Share on PinterestAn animal study has linked serotonin to worse tinnitus but what does this mean for people using SSRIs? Image credit: PhotoAlto/Getty ImagesNew research in mice suggests that higher levels of serotonin might worsen the symptoms of tinnitus, a condition where a person hears constant buzzing or ringing in one or both ears.Tinnitus can severely impact mental well-being, causing or exacerbating symptoms of depression and anxiety.Since psychiatrists often treat clinical depression and anxiety with serotonin-increasing medication, the study finding is posing an important question about how best to manage tinnitus when it co-occurs with mental health conditions.Practicing psychiatrists and tinnitus experts, however, advise that the finding ought to be treated with caution.
According to the latest available estimates, 14% of adults around the world experience tinnitus, a condition characterized by the perception of constant ringing or buzzing in one or both ears.
Given all of this, the findings of a study on tinnitus conducted by researchers from Oregon Health & Science University (OHSU) in the United States and Anhui University in China, and recently published in PNAS may not spell good news.
The study, conducted in mice, found that higher levels of serotonin, a neurotransmitter or chemical messenger that plays key roles in emotional regulation, appeared to exacerbate behavioral responses associated with worsening tinnitus symptoms, such as becoming more easily startled by noises.
If confirmed in humans, this finding may pose certain problems for the treatment and management of anxiety and depression in people who also experience tinnitus.
This is study follows up on previous research from the scientific team, published in Cell Reports in 2017. In their previous study, the scientists examined the dorsal cochlear nuclei of mice brains.
This area of the brain is associated with the experience of sound, in general, as well as the specific and persistent noise experienced in tinnitus.
Through this, the researchers found that a specific type of neurons from that brain area became overactive and hypersensitive to sound when exposed to an influx of serotonin.
This finding led them to conduct the recent follow-up study, in which they employed an optogenetic approach, using a special type of light beams to trigger serotonergic neurons, or serotonin-producing brain cells. This made the mice hypersensitive to sounds, and more easily startled by noises.
“When you stimulate these serotonergic neurons, we can see that it stimulates activity in the auditory region in the brain. We also saw that animals then behaved as if they were hearing tinnitus,” co-senior author Laurence Trussell, PhD, professor of otolaryngology in the OHSU School of Medicine, explained in a press release.
“In other words, it’s producing symptoms that we would expect to be experienced as tinnitus in humans,” Trussell said.
According to the study authors, these findings may have important implications for people with co-occurring tinnitus and mental health conditions, particularly those treated with SSRIs.
“People with tinnitus should work with their prescribing physician to find a drug regimen that gives them a balance between relief of psychiatric symptoms like depression and anxiety, while minimizing the experience of tinnitus,” Trussell advised in the press release.
Other experts, however, urged extreme caution in bringing these findings based on preliminary research to the doctor’s office.
Speaking to Medical News Today, Hamid Djalilian, MD, Chief Medical Advisor at the NeuroMed Tinnitus Clinic and professor of otolaryngology at University of California Irvine, who was not involved in the current study, stressed that he was surprised by its findings.
“This is completely the opposite of what we see in clinical practice,” Djalilian told us. He noted that adverse reactions to SSRIs involving worsening tinnitus symptoms are exceedingly rare:
“We very commonly treat tinnitus patients in our clinic with medications that increase serotonin levels in the brain, and the majority of patients have relief from this treatment, especially when combined with some lifestyle modifications. There are rare patients who are serotonin sensitive and get worse with medications that increase serotonin levels in the brain, but in our experience that is less than 5% of patients with tinnitus.”
Likewise, Sylvia Baker, MRCpsych, consultant psychiatrist at Re:Cognition Health, who was also not involved in this study, said that “these findings should be interpreted cautiously when considering human patients.”
Baker explained that, while “the new research identifies a plausible biological link between serotonin signalling and tinnitus-related activity, […] it does not show that SSRIs reliably worsen tinnitus in people.”
“Tinnitus is multifactorial and is often influenced by hearing changes, sleep, anxiety, depression, attention and general health. Some patients do report tinnitus changes while taking SSRIs, but the overall clinical evidence remains mixed and does not establish a clear causal effect,” she also noted.
While the likelihood of experiencing worsening tinnitus symptoms when taking SSRIs for the treatment of depression or anxiety is small, all the experts who spoke to MNT agreed that, for the few people who do find themselves in this situation, an individualised care plan is key.
Moreover, healthcare practitioners should take into account the possibility that mental and emotional distress may themselves be at the root cause of worsening tinnitus.
“If tinnitus changes occur during SSRI treatment, the response should be individualised rather than assuming the medication is definitely responsible,” Baker told us.
“Clinicians should assess both mental health symptoms and tinnitus severity, as anxiety and depression can themselves increase tinnitus distress. If a medication contribution seems possible, options may include slower titration, dose adjustment, or considering an alternative treatment, but patients should not stop SSRIs abruptly or without medical advice. Psychological approaches such as CBT [cognitive behavioral therapy], sleep support, and tinnitus-focused coping strategies can also be helpful.”
Speaking to MNT, Steven Allder, MD, consultant neurologist at Re:Cognition Health, likewise not involved in the recent study, said that, going forward, “there is also a need for pharmacovigilance and stratification work to identify which patients may be more susceptible to SSRI-associated tinnitus worsening, and whether this risk is influenced by dose, receptor profile or tinnitus subtype.”
What about people with ADHD who experience tinnitus? Should they worry about the recent findings?
Baker stressed that, in the context of the current study, “the implications are more indirect.”
“There is limited evidence suggesting that attentional difficulties and sensory processing differences may influence how intrusive tinnitus feels, but there is no strong evidence that ADHD itself routinely causes tinnitus,” she told MNT.
“In practice, tinnitus in someone with ADHD should be assessed in the wider context of attention, sleep, anxiety, sensory sensitivity and medication timing, rather than being attributed too quickly to a single cause. Careful baseline assessment and avoiding multiple medication changes at once can help clarify whether symptoms are coincidental or treatment-related.”
— Sylvia Baker, MRCpsych
“The overlap between tinnitus and ADHD are through shared brain network dysfunction involving attention and sensory filtering,” Djalilian explained.
“Impaired sensory gating in the brain’s salience center (the area that regulates attention) leads to ADHD and is the primary area of dysfunction that leads to bothersome tinnitus,” he continued.
Thus, he noted, “treatment is most effective for ADHD and tinnitus when it targets the neurological drivers of this attentional dysregulation.”
For Djalilian, the fact that the recent findings come from an animal study means that they ought to be understood in the context of early research, and thus not extended to clinical practice just yet.
“Animal studies of tinnitus have been controversial. While the method used to detect tinnitus in animals (gap detection test) has been used for a long time, we are making an educated guess on the presence of tinnitus [when using],” he told us.
“We can’t objectively verify that the animal has tinnitus or ask them. The gap detection test is a behavioral test when a sound with a gap is presented to the animals. It is performed only at certain frequencies and if the animal potentially has tinnitus at a frequency other than those tested, it wouldn’t be detected. Also, if the gap detection test is positive, we still can’t be 100% sure if the animal is experiencing tinnitus. There have been a number of animal studies on tinnitus that never materialized when performed in humans.”
— Hamid Djalilian, MD
Going forward, Djalilian said he “would like to see this study performed in humans with serotoninergic medications.”
Allder suggested that the current study may be “best viewed as a mechanistic bridge: It strengthens the biological plausibility that serotonergic modulation can influence tinnitus, but it does not yet establish clinical causality in humans or explain the full heterogeneity of the condition.”
He also emphasized the necessity of confirming its findings in humans, and added that “further mechanistic research should focus on receptor-level specificity, particularly which serotonin receptor subtypes are involved in modulating auditory gain, as this could inform the development of more targeted therapies.”
“Causal intervention studies will be important to test whether selective modulation of serotonergic signalling can preserve antidepressant benefits while reducing auditory side effects,” Allder concluded.