A postmarketing surveillance program to monitor Ultram (tramadol hydrochloride) abuse in the United States.

Tramadol HCl, marketed as Ultram in the USA, was introduced as a non-scheduled drug in April 1995 based on the assumption that the risk of abuse was sufficiently low to warrant a non-scheduled status. However, approval was contingent upon the development of an innovative proactive surveillance program, to be overseen by an independent steering committee, which would detect unexpectedly high levels of abuse. The postmarketing surveillance program consisted of systematic collection and scientific evaluation of reports of suspected abuse in high-risk populations surveyed through an extensive key informant network of drug abuse specialists and all spontaneous reports of abuse received through the FDA MedWatch system. Methods to estimate the number of patients prescribed tramadol were also developed. Monthly rates of abuse were calculated as an index of the risk-benefit ratio (i.e., abuse cases per 100,000 patients prescribed the drug). The data for the 3 years since the drug was introduced show that the reported rate of abuse has been low. Although a period of experimentation seemed to occur in the first 18 months after its introduction--which reached a peak rate of approximately two cases per 100,000 patients exposed--during the 2 year period prior to June 1998, the reported rate of abuse has significantly (P = 0.011) declined, reaching levels of less than one case per 100,000 patients in the last 18 months. The overwhelming majority of abuse cases (97%) have been found to occur among individuals with a history of substance abuse and the abuse has been confined to isolated pockets around the country-notably none of which have significant populations of street drug abusers. Thus, the data support the decision not to schedule tramadol and, furthermore, suggest that a proactive post-marketing surveillance program can be successfully developed to effectively monitor abuse of new medications.

Interventions/Wilmer: a continuum of care for substance abusers in the criminal justice system.

This article describes a 300-bed substance abuse treatment program that is part of a continuum of care focused on preventing drug and criminal recidivism in substance abusing criminals incarcerated in Dallas County, Texas. It is the product of a joint effort of the judiciary, the Dallas County Supervision and Corrections Department, the State of Texas Criminal Justice Division, and Interventions Co., a not-for-profit treatment provider. The program is rooted in over 25 years of treatment experience and incorporates therapeutic community (TC) technology combined with 12-Step programming, behavior modification, job training (having a job is required for graduation), educational, and medical/psychiatric elements. Treatment is conceived as part of a continuum of care to provide substantial and sustained support for the inmate in the difficult process of adapting to the community post incarceration. Treatment plans are individualized and are based on an extended workup in which the individual's status in a number of domains is assessed. Specialized services, such as transportation and childcare, facilitate recovery. Once in the community, urine monitoring, groups, and counseling continue. The program is beginning its fourth year of operation and approximately 600 inmates have started the program. A formal evaluation is in process.

Medical maintenance: an interim report.

In a pilot study, 130 methadone maintained subjects with a six-month history of good treatment performance were assigned randomly, for a one-year study period, to an experimental condition (once per month non-random urine screen, counseling session and doctor visit, two times per month methadone pick up, a quarterly true random urine screen, and participation in a diversion control program), or they were assigned to a control condition of staying under standard conditions for six months and then being transferred to the experimental condition for six months. Three out of four subjects (73%) completed the year in good standing with no differences between control and experimental conditions. Subject satisfaction was such that the Institutional Review Board judged that return to standard conditions would be a hardship. A Study of Medical Maintenance (SMM) continues and extends the pilot study with two protocols: (1) for new subjects and (2) for subjects entered from the pilot study. SMM requires a once per month random urine screen and extends the experimental condition to two years but is otherwise identical to the pilot study; 71 of 107 S's (66%) entered protocol 1 and are in good standing. Pilot subjects (N = 75) are holding their good performance, some for over four years. The reduced levels of services in these studies free up resources which can be applied to entering IDU's into treatment thereby contributing to a slowing of the HIV epidemic.

Medical maintenance: a pilot study.

In a one year study, 130 methadone maintained subjects with a six month history of good treatment performance were assigned randomly to an experimental condition of one monthly non-random urine screen, one monthly counseling session, one monthly doctor visit, two times per month methadone pick up, a quarterly true random urine screen and participation in a diversion control program or to a control condition of staying under standard conditions for six months and then being transferred to the experimental condition for six months. Results of urine screens and scores on the Addiction Severity Index (ASI) at entrance and six month intervals showed no differences between groups. Three out of four subjects completed the year in good standing. Subject satisfaction was such that the IRB judged that return to standard conditions would be a hardship. Experimental conditions were cheaper such that resources freed up could be applied to the HIV epidemic.

Drug abuse and public health. A global perspective.

During the past 20 years there has been a substantial increase in the data available on the prevalence and consequences of the use of drugs which are liable to abuse. The body of data is sufficiently scientific, comprehensive and global in scope to enable an overall profile of the use patterns of these drugs to be drawn in this review. The studies evaluated include those which surveyed populations of hundreds, thousands, or even more, covering a range of common drugs of abuse and using specified research methods. The data are summarised for North America, Europe, Asia and the West Pacific, Africa and South America. A complex picture has emerged, confounded by an array of factors, which this review does not address in detail, such as youth alienation, the changing role of women and the increasing sophistication of criminal networks. From a global perspective, the evidence reviewed from the various regions indicates that the use of drugs with liability for abuse is widespread and associated with public health and social problems of great magnitude. The major set of problems appears to be related to primary pattern drugs such as alcohol, nicotine, cannabis and the opioids. Cocaine may also be a worldwide threat in view of the problems it has created in some regions. Drug abuse usually starts in adolescence, and both sexes now appear to be involved where in the recent past it was predominantly men who were affected. The concurrent use of multiple substances is now becoming the modal pattern, and drug-related problems correlate with one another and with somatic, psychiatric and social pathology. Opioid use now tends to be via intravenous administration, and the doses of cannabis and cocaine base which are used are increasing. Substances with therapeutic effects on DSM-III-R diagnosable disorders, such as antidepressants and benzodiazepines, require careful consideration by policymakers because the risk:benefit ratio is different to that of primary-pattern intoxicants, especially taking into consideration the broad and proven therapeutic use of these substances and the need for their availability for patients and physicians. In conclusion, the data presented in this review indicate that the scientific description of trends and consequences of drug abuse is an indispensable first step in rational policy making. The review also identifies areas for further study and research.

Addictive behaviors and benzodiazepines: 2. Are there differences between benzodiazepines in potential for physical dependence and abuse liability?

This paper examines data on the question of possible differences between benzodiazepines in abuse liability and potential for causing physical dependence. The data on potential for causing physical dependence indicates that all benzodiazepines cause physical dependence and there is little evidence for substantial differences between them in this respect. The evidence for substantive differences between benzodiazepines with respect to abuse liability is reviewed: problems with methodology and with definitions make problematic the assertion of some authors that there are clinically meaningful differences in abuse liability. There is general agreement that all benzodiazepines have at least some abuse liability.

Addictive behaviors and benzodiazepines: 1. Abuse liability and physical dependence.

A review of scientific and clinical evidence indicates: (1) benzodiazepines have an abuse liability and can cause physical dependence, (2) abuse liability is of a lower order of magnitude than that associated with common intoxicants such as barbiturates, opioids or stimulants, (3) sustained, exclusive use of benzodiazepines for inducing intoxication occurs but, it is infrequent, (4) benzodiazepines tend to be secondary drugs to a preferred primary intoxicant; in experimental paradigms normals prefer placebo to benzodiazepines, (5) susceptibility to physical dependence varies widely as low doses are sufficient to produce it in some but very high multiples are not sufficient to produce it in many others, (6) factors predisposing to physical dependence are: total lifetime dose, previous exposure to drugs cross-tolerant, such as alcohol or barbiturates, concomitant severe medical/psychiatric problems, and severe persisting stress. Individual susceptibility to abuse and to become dependent on benzodiazepines should be investigated much more vigorously than it has heretofore.

Methadone maintenance treatment.

This paper reviews the world literature on methadone. Methadone has been used in hundreds of thousands of patients, in disparate social, economic, cultural, and geographic situations; it has been evaluated in scores of studies. The large majority of evaluations demonstrate that opioid use, criminality, and general health status are affected positively in many addicts. Smaller gains in job and family functions are noted. Alcoholism and multiple drug use complicate treatment for some addicts. Despite the positive data, public opinion remains negative about this treatment. The use of methadone in withdrawal from opioid dependence and in pregnancy complicated by opioid dependence is discussed.

Clinical experience with T's and B's.

'T's and B's' started to become widely used in Chicago in the early 1970s. Users reported an interaction between the two drugs which was expressed in slang terms such as 'Toms and Bettys', 'T'shirts and Blue Jeans.' By the late 1970s, T's and B's users occupied 10% of the treatment census in Chicago. Soft tissue damage was more pronounced with 'T's and B's' than with heroin and a number of serious medical complications were observed, e.g. pulmonary hypertension. The introduction of Talwin NX appears to have decreased greatly the use of T's and B's as demand for treatment for primary abuse of this combination is close to zero in 1983-84.

Methadone detoxification: self versus physician regulation.

We studied 108 heroin-dependent patients who had been "stabilized" on methadone, i.e., had no change in methadone dose for at least 2 weeks. With respect to their methadone detoxification regimen, 65 of the study patients preferred physician regulation and 43 study patients preferred self-regulation. Half of each group was randomly assigned to self- or physician regulation. Twenty-five of the 108 patients reached abstinence following a regimen which lasted 22 weeks; there was no statistically significant difference in proportion of subjects reaching abstinence from any of the four study groups. We observed no differences in treatment retention, symptom severity, frequency of urines positive for morphine or quinine, or psychosocial functioning. Study subjects preferring self-regulation had statistically significant increases in the number of dose raises. We conclude that there is no evidence to support the belief that physician regulation is superior to self-regulation in opioid detoxification regimens.

Drugs and homicide: a theory.

In this paper we report our experience with 24 cases in which there was a homicide or homicides committed in association with use of large amounts of psychoactive drugs. Many, if not most of these homicides, would not have occurred without drug effects, for frequently there was evidence of grossly illogical thinking in close temporal association with use of intoxicants and in many cases there was no previous history of violence, no evidence of premeditation, no plan to avoid arrest and little or no discernible motivation. Usually there were multiple losses or other severe stress in the lives of the persons committing the homicide in the months preceding the crime. The stress increase was accompanied by increased and extraordinary intake of psychoactive substances. We theorize that high doses of psychoactive drugs impaired severely the brain systems upon which the mental functions of reality testing and judgment depend. Drug induced impairment of reality testing and judgment is frequently uncritically equated with hallucinations, disorientation, changes in time perception or other drug induced mental phenomena. Impairment of reality testing and judgment are basic criteria for linking drug effects with the behavior of homicide in the cases reviewed.

Careers with heroin.

This report examines heroin use careers within a sample of 147 Black male heroin addicts and their nonaddicted friends. Based on the extent of their heroin use, subjects were classified into the following subgroups: "light" experimenters, "moderate" experimenters, "heavy" experimenters, and addicts. Our findings indicate that no single career line of pattern characterizes all heroin users. While some users quickly progress from initiation to heroin to regular, intermittent use or "chipping" to daily heroin use and physical dependence, others are deflected at various points along the way. In this report we describe some of the sociobehavioral processes or career contingencies associated with movement from one level of heroin use to the next.

Evaluating service needs in drug-abusing clients.

Patients applying for treatment to the State of Illinois' Chicago Central Intake Facility were interviewed to assess their service needs and treatment expectations; a subgroup was reinterviewed after 4 months. Patients were classified as long-term opioid-dependent, short-term opioid-dependent, or as polydrug nonopioid dependent abusers. We found high levels of housing, employment, and legal needs among all subgroups at both first and second interviews. There were significant differences between drug-use groups in reasons for seeking treatment; opioid-dependent groups gave drug-related reasons more frequently while polydrug abusers cited legal reasons. Length of time patients remained in treatment was not related to service needs.