Suboxone Side Effects

I’ve received questions over the years from people claiming a range of symptoms from Suboxone or buprenorphine, from back or muscle pain to fatigue, depression, or irritability. I didn’t invent Suboxone, so I don’t take it personally when people blame commonly-occurring symptoms on the drug. But I get bored by the non-scientific thinking behind such claims— that since they started buprenorphine at some point in the past ten years, every symptom or illness that comes along must somehow be related to buprenorphine. No matter, apparently, that people who DIDN’T start buprenorphine often develop the same symptoms. And no matter that they themselves have done a number of things over the past few years BESIDES start buprenorphine. But over and over, people insist that they know, without a doubt, that buprenorphine has to be the problem.
I also get frustrated answering questions about these symptoms when people who complain about them are closed off to other explanations. When I point out that many non-buprenorphine patients have the same complaints, my comments provoke anger. Sometimes I’m accused of having a vested interest to keep people on buprenorphine (I don’t-beyond wanting to provide good medical care).
I have a long waiting list of patients and buprenorphine is only a small part of my practice, so I have no reason to compel use of buprenorphine. But I don’t like the risk that my own patients, or others, might be swayed by faulty logic and fret over problems that have no logical basis.
To the people who have written to ask about feeling depressed, anxious, irritable, numb, sleepy, wakeful, or dulled by buprenorphine, my answer is that in almost all cases, people on buprenorphine feel the same way they would feel if they were not on buprenorphine. People develop full tolerance to the effects of buprenorphine at the mu opioid receptor, so from a scientific standpoint, people on stable doses of buprenorphine should feel ‘normal’. Beyond the science, I can say that after treating over 800 patients with buprenorphine over the past ten years, I have seen no evidence that buprenorphine causes depression, irritability, chronic pain, emotional numbness, lack of interest in things, or personality changes. Honest.
Whenever I answer an email or forum post about buprenorphine I try to think of an explanation for the person’s perception. I try to give the person’s history the benefit of the doubt. I might have a couple of explanations for why someone might feel different on buprenorphine.
One case would be a person who is taking too little buprenorphine to stay above the ceiling threshold. Many doctors, and some patients, apply constant downward pressure to the dose of buprenorphine, I assume because of thinking that less buprenorphine is closer to total abstinence than a full dose of buprenorphine. But the benefits of buprenorphine are lost in doses insufficient to reach the ceiling effect of the medication. People taking too little buprenorphine will experience irritability, fatigue, sweating, and depression when the drug concentration drops below that level. The solution is to increase the dose enough for blood levels to stay above the ceiling threshold.
Another possible cause of irritability requires some speculation on my part. Actively-using addicts have very straightforward problems, which boil down to having enough narcotic to avoid getting sick every few hours. I’ve noticed that my own patients sometimes feel stressed or anxious in early buprenorphine treatment, as they become aware of all of the problems that were less-visible during active addiction. Most of that anxiety is only temporary, resolving as patients catch up with bills, settle legal issues, and feel less shame about behavior during active addiction.
Along the same line, active addiction sometimes allows people to postpone changes that really should be made, but were not possible during active addiction. Bad marriages seem less bad when surrounded by misery and chaos. But when a person finds happiness and moves forward in life, a miserable or abusive partner becomes more noticeable. Or maybe a marriage seemed ‘healthier’ when the partner was making the money necessary to support a drug habit. Effective treatment of opioid dependence empowers patients to make positive changes. But even positive changes come at the cost of emotional pain.
The people who remain convinced that buprenorphine is causing side effects would be best served by an open mind. Most of the complaints that I read about are identical to the complaints of my non-buprenorphine patients, and the most successful interventions include healthy living, stress reduction, and moderate exercise. Stopping buprenorphine is not going to be helpful in the absence of these interventions.
There is also the risk that the symptoms are caused by something other than buprenorphine—something more serious. An extreme example would be blaming buprenorphine for fatigue that in reality is caused by anemia, thyroid dysfunction, or heart disease. That situation is made even worse by the common behavior of doctors, who tend to blame any unexplainable symptom on the medication the patient is taking that the doctor knows the least about. Too often I’ve told patients to go to their GP because of unexplained muscle weakness, numbness, headaches, fatigue, or weight loss, only to have the doctor send them out without any tests or treatments, other than telling them to ‘stop Suboxone!’
Anyone reading this post, who truly suffers from adverse effects from buprenorphine, should report the side effects to the FDA web site so that clusters of symptoms, if present, can be identified.

Hot Flashes from Suboxone and Buprenorphine Treatment

First Posted 1/13/2014
A viewer on YouTube commented on my video about hot flashes  from Suboxone, but I don’t know if that is because the symptoms dissipate, or if people learn to deal with the symptoms.  I suspect that both are true.  But for some people, the sweating and heat are no small matter:
Here is what I wrote back, and a few more thoughts:
There seems to be a form of tolerance that develops more slowly than tolerance to the analgesic and euphoric effects of buprenorphine.  At least in the patients I’ve followed, complaints about constipation and hot flashes only go away over a period of months– after the other subjective effects of buprenorphine are long-gone.
Those who struggle with hot flashes may find relief by reducing the daily dose to the lowest amount that keeps blood levels above the ceiling threshold, around 4-8 mg per day. I think that in some case, people make the mistake of blaming withdrawal for the sweats and taking more and more buprenorphine, when the problem is too much opioid effect, not too little.
I recommend that patients carry a damp cloth or folded paper-towel, to use to create a chill when hot flashes start by touch the cloth to the face or neck. Another trick is to find a sink, and run cold water over the backs of the hands.  Anything that creates a chill—a blast of air conditioning to the face in the car, or an ice-cube touching the neck– will turn hot flashes off before they get started.
Nerves release acetylcholine to activate sweat glands in the skin, so medications that block acetylcholine reduce sweating.  But acetylcholine is also the neurotransmitter for salivary glands, so medications that block sweating will cause dryness of the mouth.  Many medications with unrelated primary functions have blocking effects at the acetylcholine receptor, causing ‘anticholinergic side effects.’   Anticholinergic effects are so common that medical students use a mnemonic as a reminder to keep the side effects in mind, when patients present with a certain pattern of symptoms:  dry as a bone, red as a beet, blind as a bat, hot as a hare, and mad as a hatter.  The symptoms are particularly common in the elderly, but can occur in younger patients taking high doses of anticholinergic medications.
The goal is to take an amount of an anticholinergic medication that reduces the worst of the sweating, without causing other anticholinergic effects.  Oxybutynin and glycopyrrolate are two medications used off label to reduce perspiration.  Sweating serves a valuable function by cooling the body, particularly in warm atmospheres.  Anticholinergic medications have the potential to cause hyperthermia, and even death.  Anticholinergic medications can also cause memory problems, particularly in older people.
Most of my patients have found that hot flashes, like constipation, become less severe over time.

Withdrawal Symptoms on Suboxone

Originally posted 11/7/2012
I struggle with the length of my posts.   I shoot for 1000 words—an amount of reading that most people can knock off in a typical trip to the bathroom— but I find it difficult to limit posts to that size.  So as I have done in the past, I will break this post into a couple of sections.  In the first, I’ll lay the groundwork for investigating symptoms of withdrawal in a patient taking buprenorphine.   The second post will go into greater detail.
A patient recently contacted me to complain that he was experiencing withdrawal symptoms for several hours after each dose of Suboxone.  I will describe my thought process, in case the description helps someone else experiencing similar symptoms.
My first decision point is whether or not the person is truly experiencing symptoms of withdrawal.  Some people will misinterpret symptoms from excess opioid stimulation as withdrawal symptoms, for example.  Nausea is a not-uncommon complaint among people taking buprenorphine, and patients often assume that nausea is the result of insufficient opioid activity, and so take higher doses of buprenorphine.  But nausea is actually more common in opioid overdose than during opioid withdrawal, along with constipation, whereas withdrawal primarily causes diarrhea.
Pupil diameter is a good indicator of withdrawal vs. overdose; small or ‘pinpoint’ pupils suggest an excess of opioid activity, whereas withdrawal is associated with very large pupil diameter.
Other symptoms are also misinterpreted as withdrawal.  Many opioid addicts develop a strong fear of withdrawal over years of using, and so ‘withdrawal’ is often the first thing to come to mind, during unpleasant symptoms.  I also believe that the experience of withdrawal becomes learned in a way that allows the symptoms to re-occur after certain triggers.  I remember an experience years ago, when I awoke from a dream experiencing significant withdrawal symptoms, even though I had not taken an opioid agent for years.  I feel back asleep, and was grateful to find that the symptoms were gone, when I woke the second time.
People are angered by the notion that their symptoms have ‘psychological’ origins. But as a psychiatrist, I have seen people blinded or paralyzed by conversion disorder.  If the mind can cause paralysis (and it can), I have little doubt that the mind can cause other physical symptoms.
If, after these considerations, the symptoms seem consistent with symptoms of opioid withdrawal, the next step is to compare the timing of the symptoms with what would be expected from various causes.  For example, withdrawal symptoms occurring shortly before the next dose of buprenorphine (or Suboxone) suggest that the dose is not quite high enough.  Buprenorphine eliminates cravings if kept at a blood level above that necessary to maximally occupy mu opioid receptors, because then fluctuations in blood level have no effect on opioid activity.  But if the blood level of buprenorphine decreases below that threshold, cravings and/or withdrawal symptoms will occur.
If the symptoms occur shortly before dosing, the solution would be to increase the daily dosage of buprenorphine, decrease the dosing interval, or increase the efficiency of dosing.  I have discussed ways to increase dosing efficiency here.
This particular patient describes symptoms of withdrawal beginning about an hour after taking Suboxone.  Absorption of buprenorphine takes 1-2 hours, and so the timing could suggest that the dose needs to be increased.  But if dosage is truly the problem, we would expect even worse symptoms if he delays his daily dose by several hours—as that would allow the blood level of buprenorphine to fall even further.  But in this person’s case, delaying the dose of Suboxone delays the withdrawal symptoms.  The symptoms continue to occur about an hour after taking the medication, suggesting that the dosing itself is causing the symptoms.
I cannot imagine a scenario where a sublingual dose of buprenorphine would cause true symptoms of withdrawal, an hour after the dose.  At this point we need to look at the naloxone component of the medication, and determine whether the naloxone is causing unpleasant symptoms— and if so, why.
To be continued…

Leg edema from Suboxone

A reader’s question:
I have been on Suboxone for 2 years. My addiction was Oxycontin.  I had knee replacement surgery and was successfully able to take pain meds and then get off them and go back to Suboxone. My medical Doc and I noticed that when I restart the Suboxone, I get 2-3 plus pitting edema in my legs, severe enough to require diuretics– and they don’t even work very wel. When I have stopped Suboxone in preparation for surgery, I immediately lose 15 lbs and the edema goes away. My Suboxone Doc says that there are no side efffects. I am 53 and have heart disease, and I know that this extra fluid is not good for my heart. My kidneys are normal. Have you heard other comments of this nature? Is it dose related?  This is a serious situation for me.
Reply:
I have had two or three patients with similar complaints.  To put things into perspective, though, over 5 years I have treated over 400 people with Suboxone or buprenorphine.  One person in particular had very bad edema, that caused a great deal of pain in his legs– so much that he stopped the Suboxone and went back on opioid agonists.  In his case, though, the edema did not lessen on agonists and he still struggles with edema a couple years later.  I don’t know if he had edema before I met him and started Suboxone;  he claimed that the edema was a new development, but I have learned that people sometimes notice things related to their health status that differs from the perspective of an independent observer.  This is why, by the way, I don’t fully jump into agreeing with people who report tooth decay ‘that starts after starting Suboxone.’  I had a patient with that complaint, and to look into things we got a copy of his dental records;  they showed that the decay was well underway years before he took Suboxone, at least according to dental notes and x-rays.  But in his mind, it all started after the Suboxone.  The mind sometimes plays tricks on us.
When I worked as a psychiatrist in the WI prison system, women in the maximum security prison reported leg edema from many different medications.  I never knew what to make of it, to be honest.  Most of the time the medications complained about were easy to replace;  if someone felt that the Seroquel caused edema, we could change it to Risperdal.  If someone complained about Risperdal causing leg edema, we could change it to Seroquel.  It reminded me of the old Dr Seuss story about the Star-Bellied Sneetches.  I strongly recommend the story for those who haven’t read it…
I like to think in terms of mechanisms, and I don’t have a good theoretical mechanism for leg edema from buprenorphine or from naloxone.  The collection of edema in the legs usually comes from an imbalance of the natural forces that should be in equilibrium;  gravity or ‘hydrostatic pressure’ causes fluid to leak out of blood vessels into the interstitial spaces, salts in the plasma and interstitium create ‘osmotic pressure’ that becomes balanced, with a neutral overall effect on fluid movement; and proteins in the plasma cause ‘oncotic pressure’ that draws fluid back into the blood vessels.  Veins in the legs are emptied by the effects of muscles that squeeze them during walking or exercise; one-way valves prevent the blood from moving backward or standing in place during this activity.  Taking all of this into account, edema is favored during immobility, when the legs are ‘dependent’ (not elevated), when protein levels are low from malnutrition or liver failure, or when the valves in leg veins have become damaged by standing too much in life.
Preventing edema involves keeping legs elevated as much as possible, reducing salt intake, wearing support stockings, and sometimes taking diuretics or ‘water pills’ to eliminate extra fluid at the kidneys.    Opioids do have effects on a number of hormones;  there are large protein molecules that are cut into smaller pieces that include endorphin and enkephalins, the brain’s ‘natural opioids’.  Other parts of those same large molecules have effects on fluid balance, among other things– the inter-relationships are complex and not entirely predictable.
I am posting this in case others have noticed similar effects, or in case a good endocrinologist or nephrologist has a pet theory.  Anyone?

Buprenorphine, methadone, and testerone

A member at the buprenorphine forum wrote about his own health issues including hormonal imbalances, prompting me to do a literature search on buprenorphine and testosterone.    I found a couple interesting studies and invite people to visit the forum and read about them, and comment if you wish.  To find the comment thread, just go to the bottom of the first page and the ‘index’ will list the new topics.
Oh– and please consider signing up while you are there.  Feel free to use an alias to maintain confidentiality.  Our numbers are growing, and the forum is open for anyone– including friends and family members of opiate addicts, or even people who only have an interest in the topic of opiate dependence.  We ask only one thing– that those who are looking to debate whether or not buprenorphine maintenance is ‘good’ or ‘bad’ take it outside.  Addicts have enough shame to digest already, and this is one place where the need for chronic treatment is a given.
JJ
A quick addendum– a reader had trouble finding the articles– they are at this link.

Suboxone and other medications; Xanax?

Q/A with a person from suboxforum.com:
I have a question regarding suboxone and i cant figure out how to post comments so i figured i would email to see if i can get my questions answered that way.
1) I know that suboxone has some kind of ceiling effect to where if you take too much it is either pointless or does the opposite, Is this true?
2) I am prescribed to xanax and zoloft as well.Will my anxiety medicine or my depression medicine (xanax/zoloft) not work with me being on suboxone? Does it block out benzos like xanax and valium and soma? Or does it just block opiates?
3) My boyfriend is on suboxone as well but I worry that he is abusing it? Can he get high off taking more than his prescribed amount or is it absolutely impossible to get high off suboxone alone?

My Response:
Hi–
I encourage you to keep fiddling with the site, using the username and password below– you can change the password on the site if you like. That way you can participate in the discussions. But for now…
Yes, Suboxone has a ‘ceiling’ at a dose of about 4 mg, assuming it is being taken correctly (it has to be absorbed through the mouth; whatever is swallowed is destroyed and inactive). Above about 4 mg there is no more opiate effect; at very high doses (above 40 mg) it starts to ‘block itself’ and have even less effect, so a person can cause withdrawal by taking a real large amount.
The active ingredient in Suboxone is buprenorphine; buprenorphine selectively activates and blocks the mu opiate receptor and will not interfere with xanax or other benzos, and will not interact with soma. BUT… buprenorphine will cause respiratory depression in people who do not have a high opiate tolerance, at least until the person gets used to Suboxone (after a few days). Benzos also depress respiration and there have been deaths from the combination of Suboxone and benzos in people who are naive to one or both of the drugs. Also, Xanax and other benzos cause tolerance even faster than opiates do; the first-line treatment for anxiety is serotonin (an SSRI) and benzos are best avoided by people with addictions. Benzos will reduce anxiety, at least for a few weeks, but they are very addictive in their own way, and the withdrawal from them can be fatal. The early withdrawal consists of severe anxiety, which patients often misinterpret as their own ‘anxiety disorder’, for which they think they need more benzos… and the cycle continues. All of us opiate addicts are too focused on how we ‘feel’, and benzos only reinforce turning our attention inward, when what we really should be doing is trying to ignore how we feel and instead focus on things ‘outside’ of us. You can tell, I’m sure, that I don’t like benzos. But patients sure love their benzos– patients get more attached to their benzos than to any other med in my experience, and it is very hard to get a person to give them up.
As for your boyfriend, a person can get high off suboxone if he/she takes it only intermittently and never becomes tolerant to it. That would be very difficult for most addicts to do, as the person would have to take it and then come down, wait a few days, and take it again. Most opiate addicts would not be able to ‘come down’– they would just keep taking it. I cannot imagine how a person could get a high with regular use, as tolerance would prevent it. BUT… I have had Suboxone patients who (unfortunately) took oxycodone or another agonist while taking Suboxone; they had no effect from the agonist but they still could not stop taking it. It appears silly on the surface, taking something so expensive like oxy and getting no effect, yet not being able to stop. But opiate addiction is complex– it is more than just taking something because it feels good. In fact most addicts will admit that they have not had a ‘high’ in years, but they still have to keep using. Using ‘serves many masters’, and each person may have a different master. For example, a person who is actively using becomes completely absorbed in the drug– finding it, playing with it, using it, worrying about finding it again… Some people after starting Suboxone have a great deal of anxiety– the way I see it is that suddenly they don’t have the obsession with opiates occupying their minds, so they are free to worry about the other things in their lives. One reason for their use, then, is to reduce anxiety… and perhaps that is what is going on with the people I know who are on suboxone but are still using. By the way, I do not keep people in such a state– I may give the person who uses one more chance, maybe with a higher dose of Suboxone, but if he/she can’t stay clean (and after crossing that line, most do not stay clean) then methadone or residential treatment is their only hope.
I am going to answer your question ‘publicly’ but I will take away your e-mail info. Please continue to visit the site, and post when you get it figured out!