Cyclobenzaprine/Flexeril

Hello,

Anyone know anything about Cyclobenzaprine (Flexeril)? It's quite new.

→ Reduction of tinnitus severity by the centrally acting muscle relaxant cyclobenzaprine: an open-label pilot study

 

I have tried it. Prescribed by Prof. Dirk De Ridder at Brai2n at Antwerp. It had no effect on my tinnitus. It relaxed my jaw muscles pretty well though. I think it was a low dose but I am not sure.

 

I tried Cyclobenzaprine (Flexeril) at the low dose of 5 mg. It resulted in no significant difference in the pattern of my tinnitus. Of course, the study recommends 30 mg at a time. I should note that a friend of mine tried this high dose protocol and did notice some benefits. But like me, he has intermittent tinnitus, and we suspect that the sedating effect was the key to any improvements. I have since taken the odd 5 mg dose (when muscles were sore) and awoken to find my tinnitus gone. But again, this is almost certainly because the drug made me really tired.

Of interest is that Flexeril is a close cousin (chemically speaking) to Elavil (Amitripyline): a tricyclic antidepressant that is often prescribed for individuals with tinnitus!

-Golly

 

In 2010, five inventors filed a patent for a sustained-release version of Flexeril for tinnitus. Anyone interested in this drug should read the patent information. According to the inventors, better efficacy is obtainable through a sustained-release formulation of the drug.

Here are some extracts from the patent application, published in 2013:

Treatment of tinnitus and related auditory dysfunctions

ABSTRACT

The invention provides an extended-release dosage form of cyclobenzaprine for use in the treatment of tinnitus and related auditory dysfunctions by once-a-day oral administration, wherein the dosage form is a tablet or capsule comprising cyclobenzaprine as active agent in an amount from 10-80mg, preferably from 10- 60mg. The active agent is associated with a polymer coating or matrix that comprises a water-insoluble polymer, the polymer coating or matrix providing the dosage form with an extended release of the active agent over at least 12 hours and preferably over at least 16 hours when the dosage form is administered to a patient.

...

Cyclobenzaprine is a skeletal muscle relaxant. The exact mechanism of action for cyclobenzaprine is unknown. Current research appears to indicate that cyclobenzaprine acts on the locus coeruleus where it results in increased norepinephrine release, potentially through the gamma fibers which innervate and inhibit the alpha motor neurons in the ventral horn of the spinal cord. Decreased firing of the alpha motor neuron results in decreased muscular tone. Cyclobenzaprine is a muscle relaxant acting primarily on the central nervous system. It is structurally similar to Amitriptyline, differing by only one double bond. Cyclobenzaprine is typically prescribed to relieve pain and muscle spasms. Typically, muscle spasms occur in an injury to stabilize the affected body part and prevent further damage. Whereas this is beneficial in acute injury, muscle spasm frequently persists over time, becomes dysfunctional and can increase the pain level. It is believed that by decreasing muscular spasm, pain is diminished. A common application would be that of a whiplash injury in a car accident. Cyclobenzaprine has also been studied in the treatment of fibromyalgia. In a study of 120 fibromyalgia patients, those receiving Cyclobenzaprine (10 to 40 mg) over a 12 week period had significantly improved quality of sleep and pain score. Interestingly, there was also a reduction in the total number of tender points and muscle tightness. It is also prescribed off-label as a sleeping-aid.

...

As-yet unpublished PCT patent application PCT/IB2010/051373, filed 30 March 2010, relates to cyclobenzaprine for use in the treatment of tinnitus and related auditory dysfunctions by oral administration or by parenteral administration through intramuscular, intravenous, subcutaneous or intrathecal injection or infusion, and presents data demonstrating the efficacy of cyclobenzaprine for these treatments. This unpublished PCT patent application mentions the use of extended release cyclobenzaprine for tinnitus by once-a-day administration but does not provide any details thereupon, neither of the means for providing extended release, nor any other details. Background art on extended-release drug formulations.

...

As shown by the tests reported below, which are taken over from the above- mentioned PCT patent application PCT/IB2010/051373, cyclobenzaprine has a positive effect on tinnitus severity and on tinnitus loudness in the tested subjects, it is safe to administer and though common side effects (like constipation and dry mouth) may be experienced, it is tolerated well by most subjects. Similar results are expected for associated auditory dysfunctions. Generally, according to the invention, the described extended release form of cyclobenzaprine is effective for the treatment of an auditory dysfunction selected from tinnitus, hyperacusis, auditory hallucinations, misophonia, phonophobia and central auditory processing disorders. General aspects of extended-release cyclobenzaprine for treating tinnitus

For many chronic conditions such as chronic pain, management guidelines recommend the use of long-acting, extended-release formulations. Guidelines for pharmacological treatment of tinnitus however have not been established, although tinnitus is a chronic condition. As such, the goal of pharmacological therapy for tinnitus is to provide sustained relief. The use of long-acting, extended-release formulations for tinnitus is desirable because they provide prolonged, more consistent plasma concentrations of drug compared with short-acting agents, thus minimizing fluctuations that could contribute to end-of-dose breakthrough tinnitus. In this regard, a randomized, open-label, two-period crossover, single-centre study, has demonstrated that single-dose pharmacokinetics of once-daily cyclobenzaprine extended release 30 mg versus cyclobenzaprine immediate release 10 mg three times daily in healthy young adults, provides a controlled release of cyclobenzaprine with sustained plasma concentrations, in contrast to the fluctuating profile of cyclobenzaprine immediate release with comparable systemic exposures.

Better efficacy and fewer side effects

[emphases added]

Reference: http://www.google.com/patents/EP2621475A1?cl=en

Here's a summary of the patent's history:



If anyone takes this new formulation, please let us know!

 

I took 50 mg of Flexeril yesterday. It helped my TMJ as expected; does nothing to my tinnitus either way.

 

I asked my ENT to trial Cyclobenzaprine as I had read several reports of it helping with tinnitus. I thought it could be a good idea since I suspect my additional symptoms (hyperacusis, fullness, fluttering and headaches/pressure) might be the results of TMJD that was induced by the tinnitus.

Tuesday - 10 mg before bed
Wednesday - 10 mg x2 spread out
Thursday - 10 mg x3 spread out
Friday - 10 mg x2 (morning and afternoon)
Saturday (today) - nothing

The last few days my tinnitus has been louder and intrusive. My hyperacusis seems to be getting better but I can' tcorrelate improvement to Cyclobenzaprine. I have constant feeling of liquid in my ears when swallowing and that felt like it improved a bit initially but by Friday night, I didn't really feel an improvement.

So fast forward to today, Saturday morning. I woke up with usual tinnitus, not lower but not necessarily louder. I decided I wasn't going to take Cyclobenzaprine again and went about my day. My ears are a little more sensitive than normal and I feel a bit on edge, antsy and anxious. I took a cold shower a few hours ago and while my other symptoms are better my tinnitus is probably about 50% of what it has been over the past couple weeks. I am sitting at my desk realizing I can hear my computer fan and I haven't really been able to hear it for a couple weeks. I don't know why, but at least for the time being, it seem like coming off the Cyclobenzaprine has reduced my tinnitus quite a bit. I would say its possible that some of my other symptoms might be a tad worse but I feel like they are anxiety based.

The only other thing I've done differently is done some TMJ massages over the last two days but I can't say for sure they contributed yet. I would think this is something that has to do with the TCA-like properties of Cyclobenzaprine and 5-HT2 receptors.

 

When I did Cyclobenzaprine for a back injury I didn't notice much of a difference either way

 

The Regensburg Tinnitus Clinic started a trial with Cyclobenzaprine years ago. They wanted to replicate a study showing effects on tinnitus. It failed.

I and a friend of mine was part of the study. It didn’t help us either.

 

Just FYI, cold showers are known to help with tinnitus as they supposedly help calm the nervous system. So it might be unrelated to the medication change. You might test this theory by taking a cold shower while on Flexeril.

 

I agree but I’ve been taking cold showers for a couple months now and haven’t noticed this dramatic of a change.

I should add that about 10 hours later and it’s noticeably louder. Not exactly sure of the triggers.

 

Bumping this thread as I just started Flexeril today. I took 10 mg about an hour ago (2:50pm my time). My doctor wants me to start low (15 mg a day) and I can increase if I tolerate it and see/hear/feel any benefit.

For those who have seen benefit with Flexeril, and are still around to read this, how soon did you notice improvements? About how many days should I give it to take effect? Thank you!

 

Update: After taking 15 mg of Cyclobenzaprine a day for 7 days, I am stopping due to increased sensitivity with tinnitus. I think this more has to do with its effect on hormones (it affects progesterone) and I already deal with low progesterone. Imbalanced hormones = exacerbated tinnitus. So unfortunately, it’s a no go for me.

 

Trial and error. Keep proceeding forward.

 

Lamictal is a no go. I found out that it can wreck a woman's hormone cycle, and that appears to be every anticonvulsant's side effect. I am not in a position to risk that as I already deal with hormonal issues. And I do not want to do Zoloft, so I have no idea what is going to come of it. I talk with him in a half hour.

 

I dropped the Mirtazapine last night and took 10 mg of Cyclobenzaprine. Could be a complete coincidence but I woke up today with the tinnitus 20% lower.

I will need to do this again, maybe next week, before I can establish if there is a pattern.

I read it's unlikely but possible there can be an interaction between Mirtazapine and Cyclobenzaprine, so it's not easy for me to take an extended trial without dropping the Mirtazapine for a while. That may cause an increase in depression.

 

Are you feeling better after taking Cyclobenzaprine?

In your opinion, does the role of this drug lie more in the muscle relaxant effect or in the brain and serotonin?

With regard to the muscle relaxant effect, could Alprazolam have a similar effect to Cyclobenzaprine?

 

Completely different MoA.

 

Are you still taking Cyclobenzaprine?

Do you remember posting this thread?

Cyclobenzaprine is a 5-HT1A receptor agonist.

5-HT1a receptors in the cochlear nucleus have a possibly inhibitory effect on tinnitus. It also binds to adrenergic receptors and muscarinic acetylcholine receptor M1. Stimulation of that receptor "increases neuronal excitability by suppressing the M-current generated by the Kv7 channel family."

 

I do remember. I had a handful shipped from America. I only took one sporadically, but it meant dropping the Mirtazapine due to possible interactions. So no updates. It has good evidence in 2 human trials and 1 animal trial. Basically 25% got a big reduction.

 

Did you have any trouble with UK customs?

Cyclobenzaprine also does not seem to be approved by the EMA. Interesting that Dr. De Ridder would prescribe medication that isn't even available in his own country.

On a side note, the assistant of Brai3n told me they usually do not offer consults with Dr. De Ridder alone, you have to do an intake interview in-person with Jan Ost first and get a QEEG done. Besides not having too much faith in the largely experimental electrical and magnetic stimulation and neurofeedback methods helping my severe hyperacusis, the clinic is also too far away from my home.

 

No issues getting Cyclobenzaprine over to the UK.

 

A guy I spoke to says his loudness hyperacusis symptoms were 100 percent gone for two weeks while on Cyclobenzaprine, after which the symptoms returned again while still on Cyclobenzaprine.

"Cyclobenzaprine is used, in conjunction with physical therapy, to treat muscle spasms that occur because of acute musculoskeletal conditions. After sustaining an injury, muscle spasms occur to stabilize the affected body part, which may increase pain to prevent further damage. Cyclobenzaprine is used to treat such muscle spasms associated with acute, painful musculoskeletal conditions. It decreases pain in the first two weeks, peaking in the first few days, but has no proven benefit after two weeks."

Questions:

• Overlap mechanism of action Cyclobenzaprine and hyperacusis?
• Loudness hyperacusis caused by muscle spasms/musculoskeletal conditions?
• To what extent are the pain relieving/loudness hyperacusis alleviating properties of Cyclobenzaprine a function of its muscle relaxation (which may indirectly reduce pain transmission as well) versus its direct pain signal blocking abilities (at the receptor level)?

 

I was at Brai3n in 2018. Jan Ost suggested TMS, but I said I'm not desperate enough to try something experimental like TMS, maybe in 5 years. You might not have tinnitus in 5 years, he said. That was an odd statement and he definitely was wrong.

I talked to Dr. Boedts about Cyclobenzaprine yesterday; he had never heard of it. And it isn't available in Belgium.

 

It's something Dr. De Ridder often adds to his cocktail if the patient has somatic tinnitus.

 

Have you continued with Cyclobenzaprine and, if so, what’s your experience been?

I ask because I’m looking for an (even off-label) anti-anxiety medication that has the lowest risk of exacerbating my tinnitus. My psych prescribed Duloxetine / Cymbalta, but from reading the threads on Tinnitus Talk, it seems like Cyclobenzaprine would be about the best candidate available.

Many thanks!

 

Hey @mrpetrov.

I got 7x 10 mg tablets from a friend in the USA. I tried them, and the next day my tinnitus seemed quieter. I wouldn't say they helped either way with anxiety, but maybe. The study used 30 mg/day. TCA-type medication, so check with your doctor if you take any other TCAs or antidepressants.

Cyclobenzaprine is a pretty safe medication if it does not interact with other medications. It is used as a muscle relaxer.

I live in the UK, and it's not prescribed here, pal.