Placebos for Tinnitus:
Timothy C. Hain, MD. •. Page last modified:
May 7, 2021
•.See also: "how to lie with statistics", a book by Daryll Huff.
New: Desyncra device. The data so far does not prove that it is not a placebo.
|Homeopathic preparation for tinnitus -- contains aspirin ! Most if not all homeopathic preparations are placebos.
Some medical authorities seem to get pleasure from "bashing" tinnitus drugs, and writing papers that show that they are indistinguishable from placebo. We suspect that this comes from a combination of righteous indignation about groups attempting to exploit tinnitus sufferers, a general and reasonable suspicion that there is currently no method of replacing damaged or lost sensory systems. Vendra et al (2018) stated:
"A wide array of unproven OTCTR exist on today's market. All make unfounded claims of relief from ear ringing. Most of the products considered in this study consist of mixtures of inexpensive and common vitamins, minerals, and/or herbs sold at a premium compared to similar preparations not expressly advertised for tinnitus. Certain brands, most notably Arches Tinnitus Formula (Arches Natural Products Inc., Salt Lake City, UT) and Lipo-Flavonoid (Clarion Brands Inc., Solon, OH), target otolaryngologists by advertising in specialty journals and prominently featuring supposed endorsement by "Ear-Nose-and-Throat Doctors" in their marketing." (Bold added by author of page)
We find it interesting that they mention Lipo-Flavonoids in particular, as many of our patients that see us for tinnitus are taking this version of vitamin C.
On the other hand, tinnitus is extremely distressing, and our position is that it is often worth the effort to attempt treatment with medications that are reasonably safe, and have some rationale for use.
Tinnitus is a difficult disorder to study and it seems likely to us that almost all tinnitus drug studies are "underpowered" -- i.e. unable to detect small effects, due to rare efficacy of medications. There is an essential intractability of studying disorders that have diverse causes, most of which are undiagnosed without an autopsy.
Without a way to separate out tinnitus into causal subcategories, we think that almost any controlled study of a reasonable size (i.e.. 100 subjects) is bound to report failure. In other words, we think that all controlled tinnitus drug studies of moderate size should report that the drug is a placebo (or worse).
We think that smaller studies -- between 1-30 patients, will be "all over the map", but with more positive studies being reported than negative studies, as it is easier to get positive studies accepted in peer reviewed journals. We think that these are generally likely to be overly enthusiastic, as they have taken chance improvements as response, and managed to get it published.
Response to anything, including placebo, is still a response. Also, we think there is some value to having hope that a successful intervention may be eventually found.
Some medications below may actually work via psychological mechanisms -- mood stabilizers for example. Others might be modulating other diseases, such as anticonvulsants and migraine. Again, what is important is a response, not the mechanism.
This list is an attempt to rank medications according roughly as to whether they are clear placebos (such as homeopathic drugs), or just probable placebos for most, but possibly not all tinnitus patients.
Drugs that are probably (or certainly) placebos for idiopathic tinnitus
- Baclofen -- rarely helpful, has significant side effects, but overall reasonable to try.
- Botox. It makes no sense to use a neuromuscular blocker for tinnitus in a general sense. There may be a few instances where it is rational for treatment of tinnitus associated with muscle spasm. www.innovations-report.com/html/reports/medicine_health/report-33760.html for more information about a study on Botox for tinnitus.
- B12 (1000 ug per week). Reasonable for persons with B12 deficiency, not for anyone else.
- Carbamazepine (Tegretol) -- an anticonvulsant. (Dobie RA, 1999). We have had a few responders to this drug however. In theory, it might help in persons with microvascular compression induced tinnitus. Trileptal would be generally a better choice than carbamazepine due to less side effects. Almost all anticonvulsants have some mood stabilizing effects.
- Cinnarizine (Dobie, 1999). Not available in the US.
- Dexamethasone (Intratympanic) (Araujo et al, 2005). This drug seems reasonable only for Meniere's disease or related conditions such as autoimmune inner ear disease. Cole et al (1992) felt that while the drug is well tolerated, it is not effective.
- Ear drops of any kind, with intact tympanic membrane. In general, all ear drops are placebos, as they have no way to get into the inner ear. A rare exception might be ear drops in persons who have perforations in their ear drum.
- Gabapentin (Neurontin). (Piccirillo et al, 2007 indicates that it is a placebo; also see Witsell et al (2007)) A weak mood stabilizer.
- Ginkgo Biloba (Alternative medicine
found in health food stores, 120-240 mg twice daily -- some anecdotal evidence
of efficacy) (Seidman and Keate, 2002), but also papers suggest no effect (Canis et al, 2011)
- Homeopathic preparations -- (see above) these are certainly placebos !
- Lamotrigine (an anticonvulsant). We have had no experience with this one. Might be helpful for persons with migraine induced tinnitus, or microvascular compression. There are better drugs for both migraine and MVC. Lamotrigine is also used as a mood stabilizer.
- misoprostol, Cytotec (300 mg TID) -- we have never encountered a patient
that responded to this
- Ondansetron. A recent randomized double-blind trial suggested that patients on 16 mg/day of ondasetron scored better on the "tinnitus severity index". (Taslimi et al, 2013). In this study, there were a total of 5 outcome measures, 4 of which were unchanged. While it is exciting to have a drug that has some effect on tinnitus, we are dubious that this is a real effect. We would like to see this study replicated.
- Serc (8 - 16 mg TID). We have had some good results in some patients with Serc.
Also other medical treatments of Meniere's
disease may be worth considering.
- Tocainamide (more than 1200 mg/day) -- a cardiac drug related to the local
anesthetics (Dobie, 1999). See comments above due to Shea, who feels that tocainamide is sometimes effective.
- Zinc supplements (50 mg daily). Zinc has been used for many years as a treatment of tinnitus. Most studies show no significant effect (e.g. Arda et al, 2003). It seems most likely at this writing (2007) that zinc is a placebo.
Comment: Some of these drugs may be worth considering depending on ones
personal situation. The ones with the least adverse effects would seem most
logical. If one understands the mechanism of one's tinnitus, it seems more likely that a drug like this might work.
Dubious, non-drug treatments
- Acupuncture. This probably a placebo treatment although acupuncture is preferred to placebo (Dobie, 1999).
- Bimodal neuromodulation combining sound and tongue stimulation. (Conlon et al, 2020). This uncontrolled trial compared three different electrical settings for a device that electrically stimulates the tongue while producing noise. The obvious fallacy of this paper is that there was no placebo arm. Subjects in all three arms improved. This is very suspicious. This study, unencumbered by a rationale or physiology, needs to be redone with a placebo.
- Desyncra -- an unproven device with a number of papers lacking control subjects. Probably a placebo.
- Electrical stimulation. Two randomized controlled trials in the 1980's found a device ineffective compared with a placebo (Dobie, 1999). There is probably no harm other than to the pocketbook. There is some data for TENS however.
- Electromagnetic stimulation. Again, no help for the simple devices. (Ghossaini et al, 2004). However, see the TMS entry below for the high intensity version.
- Laser treatments. Gungor and colleagues (2008) recently reported that 5 mw laser applied to the external ear canal is useful in tinnitus. It is difficult for us to see how shining a bright light on the ear canal could affect tinnitus coming from the inner ear as the laser cannot reach the inner ear. Almost certainly a placebo.
- LEVO system. This is a sound device used during sleep. This product has been heavily marketed and there are some statements that make it sound like a miraculous device. There was a single research article published in an open access journal (American J Audiology) (Theodoroff et al, 2017). This article can be accessed online. They compared three different sounds delivered during sleep. One was the "LEVO" system with a sound matched to tinnitus (TM), another was a variant of the LEVO stimulus with white noise (NS), and the third was a "Marsona 1288 Sound conditioner/Tinnitus masker" (BSG). They state that " We are at least 87% certain that treatment with TM or NS reduces mean TFI compared to treatment with BSG, with an estimated relative efficacy of 4.5–5 points greater reduction." They say that "Finally, there is at least 84% certainty that any of the study devices will improve TFI outcomes, although there is little basis for preferring any particular sound therapy device". This study was not "blinded" by its nature -- so subjects knew which treatment was administered. The statistics section of this paper was almost as long as the results section - -this is always worrisome as treatments that have strong effects do not generally need sophisticated statistical analyses. Overall, someone else needs to repeat this study with a much larger 'n'. Perhaps this will be made possible from the aggressive marketing effort by this company, Otoharmonics.
- Magnetic Stimulation: Of course, magnetic head-bands or the like are almost certainly placebos. Little data is available (Dobie, 1999) TMS on the other hand has some evidence.
- Neuroprobe 500. This is basically a pain control device. We see no reason why this would work in tinnitus, as we don't see how this device could be used on a long term basis.
- Phase-out system. This device attempts to cancel internally generated sounds by using a phase-shifted signal that reduces tinnitus.The signal is shifted progressively and presented into the headphones for 30 minutes each. We have had no experience with this device. It seems to us that it would be unlikely that the frequency of tinnitus could be identified precisely enough that this methodology could work. Just a few hertz error would make the phase matching into a useless process. Almost certainly a placebo.
- Transcutaneous vagal nerve stimulation. (Hyvarinen et al, 2015). This is an investigational procedure. It is too soon to tell, but we find the logic of it difficult to follow.
- Ultrasound: No difference from placebo (Dobie, 1999). The "Ultraquiet" is one example (see Goldstein et al for more information). The Hisonic-TRD is another.
- Arda HN; Umit
Tuncel; Ozgur Akdogan; Levent N. Ozluoglu. The Role of Zinc in the Treatment
of Tinnitus. Otology & Neurotology 2003; 24(1):86-89
- Coles, R. R., A. C. Thompson, et al. (1992). "Intra-tympanic injections in the treatment of tinnitus." Clin Otolaryngol Allied Sci 17(3): 240-2.
- Conlon B and others. Science Translational Medicine 2020; 12, 564,
- Dobie RA. A review of randomized clinical trials in tinnitus. Laryngoscope
- GHOSSAINI SN, Spitzer JB, Mackins CC, Zschommler A, et al. High-frequency
pulsed electromagnetic energy in tinnitus treatment. Laryngoscope 2004;114:495-500.
- Goldstein BA, Lenhardt ML, Shulman A. Tinnitus improvement with ultra-high frequency vibration therapy. Int Tinnitus J Vol 11, No 1, 14-22, 2005. This uncontrolled study reports improvement.
- Gungor A and others, J Laryngol Otol. 2008 May;122(5):447-51
- Hyvärinen P1, Yrttiaho S, Lehtimäki J, Ilmoniemi RJ, Mäkitie A, Ylikoski J, Mäkelä JP, Aarnisalo AA.Transcutaneous vagus nerve stimulation modulates tinnitus-related beta- and gamma-band activity. Ear Hear. 2015 May-Jun;36(3):e76-85. doi: 10.1097/AUD.0000000000000123
- Piccirillo JF and others. Relief of idiopathic subjective tinnitus. Is Gabapentin effective ? Arch Otol HNS 2007;133:390-397. [This paper says it is the same as placebo]
- Taslimi S and many others. Ondansetron in patients with tinnitus: randomized double-blind placebo-controlled study. Eur Arch Otorhinolaryngol 2013 270:1635-1641
- Theodoroff SM, GP. McMillan,TL. Zaugg, M Cheslock,C Roberts, and JA. Henry. Randomized Controlled Trial of a Novel Device for Tinnitus Sound Therapy During Sleep. American Journal Audiology, 26, 543-554, 2017
- Vendra V, Vaisbuch Y, Mudry AC, Jackler RK.Over-the-Counter Tinnitus "Cures": Marketers' Promises Do Not Ring True. Laryngoscope. 2018 Dec 25. doi: 10.1002/lary.27677. [Epub ahead of print]
- Witsell DL and others. Treatment of tinnitus with gabapentin: a pilot study. Otol Neurotol 28:11-15. 2007