Long‐acting naltrexone has long‐acting benefits and 100% induction rates are not difficult to achieve

Jarvis et al.’s comprehensive review of Vivitrol (extendedrelease-naltrexone/XR-NTX) [1] included three important clinical issues worth expanding. First, their discussion of low ‘rates of induction’ onto XR-NTX, defined as the percentage of those offered XR-NTX who received their first injection, ignores evidence from studies of implanted NTX that intention-to-treat induction rates of 100% have been routinely and safely achieved for many thousands of patients with relatively simple techniques [2–4], including one that requires no nursing or medical presence. To describe induction procedures lasting 7–8 days as ‘rapid’ suggests unfamiliarity with these methods, which eliminate what is perhaps the biggest obstacle to wider use of XR-NTX. Carreño et al.’s definition of ‘rapid’ induction techniques (those that, inter alia, enable patients to have taken full therapeutic doses of NTX within 24 hours) [5] has not been disputed. Secondly, quantifying ‘opioid use’ by ‘the percentage of urine samples negative for opioids’ is arguably an inappropriate sole measure of opioid intake in patients receiving adequate doses of XR-NTX because (unlike patients on agonist maintenance) NTX patients usually develop no agonist effects from even large doses of opiates [6,7]. Continued use of opiates despite complete blockade is an interesting and challenging phenomenon [7–11], but compatible with complete abstinence from opiates at the neuropharmacological level. Even persistent opiate use (usually intravenous) during the first weeks of parenteral NTX treatment sometimes disappears eventually. Habit and curiosity often drive early use. That curiosity may reflect hopes that the blockade can be over-ridden, or is waning, but it often reflects understandable needs for reassurance that NTX really does block opiates, thus reinforcing initially fragile beliefs in the possibility of remaining opiate-free for long enough for new opiate-free habits to become both automatic and effortless [12]. This leads to the third issue. They note, correctly, that other forms of XR-NTX can provide opiate blockade for as much as 7months, but the crucial clinical relevance of this advantage is obscured by their claim that ‘the effects of XRNTX have been shownnot to persist once discontinued’. On both theoretical and empirical grounds, that claim is questionable except for very short-term treatment. Patients who persist with XRor implanted NTX are, by definition, ‘good compliers’ and thus more likely to do well when NTX is discontinued [13]. Furthermore, being unable to experience agonist effects for several months, rather than having to decide every month to continue treatment (or not), makes it more likely that patients will adapt to opiate-free habits even if their motivation was initially poor. We have previously noted the many (largely unrecognized) similarities between disulfiram in alcohol dependence and NTX in opiate dependence. In the remarkably successful Out-patient Long-term Intensive Therapy for Alcoholics (OLITA) alcoholism programme, patients took supervised disulfiram for an average of about 3 years but 75% were still abstaining after 9 years [14]. In a British audit of long-acting NTX implants, 52% of patients who had one implant (and 100% of those who had two) remained opiate-free at 24 months, long after opiate-blockade had disappeared [15].