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[The advertiser responds:]

The statement criticized by Dr. Rashiq (“some patients may also experience fewer side effects than with morphine”) is fully consistent with the literature on opioid rotation that has become available over the past 15 years.

Portenoy and Coyle1 were among the first to comment on individual patient variability in opioid response, and an early report by Galer and colleagues2 described the management of inadequate therapeutic response to and severe adverse effects from morphine, by switching to alternate opioids — including hydromorphone.

The other cited paper3 describes 191 patients in the Palliative Care Unit at Edmonton General Hospital, of whom 42% required a switch in opioid because of serious toxicity or inadequate analgesia. The most frequently used initial and alternative opioids were morphine and hydromorphone, respectively. Improvement in both pain levels and the primary symptom necessitating a change in opioid, occurred on conversion from morphine to hydromorphone (or other opioids).

Later studies, also published by the University of Alberta group,4^,5 further discuss the clinical role of opioid rotation, including the equianalgesic dose ratios for switching between morphine and hydromorphone.

Recently, Nauck and colleagues6 reported on a series of patients who showed improvements in pain control and side effects when switched from morphine to controlled-release hydromorphone.

An interesting case of differential response to morphine and hydromorphone was described by Katcher and Walsh.7 Uncontrollable itching on morphine (an infrequent side effect attributed to cutaneous histamine release) fully resolved within 24 hours of conversion to hydromorphone.

The mechanisms underlying a differential response to hydromorphone and morphine are not established, but possibilities include: differences in metabolism — hydromorphone is metabolized primarily to hydromorphone-3-glucuronide and, unlike morphine, does not form a 6-glucuronide metabolite that has opioid activity;8 incomplete cross-tolerance; or as yet uncharacterized differences in opioid receptor subtype activity.

We believe that the clinical evidence for individual differences in opioid response, recently summarized in a comprehensive review of hydromorphone from the Cleveland Clinic,9 fully supports the accuracy of the statement in the advertisement criticized by Dr. Rashiq.