Saturday, August 28, 2010

St. John’s Wort May Thwart Opioid Analgesia

Research UpdateChronic pain is often associated with depression and many herbal over-the-counter remedies for self-treatment of depression or anxiety contain St. John’s wort. New research suggests that taking this herbal product can incur drug interactions that may reduce effects of oxycodone and many other opioid analgesics.

Researchers in Finland designed a randomized, placebo-controlled, cross-over trial in which 12 healthy subjects were administered either St. John’s wort or placebo three-times daily for 15 days and given oral oxycodone hydrochloride 15 mg on day 14 [Nieminen et al. 2010]. Following St. John’s wort administration oxycodone plasma concentration was significantly decreased by 50% and its half-life was shortened by 27%, resulting in the self-reported drug effects of oxycodone decreasing significantly (p=0.004). The authors conclude that this interaction of St. John’s wort and oxycodone could be of clinical significance when treating patients with chronic pain.

CLINICAL CONCEPTS: Small, single-dose, short-term studies of this nature have inherent limitations for demonstrating the true impact of drug interactions on analgesic efficacy. However, St. John’s wort is a well-known inducer of CYP450 liver enzymes, and these enzymes play important roles in the metabolism of many opioid analgesics, except for morphine, hydromorphone, or oxymorphone (which have a different pathway of metabolism). Based on this Finnish study, it could be expected that St. John’s wort might alter effects of oxycodone as well as other opioids metabolized via CYP450 pathways.

This same research team from Finland, using a similar experimental design, had previously reported that grapefruit juice (a CYP450 inhibitor) significantly increased the plasma concentration of oxycodone and extended its half life. In this case, analgesic effects of oxycodone were not altered but there were impairments on self-reported performance measures [see our discussion of this study here].

The clinical implication is that the metabolism of many opioids can be significantly affected by interactions with other agents that may increase or decrease plasma concentrations of the analgesic and its effects. Therefore, when a patient is not responding to a particular opioid or dose as expected, a thorough investigation of all other agents the patient is taking — prescribed or OTC — as well as dietary habits, could be essential for understanding what is happening. Admittedly, however, this can be a challenging task. For example, in the case of St. John’s wort, it comes from the plant Hypericum perforatum of which there are 370 species worldwide, and it is sometimes called Tipton’s Weed, Chase-devil, Klamath weed, and by other names. It could be an unrecognized ingredient in many over-the-counter (OTC) herbal remedies, and of unknown origin, quality, and/or quantity.

REFERENCE: Nieminen TH, Hagelberg NM, Saari TI, et al. St John’s wort greatly reduces the concentrations of oral oxycodone. Eur J Pain. 2010(Sep);14(8):854-859 [abstract here].