Study analysis · American journal of otolaryngology · 2021
This antidepressant makes tinnitus less annoying—but it might make you more anxious.
Fluoxetine helps people feel less sad and less bothered by ringing in their ears, but it can make them more anxious—and it doesn’t make the ringing quieter.
Overview
What the study found
The study in plain English — the bottom line, every takeaway we extracted, and what to do with them.
In simple terms
This study tested two medicines to see if they help people with ringing in the ears feel better. It randomly gave some people one medicine, some another, and some a sugar pill. It found that both medicines helped people feel less bothered by the ringing, but one wasn’t better than the other. So we can say they probably help, but they don’t fix the ringing itself.
What’s the bottom line?
This study tested if taking fluoxetine (an antidepressant) or fluoxetine plus a calming pill helps people with constant ringing in the ears feel better.
How strong is this study?
This study was well-designed because nobody knew who got which medicine — not the patients, not the doctors — so no one’s expectations messed up the results. It also compared people to a sugar pill group, which is the gold standard. That means we can trust the results more than if they just asked people how they felt without a fair comparison.
40 / 100
- COI disclosure+40/40
- Data availabilitydata not shared
- Code availabilitycode not shared
76 / 100
- Randomization+20/20
- Blinding+15/15
- Control group+15/15
- Sample size (n=147)+10.4/20
- Follow-upno follow-up reported
100 / 100
54 / 100
- P-values+15/15
- Effect size+20/20
- Confidence intervalsno confidence intervals
- Pre-registrationnot pre-registered
Each component is scored out of 100 and then capped by the study design — a case series cannot reach the ceiling a randomised trial can, however well it is reported.
Where it sits
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 568 / 100
Probability of being correct
Participants are randomly assigned to treatment or control groups, minimizing bias. The gold standard for testing whether an intervention causes an effect.
This design can establish causation. This is a randomized controlled trial with placebo control and double blinding, which allows for causal inference between the interventions (fluoxetine, combination therapy) and outcomes. However, the effect sizes are small to medium, and the study did not find a significant difference between combination and single-drug therapy, limiting the strength of causal claims for superiority of combination therapy.
No Conflicts
No conflicts of interest identified
No conflicts of interest were declared, and funding was provided by a public academic institution with no involvement in study design, analysis, or publication.
Funders
Conflict Details
Guilan University of Medical Sciences: Research funded by institution; no other relationships disclosed
Guilan University of Medical Sciences: Research funded by institution; no other relationships disclosed
Guilan University of Medical Sciences: Research funded by institution; no other relationships disclosed
Guilan University of Medical Sciences: Research funded by institution; no other relationships disclosed
Guilan University of Medical Sciences: Research funded by institution; no other relationships disclosed
Independent Analysis Safeguards
- Double-blinded clinical trial design
- Funding institution had no role in study design, analysis, or publication
Study was funded by a public academic institution with no industry ties. Authors explicitly declared no conflicts of interest. All authors appear to be affiliated with the funding institution, but no employment or financial ties to pharmaceutical companies were disclosed. The study design and analysis appear independent.
Key takeaways
- 01
Fluoxetine made tinnitus feel less upsetting (THI/VAS improved) and lifted mood (BDI down), but made anxiety worse (BAI up).
- 02
The combo pill helped mood more, but not enough to be sure.
- 03
Neither changed how loud the ringing sounded (TSI unchanged).
- 04
The improvement in distress is real but small — it helps people feel less bothered emotionally, but doesn’t silence the ringing.
Surprising findings
- Fluoxetine increased anxiety (BAI) while reducing depression (BDI) in tinnitus patients.SSRIs like fluoxetine are widely prescribed for anxiety and depression together—this is the first major study showing they can worsen anxiety in tinnitus patients despite improving mood.
- Combination therapy (fluoxetine + alprazolam) showed no significant advantage over fluoxetine alone.Alprazolam is a potent anti-anxiety drug—logically, adding it should help more, especially since anxiety was worsened by fluoxetine alone.
Practical takeaways
If you have tinnitus and depression, ask your doctor if fluoxetine is the best choice—or if therapy, sound therapy, or non-SSRI antidepressants might be safer.
This study only tested fluoxetine and alprazolam for 8 weeks—long-term effects and individual responses may vary.
medium confidenceWhy this study matters
Fluoxetine Reduces Sadness But Increases Anxiety
In the study, fluoxetine lowered depression scores (BDI) by a small effect size (0.075) but increased anxiety (BAI) with a medium effect size (0.135)—meaning while mood improved slightly, anxiety got worse. This is unusual because SSRIs like fluoxetine typically reduce both.
Most people assume antidepressants make you feel better overall—but here, one part of mental health got worse while another improved, revealing a hidden trade-off for tinnitus patients.
The Combo Pill Didn’t Help—Despite the Hype
Fluoxetine + alprazolam was expected to outperform fluoxetine alone, since alprazolam treats anxiety. But the study found no statistically significant difference—meaning adding a calming drug didn’t boost results.
Doctors often prescribe combo therapies for complex conditions—this study shows that even when logic says it should work, it often doesn’t.
It Doesn’t Silence the Ringing—Just Your Reaction to It
Neither fluoxetine nor the combo reduced the Tinnitus Severity Index (TSI)—the actual perceived loudness or intensity of the sound. Only emotional distress (THI, VAS) improved.
People think meds can 'cure' tinnitus—but this shows it’s about managing the emotional burden, not the sound itself.
Want the whole report?
Detailed mode opens the full scientific breakdown — every score component, the methodology, conflicts of interest, the evidence analysis behind each claim, and the raw study data.
Overview
What the study found
The study in plain English — the bottom line, every takeaway we extracted, and what to do with them.
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
This study tested if taking fluoxetine (an antidepressant) or fluoxetine plus a calming pill helps people with constant ringing in the ears feel better.
Research results
Fluoxetine made tinnitus feel less upsetting (THI/VAS improved) and lifted mood (BDI down), but made anxiety worse (BAI up). The combo pill helped mood more, but not enough to be sure. Neither changed how loud the ringing sounded (TSI unchanged).
What this means - more context
The improvement in distress is real but small — it helps people feel less bothered emotionally, but doesn’t silence the ringing.
To evaluate whether fluoxetine alone or fluoxetine plus alprazolam reduces tinnitus-related distress compared to placebo in adults with chronic tinnitus.
Fluoxetine modestly reduced tinnitus distress (THI, VAS) and depressive symptoms (BDI) but increased anxiety (BAI). Fluoxetine plus alprazolam improved mood and anxiety more than fluoxetine alone, but not significantly. Neither treatment reduced objective tinnitus severity (TSI). Combination therapy offered no significant advantage over fluoxetine alone.
Methods Used
Double-blinded, placebo-controlled randomized trial with 147 adults with chronic tinnitus randomized to fluoxetine (20 mg/day), fluoxetine + alprazolam, or placebo for 8 weeks. Outcomes measured via THI, VAS, TSI, BAI, and BDI.
Main Finding
Fluoxetine modestly reduced tinnitus distress (THI, VAS) and depression (BDI; effect size 0.075 small) but increased anxiety (BAI; effect size 0.135 medium). Neither fluoxetine nor fluoxetine + alprazolam reduced tinnitus severity (TSI). Combination therapy showed no statistically significant benefit over fluoxetine alone.
Confidence Level
Moderate. Study is a well-conducted double-blind RCT with placebo control and validated outcome measures, but lacks confidence intervals and has modest sample size with notable dropout (11 excluded).
Study Flags
Red Flags
- •Fluoxetine increased anxiety (BAI) despite reducing depression (BDI), suggesting complex or adverse psychopharmacological effects
- •No confidence intervals reported for effect sizes
- •Dropout rate of 11/158 (7%) with unclear reasons for exclusion
No biological mechanisms were identified in this study. This may be an epidemiological, observational, or survey-based study that reports associations rather than proposing causal biological pathways.
Surprising Findings
Fluoxetine increased anxiety (BAI) while reducing depression (BDI) in tinnitus patients.
SSRIs like fluoxetine are widely prescribed for anxiety and depression together—this is the first major study showing they can worsen anxiety in tinnitus patients despite improving mood.
Practical Takeaways
If you have tinnitus and depression, ask your doctor if fluoxetine is the best choice—or if therapy, sound therapy, or non-SSRI antidepressants might be safer.
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 568 / 100
Probability of being correct
Participants are randomly assigned to treatment or control groups, minimizing bias. The gold standard for testing whether an intervention causes an effect.
Human RCT
Subject
Moderate probability
on the GRADE evidence scale
This study tested two medicines to see if they help people with ringing in the ears feel better. It randomly gave some people one medicine, some another, and some a sugar pill. It found that both medicines helped people feel less bothered by the ringing, but one wasn’t better than the other. So we can say they probably help, but they don’t fix the ringing itself.
No conflicts of interest were detected in this study. No score impact.
Strengths
- Randomized controlled trial with placebo control
- Double-blinded design reducing detection and performance bias
- Clear inclusion/exclusion criteria
Weaknesses
- Small to medium effect sizes limit clinical significance
- No long-term follow-up to assess durability of effects
- No reporting of adverse events or dropout reasons beyond replacement
Methodology
Evidence Keywords
Statistical Reporting
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
This study tested if taking fluoxetine (an antidepressant) or fluoxetine plus a calming pill helps people with constant ringing in the ears feel better.
Research results
Fluoxetine made tinnitus feel less upsetting (THI/VAS improved) and lifted mood (BDI down), but made anxiety worse (BAI up). The combo pill helped mood more, but not enough to be sure. Neither changed how loud the ringing sounded (TSI unchanged).
What this means - more context
The improvement in distress is real but small — it helps people feel less bothered emotionally, but doesn’t silence the ringing.
To evaluate whether fluoxetine alone or fluoxetine plus alprazolam reduces tinnitus-related distress compared to placebo in adults with chronic tinnitus.
Fluoxetine modestly reduced tinnitus distress (THI, VAS) and depressive symptoms (BDI) but increased anxiety (BAI). Fluoxetine plus alprazolam improved mood and anxiety more than fluoxetine alone, but not significantly. Neither treatment reduced objective tinnitus severity (TSI). Combination therapy offered no significant advantage over fluoxetine alone.
Methods Used
Double-blinded, placebo-controlled randomized trial with 147 adults with chronic tinnitus randomized to fluoxetine (20 mg/day), fluoxetine + alprazolam, or placebo for 8 weeks. Outcomes measured via THI, VAS, TSI, BAI, and BDI.
Main Finding
Fluoxetine modestly reduced tinnitus distress (THI, VAS) and depression (BDI; effect size 0.075 small) but increased anxiety (BAI; effect size 0.135 medium). Neither fluoxetine nor fluoxetine + alprazolam reduced tinnitus severity (TSI). Combination therapy showed no statistically significant benefit over fluoxetine alone.
Confidence Level
Moderate. Study is a well-conducted double-blind RCT with placebo control and validated outcome measures, but lacks confidence intervals and has modest sample size with notable dropout (11 excluded).
Study Flags
Red Flags
- •Fluoxetine increased anxiety (BAI) despite reducing depression (BDI), suggesting complex or adverse psychopharmacological effects
- •No confidence intervals reported for effect sizes
- •Dropout rate of 11/158 (7%) with unclear reasons for exclusion
No biological mechanisms were identified in this study. This may be an epidemiological, observational, or survey-based study that reports associations rather than proposing causal biological pathways.
Surprising Findings
Fluoxetine increased anxiety (BAI) while reducing depression (BDI) in tinnitus patients.
SSRIs like fluoxetine are widely prescribed for anxiety and depression together—this is the first major study showing they can worsen anxiety in tinnitus patients despite improving mood.
Practical Takeaways
If you have tinnitus and depression, ask your doctor if fluoxetine is the best choice—or if therapy, sound therapy, or non-SSRI antidepressants might be safer.
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 568 / 100
Probability of being correct
Participants are randomly assigned to treatment or control groups, minimizing bias. The gold standard for testing whether an intervention causes an effect.
Human RCT
Subject
Moderate probability
on the GRADE evidence scale
This study tested two medicines to see if they help people with ringing in the ears feel better. It randomly gave some people one medicine, some another, and some a sugar pill. It found that both medicines helped people feel less bothered by the ringing, but one wasn’t better than the other. So we can say they probably help, but they don’t fix the ringing itself.
No conflicts of interest were detected in this study. No score impact.
Strengths
- Randomized controlled trial with placebo control
- Double-blinded design reducing detection and performance bias
- Clear inclusion/exclusion criteria
Weaknesses
- Small to medium effect sizes limit clinical significance
- No long-term follow-up to assess durability of effects
- No reporting of adverse events or dropout reasons beyond replacement
Methodology
Evidence Keywords
Statistical Reporting
Scoring
How strong is this study?
This study was well-designed because nobody knew who got which medicine — not the patients, not the doctors — so no one’s expectations messed up the results. It also compared people to a sugar pill group, which is the gold standard. That means we can trust the results more than if they just asked people how they felt without a fair comparison.
40 / 100
- COI disclosure+40/40
- Data availabilitydata not shared
- Code availabilitycode not shared
76 / 100
- Randomization+20/20
- Blinding+15/15
- Control group+15/15
- Sample size (n=147)+10.4/20
- Follow-upno follow-up reported
100 / 100
54 / 100
- P-values+15/15
- Effect size+20/20
- Confidence intervalsno confidence intervals
- Pre-registrationnot pre-registered
Each component is scored out of 100 and then capped by the study design — a case series cannot reach the ceiling a randomised trial can, however well it is reported.
Where it sits
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 568 / 100
Probability of being correct
Participants are randomly assigned to treatment or control groups, minimizing bias. The gold standard for testing whether an intervention causes an effect.
This design can establish causation. This is a randomized controlled trial with placebo control and double blinding, which allows for causal inference between the interventions (fluoxetine, combination therapy) and outcomes. However, the effect sizes are small to medium, and the study did not find a significant difference between combination and single-drug therapy, limiting the strength of causal claims for superiority of combination therapy.
No Conflicts
No conflicts of interest identified
No conflicts of interest were declared, and funding was provided by a public academic institution with no involvement in study design, analysis, or publication.
Funders
Conflict Details
Guilan University of Medical Sciences: Research funded by institution; no other relationships disclosed
Guilan University of Medical Sciences: Research funded by institution; no other relationships disclosed
Guilan University of Medical Sciences: Research funded by institution; no other relationships disclosed
Guilan University of Medical Sciences: Research funded by institution; no other relationships disclosed
Guilan University of Medical Sciences: Research funded by institution; no other relationships disclosed
Independent Analysis Safeguards
- Double-blinded clinical trial design
- Funding institution had no role in study design, analysis, or publication
Study was funded by a public academic institution with no industry ties. Authors explicitly declared no conflicts of interest. All authors appear to be affiliated with the funding institution, but no employment or financial ties to pharmaceutical companies were disclosed. The study design and analysis appear independent.
Standing
The people behind it
The researchers who wrote the study this analysis is built on.
Authored by
5 researchersIf this is your work, this is how we attribute it on Fit Body Science. Alia Saberi is listed as the lead author.