Do Opioids Hurt Hearing? A new study finds no such link when they’re taken as prescribed, but it’s less clear what happens when they’re abused. Features
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Features  |   November 01, 2018
Do Opioids Hurt Hearing?
Author Notes
  • Kathleen C. M. Campbell, PhD, CCC-A, is a distinguished scholar and research professor at Southern Illinois University School of Medicine. Her research focuses on ototoxicity and noise-induced hearing loss. kcampbell@siumed.edu
    Kathleen C. M. Campbell, PhD, CCC-A, is a distinguished scholar and research professor at Southern Illinois University School of Medicine. Her research focuses on ototoxicity and noise-induced hearing loss. kcampbell@siumed.edu×
Article Information
Hearing & Speech Perception / Hearing Disorders / Features
Features   |   November 01, 2018
Do Opioids Hurt Hearing?
The ASHA Leader, November 2018, Vol. 23, 50-55. doi:10.1044/leader.FTR2.23112018.50
The ASHA Leader, November 2018, Vol. 23, 50-55. doi:10.1044/leader.FTR2.23112018.50
Your patient sits looking at you as you explain her hearing loss—the way it slopes down from low to high frequencies. You describe how the loss at higher frequencies will pose problems with hearing in background noise, hearing women’s and children’s voices, and understanding soft-spoken dialogue in movies. The patient asks, “Why?”
Together you sort through the risk factors over the patient’s lifetime: noise exposure, dietary factors, exercise habits, genetics and … any medications? She produces the requested list, which includes hydrocodone. Now what to say? While we do not advise patients whether to take various medications (over-the-counter or prescribed), we are often asked which ones can affect hearing, and if so, how.
The fact is, most of our training in ototoxicity focuses on platinum-based chemotherapeutics and aminoglycoside antibiotics, both usually used to treat life-threatening disease. We know other drugs can possibly affect hearing, but many times the literature is unclear.
With opioids, the dilemma is immediately apparent: For a patient with chronic pain, the thought of not being able to control their pain may be unbearable. But if they have hearing loss, and progression could lead to further isolation and loneliness—and sometimes limit employment—that possibility is one more worry in an already complicated life.
So how clear is the literature on a link between hydrocodone and hearing loss? Not very, which only adds to our dilemma. There’s been uncertainty about whether an opioid could damage hearing in isolation, or only when in combination with other medications (see sources below). Most reports in the literature have been anecdotal, involving patients abusing opioid drugs in combination with acetaminophen (the latter can be included with the opioid in, for example, Vicodin and Percocet, but people also may add it separately). In cases of abuse, usually no pre-drug baseline hearing test is available to determine actual change, and the patient may have multiple health risk factors, including other drug use, poor diet, alcohol use, smoking and noise exposures.
Without research that controls for such factors, we can’t tell if the hearing loss could be secondary to the opioid, and if so, to what extent. We also can’t pinpoint other factors that could contribute to hearing loss, such as drug dosage. But we do see that, in some reported cases of abuse, the loss was bilateral, rapidly progressive, and possibly severe to profound. As it turns out, I had the opportunity to investigate these issues in a controlled trial specifically focused on hydrocodone. Results indicate that, when properly taken under the supervision of a physician, the drug may not affect hearing. But when it is abused, the effects on hearing are uncertain.

Usually no pre-drug baseline hearing test is available from the patient abusing opioids to determine actual change.

Unraveling a mystery
To investigate a potential drug effect as complicated as this, our best hope for answers is a double-blind, placebo-controlled, carefully designed and monitored clinical trial. I was fortunate to help design audiologic testing for possible ototoxicity in large-scale Phase 3 clinical trials for hydrocodone (see sources). With the approval of my university, but with the work completely separate from it, I served as a paid audiology consultant on this largest study to date to determine if hydrocodone caused hearing loss within therapeutic dosing levels.
We conducted two Phase 3 studies, both under an Investigational New Drug Application filed with the FDA and approved by the Copernicus Group Institutional Review Board. All 1,207 participants were adults, age 18 or older, with lower back pain for more than three months that was uncontrolled by other analgesics. We excluded patients from participating if they had a history of depression or other psychiatric disorders, pre-existent hearing loss that could possibly fluctuate, exposure to cisplatin or aminoglycoside or head and neck radiation in the last six months, or conductive or asymmetric hearing loss. We included patients with symmetric, non-fluctuant hearing loss.
In one study, participants took either placebo or hydrocodone adjusted for pain control across specified dosing levels. During the 12-week, double-blind period of this study, participants were not allowed to take other analgesics. In a concurrent open-label study, participants were allowed to take non-opioids and short-acting opioids.
The methods likely sound familiar to audiologists who routinely see patients for ototoxicity concerns. However, one of the main differences between seeing these patients in a general clinical practice and having them tested in a clinical trial is that clinical trials impose significantly more stringent standardization of methods, involving equipment, procedures, recording and reporting. For example, in our research, all sites received identical audiometers and tested hearing thresholds in the conventional (0.25–8 kHz) and high-frequency (10–16 kHz) audiometry ranges on all participants.
All sites monitored tympanometry for possible middle ear abnormality. To monitor participants for possible tinnitus, they administered the Tinnitus Handicap Inventory (THI), and to test for vestibular disorder, they administered the Dizziness Handicap Inventory (DHI) on each visit. To test for significant changes in hearing thresholds, we used the ASHA criteria: ≥ 20 dB from baseline at any frequency, change of ≥10 dB from baseline at any two adjacent frequencies, or loss of response at three consecutive frequencies where responses were obtained at baseline.
Following the original ASHA guidelines, we considered these changes real only if confirmed by repeat testing within 24 hours of the original testing. We rechecked the testing to ensure the patient showed a true change and wasn’t just experiencing erosion of attention due to, for example, lower back pain or the effects of the opiate itself.
I also have been using the ASHA criteria in several clinical trials to look at what I call “reverse ASHA criteria”—using the same criteria to check for improvement, rather than worsening, of thresholds. If thresholds in a clinical trial improve as much and as often as they deteriorate, you then know you may be dealing with some random variability rather than true ototoxicity. Checking this can also help you work with your clinical trials sites to tighten up on test methods if needed.
ASHA-specified changes do not necessarily mean that ototoxicity has occurred, in that they are designed to provide early warning. However, in these studies, if an ASHA-level change occurred, we flagged the patient for follow-up audiologic work-ups. We scheduled these as recommended by the otolaryngologist, generally at one, two, three, six and beyond six months, until the change resolved or stabilized. Resolved meant that results, compared to baseline, no longer met ASHA criteria. Stabilized meant that no further changes ≥10 dB occurred, and progressive meant that hearing thresholds had deteriorated more than an additional 10 dB.

Does hydrocodone cause hearing loss? Based on these studies, it appears that the answer is “no” when it’s administered at therapeutic dosing levels up to 12 months.

Answers … when dosing is controlled
To determine if hearing loss resulted from hydrocodone dosing, we pooled data from 1,207 participants in the double-blind and open-label studies for an integrated analysis. We compared these data with those from 292 placebo participants. Although the study drug was hydrocodone, some patients took other possible ototoxic medications, including macrolides, PDE-5 inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDS) or acetaminophen, in the 30 days before screening, during the study or both. However, we didn’t monitor use of these additional medications.
Here’s what we found: There were no greater changes or variability in pure-tone thresholds in the hydrocodone group, as compared to placebo group, for either the conventional or high-frequency audiometry (10–16 kHz) ranges. In fact, we more often saw slight improvement, rather than decrements, in pure-tone thresholds. This could indicate a small learning effect, as patients became better at concentrating on threshold-level signals. They may also have felt better over time, possibly affecting the hearing test results as the hydrocodone helped control their pain (because a patient in severe pain may have trouble concentrating on listening for soft signals.) The slight improvements also happened in the placebo group, most likely indicating a learning effect. But most patients showed no ASHA-level changes in either direction.
When participants did show ASHA-level threshold changes that were decrements, they all fully resolved or stabilized. None showed progression or developed severe or profound hearing loss. Also, in cases of drug-induced ototoxicity, we’d expect to see threshold changes increase along with drug dosing, but that didn’t happen. Most patients in the study also used other drugs that could potentially affect hearing, including macrolides, PDE-5 inhibitors, NSAIDS or acetaminophen, but as the use was balanced between the hydrocodone and placebo groups, it would not alter the outcome. Also, we noted no synergy between any of these agents in conjunction with the hydrocodone.
And we saw no clinically meaningful changes in speech-reception threshold, word recognition, THI or DHI scores.

The results of these carefully controlled studies don’t address what may happen when people abuse hydrocodone and other opioids, or become addicted to them.

But what about abuse?
So does hydrocodone cause hearing loss? Based on these studies, it appears that the answer is “no” when it’s administered at therapeutic dosing levels up to 12 months. We also saw no obvious impact on hearing when hydrocodone was combined with other possibly ototoxic agents.
However, the results of these carefully controlled studies don’t address what may happen when people abuse hydrocodone and other opioids, or become addicted to them. Anecdotal reports in the literature have largely focused on a link between long-term opioid abuse and hearing loss. But as previously discussed, numerous other risk factors may contribute to these patients’ hearing-loss risk. And with no baseline hearing tests for comparison, they may be poor historians.
So hearing is likely not threatened when hydrocodone dosing adheres to therapeutic guidelines and is closely monitored. That said, this study cannot address whether other pain medications, including other opioids, affect hearing. Also, many drugs, including opioids, are toxic or lethal when taken in excess. For the drug abuser, time and overdosing may be the biggest threats to hearing health.
Sources
Campbell, K., Kutz, J., Shoup, A., Wen, W., Lynch, S.Y., He, E. … Ripa, S. R. (2017). Evaluation of the ototoxicity potential of once-daily, single-entity hydrocodone in patients with chronic pain: results of two phase-3 clinical studies. Pain Physician, 20(1), E183–E193. [PubMed]
Campbell, K., Kutz, J., Shoup, A., Wen, W., Lynch, S.Y., He, E. … Ripa, S. R. (2017). Evaluation of the ototoxicity potential of once-daily, single-entity hydrocodone in patients with chronic pain: results of two phase-3 clinical studies. Pain Physician, 20(1), E183–E193. [PubMed]×
Friedman, R. A., House, J. W., Luxford, W. M., & Mills, D. (2000). Profound hearing loss associated with hydrocodone/acetaminophen abuse. American Journal of Otolaryngology, 21(2), 188–191. [Article]
Friedman, R. A., House, J. W., Luxford, W. M., & Mills, D. (2000). Profound hearing loss associated with hydrocodone/acetaminophen abuse. American Journal of Otolaryngology, 21(2), 188–191. [Article] ×
Ho, T., Vrabec, J. T., & Burton, A. (2007). Hydrocodone use and sensorineural hearing loss. Pain Physician, 10(3), 467–472. [PubMed]
Ho, T., Vrabec, J. T., & Burton, A. (2007). Hydrocodone use and sensorineural hearing loss. Pain Physician, 10(3), 467–472. [PubMed]×
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November 2018
Volume 23, Issue 11