Sidney H. Schnoll

Screening for Alcohol Abuse Using CAGE Scores and Likelihood Ratios

OBJECTIVE To assess the performance of the CAGE (acronym referring to four questions, see below) questionnaire in discriminating between medicine outpatients with and without an alcohol abuse or dependence disorder. DESIGN A cross-sectional design of a sample of consecutive patients who received both the alcohol module of the diagnostic interview schedule and the CAGE (Cut down, Annoyed, Guilty, Eye-opener) screening questionnaire. SETTING The outpatient medical practice of an urban university teaching hospital. PATIENTS All patients 18 years or older who signed a consent form approved by the universitys institutional review board. MEASUREMENT Calculation of the sensitivity, specificity, receiver operating characteristic (ROC) curve, and likelihood ratio for CAGE scores of 0 to 4. RESULTS Thirty-six percent of the sample group met criteria for a history of alcohol abuse or dependence. A CAGE score of 2 or more was associated with a sensitivity and specificity of 74% and 91%. The calculated area under the ROC curve was 0.89, whereas the likelihood ratios for CAGE scores of 0 to 4 were 0.14, 1.5, 4.5, 13, and 100, respectively. These ratios were associated with posterior probabilities for an abuse or dependence disorder of 7%, 46%, 72%, 88%, and 98%, respectively. CONCLUSION Clinicians can improve their ability to estimate a patients risk for an alcohol abuse or dependence disorder using likelihood ratios for CAGE scores.

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.

An Analysis of the Root Causes for Opioid-Related Overdose Deaths in the United States

OBJECTIVE A panel of experts in pain medicine and public policy convened to examine root causes and risk factors for opioid-related poisoning deaths and to propose recommendations to reduce death rates. METHODS Panelists reviewed results from a search of PubMed and state and federal government sources to assess frequency, demographics, and risk factors for opioid-related overdose deaths over the past decade. They also reviewed results from a Utah Department of Health study and a summary of malpractice lawsuits involving opioid-related deaths. RESULTS National data demonstrate a pattern of increasing opioid-related overdose deaths beginning in the early 2000s. A high proportion of methadone-related deaths was noted. Although methadone represented less than 5% of opioid prescriptions dispensed, one third of opioid-related deaths nationwide implicated methadone. Root causes identified by the panel were physician error due to knowledge deficits, patient non-adherence to the prescribed medication regimen, unanticipated medical and mental health comorbidities, including substance use disorders, and payer policies that mandate methadone as first-line therapy. Other likely contributors to all opioid-related deaths were the presence of additional central nervous system-depressant drugs (e.g., alcohol, benzodiazepines, and antidepressants) and sleep-disordered breathing. CONCLUSIONS Causes of opioid-related deaths are multifactorial, so solutions must address prescriber behaviors, patient contributory factors, nonmedical use patterns, and systemic failures. Clinical strategies to reduce opioid-related mortality should be empirically tested, should not reduce access to needed therapies, should address risk from methadone as well as other opioids, and should be incorporated into any risk evaluation and mitigation strategies enacted by regulators.

Screening for Drinking Disorders in the Elderly Using the CAGE Questionnaire

To assess the performance of the CAGE questionnaire in identifying elderly medicine outpatients with drinking problems.

Do Prescription Monitoring Programs Impact State Trends in Opioid Abuse/Misuse?

OBJECTIVE Prescription monitoring programs (PMPs) are statewide databases containing prescriber and patient-level prescription data on select drugs of abuse. These databases are used by medical professionals or law enforcement officials to identify patients with prescription drug use patterns indicative of abuse or providers engaging in illegal activities. Most states have implemented PMPs in an attempt to curb prescription drug abuse and diversion. However, assessment of their impact on drug abuse is only beginning. This study aimed to evaluate the relationship between PMPs and opioid misuse over time in two drug abuse surveillance data sources. METHODS Data from the RADARS® System Poison Center and Opioid Treatment surveillance databases were used to obtain measures of abuse and misuse of opioids. Repeated measures negative binomial regression was applied to quarterly surveillance data (from 2003 to mid-2009) to estimate and compare opioid abuse and misuse trends. PMP presence was modeled as a time varying covariate for each state. RESULTS Results support an association between PMPs and mitigated opioid abuse and misuse trends. Without a PMP in place, Poison Center intentional exposures increased, on average, 1.9% per quarter, whereas opioid intentional exposures increase 0.2% (P = 0.036) per quarter with a PMP in place. Opioid treatment admissions increase, on average, 4.9% per quarter in states without a PMP vs 2.6% (P = 0.058) in states with a PMP. In addition to the time trend, population and a measure of drug availability were also significant predictors. A secondary analysis that classified PMP based upon ideal characteristic showed consistent though not significant results. CONCLUSIONS Two observational data sources offer preliminary support that PMPs are effective. Future efforts should evaluate what PMP characteristics are most effective and which opioids are most impacted.

Challenges in the development of prescription opioid abuse-deterrent formulations.

Opioid analgesics remain the cornerstone of effective management for moderate-to-severe pain. In the face of persistent lack of access to opioids by patients with legitimate pain problems, the rate of prescription opioid abuse in the United States has escalated over the past 15 years. Abuse-deterrent opioid products can play a central role in optimizing the risk-benefit ratio of opioid analgesics—if these products can be developed cost-effectively without compromising efficacy or creating new safety issues for the target treatment population. The development of scientific methods for assessing prescription opioid abuse potential remains a critical and challenging step in determining whether a claim of abuse deterrence for a new opioid product is indeed valid and will thus be accepted by the medical, regulatory, and reimbursement communities. To explore this and other potential impediments to the development of prescription opioid abuse-deterrent formulations, a panel of experts on opioid abuse and diversion from academia, industry, and governmental agencies participated in a Tufts Health Care Institute-supported symposium held on October 27 and 28, 2005, in Boston, MA. This manuscript captures the main consensus opinions of those experts, and also information gleaned from a review of the relevant published literature, to identify major impediments to the development of opioid abuse-deterrent formulations and offer strategies that may accelerate their commercialization.

Physician detection of drinking problems in patients attending a general medicine practice

Objective:To assess the patient and physician characteristics that influence physicians’ detection of problem drinking in their medical patients.Setting:The outpatient medical clinic at an urban university teaching hospital staffed by interns and residents.Design:Cross-sectional study of a rendomly chosen subsample of consecutive patients.Measurement:Univariate and multivariate analysis with calculated adjusted odds ratios of factors associated with physician detection of drinking problems. A problem was diagnosed according to the patient’s results on the alcohol module of the Diagnostic Interview Schedule (DIS).Results:Physicians detected 22% of 189 presumably inactive problems and 49% of 92 current problems, i.e., those that have occurred within the preceding year. Multivariate correlates of detection of active problems included male patient gender, presence of gastrointestinal complications of excessive drinking, number of concurrent medical disorders, and previous medical record reference to alcohol (p<0.05). Physician gender and year of training were not associated with detection.Conclusion:Our physicians appear to rely on specific patient characteristics as well as the patient’s medical record to detect drinking problems in their ambulatory patients. Their reliance upon these factors may hinder their detection of drinking problems in women patients and less seriously impaired individuals.

Perinatal substance abusers : psychological and social characteristics

Forty perinatal substance abusers were administered multiple psychosocial, addiction, and psychological measures before beginning treatment. Results indicate that these patients are limited intellectually, educationally, financially, and emotionally. Psychiatric comorbidity was high, with 45% having non-substance abuse axis I diagnoses and 75% having confirmed (by two or more tests) axis II pathology. The most frequently identified axis I disorders were depression and anxiety. The most frequently detected personality disorders were antisocial, borderline, paranoid, and dependent. The average IQ was 87 (low average range) and nearly one third of the sample were found to be somewhat impaired intellectually. These data suggest that treatment programs must take psychological characteristics into account if they are going to succeed in helping these women achieve and maintain abstinence.

Physical dependence on Ultram® (tramadol hydrochloride): both opioid-like and atypical withdrawal symptoms occur

In 1994, the Drug Abuse Advisory Committee (DAAC) of the Food and Drug Administration (FDA) concluded that Ultram (tramadol hydrochloride) could be marketed as an analgesic drug without scheduling under the Controlled Substances Act based upon extensive pre-clinical, clinical and European epidemiological data. However, to guard against unexpectedly high levels of abuse in the United States, the DAAC recommended that an independent steering committee (ISC) be appointed to proactively monitor abuse/dependence. In the event that high rates of abuse were found, this ISC was given the authority to immediately recommend to the FDA that Ultram be scheduled. In the course of the surveillance project, the ISC received reports of withdrawal following abrupt discontinuation of Ultram and in some instances, following dose reductions. In most cases, the withdrawal symptoms consisted of classical opioid withdrawal, but in some cases were accompanied by withdrawal symptoms not normally observed in opiate withdrawal, such as hallucinations, paranoia, extreme anxiety, panic attacks, confusion and unusual sensory experiences such as numbness and tingling in one or more extremities. Withdrawal symptoms of either type were one of the more prevalent adverse events associated with chronic Ultram use, comprising nearly 40% of all adverse events reported with Ultram. Most of these consisted of typical opiate withdrawal symptoms, but 1 in 8 cases presented as atypical. These results indicate that physicians and other healthcare professionals need to be aware of the potential of Ultram to induce withdrawal of the classical opioid type, and that atypical withdrawal may also occur.

Methadone Treatment During Pregnancy

Methadone maintenance has been used for decades to treat opioid-dependent pregnant women. The outcomes of pregnancies thus treated are vastly improved over the outcomes of pregnancies complicated by street drug use. Despite its long history of successful use during pregnancy, little is known about the long-term effects of methadone on the fetus and the newborn. Studies done in animals suggest there may be subtle effects on brain and behavior. Only recently have other treatments for opioid dependency during pregnancy been investigated. There is increasing evidence that altering the traditional methadone maintenance protocols may be beneficial, and that tapered withdrawal can be safely achieved under some circumstances.