Propofol-Interrupted Tinnitus Later Suppressed by Amantadine: a Case-Report

[joejunior]

http://www.ncbi.nlm.nih.gov/pubmed/23426878?dopt=Abstract

 

[calin]

Interesting find Joejunior! I will post it here


J Clin Pharmacol. 2013 Mar;53(3):356-8. doi: 10.1002/jcph.6. Epub 2013 Feb 20.
Propofol-interrupted tinnitus later suppressed by amantadine: a case-report.
Dardennes R, Al Anbar N, Rouillon F.

Source
Faculty of Medicine, Paris Descartes University, Paris, France; Sainte-Anne Hospital (CMME), Paris, France; Center of Psychiatry and Neuroscience, Sainte-Anne Hospital, Inserm U894, Paris, France.

Abstract
Tinnitus is a frequent condition without consistently effective remediation. Mr V. was a 64 year old man with Behcet's disease, a generalized systemic relapsing vasculitis. Tinnitus appeared in 1998 and he had been both aware and distressed by his tinnitus 80% of his awake time. After his last colonoscopic examination, he mentioned a transient interruption of his tinnitus. Mr V. only received propofol, an anesthesic drug that selectively down-regulates glutamatergic synaptic transmission. Amantadine, another glutamate antagonist, was later prescribed and durably suppressed tinnitus. Systematically inquiry about post-anesthesia effects on tinnitus may help decide if amantadine may be tried on an individual basis.

 

[calin]

How did you find this?

 

[joejunior]

Hi Calin, I occasionally use this tool

http://www.authormapper.com/search.aspx?q=Tinnitus

 

[joejunior]

i dont know if Propofol or amantadine have been assessed before for tinnitus?

 

[Aisling]

I too have read that anestesia suppresses tinnitus! It makes sense that it would by calming the nerves down.
Although the study I read stated that it was an epidural of lidocaine that worked.

 

[mock turtle]

interesting, i too found that after anesthesia my tinnitus was suppressed

thanks joejunior for the find
best
mt

 

[Aisling]

Mock turtle how long did the suppression last after the anestesia. The study I read used lidocaine through an epidural and I think the suppression was permenant. I will look at it again.

 

[joejunior]

propofol is anesthesia but dont think amantadine is? has anyone heard of it in relation to tinnitus ?

 

[Hudson]

http://www.ncbi.nlm.nih.gov/pubmed/23426878?dopt=Abstract

Does anyone know of any ongoing or upcoming research into the possible use of this compound to treat tinnitus? It would be interesting to see if a clinical trial was/is initiated.

 

[Hudson]

I should have been more specific, I was referring to the amantadine. I guess I wouldn't consider propofol to be any kind of treatment any more than I would diamorphine.

 

[erik]

Amantadine is an anti viral medication. Amantadine is a weak antagonist of the NMDA type glutamate receptor, increases dopamine release, and blocks dopamine reuptake. Would be interesting to know if it was suppressed permanently or do you have to take it daily to achieve this effect. Also what are the side effects of use and long term use.

 

[joejunior]

I wonder why these studies are not picked up by experts and commented on in a formal way, and if considered promising advanced further. The process seems to be too random.

 

[jazz]

I wonder why these studies are not picked up by experts and commented on in a formal way, and if considered promising advanced further. The process seems to be too random.

It's random because tinnitus is a low profile disease with inadequate funding. Only two research and policy groups are focusing on tinnitus: the ATA and TRI. And they are small compared with other medical and policy groups. Fortunately for us, the Dept of Defense is now giving this disease serious attention because of tinnitus is a major cause of disability for new veterans.

Three clinical studies are currently testing Amantadine for various illness, none are tinnitus related. There's also many smaller trials going on with Amantadine and traumatic brain injury.

Tinnitus needs higher visibility and institutional/pharmaceutical sponsorship to investigate the various drugs that have shown promise in either attentuating or curing the disorder. There's more than a dozen drugs over the past 10 years that should be investigated.

 

[Twitch]

Sorry to dig up a 2 year old thread. I was doing some reading up as I am having surgery under anesthesia this week and found the full case report of the abstract in the OP. What interested me most was the quote below:

A carryover effect was then observed as tinnitus reappeared only 3 months after treatment removal. For the last 3 years,Mr. V. had been free of tinnitus with 1-month amantadine treatment every 4 months.

Perhaps we can have our own TT trial of amantadine

Full case report below:

Tinnitus, defined as the perception of noise in the absence of an acoustic stimulus, is a frequent condition with a prevalence of around 14% for males of 60 years or older. A wide variety of interventions are proposed but none of these is consistently effective. Animal data suggest that tinnitus is mediated by cochlear glutamate N‐methyl‐D‐aspartate (NMDA) receptors and is reversed by localapplication of NMDA antagonists. Only two clinical trials with modulators of NMDA neurotransmission have been published but gave opposite results.

We present acase which suggests that NMDA antagonists may be efficacious for a subset of individuals with tinnitus who may be identified by inquiring about tinnitus responsive-ness to medical events that required individuals to besedated with anesthetics.

Case Report
Mr. V. is a 64‐year old man with Behcet's s disease since 1988, a generalized systemic relapsing vasculitis of the arteries and veins of unknown origin. Mr. V., presented cardinal signs of disease, such as eye inflammation, oral and genital ulcerations and characteristic skin lesions, and also presented with aortic aneurysm, multiple recurrent venous thromboses, and gastrointestinal involvement. Treatment with oral prenisone 11 mg/day, azathioprine50 mg/day, and fondaparinux 7.5 mg/day normalized inflammatory markers (CRP = 0.3 mg/mL, Hb = 14.3 g/L, and platelet count = 241 000) but did not fully prevent episodic manifestations, mostly superficial venous thrombosis. Comorbid hypertension was treated with amlodipine 10 mg/day, amiloride 5 mg/day, hydrochlo-rothiazide 50 mg/day, and atenolol 100 mg/day, and the renal function was normal. Comorbid recurrent depressive disorder required a regular psychiatric care and periodic antidepressant treatment.

Mr. V. had several colonoscopies (1988, 2004, 2008, 2011) in order to prevent malignant transformation of colorectal polyps; after the third colonoscopic examina-tion, he mentioned that, immediately after waking from anesthesia, he noticed that his tinnitus had completely disappeared for the following 10 days. Yet, the tinnitus was continuously present during the week before colonoscopy. This phenomenon prompted our interest in a symptom usually shaded by other predominant and acute manifestations of Behcet's disease.

In order to systematically evaluate his condition, we used the case history questionnaire of the Tinnitus Research Initiative. Mr. V. disclosed that her mother also complained of tinnitus. Tinnitus appeared gradually in 1998 and initial onset was related to physical efforts. It had been permanently perceived inside the head, and had been sounding like a very high- pitched hissing without pulsate pattern. Loudness progressively increased along the day to reach a very loud intensity around 4PM. He had been both aware and distressed by his tinnitus for more than 80% of his awake time. Tinnitus was worsened by loud noises and stress, and reduced by music and ambient sounds. While Mr.V. was saying that it was reduced when he had a good sleep at night, he did not find that day naps were changing anything. The head and neck movements did not affect it neither. He did not complain of hearing problems but had found that usual sounds were hurtful and uncomfortable. Mr. V. was used to experiencing pain due to disseminated ulcerations and cervical arthrosis. He did not suffer from vertigo and was not aware of a temporomandibular disorder.

He was receiving medications that were partially relieving his tinnitus: piribedil, 100 mg/day, and clonaze- pam 2.5 mg/day. He was also receiving 3 200 mg/day of gabapentin for his chronic pain and felt that this drug helped him to feel more indifferent to his tinnitus. During the past 12 years, he had never experienced a total disappearance of his tinnitus before his last colonoscopy.

Information was sought after his gastroenterologist, who wrote back that Mr.V. only received a total dose ofpropofol (Diprivan® ,AstraZeneca®) of 400 mg for moderate to deep sedation, provided by an anesthesia specialist. He had no premedication and the monitoring of vital signs did not show hypotension or oxygen desaturation. A pubmed search disclosed the pharmacological properties of propofol and it was hypothesized that tinnitus‐suppressant effect of propofol may be mediated by NMDA antagonism. We looked for other available medications with NMDA antagonism properties through computerized literature search and proposed Mr. V. a trial of 100 mg/day of amantadine. After 1 month of treatment, he returned and reported that tinnitus had completely disappeared after 4 days. But he complained of severe constipation that he could not accept because he had risks of colic perforation. Treatment with physostigmine reduced his constipation but Mr. V. decided to stop taking amantadine. A carryover effect was then observed as tinnitus reappeared only 3 months after treatment removal. For the last 3 years, Mr. V. had been free of tinnitus with 1‐month amantadine treatment every 4 months.

Discussion
Audio‐vestibular disturbance are frequent in patients with Behçet's disease and may be related to severity of Behcet's disease. Mr. V. had normal inflammatory biomarkers. Gastrointestinal involvement gave the oppor-tunity of repeated endoscopic examinations. To our knowledge, there was another case report of a transient interruption of tinnitus following anesthesia by fentanyland propofol. In this case, tinnitus disappeared for 10 days after anesthesia.

The prevalence of frequent tinnitus is considered to be highest among adults with hypertension or major depressive disorder. Hypertension and mood disorders are frequent adverse effects of chronic corticosteroid
treatment. Propofol's hypotensive effect may have contributed to relieve tinnitus. Nevertheless, Mr V. had normal blood pressure for the last 10 years under treatment; moreover, tinnitus' severity was not related neither to depression nor antidepressant treatment during the 15 years follow‐up.

Propofol may also have potentiated clonazepam's effect on tinnitus through GABA agonism but, on theother side, amantadine may also antagonize GABA activity. Propofol is a general anesthesia that selectively modulates glutamatergic transmission via phosphoryla-tion‐mediated down‐regulation of glutamatergic synaptictransmission. Glutamate is the main excitatory neuro-transmitter in both the cochlea and the central auditory pathways and experimental data have suggested that glutamate NMDA receptors may be involved in the generation and maintenance of tinnitus. Amantadine is an uncompetitive NMDA receptor antagonist that is used for the treatment of Parkinson's disease; it has been demonstrated that different NMDA antagonists do not have the same potency in different brain structures and this may contribute to explain why another NMDA antagonist, memantine, did not show evidence of tinnitusimprovement in a controlled study.

Thus, the NMDA hypothesis seemed to be the most parcimonious explanation for the transient disappearance of tinnitus using propofol and its durable suppression with amantadine, and fitted best with available clinical data. As propofol is being increasingly used for gastrointes-tinal endoscopy, which is a frequent medical investiga-tion, it may be useful to systematically ask patients with tinnitus about post‐sedation effects on it. The high safety profile and very short half‐life of propofol may authorize the development of a test of tinnitus sensitivity to NMDA antagonists.

Conclusion
NMDA antagonists such as amantadine may be tried on an individual basis, while gathering data of controlled trials in a subpopulation of patients with propofol‐positive tinnitus.

Corresponding Author:
Prof. Roland Dardennes, MD, MS, Hôpital Sainte‐Anne—Clinique desmaladies mentales et de l'encéphale, 100 rue de la santé, Cedex 14, Paris 75674, France

Email: r.dardennes@ch‐sainte‐anne.fr

Also some useful info on Amantadine
Amantadine uses and side effects
Amantadine, Old Flu Drug, Speeds Brain Injury Recovery: Study [Huffington Post]

 

[Twitch]

Just to report back, I came out of theater just over 24 hours ago after being sedated under general anesthetic (propofol) for 2 and a half hours. On coming around and throughout the day, there was no increase in tinnitus and sadly no temporary cessation of tinnitus either apart from a really sore throat

Like in this article, the subjects tinnitus disappeared for 11 days meaning glutamate excitotoxicity played a role in his tinnitus. This goes goes to show as in my case, there are various etiologies of tinnitus and what may work for one person may not work for another. This is really important when it comes to analysing trial drug efficacy and people who are on the trial whose tinnitus etiology is completely different to what the drug is targeting may not see any positive results and thus cause a trial drug being unnecessarily banished which may actually cure some cases of tinnitus with a specific etiology.

 

[Quiet please]

I recently had an auto. accident where my vehicle was slammed in the rear. I had a severe concussion, whip lash & back pain. For the back pain, I had a lumbar epidural of 2 medications and the T went completely silent for about 2 days. I also couldn't fall asleep for 36 hrs, so that was bad. When it wore off, I had the worst lumbar spine headache for 24+ hrs. and the T came back 10-fold. It was just awful!!! Its since subsided to its normal 5-6. I would never have this procedure done again.

 

[Mic]

I had a lumbar epidural of 2 medications and the T went completely silent for about 2 days.

Could you also inform us with a little bit more information about your experience:

1. Which 2 meds were injected?
2. For how long did you have tinnitus?
3. What is the character of your tinnitus (pitch, both sides/one side, constant/changing etc.)?

Note For everyone else: please describe your experience with all the details. This is important for researchers that might visit the forum.

 

[Quiet please]

The lumbar injection shot had 2 medicines; Lidocaine & methylprednisolone. Pretty standard in the US I've been told.
My Tinnitus life-sentence year is on my profile; since 2008. My 9th anniversary was May 2017.
The pitch is usually rather high and the volume varies. I base it on 1-10. when its a 6 or under, I can tolerate it and am able to basically ignore it. I perceive the sounds in my head & both ears as a buzz or hum, high pitched squeak, sound of a vibrating motor, etc. I'm blessed with a variety show.