infections, ischaemia or venous thrombosis. Tighter regulations on prescription and consumption of Subutex®may be useful in preventing these complications, in addition to increasing public awareness and education of the risks of parenteral abuse for patients on cessation programme.

Complications arising from intravenous buprenorphine abuse

Sir, Following its introduction in the 1980s, buprenorphine (Subutex, Schering Plough) abuse has been reported worldwide.1,,2 Within a year of its introduction to treat opioid dependence in Singapore in 2002, buprenorphine became the second top-selling new pharmaceutical product in 2003, and the fourth best-selling product in 2005.3 This rise in popularity was in turn accompanied by an increase in the number of reported cases …

The effects of buprenorphine on fentanyl withdrawal in rats

Fentanyl is a potent mu-opioid receptor agonist that is widely used for the treatment of severe chronic pain. Discontinuation of fentanyl administration has been shown to induce a negative emotional state. The aim of the present studies was to investigate the effects of the partial mu-opioid receptor agonist buprenorphine on the negative emotional state associated with precipitated and spontaneous fentanyl withdrawal in rats. Fentanyl and saline were chronically administered via osmotic minipumps. A discrete-trial intracranial self-stimulation procedure was used to provide a measure of brain reward function. Somatic signs were recorded from a checklist of opioid abstinence signs. Naloxone induced a deficit in brain reward function in rats chronically treated with fentanyl. Buprenorphine dose-dependently prevented the naloxone-induced deficit in brain reward function. Discontinuation of fentanyl administration was also associated with a deficit in brain reward function. After explantation of the minipumps, the administration of buprenorphine induced a potentiation of brain reward function in the fentanyl-withdrawing rats, but did not affect brain reward function of saline-treated control rats. Buprenorphine prevented the somatic withdrawal signs associated with spontaneous fentanyl withdrawal and attenuated the somatic signs associated with precipitated fentanyl withdrawal. Buprenorphine prevents affective and somatic fentanyl withdrawal signs. Moreover, buprenorphine is rewarding in rats previously exposed to fentanyl, but not in opioid-naïve rats. This pattern of results suggests that buprenorphine may be an effective treatment for the anhedonic-state associated with fentanyl withdrawal, but further study of buprenorphine's abuse potential is warranted.

Abuse liability of buprenorphine–naloxone tablets in untreated IV drug users

Buprenorphine (Subutex ®) is widely abused in Finland. A combination of buprenorphine plus naloxone (Suboxone ®) has been available since late 2004, permitting a comparison of the abuse of the two products among untreated intravenous (IV) users. A survey was distributed to attendees at a Helsinki needle exchange program over 2-weeks in April, 2005, At least 30% were returned anonymously. Survey variables included: years of prior IV opioid abuse, years of buprenorphine abuse, frequency, dosage, route of administration and reasons for use, concomitant IV abuse of other substances and amount paid on the street for both buprenorphine and buprenorphine + naloxone. Buprenorphine was the most frequently used IV drug for 73% of the respondents. More than 75% said they used IV buprenorphine to self-treat addiction or withdrawal. Most (68%) had tried the buprenorphine + naloxone combination IV, but 80% said they had a “bad” experience. Its street price was less than half that of buprenorphine alone. The buprenorphine + naloxone combination appears to be a feasible tool, along with easier access to addiction treatment, for decreasing IV abuse of buprenorphine.

A survey of buprenorphine related deaths in Singapore

Buprenorphine is available in Singapore as substitution treatment for opioid dependence since 2002. This study surveys buprenorphine related deaths in Singapore between September 2003 and December 2004. The aims are to establish the autopsy prevalence of buprenorphine related deaths and the demographical and toxicological profile of the cases. Toxicological screening was performed for all unnatural deaths, deaths involving known drug addicts, as well as when autopsy revealed no obvious cause of death. Twenty-one cases had buprenorphine detected in post-mortem blood and/or urine samples. Eighteen were sudden deaths. There were two fatal falls from height and one death by hanging. All subjects were male. The age range was 24–48 years. Fourteen subjects were between 30 and 39 years of age. The mean age was 35 years. The majority (62%) were Chinese. Eleven (52%) were known drug abusers. For sudden deaths, two groups were identified. Six cases died from natural causes. Blood buprenorphine levels ranged from undetected (detected in urine) to 3.2 ng/mL (mean 1.4 ng/mL). Twelve cases were attributed directly and indirectly to mixed drug poisoning. Blood buprenorphine levels ranged from undetected (detected in urine) to 17 ng/mL (mean 3.2 ng/mL). Nineteen cases showed concurrent abuse of buprenorphine and benzodiazepine, diazepam being the most frequently detected, followed by nitrazepam and midazolam. The availability of buprenorphine as substitution therapy is associated with an increase in buprenorphine related deaths. The danger of co-abuse of buprenorphine and benzodiazepines is highlighted.

Abuse of Prescription Buprenorphine, Regulatory Controls and the Role of the Primary Physician

Buprenorphine is an opioid partial agonist approved in several countries for the treatment of opioid dependence. It was approved in Singapore in 2002 for this indication, and is more widely available in the primary care setting and can be prescribed by all licensed physicians who have undergone designated training. There is limited literature addressing the risk of its illicit abuse via intravenous self-administration. We report 2 such cases of the abuse of prescription buprenorphine in the psychiatric consultation-liaison service of a general teaching hospital, the treatment approaches and outcomes. We also briefly review the indications, uses and abuses of buprenorphine in Singapore, and as reported in other countries, and the roles of primary care physicians, in order to stimulate greater awareness and understanding among specialists and general practitioners, who would encounter these patients in various settings.

Socio-demographic Profile and Help-seeking Behaviour of Buprenorphine Abusers in Singapore

The US Food and Drug Administration (FDA) approved buprenorphine or Subutex for the treatment of opiate dependence in October 2002. Buprenorphine is a partial agonist of the mu-opioid receptor; although initial animal research suggested a low abuse potential for buprenorphine, it was subsequently shown to have an abuse potential similar to that of morphine or hydromorphone. The objectives of this study were to establish the sociodemographic profile and help-seeking behaviour of buprenorphine abusers attending the deaddiction treatment clinics of the Community Addictions Management Programme. One hundred and twenty subjects, all buprenorphine abusers fulfilling the diagnostic criteria for opiate dependence, who consented to the study, completed an interviewer-administered questionnaire. The mean age of those participating in the study was 39.2 [standard deviation (SD) 8.0] years. The majority of the participants were male (90%), 52.5% were currently employed and 98% had at least primary education. A family history of drug abuse was reported by 27% of the subjects. Illicit drug abuse occurred at an early age with mean age of onset of illicit drug abuse being 16.9 (SD 4.8) years with gateway drugs like marijuana and glue. It is vital for our medical profession to be aware of the trend in the local population to move from the abuse of illicit substances, to the abuse of prescriptive medications. It makes it necessary to increase the understanding of addictions both amongst our practising medical fraternity, and amongst those training to enter the profession. At the hospital level, it necessitates a higher level of vigilance among our emergency room physicians and those treating infectious diseases.

Complications Relating to Intravenous Buprenorphine Abuse: A Single Institution Case Series

We present a retrospective descriptive study of cases admitted to Tan Tock Seng Hospital from March 2005 to October 2005 with complications of Subutex abuse. A total of 8 patients were studied. Of the 8, 7 were male and one was female. Their complications consist of the following: arterial pseudoaneurysm (2), arterial pseudoaneurysm with infective venous thrombus (1), infective venous thrombus (1), venous thrombus (2), end arterial spasms (1) and sympathetic dystrophy (1). For the patient who presented with buprenorphine-associated neuropathy, non-operative treatment with analgesics was given. Conservative medical therapy involving deep venous thrombosis treatment was instituted for the patient with deep venous thrombosis. Repair, restorative bypass and embolectomy surgery were performed for patients who had severe embolic/thrombotic complications. One of the patients who received the above surgery required amputation of his lower limb. Of the 8 patients, 4 were treated medically, 3 required surgery and 1 required amputation. Their recoveries were uneventful. Of the 8, 1 absconded and was not followed up with. Parenteral injection of buprenorphine can cause a wide range of vascular complications from simple vascular irritation to severe infective thrombosis and pseudoaneurysms requiring limb amputations. Non-sterile preparation of an injected substance or non-sterile injection sites and the repeated punctures of major vessels are possible culprits in those who are seen to have acute infection of injection sites.

Clorazepate affects cell surface regulation of δ and κ opioid receptors, thereby altering buprenorphine-induced adaptation in the rat brain

Concomitant abuse of buprenorphine (BPN) and benzodiazepines (BZD) may relate to a pharmacodynamic interaction between the two. The objective of the present work was to investigate the acute and chronic effects of clorazepate (CRZ) alone or in combination with BPN on selective κ opiate tritiated ligand [ 3H]-U69 593 and δ opiate radioligand [ 3H]-deltorphine II binding in the rat brain. Bmax (maximal receptor density) and Kd (the dissociation constant) were directly determined at different brain regions of interest (ROI) selected for high densities of κ and/or δ receptors in rats treated with BPN and/or CRZ. The agents were administered either once or for 21 consecutive days. Differences in Bmax and Kd (for both specific ligands) were related to drug treatment and receptor location. Globally, single BPN administration induced no changes in κ or δ opiate receptor binding, whereas repeated BPN administration up-regulated κ receptor density and decreased δ affinity. At the κ receptor level, repeated administration of CRZ acted only on Kd, whereas the δ receptor was up-regulated. Repeated addition of CRZ to BPN had no effect on κ receptor Bmax versus chronic controls. By significantly decreasing Bmax, CRZ nullified the effect of chronic BPN on the κ receptor. The modifications were strongest in the nucleus accumbens, where both types of receptor occur. Treatments had region-selective effects in some brain areas, such as the amygdala, periaqueductal gray matter, hypothalamus and caudate putamen. Increased μ and δ receptor densities would be expected to provide reinforcement by enhancing reward, and impairment of κ receptor availability would be expected to decrease aversion. The effects described are likely to influence addictive behavior among people abusing BZD and BPN.

Potential for Abuse of Buprenorphine in Office-Based Treatment of Opioid Dependence

To the Editor: Buprenorphine was approved by the Food and Drug Administration (FDA) in 2002 for the treatment of opioid addiction in certified physicians' offices. However, the FDA and the Drug Enf...

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■ Aims Official records indicate that in 1996 no more than five drug addicts in Finland received medically assisted treatment. By 2004 that figure had grown to 600–700 persons. This article retraces the path to this crucial change. ■ Design Several factors of this change are scrutinised. In the latter part of the 1990s, Finland saw a significant increase in drug-related harms, resulting in a gradual revision of drug policies. Medically assisted treatment was brought under the spotlight through serious public controversies, centred on two private doctors prescribing buprenorphine for their heroin-using patients. Claims-makers, representing a variety of agencies, stood up for substitution treatment. International trends in substitution treatment, as well as scientific research, facilitated the advocacy of such treatment. ■ Results The drug user has been redefined in terms of private and public health, and civil rights, engendering a more liberal attitude towards substitution treatment. National drug policy is characterised by a joint move: social and health policy initiatives, on the one hand, and criminal policy, on the other, are running on separate tracks, making it possible to increase control powers and to expand treatment services. ■ Conclusions Several questions are still unresolved. For example, there has been very little debate on the widely known problem of buprenorphine abuse.

Localisation bronchique révélatrice d’une maladie de Hodgkin

Bronchial localisation of Hodgkins disease has been described only rarely and it is exceptional as the presenting feature. More frequently the clinical presentation is extrinsic bronchial compression. Mr B.C., 34 years old, had a past history of cured alcoholism and abuse of cannabis and buprenorphine. In February 2001 he presented with generalised pruritus, weight loss of 8 kg in one year, a 1 cm node above the right clavicle, hypereosinophilia, and CT evidence of non-obstructive mediastinal adenopathy and interstitial lesions in the right lower lobe. Five months later he was admitted to hospital with a febrile illness. The right supraclavicular node had disappeared but there was gross mediastinal adenopathy, associated with a right perihilar soft tIssue mass encircling the upper, middle and lower lobe bronchi and multiple peripheral parenchymal nodules. Bronchoscopy revealed complete stenosis of the right upper lobe bronchus and bronchial histology confirmed Hodgkins disease. Bronchoscopy is an effective investigation for the detection of endobronchial Hodgkins disease, often overlooked because parenchymal abnormalities are attributed to extrinsic compression. In order to determine the disease stage more precisely we advise immediate bronchoscopy when there is suspicion that Hodgkins disease may be the cause of clinical.

Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine

Buprenorphine and naloxone sublingual (s.l.) dose formulations may decrease parenteral buprenorphine abuse. We evaluated pharmacologic interactions between 8 mg s.l. buprenorphine combined with 0, 4, or 8 mg of naloxone in nine opiate-dependent volunteers stabilized on 8 mg s.l. buprenorphine for 7 days. Combined naloxone and buprenorphine did not diminish buprenorphine's effects on opiate withdrawal nor alter buprenorphine bioavailability. Opiate addicts stabilized on buprenorphine showed no evidence of precipitated opiate withdrawal after s.l. buprenorphine-naloxone combinations. Buprenorphine and naloxone bioavailability was ∼40 and 10%, respectively. Intravenous buprenorphine and naloxone produced subjective effects similar to those of s.l. buprenorphine and did not precipitate opiate withdrawal.

TASTE CONDITIONING EFFECTS OF BUPRENORPHINE IN MORPHINE-NAIVE AND MORPHINE-EXPERIENCED RATS

Male Sprague–Dawley rats were injected daily with saline (morphine-naive rats) or 20 mg kg−1morphine (morphine-experienced rats), starting 15 days before the experiment. Subsequent taste conditioning indicated that 0.1 mg kg−1buprenorphine significantly decreased 0.025% saccharin consumption in morphine-naive, but not in morphine-experienced rats. A 10 mg kg−1dose of morphine gave similar results, whiled-amphetamine (0.75 mg kg−1) was consistently aversive. It was concluded that morphine experience selectively blocks the aversive effects of buprenorphine in rats; thus it possibly increases the potential for buprenorphine abuse.

Motivational properties of buprenorphine as assessed by place and taste conditioning in rats.

Buprenorphine, a mixed agonist-antagonist opioid with considerable analgesic activity, is currently indicated as a therapeutic agent with low abuse potential. Nevertheless, buprenorphine abuse has been recently reported from some countries. Thus the present experiments were performed to characterize further the motivational properties of buprenorphine in rats. Rewarding and aversive effects were assessed by place preference and taste aversion conditioning, respectively. It was found that buprenorphine (0.025, 0.050, 0.100 mg/kg s.c.) causes a significant increase in the amount of time spent on the conditioned side, but no significant decrease in saccharin consumption. Therefore buprenorphine data are not consistent with the general finding that psychoactive drugs cause rewarding and aversive effects within a similar dose range.

Recurrent Koro in repeated i.v. buprenor‐phine withdrawal

AddictionVolume 91, Issue 1 p. 145-146 Free Access Recurrent Koro in repeated i.v. buprenor-phine withdrawal Ababindan N. Chowdhury, Ababindan N. Chowdhury Institute of Psychiatry, 7, D.L. Khan Road, Calcutta - 700025, IndiaSearch for more papers by this authorGautam Banerjee, Gautam Banerjee Institute of Psychiatry, 7, D.L. Khan Road, Calcutta - 700025, IndiaSearch for more papers by this author Ababindan N. Chowdhury, Ababindan N. Chowdhury Institute of Psychiatry, 7, D.L. Khan Road, Calcutta - 700025, IndiaSearch for more papers by this authorGautam Banerjee, Gautam Banerjee Institute of Psychiatry, 7, D.L. Khan Road, Calcutta - 700025, IndiaSearch for more papers by this author First published: January 1996 https://doi.org/10.1046/j.1360-0443.1996.91114516.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Yap, P. M. (1965) Koro–a culture-bound depersonalization syndrome. British Journal of Psychiatry, 111, 43 – 49. 2 Chowdhury, A. N. & Bagchi, D. J. (1993) Koro in heroin withdrawal. Journal of Psychoactive Drugs, 25, 257 – 258. 3 Yap, P. M. (1965) Koro in a Briton. British Journal of Psychiatry, 111, 774 – 775. 4 Chowdhury, A. N. & Bera, N. K. (1994) Koro following cannabis smoking: two case reports. Addiction, 89, 1017 – 1020. 5 Dow, T. W. & Silver, D. (1973) A drug-induced Koro syndrome. Journal of the Florida Medical Association, 60, 32 – 33. 6 Chowdhury, A. N. & Chowdhury, S. (1990) Buprenorphine abuse: report from India. British Journal of Addiction, 85, 1349 – 1350. Volume91, Issue1January 1996Pages 145-146 ReferencesRelatedInformation

Consumption of buprenorphine and other drugs among heroin addicts under ambulatory treatment: results from cross–sectional studies in 1988 and 1990

We assessed the prevalence of consumption of buprenorphine and other drugs among heroin addicts under ambulatory treatment in two cross-sectional studies conducted in 1988 (188 subjects) and in 1990 (197 subjects). Patients were enrolled in one of three different programmes: methadone maintenance programme (MMP), antagonist maintenance programme (AMP) and drug-free programme (DFP). Information given by participants was compared with results of urine screening for drugs. Urine samples were tested using enzyme immunoassay for the detection of heroin, cocaine, dextropropoxyphene, cannabis and benzodiazepines, and radioimmunoassay for buprenorphine. Sixty-six percent of patients in 1988 and 71% of patients in 1990 reported having consumed buprenorphine at some time during their history of drug dependence (period prevalence) and 5.9% and 6.1%, respectively, tested positive to the drug (point prevalence). In over 70% of these patients consumption was by the intravenous route. Consumption of cannabis, cocaine and benzodiazepines was also very high in the study population. Overall, patients in the DFP group consumed the largest number of the drugs tested, while those in the AMP group consumed the smallest number. Abuse of buprenorphine could be more widespread than previously reported.