The neurotransmitter most commonly used to treat depression and anxiety may also worsen a frustrating condition called tinnitus, according to new research published in the Proceedings of the National Academy of Sciences.
Tinnitus—a persistent ringing, buzzing, or other noise in the ears—affects as many as 14% of people worldwide. For some, it’s a mild annoyance; for others, it causes significant distress or severe anxiety. In a mouse study, researchers from Oregon Health & Science University (OHSU) and Anhui University in China found that higher levels of serotonin in the brain increased behavioral signs of tinnitus.
“These findings are particularly relevant for the millions of people living with tinnitus,” said co-senior author Laurence Trussell, Ph.D., a professor of otolaryngology at OHSU and scientist at the OHSU Vollum Institute and Oregon Hearing Research Center.
“People with tinnitus should work closely with their doctor to find a medication balance that effectively treats depression or anxiety while keeping tinnitus symptoms as minimal as possible,” Trussell advised.“ This study underscores the need for clinicians to listen to and validate patients who report that their medication is making tinnitus worse.”
The medications in question include selective serotonin reuptake inhibitors (SSRIs), a widely prescribed class of antidepressants that work by raising serotonin levels in the brain.
“We’ve long suspected serotonin played a role in tinnitus, but we didn’t know the mechanism,” said co-author Zheng-Quan Tang, Ph.D., of Anhui University. “Using mice, we’ve now identified a specific serotonin circuit that projects directly to the auditory system and can trigger tinnitus-like effects. When we switched that circuit off, the tinnitus symptoms improved dramatically. This gives us a much clearer understanding of what’s happening in the brain and opens the door to new treatment strategies.”
A delicate balance
The new study builds on the team’s earlier 2017 findings with significant advances in technique and insight. Using optogenetics, researchers precisely stimulated serotonin-producing neurons in the mice’s brains with light delivered through fiber optics. They then assessed the animals’ responses using a modified auditory startle test.
“When we activate these serotonergic neurons, we see increased activity in the auditory region of the brain,” Trussell explained. “The mice then behave as if they’re experiencing tinnitus—exactly the kind of symptoms we would expect to see in humans.”
These results align with patient reports of tinnitus worsening after starting serotonin-boosting medications like SSRIs.
“Our study points to a delicate balance,” Trussell said.“ In the future, it may be possible to design drugs that raise serotonin in specific brain regions or cell types while avoiding others. That way, we could preserve the beneficial effects on mood without the unwanted impact on hearing.”
