Can long-term use of tramadol (opioid analgesic) cause tinnitus in patients with a history of chronic pain?

Can Tramadol Cause Tinnitus After Years of Use?

Yes, tramadol can cause tinnitus, and this adverse effect can occur even after prolonged use, though the mechanism appears to be a direct opioid receptor-mediated effect rather than duration-dependent toxicity.

Evidence for Tramadol-Associated Tinnitus

The FDA drug label for tramadol explicitly lists tinnitus as a documented adverse reaction occurring in less than 1% of patients in clinical trials and post-marketing surveillance 1. This establishes tinnitus as a recognized, albeit uncommon, side effect of tramadol therapy.

A 20-year retrospective analysis of poison center data identified tramadol among the opioids associated with ototoxicity, including tinnitus, with 3 documented cases of tramadol-related hearing complications 2. This study is particularly important because it demonstrated that opioid-associated ototoxicity appears to be hypoxia-independent—only 34% of cases involved a potential hypoxic event, suggesting a direct opioid receptor-mediated mechanism in the auditory system rather than secondary damage from oxygen deprivation 2.

Mechanism and Clinical Characteristics

The ototoxic effect appears to be a class effect of opioids rather than specific to tramadol, supporting an opioid receptor-mediated mechanism in the cochlea or auditory pathways 2. In the documented cases, hearing loss manifested as:

• Tinnitus alone in 24% of cases
• Mixed presentations in 10% of cases
• The effect may be self-limited, though 21% of cases showed no improvement at hospital discharge 2

Duration of Use Considerations

The available evidence does not suggest that tinnitus risk increases specifically with duration of tramadol use—rather, it appears to be an idiosyncratic adverse effect that can occur at any point during therapy 1, 2. However, this must be contextualized within broader concerns about long-term tramadol use:

• Clinical trials supporting tramadol efficacy extend only up to 3 months for chronic pain conditions like osteoarthritis 3
• No randomized controlled trial evidence exists for tramadol safety or efficacy beyond 1 year 4
• Long-term tramadol use is associated with various neurological complications including seizures, serotonin syndrome, and neurobehavioral deficits through mechanisms involving altered redox balance and neurotransmitter dysregulation 5

Clinical Management Approach

If a patient on chronic tramadol therapy develops tinnitus, the following algorithm should be followed:

1. Immediate assessment: Rule out other common causes of tinnitus (acoustic trauma, Meniere's disease, acoustic neuroma, ototoxic medications beyond tramadol) 1

2. Consider opioid-mediated mechanism: Given that peripherally acting μ-opioid receptor antagonists (naldemedine 200 μg/day) have successfully treated opioid-associated tinnitus without compromising analgesia in case reports, this represents a potential therapeutic option if tramadol cannot be discontinued 6

3. Reassess necessity of tramadol: Guidelines emphasize that tramadol should be used as a second- or third-line agent only when first-line therapies (acetaminophen, NSAIDs) have failed, and only for time-limited trials 3, 4

4. If discontinuation is planned: Tinnitus may resolve with drug cessation, as documented in case reports with other opioids 6, though the 21% non-resolution rate at discharge suggests some cases may persist 2

Critical Caveats

• Do not assume the tinnitus is unrelated simply because the patient has been on tramadol for years without prior symptoms—the FDA label and poison center data confirm this can be a late-onset adverse effect 1, 2

• Recognize that tramadol carries additional risks beyond typical opioids: It has serotonergic activity (contraindicated with MAO inhibitors, requiring extreme caution with SSRIs/SNRIs due to serotonin syndrome risk) and can lower seizure threshold 4, 7, 5

• Long-term tramadol use lacks evidence support: Most patients on chronic tramadol are being prescribed outside the evidence base, which extends only to 3 months for conditions like osteoarthritis 3, 4

• Consider that the patient may have developed narcotic bowel syndrome if they are on long-term opioids, which occurs in approximately 6% of chronic opioid users and is characterized by paradoxical pain increases despite continued or escalating doses 3