Mechanism of Action: Antidepressants in Tinnitus Management
Direct Answer: Neither Wellbutrin nor Prozac Should Be Used for Tinnitus Treatment
The American Academy of Otolaryngology-Head and Neck Surgery explicitly recommends against using antidepressants, including both bupropion (Wellbutrin) and fluoxetine (Prozac), for the primary treatment of persistent, bothersome tinnitus due to insufficient evidence of benefit and potential for harm, including worsening tinnitus. 1, 2, 3
Why These Medications Are Not Recommended
Evidence Against Antidepressant Use for Tinnitus
No proven direct mechanism of action exists for antidepressants in treating tinnitus itself—any theoretical benefit relates only to treating comorbid depression or anxiety, not the tinnitus symptom 1, 3, 4
A comprehensive Cochrane review of 610 patients found insufficient evidence that antidepressant drug therapy improves tinnitus, with methodological concerns about whether any observed benefits were due to treating depression rather than tinnitus directly 4
The highest quality trial using an SSRI (like Prozac) found no overall improvement in validated tinnitus outcome measures, though a subgroup receiving higher doses showed possible benefit requiring further investigation 4
Specific Concerns with Wellbutrin (Bupropion)
Bupropion is itself reported as a cause of tinnitus as a side effect, making it particularly problematic for tinnitus patients 5
The FDA drug label for bupropion does not list any indication for tinnitus treatment and notes multiple neurological side effects 6
If tinnitus worsened after starting or increasing Wellbutrin, the medication should be reduced to the previous dose or discontinued entirely due to the clear temporal relationship suggesting medication-induced tinnitus 2
Specific Concerns with Prozac (Fluoxetine)
Fluoxetine has been reported both as a cause of tinnitus (as a side effect) and in tinnitus associated with antidepressant withdrawal 5
While case reports exist of fluoxetine use in tinnitus patients, these lack the rigor of controlled trials 5
The single high-quality SSRI trial showed no benefit for tinnitus severity 4
Theoretical Mechanisms (When Antidepressants Are Studied)
Proposed Serotonergic Mechanism
The theoretical mechanism involves serotonergic modulation of auditory pathways, as serotonin receptors exist in the cochlea and auditory brainstem 7, 5
However, this remains speculative—bupropion does not inhibit serotonin reuptake (it primarily affects norepinephrine and dopamine), making any serotonergic mechanism irrelevant for Wellbutrin 6, 7
Indirect Mechanism Through Depression Treatment
Antidepressants may help tinnitus patients only when significant depression or anxiety coexists, by improving the psychiatric comorbidity rather than the tinnitus itself 7, 8, 5
One retrospective study of 30 depressed tinnitus patients on SSRIs (with concurrent psychotherapy) showed improvement in Tinnitus Severity Index scores, but this improvement may reflect better coping due to reduced depression 8
Tricyclic antidepressants showed no greater effectiveness than placebo at reducing tinnitus severity, though they may improve comorbid depression 9
What Should Be Done Instead
Evidence-Based First-Line Treatments
Cognitive Behavioral Therapy (CBT) has the strongest evidence for improving quality of life in patients with persistent, bothersome tinnitus—this should be the primary intervention 1, 3
Hearing aids should be evaluated for any patient with hearing loss and tinnitus, even if hearing loss is mild or unilateral 1, 3
Education and counseling about tinnitus management strategies must be provided to all patients with persistent tinnitus 1, 3
Critical Pitfall to Avoid
Do not add additional antidepressants or anxiolytics for primary tinnitus treatment, as this risks medication side effects (including paradoxically worsening tinnitus) without proven benefit 1, 2, 3
Avoid dietary supplements (Ginkgo biloba, melatonin, zinc) as they lack evidence of efficacy 1, 3
When Antidepressants Might Be Appropriate
Antidepressants should only be prescribed when treating diagnosed major depression or anxiety disorders that coexist with tinnitus—not for the tinnitus itself 7, 8
If antidepressants are used for comorbid psychiatric conditions, SSRIs are preferred over tricyclics due to better tolerability, though they should always be combined with psychotherapy 7, 8
Monitor closely for tinnitus worsening as a medication side effect, particularly with bupropion 2, 5