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Suboxone Patients at High Risk for Serotonin Syndrome

Swimmingdancer

Bluelight Crew
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Title: Ankle Clonus a Simple Way to Identify Serotonin Syndrome
Author: Fran Lowry
Source: Medscape Medical News
Date: Dec 13, 2012

The prevalence of serotonin syndrome, which, at its most severe, is a potentially life-threatening drug reaction that increases serotonin levels, is strikingly high in patients receiving buprenorphine (Suboxone, Reckitt Benckiser) on an outpatient basis for opioid addiction, a single-center study shows. ...the study showed that 43% of patients attending a single burprenorphine clinic had mild to moderate serontonin syndrome.

Dr. Shawn Cassady
"The Suboxone clinic presented so many cases, so many women having ankle clonus and agitation and tremor, I thought that this was worth reporting. In fact, 43% of our patients showed some degree of serotonin syndrome. Yet, many mild and moderate cases of serotonin syndrome go unrecognized," lead researcher Shawn Cassady, MD, from the First Step clinic, in Cockeysville, Maryland, told Medscape Medical News.

However, he added, the good news is that serotonin syndrome can be easily identified with a simple reflex examination for ankle clonus, involuntary muscular contraction, and relaxation in rapid succession in the ankle.

....

Early studies indicated that an SSRI overdose was the main cause of serotonin syndrome, but according to Dr. Cassady, this is not the case. "[SSRI overdose] may account for about 15% of serotonin syndrome, but it was only the fatal and severe cases that were recognized. Mild to moderate serotonin syndrome was not."

More recently, serotonin syndrome has also been seen with other medication combinations with hidden or lesser serotonin activity, including buprenorphine.

Dr. Cassady noted that in this study, the prevalence is much higher than previously reported — even higher than rates found in psychiatric clinics.

In this naturalistic study, the investigators examined clinical findings from 58 patients that were recorded from July 2010 to August 2012 during monthly outpatient clinic visits or weekly inpatient treatment for opioid dependence.

.....

Medications thought to contribute to the development of serotonin syndrome were duloxetine, fluoxetine, sertraline, citalopram, escitalopram, buspirone, ziprasidone, amitriptyline, ondansetron, cyclobenzaprine, lithium, oxycodone, dextromethorphan, and high-dose buprenorphine and naloxone.

"It's important to recognize mild or moderate serotonin syndrome, because not recognizing it means that these women will often drop out of treatment and relapse," he said.

.....

Dr. John Robertson
Commenting on the findings for Medscape Medical News, John B. Robertson, MD, from the Center for Family Psychiatry, Knoxville, Tennessee, said the "pearl" from this study is that clonus is a great way of picking up mild to moderate serotonin syndrome.

"I had not known about that. Oftentimes, you confuse the mild serotonin syndrome with akathisia or other things like anxiety disorders, increased craving, psychosocial stressors, and all these other things that it can be confused with," Dr. Robertson said.

"If you can identify this as a mild serotonin syndrome, then you are going to treat it very differently. Perhaps you will lower the dosages or get rid of some medication, as opposed to adding medication or escalating dosages, so that was the beauty of specifically that finding.

"It's easy for any physician to check somebody's ankle reflex. It doesn't take much expertise, it's readily done. You can also look for the tongue tremor, also a good marker for serotonin syndrome, and then regularity of the hand tremor," he said.

"But the ankle clonus, I thought, was pretty neat. I've not heard about that at all from anybody, so that's pretty important."
 
Thought this had some good info on how to detect serotonin syndrome too. Serotonin syndrome is so vague and hard to diagnose, and we get so many people asking if they have or had serotonin syndrome here on BL.
 
I'd take my risks with SS instead of having to endure the testosterone plummet (and prolactin surge?) that comes with long term methadone use. I've discontinued methadone programs like 5 times because after a few months I always feel like a limp lump.

636_061711_fx_fat_fish.jpg
 
I'd take my risks with SS instead of having to endure the testosterone plummet (and prolactin surge?) that comes with long term methadone use. I've discontinued methadone programs like 5 times because after a few months I always feel like a limp lump.

My sub doctor checks my test every month, apparently sub can lower it too. When I started treatment I was at like 500, I'm at 380 now with no major changes in my life outside of my sub usage. He said we don't start treating (with either injections or topical solution) it until it gets below 300.

I didn't know anything about sub lowering test until my doctor mentioned it during my intake (very first appointment)

I don't know how it compares to methadone in that aspect though
 
I'd take my risks with SS instead of having to endure the testosterone plummet (and prolactin surge?) that comes with long term methadone use. I've discontinued methadone programs like 5 times because after a few months I always feel like a limp lump.

I think that the article is not really saying Suboxone itself is a huge risk for SS but that it can be in combination with other drugs and a lot of Sub patients are on antidepressants at the same time. More like Sub patients are at risk for SS, due to numerous factors. There was a correlation between things like head trauma or bipolar and SS for example.

Ugh, I hate methadone. I feel like being on it for so long has seriously harmed me. I can relate to that fish. Interesting that you mention elevated prolactin, I definitely had elevated prolactin while on methadone and not one doctor even considered that the 2 could be related (figures 8) most of them are clueless about the side effects IME).
 
My sub doctor checks my test every month, apparently sub can lower it too.

Studies have shown it doesn't. Levels can change naturally though.

I have never experienced serotonin syndrome, and suspect that it's due to people taking insanely high sublingual dosages (8mg+) of Suboxone.

I'd take my risks with SS instead of having to endure the testosterone plummet (and prolactin surge?) that comes with long term methadone use. I've discontinued methadone programs like 5 times because after a few months I always feel like a limp lump.

636_061711_fx_fat_fish.jpg

lol @ the image that went along with this statement =D

and not one doctor even considered that the 2 could be related (figures 8) most of them are clueless about the side effects IME).

A lot of doctors are very ignorant. It's possible to be more informed than your doctor is, sadly.

This challenges the traditional wisdom that we "need" doctors.
 
Studies have shown it doesn't. Levels can change naturally though.



Some studies (2 that I have found in the research for this post) have shown it doesn't. Others have shown suboxone patients with lower testosterone than control patients, although not to the extent of methadone patients.

Hypogonadism in men receiving methadone and buprenorphine maintenance treatment
International Journal of Andrology

Volume 32, Issue 2, pages 131–139, April 2009

Summary

The aim of this study was to determine the prevalence and investigate the aetiology of hypogonadism in men on methadone or buprenorphine maintenance treatment (MMT, BMT). 103 men (mean age 37.6 ± 7.9) on MMT (n = 84) or BMT (n = 19) were evaluated using hormone assays, body mass index (BMI), serological, biochemical, demographic and substance use measures. Overall 54% of men (methadone 65%; buprenorphine 28%) had total testosterone (TT) <12.0 nm; 34% (methadone 39%; buprenorphine 11%) had TT <8.0 nm. Both methadone- and buprenorphine-treated men had lower free testosterone, luteinising hormone and estradiol than age-matched reference groups. Methadone-treated men had lower TT than buprenorphine-treated men and reference groups. Prolactin did not differ between methadone, buprenorphine groups, and reference groups. Primary testicular failure was an uncommon cause of hypogonadism. Yearly percentage fall in TT by age across the patient group was 2.3%, more than twice that expected normally. There were no associations between TT and opioid dose, cannabis, alcohol and tobacco consumption, or chronic hepatitis C viraemia. On multiple regression higher TT was associated with higher alanine aminotransferase and lower TT with higher BMI. Men on MMT have high prevalence of hypogonadotrophic hypogonadism. The extent of hormonal changes associated with buprenorphine needs to be explored further in larger studies. Men receiving long term opioid replacement treatment, especially methadone treatment, should be screened for hypogonadism. Wide interindividual differences in methadone metabolism and tolerance may in a cross-sectional study obscure a methadone dose relationship to testosterone in individuals. Future studies of hypogonadism in opioid-treated men should examine the potential benefits of dose reduction, choice of opioid medication, weight loss, and androgen replacement.

In addition, here is a link to the Suboxone Forum where numerous sub patients themselves are complaining about low test levels
and another one...
and yet another for good measure


If you google around a bit more, you will find *many* other threads discussing this exact same issue. This isn't just a couple people here and there having this problem; it is a widespread issue in the buprenorphine community.

tl;dr - Just because some studies have shown suboxone doesn't lower test levels does not make it a fact. My suboxone doctor who has treated nearly a thousand patients requires every male patient to get the test (and no, he doesn't charge extra for it). As I mentioned previously, he brought this issue up at my very first appointment with him. I trust his years of professional experience, and *my* own personal experience of declining test levels on sub, as well as many anecdotal accounts by sub users on the internet more than "some studies have shown this is not true".
 
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I guess any type of agonism of the mu opioid receptor affects testosterone.

(That really is a guess)
 
People on buprenorphine could have had their testosterone levels by their previous DOC's use, especially if they were using heroin or something stronger than that. I still don't think buprenorphine has a negative effect on testosterone on its own (when being used in ORT, you have to ask whether it's the Suboxone or the previous DOC that caused such an effect).
 
This is why long term maintenance studies should be required for long term maintenance drugs. Duh.
 
I really think giving people highly likely to relapse and recreate with serotonergic substances SSRIs is a dicey move. I see the arguments for it, and granted it probably helps more people in recovery than harms them. But it can truly harm them. Because most users do relapse.
 
Interesting...i was on sub maint for a while and noticed i got more migraines than i do now that im on methadone. Taking my uusual triptan migraine med was never discussed as being contraindicated with the sub, and this was from my sub dr who actually happens to have an office in cockeysville lol pretty random. I suppose thats why low dose bupe was being trialed as an antidepressant.
 
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