Kylie Reed

Pharmacological treatments for drug misuse and dependence

Introduction: Substance misuse disorder (DSM-5) remains a major health challenge. Harm reduction is the initial treatment goal, by reducing or eliminating non-prescribed drug use. Eventual abstinence is the ultimate harm reduction goal. However the scope for evidence-based pharmacological interventions remains limited. Areas covered: The paper takes a pragmatic clinical approach to existing and developing pharmacotherapies for substance misuse. Dependence may be characterised as a cycle with three stages: binge/intoxication, withdrawal/negative affect and preoccupation/anticipation (craving). Each of these stages may be the focus of pharmacotherapeutic intervention, and current literature is discussed which is of relevance to the practising clinician. Dependence on opiates, stimulants, cannabis and prescribed medications including benzodiazepines and the current treatments are addressed. Expert opinion: Possible pharmacotherapies of the future include anti-craving medications, which are still incompletely understood. Other developments include ultra-long-acting formulations, some of which have already been produced and are being studied or are in early clinical practice. A completely new line of investigation has been drug ‘vaccines’, whereby the body is stimulated to produce antibodies to, for example, cocaine and nicotine. Despite a number of evidence-based strategies for the treatment of substance misuse disorder, the range of licensed pharmacological treatment choices nevertheless remains narrow.

Randomised comparison of a novel buprenorphine oral lyophilisate versus existing buprenorphine sublingual tablets in opioid-dependent patients: a 'first-in-patient’ Phase II randomised open label-safety study

Aims: To test the safety of new buprenorphine oral lyophilisate wafer (“bup-lyo”) versus standard sub-lingual buprenorphine (“bup-SL”). Design: Randomised (2:1) open-label study; opioid-dependent subjects; subsequent partial cross-over. Settings: Specialised clinical trials facility and addictions treatment facility. Participants: Opioid-dependent subjects (n = 36) commencing buprenorphine maintenance (personalised dose-titration) including patients co-using alcohol, cocaine and benzodiazepines (below thresholds). Measurements: Respiratory function (respiratory rate, pulse-oximetry); medication hold and dose adequacy; opiate withdrawal signs and symptoms; tablet disintegration times; treatment retention. Pharmacokinetics (PK) for plasma buprenorphine and norbuprenorphine (n = 11). Findings: Oral lyophilised buprenorphine (“bup-lyo”) completely dissolved within 2 min for 58 vs. 5% for “bup-SL.” Dose titration resulted in similar maintenance dosing (10.8 vs. 9.6 mg). There were no significant between-group differences in opiate-withdrawal phenomena, craving, adequacy of “hold,” respiratory function. No serious adverse events (AEs), nor “severe” AEs, although more AEs and Treatment-Emergent AEs with “bup-lyo” (mostly “mild”). PK found greater bioavailability of buprenorphine with “bup-lyo” (but not norbuprenorphine). Conclusions: Orally disintegrating buprenorphine oral lyophilisate wafer disintegrated rapidly. No increased respiratory depression was found and clinically no difference between medications was observed. PK found substantially increased bioavailability of buprenorphine (but not of nor-buprenorphine) with “bup-lyo” relative to “bup-SL.” In supervised dosing contexts, rapidly disintegrating formulations may enable wider buprenorphine prescribing.

Treating Opioid Dependence with Opioids: Exploring the Ethics

Publisher Summary This chapter examines the extent to which treatment is primarily driven by the patient’s best interests, as opposed to the interests of government, the treatment industry, and the pharmaceutical industry. Drug use can be initially considered a matter of personal responsibility, and persistent use despite experiencing harm may be considered a failure of personal responsibility. It seems plausible to hypothesize that there is a subpopulation of heroin users that is more likely to take risks, less likely to be deterred by social disapproval or penal sanctions, and particularly vulnerable to developing the chronic, relapsing type of addiction. A divergence of views about the most effective way to use methadone is compatible with the assumption that opioid substitution treatment (OST) is at least a well-intentioned attempt to improve the health of heroin addicts. Ethical concerns over OST go further. Prescribing opioids to heroin addicts is counterintuitive and from its inception has challenged the dominant paradigm of addiction treatment, which is based on the principle that abstinence is necessary for recovery from addiction.

Treating Opioid Dependence with Opioids

Publisher Summary This chapter examines the extent to which treatment is primarily driven by the patient’s best interests, as opposed to the interests of government, the treatment industry, and the pharmaceutical industry. Drug use can be initially considered a matter of personal responsibility, and persistent use despite experiencing harm may be considered a failure of personal responsibility. It seems plausible to hypothesize that there is a subpopulation of heroin users that is more likely to take risks, less likely to be deterred by social disapproval or penal sanctions, and particularly vulnerable to developing the chronic, relapsing type of addiction. A divergence of views about the most effective way to use methadone is compatible with the assumption that opioid substitution treatment (OST) is at least a well-intentioned attempt to improve the health of heroin addicts. Ethical concerns over OST go further. Prescribing opioids to heroin addicts is counterintuitive and from its inception has challenged the dominant paradigm of addiction treatment, which is based on the principle that abstinence is necessary for recovery from addiction.

Chapter 3 – Treating Opioid Dependence with Opioids: Exploring the Ethics

Publisher Summary This chapter examines the extent to which treatment is primarily driven by the patient’s best interests, as opposed to the interests of government, the treatment industry, and the pharmaceutical industry. Drug use can be initially considered a matter of personal responsibility, and persistent use despite experiencing harm may be considered a failure of personal responsibility. It seems plausible to hypothesize that there is a subpopulation of heroin users that is more likely to take risks, less likely to be deterred by social disapproval or penal sanctions, and particularly vulnerable to developing the chronic, relapsing type of addiction. A divergence of views about the most effective way to use methadone is compatible with the assumption that opioid substitution treatment (OST) is at least a well-intentioned attempt to improve the health of heroin addicts. Ethical concerns over OST go further. Prescribing opioids to heroin addicts is counterintuitive and from its inception has challenged the dominant paradigm of addiction treatment, which is based on the principle that abstinence is necessary for recovery from addiction.