Saturday, April 14, 2012

Lethal Cocktails: Alcohol, Sedatives, & Opioids

Drug Cocktail Taking opioid analgesics with other central nervous system (CNS) depressants can increase risks of oversedation, respiratory depression, and death due to overdose. Yet, a new study finds that sedatives are somewhat commonly prescribed along with opioids for chronic noncancer pain, and a proportion of patients add alcohol to the mix. Whether or not patients have a history of a substance use disorder does not seem to make a difference, and practitioners need to be more vigilant when prescribing opioids and sedatives for any patients.

A research team led by Kathleen W. Saunders, from Group Health Research Institute, Seattle, Washington, and colleagues from Kaiser Permanente of Northern California, report on a large survey to assess the prevalence and predictors of concurrent alcohol and sedative use among persons also prescribed long-term opioid therapy for chronic noncancer pain [Saunders et al. 2012]. The study was published in the March 2012 edition of the Journal of Pain.

Using electronic databases from two integrated healthcare plans, investigators identified patients who had been prescribed long-term opioid therapy for pain and interviewed 1,848 of them by telephone during 2008 and 2009. Overall, the sample was about two-thirds female, middle-aged (mean 56 years), and highly educated. Average pain intensity level during the 3 months prior to interviews was about 6 on a 1-to-10 scale (highest levels reported were 8.8). A relatively large proportion, 60%, also was classified as having depression.

Concurrent sedative use was characterized as a patient having taken those agents along with opioids for half or more of the 90 days preceding the interview. Sedatives were broadly considered to include benzodiazepines, barbiturates, muscle relaxants (eg, carisoprodol), and miscellaneous anxiolytics, hypnotics, and sleep aids (eg, zolpidem). Concurrent alcohol use was defined as consuming 2 or more drinks within 2 hours of taking an opioid in the prior 2 weeks. Analyses also were stratified by whether subjects had a history of substance use disorder (SUD, involving alcohol and/or other drugs), as defined by prior diagnosis indicated in the medical record and/or responses to questioning during the survey interview.

Overall, nearly a third of the subjects (31%) were found to have a history of SUD. Among subjects with SUD, sedatives were used concurrently with opioids by 39%, compared with 29% of subjects without SUD history. The total rate of concurrent alcohol use was 12% and similar in patients with and without an SUD. The following observations were also reported…

  • Subjects using alcohol with opioids were more likely to be male, prescribed lower daily opioid doses, had lower average pain intensity levels, and tended toward being less depressed. As noted above, the presence of SUD history had no impact, overall.

  • Concurrent sedative users were significantly younger, more likely to be female, prescribed higher average daily opioid doses, more likely to be depressed, and were taking opioids for more than one pain condition. Prevalence of concurrent sedative use was greater among subjects with a history of SUD than in those without.

  • The prevalence of subjects taking all 3 substances concurrently — opioids, alcohol, and sedatives — were similar in both SUD and non-SUD groups — about 3%

  • Interestingly, patients with a history of SUD and greater pain (7+) were less likely to concurrently use alcohol, but were more likely to be using sedatives.

The authors conclude that concurrent use of CNS depressants was relatively common among this sample of patients prescribed long-term opioids for chronic noncancer pain, regardless of substance use disorder (SUD) status. The presence of depression, unrelieved pain, and gender can be important variables in the risky use of CNS depressants, and is apart from any overt abuse of those substances. Prescribers should be aware of these factors when developing pharmacologic treatment plans for patients with chronic pain.

COMMENTARY: The prospective nature of this study, large number of subjects, and personalized interviews (albeit via telephone) increased the reliability of the data. However, the quality and strength of evidence are still rather low, since the study is observational in nature — in a sense, the evidence is a consolidation of data from a large series of case reports or anecdotes. Cause-effect relationships in any of the data comparisons should not be presumed.

This current report represents a subset of data from a larger study — CONSORT, or CONsortium to Study Opioid Risks and Trends — conducted by research teams at the Group Health Cooperative and Kaiser Permanente healthcare systems. Many other publications have been “milked” from the large body of collected data, and the outcomes may tell us more about clinical pain management approaches at those institutions than at typical pain practices nationwide.

A major failing of the present study by Saunders et al. is that, while they note in background material that combining opioids with sedatives and alcohol can have lethal consequences, they do not report on adverse events of any sort in their study population. An earlier article based on CONSORT data, discussed in an UPDATE [here], described 51 opioid-related overdoses, including 6 deaths, over a 9-year period. Concurrent with opioid analgesics, sedatives had been prescribed in 74% of that study sample, including benzodiazepines in 43%.

Additional questions are unanswered in the study by Saunders and colleagues:

  • With all subjects being prescribed opioid analgesia, and significant proportions being prescribed sedatives and using alcohol on their own, why were average pain intensity ratings still at moderate levels, with some patients reporting severe pain?

  • Why were nearly a third of patients with chronic pain in this population characterized as having a history of substance use disorder? Is this a typical prevalence rate among patients with chronic noncancer pain?

  • Why were concomitant CNS-depressing sedative agents prescribed so frequently for patients with a history of SUD who might be considered at high risk for adverse events or of misusing those medications?

  • Were patients cautioned about the risks of combining alcohol with their medications, and/or the use of sedatives in combination with opioids and alcohol?

  • Were patients taking their prescribed opioids and/or sedatives as directed? [The authors concede that they did not assess patient compliance with medication regimens.]

It must be stressed that, in the case of sedative use, patients were prescribed those medications — this was not illicit use or abuse. It is important to point this out because the tone of the study report makes it seems like patients, rather than their healthcare providers, were responsible for this risky combination of drugs. Certainly, patients were responsible themselves for using alcohol with their medications; however, such use was reported by only 12% of all subjects and the data did not capture if this was a regular, infrequent, or rare occurrence.

In subtle ways, the authors also imply that higher daily opioid dosages were somehow related to risky alcohol and sedative use. Yet, as average daily opioid dose increased to higher levels (eg, 120+ mg/d morphine-equivalent dose, or MED), alcohol use actually decreased in patients with or without a history of SUD. This was perhaps related to more adequate pain relief afforded by increased opioid dosing, but this theory needs testing in controlled research trials.

Use of sedatives was only modestly greater in those with or without SUD who were receiving higher opioid doses. Again, however, sedative use was by prescription and relates to clinical practices rather than patients taking more sedatives on their own. As the authors themselves remark, “the widespread practice of concurrent prescribing of opioids and sedatives, particularly among patients receiving [long-term opioid therapy] at high opioid dosages, deserves increased scrutiny.”

REFERENCE: Sanders KW, Von Korff M, Campbell CI, et al. Concurrent Use of Alcohol and Sedatives Among Persons Prescribed Chronic Opioid Therapy: Prevalence and Risk Factors. J Pain. 2012(Mar);13(3):266-275 [abstract].

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