Benzodiazepines,Methadone and Buprenorphine: Interactions and Clinical Management

Benzodiazepines (BZDs) are widely used by heroin users not in treatment, and by patients in methadone and buprenorphine (BPN) treatment. This review examines the epidemiology of BZD use by opioid users, and the range of harms that are associated with BZD use in this group, including the association of BZD use with opioid‐related mortality. Preclinical and clinical data regarding pharmacokinetic and pharmacodynamic interactions between methadone, buprenorphine, and BZDs are reviewed. An overview of treatment approaches for managing BZD use in this population is presented, including strategies for minimizing abuse and addressing BZD dependence. (Am J Addict 2009;19:59–72)     

Drug Interactions between Antiretroviral Medications and Medications Used in the Treatment of Drug Addiction: Research Needs

Today substance dependence is one of the major public health problems in the world with millions of people abusing legal and illegal drugs. In addition, almost one‐third of the world's population suffers with one or more infections. Both drugs of abuse and infections are associated with serious medical and health consequences, some of which may be exacerbated by the occurrence of pharmacokinetic and/or pharmacodynamic interactions between medications used in the treatment of these conditions when they co‐occur. This review briefly discusses issues surrounding clinical management related to drug interactions experienced by substance abusing patients. The emphasis of this paper is on the research needed to further study the extent, nature, and underlying molecular/genetic mechanism(s) of interactions between drugs of abuse, medications used in the treatment of drug addiction, and co‐occurring infections. (Am J Addict 2009;19:96–100)     

Getting to the Heart of the Matter: A Review of Drug Interactions Between HIV Antiretrovirals and Cardiology Medications

The past 20 years have seen remarkable advances in the treatment of HIV such that most people diagnosed with HIV today can live long, healthy lives by taking antiretrovirals which are usually life-long. Advancements in antiretroviral therapy include the availability of well tolerated, single tablet regimens that are associated with a lower risk of drug-drug interactions. Despite this, many people living with HIV infection might be taking antiretroviral agents that are associated with significant drug-drug interactions. Because HIV infection itself is associated with cardiovascular complications and this population is living longer, concomitant use of antiretrovirals and medications to treat cardiovascular-related diseases is often required. For this reason, it is imperative that clinicians are aware of the potential for clinically significant drug-drug interactions between antiretroviral agents and cardiac medications as well as the useful HIV drug interaction resources that might provide guidance. Available data on significant interactions are summarized and suggested guidance regarding management is discussed.     

Cannabidiol Interactions with Medications,Illicit Substances,and Alcohol: a Comprehensive Review

Cannabidiol, a non-intoxicating phytocannabinoid, has potential therapeutic effects over a broad range of disorders. Recently, there has been increased interest in CBD, as several studies showed promising anticonvulsant efficacy with few side effects. In 2018, a CBD-based oral solution, Epidiolex®, was approved by the FDA to treat two severe forms of pediatric epilepsy, Dravet syndrome, and Lennox-Gastaut syndrome. Although only these two syndromes are recognized indications for CBD, it has been consumed in an unregulated fashion for a variety of indications including chronic pain, muscle stiffness, inflammation, anxiety, smoking cessation, and even cancer. While CBD legislation in the USA is confusing due to the differences in state and federal laws, CBD has proliferated in the US market in several forms such as CBD oil or capsules, hemp oil/extract, and also as an ingredient in several dietary supplements, syrups, teas, and creams. With the ever-increasing use of CBD and its widespread availability to the general public, it is important to examine and report on possible drug–drug interactions between CBD and other therapeutic agents as well as addictive substances such as alcohol and tobacco. A detailed literature search for CBD’s possible interactions was conducted using online databases. As expected, CBD has been reported to interact with anti-epileptic drugs, antidepressants, opioid analgesics, and THC, but surprisingly, it interacts with several other common medications, e.g. acetaminophen, and substances including alcohol. This review provides a comprehensive list of interacting drugs. The possible mechanisms for these drug–drug interactions are presented in table format. Given the growing popularity of CBD as a medication and the dearth of available information on CBD drug–drug interactions, it is critical to be aware of current drug–drug interactions and it will be important to investigate the impact of CBD upon concomitant medication use in future randomized, controlled trials.KEY WORDS: cannabidiol, drug–drug interactions, cannabinoids, mechanism, cytochrome P450     

Methadone Maintenance: A Review and Critique

The problem of heroin addiction and rehabilitation has caused considerable alarm in the past few years. The number of heroin addicts alone in the United States has been estimated at 300,000 (“The Heroin Plague: What Can Be Done”, 1971, p. 27). Methadone maintenance is one approach to this problem of treating the addict so that he can become a productive member of society. It is being used in such cities as New York, Philadelphia, Pittsburg, Chicago, Mew Orleans, Portland, San Francisco, and Racine. The purpose of this paper is to present an overview of methadone maintenance by examining topics such as the program's background, the rationale behind the program, legal aspects of methadone maintenance, results, advantages, disadvantages, and criticisms of the program.     

Comorbidities and Prescribed Medications in Korean Patients with Chronic Hepatitis C: A Nationwide,Population-Based Study

Background/AimsExtrahepatic comorbidities and comedication are important to consider in the treatment of chronic hepatitis C (CHC) patients with direct-acting antivirals (DAAs) due to the risk of drug-drug interaction (DDI) and the effect of comorbidities on clinical outcomes. This study aimed to investigate the detailed profiles of comorbidities and comedication among Korean CHC patients.MethodsAll adult patients (≥18 years old) with a primary diagnostic code of CHC in 2013 were selected from the National Health Insurance claims database. For each patient, all ICD-10 codes listed as primary or secondary diagnoses and all prescribed medications were collected.ResultsAmong 47,104 CHC patients (median age, 57 years; male, 49.3%), 84.8% had at least one comorbidity for a mean number of 2.4, which increased with age. The most prevalent comorbidities were hypertension, esophagitis, dyslipidemia, diabetes mellitus, and peptic ulcer. Overall, 96.8% of the patients took at least one prescribed medication, with a mean of 8.1 medications/year, and the three most common drug types were analgesics, gastrointestinal agents, and antibacterials. Use of at least one drug with a DDI risk category of “contraindicated medication” or “required dose-reduction/additional monitoring” was observed in 97% of the overall patients. The proportion of prescribed medications that were contraindicated with DAAs varied from 2.0% to 38.9% depending on the hepatitis C virus regimen.ConclusionsThe majority of CHC patients had comorbidities; almost all patients took multiple prescribed medications, the number of which increased with age, and significant DDI risk was present in 97% of this Korean patient cohort. Comorbidities and comedication profiles should be considered during DAA therapy.     

Suicide and Psychopathology in 1,537 Patients Dependent on Prescribed Psychoactive Medications: Stockholm,Sweden

The risk of suicide among patients hospitalized because of dependence on prescribed psychoactive medications was estimated among all 1,537 such patients in Stockholm, Sweden, over an 8-year period. The suicide standardized mortality ratio was 41.0 among the women and 45.6 among the men who were dependent on such medications alone. It was of a similar magnitude (50.4 and 30.6) among women and men with concurrent alcohol/street-drug abuse. Among all deaths, 38% were suicides. Primary and secondary psychiatric disorders were common. To reduce the suicide risk, professional treatment intervention should entail thorough diagnostic assessment, behavioral/cognitive therapy, and a judicious use of psychoactive medications for anxiety, affective, and personality disorders.     

Neuropsychological Functioning of Opiate-Dependent Patients: A Nonrandomized Comparison of Patients Preferring either Buprenorphine or Methadone Maintenance Treatment

Objectives: In the present study, we investigated whether buprenorphine as a partial μ -opioid receptor agonist is associated with less cognitive impairment than methadone. Methods: Neuropsychological functioning of opioid-dependent patients, previously assigned to methadone (MMP, n = 30) or buprenorphine (BMP, n = 26) maintenance treatment according to their own preference, was compared and dose effects were investigated. Results: MMP and BMP performed equally well on all measures of neuropsychological functioning including the trail making test, the continuous performance test, and a vigilance task. However, patients receiving a higher dose of methadone were impaired in a vigilance task. Conclusions: In a free-choice administration of methadone or buprenorphine, there seems to be no difference in cognitive functioning. Possible explanations are discussed.     

Uses of Diverted Methadone and Buprenorphine by Opioid‐Addicted Individuals in Baltimore,Maryland

This study examined the uses of diverted methadone and buprenorphine among opiate‐addicted individuals recruited from new admissions to methadone programs and from out‐of‐treatment individuals recruited from the streets. Self‐report data regarding diversion were obtained from surveys and semi‐structured qualitative interviews. Approximately 16% (n = 84) of the total sample (N = 515) reported using diverted (street) methadone two–three times per week for six months or more, and for an average of 7.8 days (SD = 10.3) within the past month. The group reporting lifetime use of diverted methadone as compared to the group that did not report such use was less likely to use heroin and cocaine in the 30 days prior to admission (ps < .01) and had lower ASI Drug Composite scores (p < .05). Participants in our qualitative sub‐sample (n = 22) indicated that street methadone was more widely used than street buprenorphine and that both drugs were largely used as self‐medication for detoxification and withdrawal symptoms. Participants reported using low dosages and no injection of either medication was reported.