Can long-term use of fluoxetine (selective serotonin reuptake inhibitor) cause tinnitus?

Long-term Fluoxetine Use and Tinnitus

Long-term use of fluoxetine can potentially cause tinnitus as an adverse effect, though it is not among the most commonly reported ototoxic medications.

Evidence for Fluoxetine-Induced Tinnitus

• Selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, have been reported to cause tinnitus as a side effect, though the evidence is limited 1
• A recent analysis of the FDA Adverse Event Reporting System (FAERS) database identified duloxetine (an SNRI) as having the strongest association with tinnitus among antidepressants, but fluoxetine was not among the top 25 tinnitus-associated drugs 1
• Case reports have documented tinnitus developing with sertraline (another SSRI), suggesting a class effect may be possible 2
• Fluoxetine has been specifically reported to induce erythromelalgia (a painful vascular condition) in one patient, demonstrating its potential for unexpected adverse effects on various body systems 3

Mechanism of SSRI-Related Tinnitus

• Serotonin is involved in filtering auditory stimuli, and SSRIs like fluoxetine affect serotonergic neurotransmission in the auditory system 2
• The cochlea processes auditory input through complex interactions between serotonergic, glutamatergic, and GABAergic neurotransmitter systems, which can be disrupted by SSRIs 2
• Long-term use of fluoxetine may lead to changes in these neurotransmitter systems that could potentially manifest as tinnitus 2

Risk Factors and Considerations

• Patients with genetic variations affecting CYP2D6 metabolism (poor metabolizers) may have higher plasma concentrations of fluoxetine, potentially increasing the risk of adverse effects including tinnitus 3
• Long-term use of fluoxetine at 20mg/day has been shown to convert approximately 43% of extensive metabolizers to poor metabolizers, potentially increasing drug levels and risk of adverse effects 3
• Concomitant use of other medications that inhibit CYP2D6 could increase fluoxetine levels and potentially the risk of adverse effects 3
• Prior use of other ototoxic medications (such as aspirin or other salicylates) may create a "priming effect" that makes patients more susceptible to developing tinnitus when taking fluoxetine 2

Management Recommendations

• If tinnitus develops during long-term fluoxetine therapy, consider:

  • Obtaining a comprehensive audiologic examination to evaluate the extent of auditory impact 3
  • Distinguishing whether the tinnitus is bothersome or non-bothersome to guide management decisions 3
  • Evaluating for other potential causes of tinnitus, including other medications or underlying conditions 3

• For patients with bothersome tinnitus potentially related to fluoxetine:

  • Consider dose reduction if clinically appropriate 3
  • If necessary, discuss switching to an alternative antidepressant with potentially lower risk of ototoxicity 4
  • Discontinuation of fluoxetine may lead to resolution of tinnitus, as has been observed with other SSRIs 2

Clinical Considerations

• Tinnitus is a relatively rare side effect of SSRIs compared to other adverse effects 4
• The Cochrane review on antidepressants for tinnitus found insufficient evidence to support the use of antidepressants for treating tinnitus, highlighting the complex relationship between these medications and auditory symptoms 4
• Paradoxically, some studies have investigated SSRIs as potential treatments for tinnitus, with mixed results 5
• When evaluating a patient with tinnitus on long-term fluoxetine, consider the risk-benefit ratio of continuing the medication versus the impact of tinnitus on quality of life 3

Monitoring Recommendations

• Patients on long-term fluoxetine therapy should be asked about auditory symptoms, including tinnitus, during follow-up visits 3
• If tinnitus develops, documentation of its characteristics (unilateral vs bilateral, persistent vs intermittent, associated hearing difficulties) can help guide management 3
• For patients with risk factors (poor CYP2D6 metabolism, concomitant CYP2D6 inhibitors, history of other ototoxic medications), consider more vigilant monitoring for auditory symptoms 3