Potentiation of pain relief with hydroxyzine: a therapeutic myth?

Opioid analgesics are among the oldest known medications. In spite of long usage, clinical success in controlling pain in many settings appears to be limited by a lack of understanding of the clinical pharmacology of these agents. Efforts to achieve better outcomes often focus on the use of adjunctive agents, such as hydroxyzine, in an attempt to control postoperative pain with a minimum of toxicity. Although such combined therapies are exceedingly common, clinical data supporting a hypothesis of an "opioid-sparing" effect of hydroxyzine are marked by serious methodologic flaws, including lack of placebo control, lack of statistical analyses, and use of subjective assessments, all of which compromise the validity of such conclusions. In doses that may contribute to pain relief, hydroxyzine demonstrates a significant potential for causing respiratory depression which is additive to that of opioids, but not reversible with naloxone. In total, the data do not confirm the purported clinical benefits of hydroxyzine-opioid combinations in comparison with appropriate regimens of opioids alone.