A New Way to Stop Suboxone?

Originally Posted 10/27/2013
I usually have my wife/business partner review my posts and provide her opinion whether my arguments are sound.  For the record, she tells me that this post is technical and boring.  I disagree, but we aren’t planning to separate over the issue.  A valid criticism, I think, is that I’m doing a lot of guessing and wondering in this post.  This post is an example of the things I waste time wondering about.   I try to avoid writing things that are somewhat speculative, but I wanted to give it a shot for two reasons.  First, because there may actually be something to the idea I am about to describe.  But more important, I wish to point out some of the many ideas in the addiction world worth exploring…. And I hope that pharma continues to search for answers (i.e. spend money) in this area of medicine.
So I’ve been thinking more about ALKS 5461, the Alkermes pipeline medication that is a combination of buprenorphine and ALKS 33, which is a mu opioid antagonist also called Samidorphan with the structure shown at the left. ALKS 5461 is being developed by Alkermes for the treatment of major depression.  I don’t know much about the clinical actions of ALKS 33, (a proprietary molecule), except that it comes from a family of drugs that bind with high affinity and specificity to mu or other opioid receptors.  Samidorphan, a mu receptor antagonist, allows investigation of buprenorphine’s potential therapeutic effects at kappa and delta opioid receptors by blocking effects at the mu receptor.  Drugs with actions at other opioid receptors have be developed, and in some case patented.Until recently, theories about depression revolved around abnormalities in brain monoamine pathways or deficiencies of monoamine neurotransmitters.  Monoamines include serotonin, melatonin, and the catecholamines (noradrenaline, dopamine, and adrenaline). Most modern antidepressants act at serotonin or catecholamine receptors or reuptake sites. The new Alkermes medication ALKS 5461 is the first serious effort that I am aware of to treat depression from the opioid perspective.
Our brains contain natural opioids called endorphins and enkephalins.  Endorphins and enkephalins are neurotransmitters in pathways with a wide range of actions, including blocking pain and raising mood during injury or sexual activity. Pain pills such as oxycodone displace endorphins and hijack the natural endorphin pathways, providing euphoria without the trouble of buying flowers.  Of course, a relationship with self-administered opioids always becomes more destructive than even the most codependent partnership!
As an aside, when I presented for addiction treatment 13 years ago I told the addictionologist about my background in neurochemistry, and went on to explain that I was fairly certain that I suffered from a deficiency of natural opioids.  That doctor got a kick out of my story, and I would enjoy a sense of justification if my hypothesis someday proved to be correct.
When one considers using treating depression with buprenorphine, the obvious deal-breaker is the same issue that has prevented every other serious consideration of treating depression with opioids, namely the development of tolerance at the mu opioid receptor.  Because of tolerance, anyone who finds relief from depression with buprenorphine would be cursed by the need for eventual withdrawal, as well as other consequences of opioid dependence. I assume that Samidorphan is added to ALKS 5461 to prevent mu activation and tolerance.  Beyond partial agonist effects at the mu receptor, buprenorphine antagonizes (blocks) delta and kappa opioid receptors.  These blocking actions are not subject to tolerance, and may provide avenues for treating pain and/or depression.
Depression causes significant morbidity throughout the world, so there are huge profit incentives for new antidepressant medications. Addiction creates a large market as well, but companies rarely go as far out on a limb for addiction products as they do for other diseases. The need for new antidepressants is acute, but in an alternate universe where pain and addiction treatment take priority, Samidorphan and related opioid molecules might have a number of benefits. I’ve posted, for example, about my experience treating severe chronic pain by combining buprenorphine with an opioid agonist.  I expect the combination to be exploited eventually given the need for effective pain treatments, perhaps using an analog of Samidorphan.
Doctors use buprenorphine to treat opioid dependence.  The goal of buprenorphine treatment is to block the cycle of use and reward for some period of time, and to allow patients to create support systems, establish self-sufficiency, regain self-esteem, and practice living ‘life on life’s terms.’  The amount of time that it takes to accomplish these goals likely varies depending on the individual’s premorbid function, life experiences, insight, genetics, and other factors, but studies suggest that a year is not long enough to make meaningful headway.   It is possible that for some people, opioid dependence is a relatively permanent condition that is best controlled with life-long maintenance treatment.   But for those who would like to try to maintain sobriety off buprenorphine, the tapering process reignites the circuits that were set up by the initial addiction, causing cravings, withdrawal, and the constant obsession to delay the taper and resume the prior day’s dose of opioid.
If ALKS 33 has a long half-life and blocks buprenorphine in a dose-dependent manner, I could picture an alternate strategy for stopping buprenorphine where the antagonist (ALKS 33) is introduced to buprenorphine patients at a gradually-increasing dose.  The goal would be to eventually have the person on a daily dose of Samidorphan sufficient to block all of buprenorphine’s effects at the mu receptor, at which point the person could discontinue buprenorphine without withdrawal.  I suspect that the patient would experience withdrawal in response to each increase in dose of Samidorphan, although withdrawal would be reduced by introducing the drug at a measured pace.
What is the value in tapering in such a ‘reversed’ way?  Why would adding an antagonist be preferable to the current process, i.e. simply reducing the dose of buprenorphine over time?  The answer comes from an understanding of the nature of addiction.  A person stopping buprenorphine by gradually adding Samidorphan would face the decision once per day, whether to take the next dose of Samidorphan.  Compare that once-per-day decision to the current method of tapering buprenorphine, where the person must decide, thousands of times per day, to NOT take more buprenorphine.  I would expect that deciding to take an antagonist once per day would be more likely to succeed then CONSTANTLY deciding NOT to take buprenorphine all day long, throughout all of life’s ups and downs—times when the patient was conditioned to take opioids.
We will learn more about Alkermes new medication in coming months. I hope that someone in a power position will consider some of the other diseases that might respond to these interesting chemicals, including opioid dependence.

Treating Depression with Opioids?

I received this message today:
Hi, you probably answer this quite a bit. I’ve been depressed for as long as i can remember.
Ive been on the ssris, snris, amphetamines and methylphenadate but none of these have worked as well as opiates. (Certainly short term,I don’t take for long periods of time). But have you ever used suboxone or oxymorphone for depression.
Depression is probably a broad term, for what may be multiple conditions. For example, some people become depressed almost as if it is part of their nature—  they will get episodes of depresssion even when everything in life is going well, in spite of good marriages, healthy children, and an absence of significant baggage from the past– at least baggage that is visible.  Other people will present with depression that has developed after a series of blows to their sense of self or self-worth— after a health scare, job loss, divorce, death of a child, or perhaps from carrying around guilt or shame from abuse that occurred during their childhood.
Does it matter whether the depression is more like the first or the second category?  I think so, but I have no proof that my perception is accurate.   I will see different responses to medications by people with different types of depresssion, but I’m always challenging that perception, realizing how easy it is to be ‘fooled by randomness’, to copy a phrase from a book title.  In my experience, the second person is more likely to bounce back, providing the negative onslaught eventually stops.  But the people in the first group are more difficult to treat, especially if the depression becomes part of how a person defines him or herself—  as it is very difficult to change self-perception.
When I see someone who describes lifelong depression, my first question is whether the person was ever adequately treated with a good antidepressant.  Many times a person will say ‘I’ve taken every antidepressant out there’, but when I carefully go through the history, I find that the person has started many medications, but never took a medication long enough or in sufficient dosage to expect an effect.  I will work with such a person, coaxing the person through all of the side effects that led to stopping earlier trials of medications… and many times the person will do well on a medication that was written off years earlier.  I think it is important to get this basic info out, before launching into a discussion about more experiemental treatments.
I’ve written in an earlier post about Alkermes trials of a buprenorphine-based antidepressant;  I’m not certain where they are in the process with that medication.  I do believe that opioids play a role in depression, at least in some people.  Many of my patients on buprenorphine say that they feel better on the medication than then remember before taking it.  But I realize that all of these people went through very negative experiences as part of their opioid use, before starting buprenorphine.  I also know that recollections of emotions are extremely unreliable.  It is so important to keep good notes, as a psychiatrist, for this reason.   It is common for a patient to insist that he/she felt much better (or worse) the year before….. but then I will read through the chart with the person, and find with the patient that the perception was completely off target.
Even though buprenorphine seems to improve mood in some people, I would be extremely reluctant to prescribe the medication in a person who is not also addicted to opioids– unless or until we find a way to deal with the withdrawal that occurs when stopping buprenorphine.  That cost– the difficulty in stopping buprenorphine– is simply too high, to pass on to someone who isn’t already opioid-tolerant.
I should make it clear that I don’t buy into the complaints of people who write about being ‘stuck on buprenorphine’, who started the medication for opioid dependence.   I’ve seen enough death from opioids to recognize that buprenorphine is simply a necessary part of treating the majority of people addicted to opioids.  Most of the people who complain about being ‘addicted to Suboxone’ somehow have forgotten just how they got on Suboxone in the first place– i.e. the fact that they were stuck on opioids, usually despite multiple trials at stopping on  their own.  They also seem to have forgotten just how horrible ‘real’ addiction was– a life of getting sick every few hours, with only one true mission in mind– to find the next fix.  Being ‘addicted to Suboxone’ is nothing like that world;  the unique kinetics of buprenorphine trick the brain out of cravings for the drug, allowing the person to get on with life.    There is a huge difference between being ‘stuck’ with a tolerance to buprenorphine vs. active opioid addiction!
I am EXTREMELY interested in the recent findings about ketamine– that several infusions of the drug, in sub-anesthetic dosages, treat depression more quickly than any SSRI.  It is very possible that the actions of ketamine relate in some way to the antidepressant effects of opioids.  Ketamine acts at NMDA receptors, and also at some classes of opioid receptors.  Then again, perhaps the ketamine/NMDA system will be a novel treatment of its own.
To the writer– I noted in your message (the part I removed) that you live in my general area…  consider making an appointment, and letting me take a shot at helping you feel better.  There are SO many approaches to treating depression, that hopeless cases are rare.  I recently had a person find dramatic improvement on an MAOI, after failing everything else over a period of years.  People who take opioids now and then usually eventually become regular opioid users– and that would really be a shame.

Almost Ready to Get Help?

Another chapter from my untitled book, ‘Clean Enough,’ begins with comments from a reader of my blog.  The picture has nothing to do with anything, except that the Packer win was pretty awesome.  The view is from my seat at Lambeau during a game this season.

Lambeau Field club seats at night

I have been using various opiates for the past 2 years.  I’m sure it has affected my life in numerous destructive ways, but at the same time I feel that it has given me hope.  As a lifelong sufferer of anxiety and depression I have always looked for solace, and found it in books, art, music etc. But as I got older I got into drugs, in my case a path leading straight to opiates. As soon as   found them they were solution to all of my problems; I felt secure, safe, confident, sociable, and adventurous.  I found myself taking the risks socially, academically, and spiritually that I always wanted to. The doubt, insecurity, contempt for myself and others were rendered inconsequential. I felt I had attained a balance in my mind that allowed me to be who I really was.
On one hand the opiates must correct something that is defective in my physiology—they are the solution to my problems. This is not to say that I attain some sort of elevated state of consciousness by ingesting them, but that the opiate boost to my system allows me to function in a way that is actually healthier than my “natural” state.  But on the other hand I am afraid that my addiction is about to come to a head. I can no longer go more than a day without a dose, and all I do is think about pills. To cover up my use I drive great distances and spend thousands of dollars. The lying is increasing, and so are my withdrawal symptoms. I have tried to stop my use, but I am absolutely dejected without them.  I want to do something before I have ruined my life. But unfortunately it seems that the system is not receptive to people who are on the brink of ruining their lives–just those that already have. I have seen shrinks for the past decade, been on every anti-depressant/anxiety medication known to man all with little to no success. Is there any other, less dramatic way to detox or begin some kind of maintenance therapy without checking into an in-patient rehab center? Would buprenorphine make sense for this situation?
This letter that captures the thoughts many addicts have as they get close to seeking treatment, and I will use the letter as a backdrop for a couple broad points. My intent, as always, is not to ridicule the writer, but rather to challenge some of the writer’s perspectives.
Remember that addiction is a disease of insight, and realize that a person cannot ‘analyze himself.’  A person may see some patterns in his thought processes and make educated guesses about his unconscious motives, but he cannot ‘know’ his own unconscious—by definition, for one thing.  And if a person’s unconscious contains a conflict that affects behavior, the same unconscious mind will easily keep the conflict from conscious awareness.  So I consider it to be a waste of time for an addict seeking early recovery to try too hard to figure himself out.  A much better use of time would be to work on accepting his limitations in this regard.  In fact, one of my favorite sayings is ‘a good man knows his limitations;’ recovering addicts should have version of that idea at the ready at all times, in order to quickly end those dangerous moments when we think that we ‘understand ourselves.’
The same point is made at a meeting when someone reminds a particularly-intellectual addict the ‘KISS’ principle:  for ‘Keep It Simple, Stupid.’   I am making the point when I interrupt a patient in my office from explaining all of the reasons he relapsed, to tell him ‘it doesn’t matter.’   That’s right– IT DOES NOT MATTER.   When I write about unconscious factors that contributed so someone becoming an addict, I am writing for the sake of thinking about how the mind works—not to suggest a path to a cure.  Reflective, self-analytic thinking will not generally keep a person clean.
The writer also makes a common claim that opioids serve a purpose by medicating some troublesome psychological symptom.  Maybe someday science will support the idea that some people have ‘endogenous opioid deficiency syndrome,’ but for now the idea is not taken seriously by the addiction-treating community.   Even if the writer does have some type of deficiency, opioids are not likely the solution.  See my next paragraph for more on this issue.
All opioid addicts have the fantasy that they will find a way to keep using.  Early on, that fantasy fuels a great deal of frustration and broken promises.  “I know… I will only use on Thursdays!” we say to ourselves.  But there is NO way to make it work. End of story, period. I am a smart guy, and I tried every way possible to make it work.  And thousands of people smarter than me have tried and failed as well.  The only people who can take opioids without being destroyed are… people who don’t like taking opioids.  How is THAT for a messed up situation?  For example, my wife had kidney stones in 1993 and was given a bottle of Percocet tablets.  She took one, hated how it made her feel, and put the rest in the back of the cupboard for me to find a year later.  I decided, upon finding them, that I would take one each day to self-medicate my depression and my social anxiety.  Unlike my wife, I LIKED them.  And they were all gone two days later.  I know where the writer comes from when he says there MUST be a way to take those wonderful pills that provide safety, comfort, security, and adventure.  But smarter people than he or I have proven, many times over, that there is no way to have those good things without having the other stuff as well–   the lying, depression, and self-loathing.
My final point refers to the writer’s complaint that care isn’t present at the time, or in the form, that he needs it.  Such complaints used to be more common, and I would have answered the question ‘is there a less dramatic way to enter treatment?’ with a resounding ‘no!’  But buprenorphine has increased the options for addicts seeking treatment.  Successful treatment used to require the near-total destruction of the addict, which in turn caused sufficient desperation to fuel adequate motivation.  Buprenorphine allows treatment before the addict loses everything, provided the addict is truly sick and tired of using.  The availability of buprenorphine for treatment is an amazing step forward, but it is not a miracle.  The addict must truly want to be clean in order for buprenorphine to be effective.  But it is a far cry from the situation ten years ago, when an addict had to be at death’s door in order to ‘get’ recovery.

Endorphin Deficiency Syndrome and Buprenorphine

Every now and then I receive an e-mail  or comment that is sufficiently long to warrant a post of it’s own.  Below is the comment without interruption;  a bit lower I repeat parts of the comment, interspersed with my own responses.  I hope you find it interesting.
The comment:
I am a strange case: vegetarian, healthy, Pilates instructor, good-looking– NEVER A DRUG ADDICT — but i had a secret-  I was badly depressed for years- treatment resistant to over 30 meds, only some helped to a point… I did extensive research into the brain and opiate systems and i wondered if it was possible my endorphin system may be the culprit ( check this primer: http://www.prohibitionkills.blogspot.com/)
 I was desperate enough to try out opiates as a final solution ( and I monitored myself- I have brakes yet I was always scared of tolerance– and forever afraid to keep on that track) then i found my holy grail… i learned about Suboxone’s other use-  ( and it is now being studied for depression)
I was forced to lie to get on Suboxone, i pretended i was an Oxycontin addict etc.. i know that is wrong, but i was trying to save my life ( i was already at the point of suicide attempts)…not only did i get better, i brought my  mother in who was also treatment resistant and she was made better also within a week when even ECT failed her and messed up her brain for a good year…..she still takes what i took- 1mg in morning, 1mg in afternoon ( we both sensed that was when we needed a second dose not uncommon believe it or not for other depression sufferers that noticed a drop in the afternoon that Suboxone was again needed)
Anyway she is doing great on it to this day…saved her.
Me after intense meditation for one month- seriously no joke – i sensed i was ready to go off it.
 i do everything the hard way- so i went cold turkey off my 2mg a day after being on it for 5 years.
lucky for me- no depression- although the withdrawal did a real number on me– i was so sick from flu and withdrawal , horrible coughing, sore throat, dizzy and weak i wound up at the ER – thought i had H1N1. lol !  I was bed-ridden for almost 2 weeks; i ate nothing for a whole week but soups.
it was NO walk in the park, i was so weak i could not brush the tangles from my hair, even talk much to anyone. and the sweats were out of this world.
i am now at one month and 2 weeks.  i still feel  kind of weak and sickly, swollen glands, and sometimes a sore throat a little, my face is pale and i have huge dark circles under my eyes… the sweats have almost stopped….but my pupils still dilate… when i exercise i tend to feel worse not better — why is that?  
but my real question is this:  why does it make me look so pale and dark circles- ??? is it the interrupted sleep?? or low blood pressure or vitamin deficiencies?? Anemia – i take lots of vitamins and 3 iron pills a night (always did as a vegetarian).   i only wake up once or twice a night and i take a quarter of sleeping pill – unfortunately- every night still- otherwise i will be up forever..
And is there any nutritional things i can do to make me look less ghastly??  i look like a heroin addict and feel like people will see me that way as i can’t keep saying i have a flu forever !! ! What puts color back in the face ??
* before u lecture me about my terrible lie to the Suboxone doctor ( i think he knows anyway as he had to fudge my notes to make me a worse addict than  i claimed)  but u know what?? When i was in ER , and could hardly walk straight from my flu + withdrawal–i told the doctor while i felt like i was dying – that even then…  i was so happy i took Suboxone – it cured me and my mom FROM A LIFETIME of DEPRESSION. 
there IS NO withdrawal that is worth depression, let alone years of it, so please don’t lecture me on what i did, i saved 2 peoples’ lives by lying and i would do it again in a heartbeat…( in fact i was so angry when i found they have a cure for treatment resistant depression i tried in vain to contact media sources to publish a story on it- but who would touch that??)
Wow.  I am exhausted.  I’m not sure why- but some comments take so much energy to get through—and this was one of those comments.  Is it just me? 

First things first: Never hesitate to call drug addiction hotlines for help in drug emergency cases.

Some of my answers will likely come across as harsh, and for that I apologize in advance.  I don’t wish Edie any bad will, but my comments will probably show that I think she has gotten a bit carried away with some of her ideas.  Besides, some of the readers LIKE it when I get obnoxious.  Admit it!
My responses—for those of you who still have some energy left:
I am a strange case: vegetarian, healthy, Pilates instructor, good-looking– NEVER A DRUG ADDICT — but i had a secret-  I was badly depressed for years- treatment resistant to over 30 meds, only some helped to a point… I did extensive research into the brain and opiate systems and i wondered if it was possible my endorphin system may be the culprit (check this primer: http://www.prohibitionkills.blogspot.com/)
Most of my friends are drug addicts.  Most are not good-looking.  They all eat meat—lots of it—and laugh at people in Pilates classes.  And they AREN’T depressed.  I’m not drawing any conclusions—just pointing out an inverse correlation with an ‘n’ of about 6.  I’m also suspicious of the ’30 meds’ comment;  it would take a lifetime to give 30 meds adequate trials, even if there were 30 different meds for depression.  But I exaggerate too, so no big deal.
The primer is interesting, mainly for the collection of links to articles about the effects of opioids on mood and depression.  Edie describes doing ‘extensive research into the brain and opiate systems.’  I don’t know exactly what she did, but the long treatise at the url above is in no way scholarly, but rather is a collection of scattered, mostly-minor studies and comments with many, many incorrect statements, all intended to make the reader believe that there is a unique type of depression caused by deficiencies in the body’s endorphins.  I hardly know where to start—but the article, for example, claims that Effexor (venlafaxine) is a good antidepressant in part because of its similarity to the actions of tramadol— and that implies that venlafaxine effects the endogenous opioid system.  This is all nonsense.  Venlafaxine is an SNRI.  Tramadol has effects on norepinephrine reuptake as well.  But tramadol has entirely SEPARATE effects on the mu receptor that are NOT shared by venlafaxine.
The comments about acupuncture… there are a host of studies that show a failure of opioid antagonists to block the analgesia produce by acupuncture—evidence for an effect that does NOT involve endogenous opioids (which are blocked by naltrexone).
I honestly could go on and on and on… we know the mechanism of capsaicin on the release of substance P;  the effects are a very long shot from thinking that using (or eating!) capsaicin will somehow increase a person’s endorphins.  The writer describes a type of patient—a combination of cluster B traits from the DSM, along with assorted personality traits like ‘crying easily.’  Evidently somebody wrote a book.  Understand that the current distinctions between mood disorders, while not perfect, are based on hundreds of studies and years of input from psychiatry thought leaders—who then have their opinions examined and tossed around by more thought leaders.  Comparing the list of symptoms for ‘endorphin deficiency syndrome’ in the article with the longstanding and scientifically-validated diagnoses from the DSM is like someone writing a poem off the top of his head and saying it belongs in the Bible.
The problem is that there is such a thing as REAL science.  I actually DID study neurochemistry and neuroscience during my work for my PhD, and despite that four years of intensive labwork, lectures with distinguished scientists, searching through literature to write and defend my 150-page thesis—despite ALL of that and then my medical school training—I learned about a tiny, tiny bit of how the brain works.  The actions of receptors, neurotransmitters, and their relationships to mood and other subjective states encompasses a vast amount of knowledge, much of which contradicts itself from one study to the next.  One cannot extract a few studies out of ten thousand and use them to draw conclusions.  I’m searching for an analogy… it is like measuring the temperature during one minute from one hour of one day, in a town in Southern Wisconsin, and saying that you therefore understand the climate of the US—and that the US is a rainy and cold place.  You would be ignoring all of the other towns, times, and temperatures—and thinking that your point about the US was still valid.
I’m never going to finish this…
I learned about Suboxone’s other use-  ( and it is now being studied for depression)
I do recommend that people periodically check www.clinicaltrials.gov to see the interesting studies involving buprenorphine.  I would expect other partial agonists to appear on the scene in due course.
I was forced to lie to get on Suboxone, i pretended i was an Oxycontin addict etc.. i know that is wrong, but i was trying to save my life
I’m sorry to interrupt, but this sure sounds like something an addict would say, doesn’t it?  Nobody can be ‘forced to lie;’  we CHOOSE to lie because we like what the lie does for us.  Maybe it was justified… but ‘forced’?  C’mon.
i am now at one month and 2 weeks.  i still feel  kind of weak and sickly, swollen glands, and sometimes a sore throat a little, my face is pale and i have huge dark circles under my eyes… the sweats have almost stopped….but my pupils still dilate
So much for being good looking!  Sorry—just another bitter, bad-looking bald guy…
why does it make me look so pale and dark circles- ??? is it the interrupted sleep?? or low blood pressure or vitamin deficiencies?? Anemia – i take lots of vitamins and 3 iron pills a night (always did as a vegetarian).  
Shoot—I was just going to suggest a good T-Bone, medium rare.  But seriously, the dark circles can be caused by tiny hemorrhages around capillaries, which tend to be very fragile under the eyes… and the pallor of the skin from vasoconstriction in that part of the body—which is part of opioid withdrawal, along with the ‘goose flesh’ that is so common. 
And is there any nutritional things i can do to make me look less ghastly??  i look like a heroin addict and feel like people will see me that way
There you go again, dissing addicts!  I’m sorry, but heroin addict don’t all look the same, and they don’t  all look ‘ghastly.’  I have patients in my practice who were opioid addicts—some oxycodone, some heroin, most whichever was around— who look like the other people they work with on the job as teachers, carpenters, attorneys, nurses, and CEOs.   And no—the thing that will make you look and feel better is TIME.
* before u lecture me about my terrible lie to the Suboxone doctor
Oops—did that already!
please don’t lecture me on what i did, i saved 2 peoples’ lives by lying and i would do it again in a heartbeat…( in fact i was so angry when i found they have a cure for treatment resistant depression….
I NEVER lecture people, but I don’t know if you would get the Nobel prize in Medicine for what you did—although didn’t Al Gore get it for something already anyway?
I’ll stop here.   There is no conspiracy, and buprenorphine is not a ‘cure’ for treatment resistant depression.  Yes, it does seem to improve mood for SOME people.  But there are big downsides—for example the state that you currently are in.  You may be positive that you are not an addict, but I’m not;  your lie to get yourself on buprenorphine for a while MAY have placed something in you that you cannot yet see, that you will regret some day.  If, in five years, you are free of depression and also free of opioids, then it appears that at least in YOUR case, the experiment worked.  But frankly, the odds are against you.  You will tell me all of the reasons why you are different, and special, and why you will never use again…. But I suspect that if the depression returns, you will have a hard time avoiding another lie for another trial of opioids.  If you can’t get buprenorphine but instead buy opioids on the street, you are looking pretty similar to every other opioid addict—ghastly or not.
I have written about this topic before, and included links to some of the things linked on the url that Edie provided.  My bottom line?  If a person has a history of depression and is an opioid addict, there is one more reason to stay on buprenorphine long-term.  But I would have to think very long before conditioning a person to crave opioids—which is essentially what Edie has done.  As my treatment-roommate said (about regretting making porno movies with his wife while using), ‘there are some things that we learn, that we cannot unlearn.’    The warm, fuzzy feeling provided by opioids is one of those unlearnable things, and the lesson comes at a steep price—especially in a person who is prone to episodes of depression that only respond to opioids!
I hope I wasn’t too rough, Edie—I do wish you the best.

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.
A quick addendum– a reader had trouble finding the articles– they are at this link.

Buprenorphine (Suboxone) treatment of Refractory Depression

I can’t remember– did I ever point out this article about the use of buprenorphine for depression? I stumbled across it today while looking for something else.  The paper is from 1995, about a study done even earlier– well before Suboxone was around.
Here is the abstract:
Opiates were used to treat major depression until the mid-1950s. The advent of opioids with mixed agonist-antagonist or partial agonist activity, with reduced dependence and abuse liabilities, has made possible the reevaluation of opioids for this indication. This is of potential importance for the population of depressed patients who are unresponsive to or intolerant of conventional antidepressant agents. Ten subjects with treatment-refractory, unipolar, nonpsychotic, major depression were treated with the opioid partial agonist buprenorphine in an open-label study. Three subjects were unable
to tolerate more than two doses because of side effects including malaise, nausea, and dysphoria. The remaining seven completed 4 to 6 weeks of treatment and as a group showed clinically striking improvement in both subjective and objective measures of depression. Much of this improvement was observed by the end of 1 week of treatment and persisted throughout the trial. Four subjects achieved complete remission of symptoms by the end of the trial (Hamilton Rating Scale for Depression scores less or equal to 6), two were moderately improved, and one deteriorated. These
findings suggest a possible role for buprenorphine in treating refractory depression. (J Clin Psychopharmacol 1994;15:49-57).
Suboxone Talk Zone

Buprenorphine and Mood: Does Suboxone Treat Depression?

Thanks for the the feedback everyone! I should explain the logo… when I was doing the logo contest at logotournament.com (which is an excellent resource by the way) I asked for help in picking a winner. The logo at the top of the page was not an entry at that point, and a different logo was chosen– one that to be honest I wasn’t all that thrilled about. By the time I returned to logotournament.com there were a few more entries, including the one above– which I liked more than the one that everyone chose… so… I overruled the democratic process and picked it. Sorry! I just thought the other one looked too much like a pharmaceutical logo.
But back to more serious topics…  I received a question from a person about using Suboxone to treat depression.  The topic came up some time ago, and someone contributed some information that is in the archives somewhere.  Opiates have been tried as treatments for depression in the past;  they do raise mood in most people, and have even been implicated in the precipitation of mania in patients with bipolar disorder.  But they have never been accepted as ‘mainstream’ treatments for depression, largely because they are almost impossible (if not impossible) to take long-term without everything falling apart;  the mood effects are lost to tolerance, and the person taking them experiences cravings and the obsession to take larger and larger doses.  Enter Suboxone… a medication that causes a constant level of tolerance (instead of an ever-increasing tolerance) and prevents cravings.
Many people have told me about the ‘boost’ that opiates used to give them, wishing (fantasizing) that there was a way to keep the good feelings and avoid the misery.  There isn’t, by the way.  At least not now… although I do expect science to discover a way to prevent tolerance at some point, and I suppose that will be the end of civilization as we know it!  But I also have several patients who claim that their moods are improved by Suboxone, and I have received a few e-mails over the past few years from people who take Suboxone primarily for that reason–  to treat or prevent depression.
After the nice response to the nicotine question (thanks everyone!) I thought I’d present the question about mood the same way:  For people taking buprenorphine, have you noticed any effect on your mood?  Does anyone take Suboxone for that primary reason?  Please leave your comments below if you have a minute;  I will also direct you to SuboxForum.com, where I will be adding a new category for people to post in response to the ‘SuboxoneTalkZone question of the week’.  I can’t post this question there right now, as I am in the process of transferring the forum to a new hosting account… but assuming I don’t mess that up, it should be up and running soon.
Thanks, as always, for the feedback!

Getting Off Alprazolam (Xanax): The need for Recovery

A comment on my old blog referred to a discussion about the withdrawal from Xanax, or Alprazolam, a short half-life benzodiazepine:
Clonazepam (Klonopin) actually is not the drug of choice used in benzo withdrawal, rather it is diazepam (Valium). Clonazepam It is not a very long-acting drug, with a half-life of only 18-50 hours; diazepam’s half-life is 20-100 hours, with its metabolite hanging around for twice that long.

Absolutely the worst thing about benzo withdrawal (take it from me) is that it never ends. That is why I still take them.


My Response:

The ‘drug of choice’ for benzo withdrawal depends on many factors beyond half-life. Diazepam (aka Valium) is absorbed very quickly and so the onset of action is as fast as 20 minutes; this is useful in some situations, but is also thought to contribute to the increased addictiveness of diazeapam over clonazepam (Klonopin). Both drugs stick around long enough to accumulate with repeated dosing; diazepam has active metabolites, making the effective half-life even longer than the pharmacologic half-life. But who cares? In either case the person coming off alprazolam (Xanax) can take the longer-acting benzo four, three, or two times per day– even once per day could be sufficient to prevent seizures with either drug, providing the dose is high enough.

It is very hard for most people to get off Xanax… or any benzo. For that reason, the best medication for alprazolam withdrawal may be a non-benzodiazepine anticonvulsant. I have used valproic acid (Depakote) or phenobarbital in patients for treatment of benzo withdrawal and/or alcohol withdrawal. Pretty much anything that works for alcohol withdrawal will work for benzo withdrawal– which is consistent with the fact that alcohol, benzos, phenobarb, and valproate all have actions at the GABA receptor. Other factors to consider when choosing a medication for benzo withdrawal include liver function– diazepam in particular lasts forever in patients with bad livers. Phenobarb affects the metabolism and plasma levels of many other medications. Valproic acid can cause liver damage and tends to stimulate appetite; is also causes heartburn and nausea in many patients.

The biggest problem with coming off benzos is losing the fuzzy haze that covers life and tolerating the harsh glare of reality. Patients complain of ‘anxiety’– many times they are simply feeling what everyone feels all of the time, but they have lost the ability to tolerate the normal stresses of life. This is where 12-step programs come in; working the steps provides everything that is needed for a person to learn to tolerate reality. After 15 years of going to meetings, I am still amazed at the value contained in the 12 steps. EVERYTHING is there! How to tolerate one’s self; how to deal with others; how to cope with rejection or loneliness; how to begin to understand a purpose for living… the answers to all of these questions– questions faced by most drug addicts on a daily basis– are contained in the steps. I strongly encourage, and invite, people learning to tolerate reality to come to recovery and join the others who are looking for the same thing– and finding it at AA or NA.


Feelings, Nothing More Than Feelings….

No, I’m not a big Barry Manilow fan…
Opiate addicts, for whatever reason, become very lousy at determining what they are ‘feeling’.  Ideally, feelings serve to enrich one’s life;  feelings add the music to the story, add the heat to the dish, add the…  heck, I don’t know.  I’m no poet.  But they are good things.  They also can guide a person if they are used properly.  That last sentence is key– if they are used properly.  To explain a bit more, when people feel ‘fear’, they recognize that there is danger lurking about and they either turn and run or they at least become more cautious.  Addicts, of course, are different;  to an addict, danger may mean ‘excitement’, and may cause the addict to close his eyes and just jump right in!
One challenge facing addicts, then, is using feelings and the messages that feelings provide in sensible ways.  An even bigger challenge is identifying exactly what the feelings ARE, in the first place!  Addicts will have two feelings– great and ‘crappy’.  Or maybe ‘chill’ and ‘f’ed up’.  In my practice addicts tend to call every negative feeling ‘anxiety’.  They go to work and feel ‘anxiety’.  They come home and feel ‘anxiety’.  They sit around all weekend and feel ‘anxiety’.  I am always working to get them to identify the feelings, and to call them something other than ‘anxiety’– as usually they are not anxiety.  Anxiety is ‘worry’, whereas the feelings most addicts have are more like boredom, irritability, anger, sadness, resentment…

In my own treatment (I was in some type of group for about 5 or 6 years) we always checked in with our name, our disease (like at aa– I’m jeff, alcoholic and addict), followed by a statement of the feelings we were having.  We picked from 6 feelings, and sometimes I felt one, other times I might feel a little of all of them.  The six feelings:  sad, glad, mad, afraid, ashamed, and hurt.
I strongly encourage you to always work on your feelings.  It takes a great deal of practice, but you will get to know yourself better, and feel more ‘grounded’.   Get in the habit of ‘checking in’ every morning, and every night.  Try on the six feelings and decide which ones fit.  And whenever you feel lousy, try each feeling on and see what is going on.  The process takes minutes per day, but will pay off over time in ways that are hard to explain–  but that are certain.

As If!

A comment and question from a reader:
How’s it going people thanks for the education dr. I’ve been on Suboxone for 3 months now and am down to 2 mgs a day, I have found that getting physical exercise is such a key to my over sense of well being. I believe that it is one of the major parts in the tapering process because of the addition of natural dopamine release and just the overall feeling of wellbeing of doing something positive and constructive. I do have a question in regards to how I should taper down from 2mils should i keep doing it by halves every week or should i try and take it at 2mils every other day but i know if i get to low then it brings up cravings. Any advice would be great. Me personally I try eating a lot of fruits especially bananas along with good exercise in the sun is really helped me a lot. which when I was on opiates I would have to get loaded in the morning so I didn’t get wds which limited all my activities and made me lazy leading to an overall degraded self esteem and image when I feel so much better being able to feel good about constructive behavior and radiate positive energy to people. But ids rather stay at 2 mgs a day for the rest of my life and be happy, and positive, then go off when im ready. Rather than be in a constant struggle with trying to be happy, feel well and also the cravings. Finally what’s the long term consequences of maintenance Suboxone use I’ve heard rumors it might affect memory or something like that (at let’s say 2mg)??
My Response:
That is great that you are exercising! There is no doubt that exercise will reduce the severity of the withdrawal process—unfortunately people don’t feel like exercising when they are in withdrawal, so they usually don’t. Exercise helps so many things… it will have a positive effect on depression as well. I often tell people to ‘act as if’– a common Recovery phrase that is said in reply to the complaint ‘I don’t feel like it’. Act as if you DID feel like it—and the ‘feeling like it’ will follow.

We have to act ‘as if’ on many occasions as addicts trying to stay clean. An actively using addict does what he/she wants, and that’s that. So it is important to have a goal out in front of us—an image of who we would like to be at some point. When we feel like taking a day off, or doing something inconsistent with Recovery principles, instead we can remember our goal and act ‘as if’ we were that person already. Acting ‘as if’ is one of the little things that I have carried around since treatment that has certainly kept me out of trouble on many occasions. All alone in a relative’s home, where there are certainly going to be pill bottles? Act ‘as if’ I am not alone, or act ‘as if’ I had a urine test later in the day. Nervous about applying for a job? Act ‘as if’ you aren’t nervous. Etc.

Tapering down from 2 mg per day is tough. One thing to do is take a tab every other day for a week, then stop… the problem is that once you get to such low doses, you run the risk of going into minor withdrawal at the end of every dosing interval. Once that starts to happen one might as well just stop completely, otherwise the misery only becomes dragged out. The general mistake I see people make is that they change the dose too rapidly, given the long half-life of the drug. During the early stages of a taper, the dose should be changed no faster than weekly. I usually recommend going down by 2 mg every week, but everyone has their own preferences. But if a person goes too fast, the WD becomes ‘stacked’ up and is as severe as it would be with no taper. To explain… WD takes 3-5 days to develop in an average person on 16 mg. If a person tapers each day, he will be almost to zero per day by the time the WD starts—and will feel as if he abruptly stopped the medication.

I have not seen any credible threat to health from long-term use of buprenorphine at this point. There are plenty of junior scientists out there on the web, extrapolating from studies on mice or tissue culture—there is little relevance to clinical use in humans from what I have seen rumored on the web. There is a decrease in sex drive associated with chronic opiates, and I would assume that buprenorphine would fall into that category. When I have a patient with that side effect I usually treat it with a Viagra-type medication, or sometimes with a small dose of testosterone, particularly if their testosterone level is below the normal range for age.

Many of my patients report similar mood effects as you describe.  I interpret the effects as a bit of euphoria from the opiate action, and maybe something else– maybe the sensation of a more ‘level’ mood because of a reduction in cravings.  Opiate cravings can be manifest by irritability, depression, anger… and since buprenorphine so effectively eliminates cravings, I would anticipate a reduction in those ‘negative’ symptoms as well.

I certainly have many patients who intend to stay on Suboxone indefinitely. There are currently trials looking at other forms of buprenorphine, such as ‘Probuphine’, an implant of buprenorphine intended to last for six months. My prior post refers to all of the ‘Suboxone experts’ out there who use PubMed or another reference site to download articles, then send them to me or other people to try to prove some point—I encourage people to ignore the attempts of others to scare you off of Suboxone—or any medication, for that matter. Speaking as someone who has published a number of scientific articles I can tell you that the people who do that are always much less bright than they try to appear. I have a guy right now who is sending me articles to try to back up his argument that opiates are safe to use long-term– the last set of articles he sent have nothing to do with the issue at all, although a person in a non-science field would be swayed by the sheer volume of material! Don’t let some idiot spouting off with anger about Suboxone change your mind about how to handle YOUR health.