The forces of nature appear intent on reversing mankind’s progress toward better health.   An example is the ever-increasing resistance of bacteria to antibiotics.  A timeline of the existence of humans and bacteria shows that bacteria have been around for a very long time— much longer than mammals, and much, much longer than humans.  In fact by the dawn mankind, bacteria had been thriving, relatively uninhibited, for over 2 billion years.

Modern humans have been around for 40,000-200,000 years or so, depending on the definition of ’modern.’  Bacteria have had the upper hand during all of mans’ existence, save for the past 100 years after penicillin and other antibiotics were discovered. Only the most self-centered of species would look at a timeline and conclude that humans have won the battle with bacterial diseases.  There are always reasons for optimism, but a fair assessment of our current struggle with antibiotic resistance suggests that someday, people will look back on the current sliver of time, when humans can treat most bacterial infections, as a golden era of medicine that wasn’t appreciated as such at the time.

Viruses adapt to mankind’s health efforts too, with new variants arising from the sludge at the bottom of the food chain to infect birds, swine, or other creatures before moving on to human hosts.  The CDC and other scientists work to predict the vulnerabilities of the next super-virus, hoping to reduce the severity of the next pandemic.  As with bacteria, we are enjoying an era without smallpox, polio, or other dreaded viral diseases that used to kill otherwise-healthy people.  We take the victor’s position for granted to the point that our children don’t know why chlorine was first added to swimming pools.  Gone with the last generation are the fears associated with iron lungs, orange window-signs, and leg braces.

Even the Human Immunodeficiency Virus, an agent of certain death in the 1980’s was transformed into a chronic, treatable illness.  I was new to medicine when ‘universal precautions’ were first instituted (can our children even imagine having their teeth examined by someone not wearing latex gloves?!)  Researchers don’t celebrate, though, since medication-resistant strains of HIV were expected to emerge– and have emerged.

As a medical student I learned about ‘non-A non-B hepatitis’, a small concern at the time that has since grown into the identity of ‘Hep C’ (Funny how long it took to come up with THAT name!)   Hepatitis C is a major public health threat, since routine vaccinations for hepatitis B and the surge in IV drug use.

Not all diseases are from non-human entities.   Cancers, for example, arise from errors in our own DNA, either inherited or acquired.  Cures have been found for a few cancers, but like bacteria, cancers have emerged that are resistant to current chemotherapeutic drugs, requiring a constant search for new agents.

Some illnesses are considered ‘lifestyle diseases’ because they are  related to obesity, smoking, pollution, substance use, inactivity, or poor diet— such as hypertension, heart disease, diabetes, cerebrovascular disease, asthma, and COPD.  The model of resistance show by bacteria doesn’t fit in the same way, but many of these illnesses draw public attention as ‘epidemics’ that demand resources, with apathy or cultural phenomena function acting as resistance to those efforts.

Bear with me;  I’m working up to something that I’ve alluded to before.  My point is that like with other illnesses, addiction doesn’t respond to medications– Suboxone and buprenorphine — quite the way it used to.

When Suboxone hit the US market in 2003, large numbers of opioid addicts were scattered across the country, sick and tired of their dependence on opioids.  Heroin was considered a ‘bad drug’ back then even by those with severe addictions, and was rarely encountered by teens and young adults.  Most opioid addicts used hydrocodone or oxycodone, prescribed by doctors or obtained from people with prescriptions.  Heroin was marginalized to those with the most-severe addictions, or used sporadically in combination with other drugs (e.g. speedballing).  Known doses of oxycodone were comparatively safer than heroin, which is stepped on to varying amounts and sometimes laced with deadly fentanyl.  Oxycodone was absorbed through mucous membranes more quickly than heroin, meaning lower motivation to use needles.  So in the early 2000’s, some people addicted to opioids found a way to get by, albeit in state of chronic misery and loneliness after spouses and friends moved away.

Enter Suboxone– a new medication to treat opioid dependence.  Suboxone carried some controversy, as some in the non-medication treatment lobby did their best to tarnish the medication (as in ‘you’re not as clean as I am!).   But despite the tarnish, Suboxone and buprenorphine were medications that were to be prescribed by doctors.  People who for years kept the same horrible secret were given an option that actually worked.  People returning to my office for follow-up had tears of happiness on their faces;  they thought they would never be free from their afflictions, and were grateful as Hell for a chance to return to the living.

Many of those patients have done well for years, in treatment in my practice and others.  Many are still on buprenorphine and grateful to be on buprenorphine, as happy and productive as they’ve ever been in life, with no desire to change.

But then, just as some of us were becoming optimistic about this great new medication, the disease of addiction changed in the direction that all diseases change– for the worse.  The substrate changed; oxycodone was largely removed from the market through well-intentioned anti-diversion efforts that made Oxycontin harder to abuse…  just as the US experienced a large influx of cheap heroin.  And as in the 1960′s, heroin brought out needles– something that many opioid addicts used to take pride in for not considering.

And Suboxone changed.   People on buprenorphine or Suboxone sometimes shared a bit of their medication with friends going through dry spells. Some people on Suboxone or buprenorphine sold portions of their prescriptions.   The image of Suboxone held by active heroin addicts changed from doctor’s medication to a self-directed treatment for withdrawal.  In fact, the perceived roles of patient vs. treatment provider became blurred by needle exchange programs and programs that provide addicts with syringes loaded with naloxone.   Against a confusing backdrop of publicly-provided needles, free syringes pre-loaded with naloxone, and expensive brand film vs. affordable generic buprenorphine, the image of Suboxone turned from orange to gray.

I don’t mean to criticize the well-intentioned efforts to save lives, such as the distribution of naloxone in areas where overdoses have become epidemic.   It’s hard to predict unintended consequences.  But now, new patients consist of 18-y-o heroin addicts who see Suboxone as a tool to provide cover for a few days, when the heroin supply runs dry.  Some see Suboxone as a tool to detox, although the detoxes never accomplish anything at all—the ultimate bridge to nowhere.  The bottom line is that after seeing a few Suboxone tablets ground up, dissolved, cooked, and injected, the medication loses a bit of luster.

And finally, patients themselves have changed.  Opioid addicts in 2013 are often acutely ill from unknown doses, toxic fillers, and dirty needles, presenting to ER’s with antecubital abscesses and hepatitis C.  And despite being very, very sick, many haven’t had enough time to get sick and TIRED.   Being started on Suboxone is less of a bit deal because they’ve BEEN on Suboxone— little chips of it, over and over and over, whenever the heroin ran out.

Gone are the easy buprenorphine patients.  Now we have young, fresh, sick addicts who won’t live long enough to hate their addictions.  Addiction as a disease has adapted to our treatment efforts, and become stronger– and deadlier.  Our side had better keep up the hard work.

Woman getting injection image available from Shutterstock.

I’m always impressed by the power of our ‘unconscious.’  I realize that people have a range of models for conceptualizing how our minds work;  my own combination of education, analysis, and observation has led to an understanding that ‘works for me.’

My conscious mind works in series, holding one or two thoughts at a time and proceeding in a somewhat-linear fashion.  The unconscious, on the other hand, is an amalgam of countless processes that never end, epiphenomena of the constant barrage of sensations, emotions, and memories that are sorted, compared, associated, and recorded.

At least that’s how I see it.

The unconscious is not something that can be figured out, no matter how much insight a person may develop. During treatment for addiction I thought that if I could discover my unconscious motivations for using, my desire to use would cease.  I don’t see it that way now.  Even after more than a decade of sobriety, I am aware that my unconscious mind remains intertwined with the addictive parts of my personality, forever inseparable.

My unconscious mind protects me from unpleasant emotions.  Some insights are deemed, by whatever determines my conscious experience, as too painful.  But even when I’m not allowed to have a certain awareness, I can sometimes infer what is going on beneath the surface using the clues evident in my behavior.

For example, I’ve been struggling to write for several weeks now, since my dad’s death.  I don’t know for certain what unconscious thought or emotion is getting in the way, but I’m aware that something has changed.  The ideas that arise as potential topics seem unworthy of my attention and uninteresting to readers.  I sit down to type, but the words don’t come.

I can guess what might be going on….  maybe on some level I’m angry that he isn’t reading my posts anymore.  Maybe I wrote out of efforts to impress him, and now I have nobody to impress.  Maybe I’m just hurt or sad at the loss, and the small child in me is refusing to cooperate.  It could be any or all of those things, or none of them.  The unconscious actively decides what I am not allowed to know, so there are no ‘aha!’ moments of clarity.  Only hints, based on my behavior.

I am writing about the mind today— a topic on which I’m not an expert, and yet the words for the topic are available to me.  But on my usual topic—addiction— I’m just not ‘feeling it.’  Maybe that’s another clue—that the topic of addiction is wrapped up in memories and emotions that are enmeshed with thoughts about my dad.  Maybe writing about addiction is too….. too something.  And sure enough—right now, as I think about writing about addiction, I feel sad.

Something is blocking me;  if I were my psychiatrist, I’d say that I need to allow the painful thoughts to enter my mind, whenever my unconscious decides that I’m ready to know them.  But for whatever reason, I’m just not there yet.  Thanks for being patient.

Unconscious image available from Shutterstock

My dad passed away two days ago, one day after his 89^th birthday.  It doesn’t feel quite right to post something so personal.  But it feels more wrong to write about anything else.

Writing was a source of tension between us in some ways.  My perspectives on myself, my parents, and my upbringing have changed over the years, and I tried to share my observations with my dad in several short essays centered around memories from my childhood.  The efforts were a mistake.  I learned that insight develops in each of us at different rates and in different directions, and my ‘aha’ moments—realizations about how my dad shaped my development— felt to him like criticism.  I don’t think he fully realized that I accepted him, loved him, and respected him.

As for my ‘aha moments’, I don’t assume that my realizations and insights are accurate.  As my perceptions change over the years, I try to remain open to two alternate explanations for those changes—that with age I’ve learned, through wisdom, to see things more accurately, or that with age my thought process is becoming more rigid and any newfound ‘insight’ is an illusion, a product of that rigidity.

My dad was an intellectual, who read more books about philosophy and theology each year of his adult life than I’ve read in my lifetime.  So when our understandings of the world differed, I had to at least consider that my own judgment was off, rather than assume that old age impacted HIS judgment.

So to sort things through, I wrote.  I honestly thought that with enough effort, we would fully understand how we each see things; not that we would necessarily agree, but that we would fully understand each other’s perspective.  But I eventually decided that at least for us, differences in our individual perspectives ran too deep for us to completely understand each other— no matter how hard we tried.

My dad grew up during the depression, fought in Germany during WWII, became an attorney on the GI Bill, and worked for the Atomic Energy Commission before settling down in private practice and raising a family. He studied Christian theology and practiced daily meditation.  The internet got going when he was about 70, and he had his own blog, email address and Facebook account.

He jogged since the time when people first started jogging, before someone invented ‘running shoes.’  He worked out at the Y throughout his life, even in the weeks before his death.  I worried that the care he took toward his personal health would eventually cause problems, leaving him without a graceful exit from this world.  But he suffered a brain hemorrhage two days before his death, losing consciousness while sitting in a chair, listening to music from his I-Pad.   The next day his children, grandchildren, and wife of 55 years sat at his bedside, shared memories and sang Happy Birthday.  He died a few hours after midnight, never being one to drag things out too long.

I’m sorry if readers find this to be cryptic or overly personal, but I was stuck, and I had to get these things out before I could move on to the usual stuff.  My dad reads my posts, and there were a couple things I needed him to know.

Rainy window photo available from Shutterstock

I generally write positive articles about the use of buprenorphine for treating opioid dependence, and my articles have been reflective of my attitude toward the medication. The field of psychiatry encompasses more conditions than it does effective treatments for those conditions, and my initial experiences treating people with buprenorphine were strikingly positive.

My first buprenorphine patients were extremely desperate after multiple treatment failures, and they responded to buprenorphine the way a person with strep throat responds to penicillin.  Their lives improved so dramatically that I wondered if we needed a new understanding of ‘character defects’; whether the shortcomings should be seen not as semi-permanent flaws, but rather as dynamic, maladaptive personality traits, fueled and sustained by active obsession for opioids— and lessened when that obsession was reduced, using buprenorphine.

I still have a number of those patients in my practice, people who have done very well on buprenorphine and have little interest in discontinuing the medication.  As much as I would like to take on a few new patients, I won’t force these people off buprenorphine in order to make room under the cap.  They have worked hard, done well, and have earned the right to a medication that helps keep their illness in remission.

But I’ve noticed a change over the past couple years in the attitudes of patients coming for treatment.  I’ve been slow to specifically identify the change, but when I do an honest assessment, a clear pattern emerges.  To be blunt, young people don’t do as well on Suboxone or buprenorphine as their older counterparts. Maybe they have a harder time accepting the limits to their own mortality; maybe insight requires a longer time to accumulate life experiences.  Maybe they haven’t suffered enough consequences.   But after starting buprenorphine, instead of tearfully expressing disbelief over the lifting of cravings for opioids, younger patients are more likely to take the effects from buprenorphine in stride and continue to engage in addictive behaviors.

I always consider each new patient’s history of ‘consequences’.  I believe that consequences are what eventually spur recovery, providing the patient lives long enough for that to happen—which is certainly not a given with opioid dependence.  I note that consequences impact people similarly in some ways, and differently in other ways.  For example, most people have trouble imagining just how bad things are likely to become until they actually get to that degree of severity.  People who’ve never used a needle believe they will never do so, and people who haven’t been arrested can’t see themselves in that position.

But once consequences occur, people react to them in widely different ways.  Some people react to felony charges with horror, while others appear indifferent.    A near overdose might cause warning bells to go off in one person, yet cause little reaction in someone else. One person will be ashamed and humiliated the first time in jail, while another seems to simply adapt, as consequences move from bad to worse.

Are ‘consequences’ the missing piece of the puzzle for patients who don’t do well on buprenorphine?  If so, are the differing reactions that people have to consequences clues to helping poor responders? Should counseling efforts target for elimination those attitudes of ambivalence or indifference toward negative consequences?

In general, shame is viewed as a hindrance toward recovery.  The cycle of shame is well-known by everyone who treats addiction; the idea that ‘shame’ serves as a trigger of using, which in turn generates more shame, and so on.  But when I see a 20-y-o patient who is addicted to heroin shrug off another relapse, I wonder if in some people, a little shame would be a good thing.

A local District Attorney wrote to me last week to express his concern about the increased diversion of buprenorphine.  I often sense an undercurrent of tension when I cross paths with attorneys, aware of the different attitudes that we hold that arise from our different roles in society.

The DA wrote about the dramatic increase in overdose deaths in the Midwest.   Overdose scenes are often littered with a variety of substances, ranging from bags of heroin to the orange plastic vials used by pharmacies to dispense medications.  If the overdose victim was on Suboxone or buprenorphine, the prescribing doctor is often contacted about the death and the ensuing investigation.  Doctors notified about patient deaths have reactions beyond the grief over the loss of someone they cared about, including guilt that they couldn’t save the patient, and even fear of being blamed for doing something wrong. Every doctor has seen headlines featuring peers accused of reckless prescribing, and the addiction world is somewhat unique from other specialties in the way that patient deaths cause a sense of ‘guilt by association.’  Oncologists, for example, are not viewed with the same degree of suspicion when their patients succumb to cancer.

I felt a bit defensive about the DA’s letter.   I know that buprenorphine saves lives, beyond a doubt.  I also notice that the positive actions of medications are often taken for granted, while the risks are cited as scapegoats.  I notice how quickly people complain about others ‘on buprenorphine’, without taking the time to ponder what would likely happen were buprenorphine not available.

Some physicians’ fears stem from dilemmas faced in treating addiction that are difficult or even impossible to resolve.  For example, a DA may point out that the doctor’s patients are not behaving like ideal citizens, not realizing that the doctor is every bit as aware of the problem, yet unable to make things better.  In some cases doctors do the very best they can (or that anybody could do, yet their patients struggle to maintain sobriety.  Doctors may be tempted to abandon the problem patients altogether, to avoid being seen as impotent or worse—as ‘part of the problem.’

I know, right now, that three of my patients are struggling with buprenorphine treatment.  Maybe I’m naive and the true number is higher, but I’ll focus on the people who I know, for certain, to be struggling.

The patients I refer to as ‘struggling’ are taking buprenorphine or Suboxone, but taking it imperfectly.  For years they were conditioned by heroin, as the misery of withdrawal was relieved by the poke of a dull needle and the injection of foul liquid, hundreds and thousands of times over.   They are now ‘freed’ by buprenorphine from the need to relieve physical misery, but the urge to penetrate their skin with needles continues. Buprenorphine binds opioid receptors so tightly that heroin or oxycodone, when injected, cause no high or change in sensorium, yet users are still drawn to inject, a status referred to as ‘hooked on the needle’, where the painful piercing by a dull needle fills an otherwise-intolerable emptiness.

Their actions appear insane to people who have never ‘shot up’.  Why would someone risk endocarditis—or worse– through shared needles, when the injection causes no pleasure, and in fact causes pain? The bizarreness of the situation doesn’t, unfortunately, make it less common.  The situation exists.

I tell my patients that the one thing that results in immediate discharge from my practice is sharing or selling medication that I prescribed.  Even in the midst of insanity there must be some absolutes, and from my perspective, an absolute boundary exists where one person’s behavior harms someone else.  A patient who sells a portion of his/her Suboxone to score heroin, or for any reason, has crossed a line.

But what about the person just short of that boundary—the person who is still ‘hooked on the needle’ who is trying, most of the time, to stay off needles and smack but at 3 AM, in a room with other users—a room where he hit the needle hundreds of times before—hits the needle again?

There are plenty of reasons to terminate treatment for such a person.  He shouldn’t have done it, shouldn’t have been there, shouldn’t have been with those people… and many doctors would stop treatment at such a point, even knowing that doing so contributes to another overdose death.

We don’t treat other difficult patients the same way.  Our noncompliant teenage diabetics are given second, third… endless chances to get their insulin right.  People with post-op hemorrhages are rushed back to the OR for more treatment—not tossed to the curb, labeled ‘difficult patients.’

And I know from experience that some people hooked on the needle, in the position I described, can be saved.  For my struggling patient,maybe tonight wasn’t his night.  But tomorrow, the balance between cues, cockiness, and desperation might allow him to say ‘no’.  And with the right sequence of events, and maybe the right words of encouragement, he might put enough days together to make ‘no’ a regular thing.

Or he might not.  Maybe saying ‘yes’ one more time will end any lingering hope that he will pull it together and give life on life’s terms a try.  For this guy on Suboxone, there is still too much disease in the mind and body for any prediction beyond a guess.  And if, at any time, he happens across something larger and purer than he’s ever experienced before, the respiratory depressant effects of whatever he uses may cost him his life.

It is at this scene where I suspect the DA and I would have different opinions.  I’d expect many DA’s, viewing pictures of a cold body with a needle in the arm and a half-full bottle of Suboxone on the bathroom shelf, would say the guy had his chance and lost the right to take medication a long time ago.  I respect the DA’s position, and wouldn’t expect it any other way.  The DA’s doing what he is supposed to do.

But at the same time, I hope the DA understands MY thoughts, reviewing the same pictures.  I’d think that had my patient made it past tonight, he might have strung a few better nights together. And by the odds, I’d know that had I kicked him out of treatment for screwing up the first time, he would have died weeks ago.

Of course I don’t enjoy prescribing a medication for someone who doesn’t take it correctly, despite my strongest warnings and admonishments. But had I simply kicked him out of treatment and THEN read his obituary, I’d wonder if I’d done everything that I’M supposed to do.

Heroin photo available from Shutterstock

A late post tonight, since my new exercise program has pushed my blogging back by an hour or so each night.  My suspicions about exercise were correct, by the way; it is much easier to suggest exercise to other people than it is to actually exercise.  I’ve been at it since the beginning of the year, and I at least feel a bit less hypocritical.

While I’m on the topic…  I’ve received many comments over the years from people complaining that they’ve been taking Suboxone or buprenorphine for X many years, and they have no energy, they feel stressed, they have gained weight, they don’t sleep well or they sleep TOO well… and concluding that all of the problems are from Suboxone.

They aren’t.

The problems are the result of other things, including things that tend to occur naturally as our lives become less chaotic and more outwardly-secure.  The problems I mentioned above, for example, come from inactivity.  They come from thinking that we’ve ‘paid our dues’ at the age of 30, and it’s time to coast in life.  They come from failing to seek out challenges, and from failing to do our best to tackle those challenges.  They come from letting out minds be idle, smoking pot or watching American Idol  instead of responding to the naggings sense of boredom that ideally pushes people to join basketball, tennis, or bowling leagues.

Our minds and bodies are capable of SO much.  I (honestly) am not a network TV viewer, but I love the contrast of ‘before and after’ scenes on ‘Biggest Loser.’  People magazine (it sits in my waiting room) had a section a while back about people who lost half their body size, by exercise and dieting.  The part I found most interesting was the deeply personal answer that each person had to the question, ‘what was your turning point?’  Each cited an episode of humiliation or shame that lifted the veil of denial, and helped them do what they knew, all along, needed to be done.

We are not all capable of ‘Biggest Loser’ comebacks. But it is important for people to understand that feeling good, physically or mentally, takes work.   That incredible feeling of a ‘sense of accomplishment’ only comes when we accomplish something.  We don’t need to eliminate global hunger or cure cancer; sometimes we just need to shovel the driveway, mow the lawn, or do a crossword puzzle.  I’ve learned, as a psychiatrist, that the people who walk around with smiles on their faces usually did something that made the smile happen.  I’ve learned that ‘feeling happy’ does not just happen for most people.  And I don’t think I’ve ever met a person who answered, when asked about stress, ‘no—I don’t have anxiety.’

Once someone blames Suboxone for their problems, it becomes less likely that the real causes of those problems will become apparent. For example, If I think that my glasses are giving me headaches, I’m less likely to make changes in my diet that might make the headaches better.  Once we have something to blame, our problems become more and more engrained, and the real solutions become less and less evident.

I’m truly sorry if I am coming across as ‘preachy’; understand that I’m just trying to make my way through life like everyone else.  But I now take note of all those people power-walking at 6 AM, and I understand why they do it.  Some of them might be on Suboxone.  Some of them might not be.  But I respect all of them for opening their minds, and for their willingness to do the hard work that brings happiness—or at least points in that general direction.

There have been a number of events over the past couple weeks that have been ‘game changers’ in the efforts by Reckitt Benckiser to hang onto their profitable treatment for opioid dependence, Suboxone.  Reckitt Benckiser (RB) had asked the FDA to deny any future generic drugs based on Suboxone tabs because of deaths of several chldren, who might have confused the tabs for candy.

The FDA gave RB’s comments some thought and then discarded them, even stating that the efforts by RB might have been unlawful anticompetetive marketing.  The FDA wrote that they were referring their concerns about unlawful marketing to the FTC.

Ouch.

The FDA went on to approve two generic versions of Suboxone, or more properly, buprenorphine/naloxone tablets.  It will be interesting to see whether insurers and medicaid agencies go back to covering tabs (generic tabs), or whether they will continue to waste money on the heavily-marketed Suboxone’film.’

Just in case that isn’t enough drama for one week, the FDA announced that they will be holding hearings to determine whether to approve a buprenorphine implant called Probuphine..  I’d love to share details about the product, but at this point I don’t have further information.  The manufacturers of Probuphine are hoping that the medication will be used to treat opioid dependence.  On the surface, a number of advantages are apparent about such a product; one would expect a lower risk of diversion, for example, and better compliance.

NOT mentioned at this point, is whether the implant could help people who would like to discontinue Suboxone.  Many patients on Suboxone become resentful of the medication at some point, wishing they could be completely free from opioids.  I’m not a big proponent of such an idea, as I’ve witnessed far too much death and misery from relapse by people who stopped Suboxone.  But I could see how an implant would offer advantages for those people, depending on the release pattern of the medication.  For example, if the medication wears off slowly in the lower dose range, it may serve as a useful tapering device.  Such use would likely be off-label, and might even be illegal, depending on the wording of the product label.

The FDA hearings are open to the public.  Check back in a couple days and I’ll provide information about the hearings, including details about how you could become a participant.

Colored pills photo available from Shutterstock

A recent exchange with a reader:

I have been on buprenorphine for 5 yrs.  Recently my doctor stated that my u/a t looked like I have been ‘loading my meds.’  He said my levels where ‘backwards’ and that would happen if I took just a few doses just before my appt.   My doc had me come back in two weeks to go over my next u/a, and again it came back funky.  So my doc starts having me take my meds in front of the nurses on a daily basis.  Two weeks later with supervised u/a’s, my urine comes back the same.  My doc looked perplexed but kind of ignored the results like I was still doing something to mess with the results.  I had to come in again for another urine test and it finally came back normal.  My numbers were fine after that, and all was good until last week.

I went to my normal monthly check up and the u/a showed NO buprenorphine in my system.  My doc looked at me like I am the biggest liar.  I am perplexed.  I am taking my meds daily.  I don’t know what is going on and I need to figure it out soon before my doc kicks me out of the program. What could be wrong with the test, that is says that I have no buprenorphine in my body?

My response:

There are several directions we could go with this issue.  One aspect is whether it is always fair to believe the results of drug tests over the word of our patients.  I understand the reasons for testing, but I think that doctors sometimes lose the forest (the patient’s addiction problem) on account of the trees (quantitative testing).  This patient has been on buprenorphine for five years; I would hope to have sufficient trust established with patients after that period of time, such that the lab results wouldn’t be seen as the only answer.  There can be problems with any laboratory test.  Drug tests are one tool– not the ultimate arbiter of truth.

Most people metabolize buprenorphine a certain way, leading to the build-up of a chemical called norbuprenorphine.   I assume that by ‘backwards’ the doctor is saying that the buprenorphine level is higher than the norbuprenorphine level, whereas with daily use of buprenorphine the opposite would be true. As your doctor said, if a person takes one dose of buprenorphine and is tested an hour later, buprenorphine would be present, with only small amounts of the metabolite norbuprenorphine.

Urine tests for any substance are affected by many variables, including the actions that different parts of the kidney have on certain substances.  Some substances are concentrated at the kidneys, making urine testing more sensitive than blood testing.  But other substances might be re-absorbed by the kidneys to a varying degree, depending on hydration status, nutritional and dietary factors, hormonal factors, and personal genetics.  Because of concentration and reabsorption effects, the drug levels from urine tests are not accurate indicators of drug levels in the bloodstream.

In addition, the metabolic pathways for certain substances might be changed by the presence of other substances.   For example, if the enzyme that turns buprenorphine into norbuprenorphine is blocked or occupied by other substances, the pathway may change such that metabolites other than norbuprenorphine are formed—- including metabolites that won’t show up unless they are specifically tested for.

I asked the patient:

Are you taking any other medications?  Are you able to get the actual lab results showing the details of the test?

She replied:

I thank you for responding to me.  I am on many medications because I have fibromyalgia among many other things.  My list of meds:

Prozac 20 mg; Provigil 200 mg; Clonidine 0.1 mg 4x’s a day; Amlodipine 5mg once a day; Nabumetone 500mg 2x’s a day; omeprazole 20mg once a day; Ambien 10mg per day; Relpax when I have a migraine; Buspirone 10mg about 2x’s a day; Subutex 16 mgs per day. I also take diphenhydramine 50 mgs at bedtime when needed to help sleep, and Vitamin D3-1000 iu once per day.  I take this because my blood tests showed it was low.

I asked to see my results and my doctor told me that I didn’t need to see them; that he had told me what it said and that it should be enough for me to know.

The receptionist in the office is getting the number to the lab for me.  Do you have any questions that I should ask?  What should I know?  I am going to ask for a copy of my labs at my next visit.  I am nervous that my doc will just stop prescribing.  This medication has saved my life and I don’t know where I would be without it.  Please help me make my doctor believe in me again.  I know that is a lot to ask but I’m in trouble.  Where can I turn?  There aren’t any Suboxone docs in my area taking new patients.

(A couple thoughts)

Over my 20 years as a physician, I’ve come across times when tests were mistakenly trusted over the word of patients.  At a maximum security prison for women where I worked as a psychiatrist, for example, many women were disciplined for diverting clonazepam, until a call to the lab revealed that testing wasn’t reliable for that medication.

Over time, we learn more and more about how the metabolism of one medication impacts other medications.  One such interaction was apparent in this person’s case.

My comments:

The most obvious interaction from your list is that Provigil is an ‘inducer’ of cytochrome 3A4, the enzyme that breaks down buprenorphine.  A person taking Provigil develops greater amounts of that enzyme in the liver, which results in faster metabolism of buprenorphine.  The first step in metabolism of buprenorphine is conversion to norbuprenorphine, so levels of buprenorphine and norbuprenorphine would be affected by Provigil, in unpredictable ways.

From the program that I use to search for interactions:

buprenorphine ↔ modafinil

Coadministration with modafinil (the racemate) may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. Modafinil and armodafinil are modest inducers of CYP450 3A4, and pharmacokinetic studies suggest that their effects may be primarily intestinal rather than hepatic. Thus, clinically significant interactions would most likely be expected with drugs that have low oral bioavailability due to significant intestinal CYP450 3A4-mediated first-pass metabolism (e.g., buspirone, cyclosporine, lovastatin, midazolam, saquinavir, simvastatin, sirolimus, tacrolimus, triazolam, calcium channel blockers). However, the potential for interaction should be considered with any drug metabolized by CYP450 3A4, especially given the high degree of interpatient variability with respect to CYP450-mediated metabolism. Pharmacologic response to these drugs may be altered and should be monitored more closely whenever modafinil or armodafinil is added to or withdrawn from therapy. Dosage adjustments may be required if an interaction is suspected.
That is just one of many possible interactions. When a person takes multiple medications, there are often other, less predictable interactions.  Some medications also interfere with the testing of other medications.  You may know that there are chemicals available on the internet to block the testing for certain compounds;  some medications do the same thing.

She answered:

I can’t thank you enough for even responding to me……  You are a very kind man!  I hope this helps me.  I am very scared my doctor will take me off my meds.

But then she wrote again:

I wanted to send you an update.  My doctor wouldn’t even look at the conversation we had.  I guess for whatever reason, he refuses to look deeper into the issue.  It is sad when a doctor has had a patient for over 5 yrs and he won’t look into this further.  I don’t ever have dirty u/a’s.  I don’t drink, I don’t smoke marijuana, I only take what he prescribes to me.  He refuses to look further into the matter so much that it is clouding his judgment.  He won’t even test me another way.  He states urine test are the most accurate but there is something wrong because I know that I take my meds.  He refuses to do another supervised dosage week because he doesn’t have the manpower. 

I know in his eyes that all I am is a drug addict but I deserve respect. Why would a man who believes in science have such a closed-minded view?  I would think he would at least want to discover what is happening.  There has to be more patients like me that are being thrown away because we don’t fit a certain mold.  When he throws me out of treatment on Monday, I have nowhere to go.  There are large waiting lists to see a doctor in my area. I can’t go back on the streets for medication.  I don’t have any of those friends left in my life.  I am in so much trouble.

I don’t know why I felt the need to vent to you but my hope was to find one person that believes me in hopes that this problem could be addressed someday, somehow.  Thank you for listening.  I do appreciate it.

Drug test photo available from Shutterstock

In a recent Google search about Suboxone and pregnancy, one of the top links included the frightening statement that Suboxone and buprenorphine have been linked to SIDS or sudden infant death syndrome, commonly called ‘crib death.’

The statement was from a health forum where a woman wrote about taking Suboxone during pregnancy.  She wrote that her child went through opioid withdrawal after delivery, recovered, and then died two months later from SIDS.  She then claims that her doctors told her that Suboxone was a possible reason for her child’s death.

I don’t know if the woman’s story is true. If it is, I hope my comments do not cause her pain, and I’m sorry for her loss.  But someone should comment on the information, given the number of young women on Suboxone who become pregnant and frantically search the internet for reassurance that their baby will be OK.  I know that pregnant women in my practice lose a great deal of sleep because of guilt over taking buprenorphine.  I am not a SIDS specialist, obstetrician, or pediatrician, and I do not actively follow the SIDS literature.  But I have done some reading to prepare for this post, and I’ll do my best to address the issue.

While the causes of SIDS are not completely understood, a number of factors have been associated with sudden infant death, including maternal age and socioeconomic status (higher rates in infants of poorer, younger mothers), maternal smoking, air pollution, low birth weight, season of birth (higher in infants born in the winter), too high or too low room temperature, male sex, history of premature birth, and bottle feeding (instead of breastfeeding).

One of the biggest risk factors is the easiest to correct: sleeping position. The incidence of SIDS is thought to be about twice as high for babies who are placed prone (face-down).  Since 1992, when 4895 deaths were attributed to SIDS in the US, a public relations campaign to encourage parents to place infants on their backs may have reduced the incidence of SIDS by 50%.  I write ‘may have’ because some experts attribute the decrease to changes in how infant deaths are coded and reported, rather than to a true decrease in cases.

SIDS is a leading cause of death among healthy US infants.  But the actual risk is very low, estimated at about one death from SIDS per 2000 infants.  Deaths from prematurity or from congenital disorders are far more common than SIDS.

When I started this post, I planned to write that the link about buprenorphine causing SIDS was nonsense.  And it may be nonsense.  Realize that it is very difficult to determine the risk factors for things that rarely occur. Only relatively common factors like smoking or prematurity are identified as risks for SIDS in controlled studies.  Unless the connection is very strong (and it isn’t), there are not enough pregnant women on buprenorphine to cause a detectable rise in deaths from SIDS, even in the largest studies.

So what about the link in search engines about SiDS and Suboxone?  From what I can tell, the connection between buprenorphine, Suboxone and SIDS comes from a 2007 study in Finland that prospectively followed 67 women who had babies while prescribed buprenorphine.  In that study, 2 of the 67 infants were reported to have died from SIDS, an incidence of 3%.  A number that high is certainly frightening. But at the same time, an effect that strong would be evident in the larger SIDS studies—- especially those including thousands of women.

A closer look at the Finnish study reveals that the two infants who were thought to have died from SIDS were born to women who were not compliant with the buprenorphine program, i.e. who were using other opioids including heroin.  The associations between SIDS and other risk factors—risk factors that are common among active drug users, such as smoking, low socioeconomic status, low birth weight, and prematurity— confound the results of the study.  Are women struggling with active opioid dependence as likely to know that infants should be placed on their backs? Some SIDS researchers have questioned the numbers from the Finnish study, The forensic uncertainties often associated with SIDS, the significant risk of death associated with co-sleeping, and the challenge of monitoring women who are actively using opioids further confound the Finnish study.

One possible cause of death in SIDS is the accumulation of carbon dioxide in soft blankets or clothing, close to the mouth and nose of a baby sleeping prone (face down).  That cause of death suggests danger for an infant who is for some reason administered opioids, since opioids reduce respiratory response to carbon dioxide.  Opioids are secreted in breast milk, including buprenorphine.  The infants of mothers on Suboxone/Subutex would be tolerant to any buprenorphine in breast milk, since the exposure would be less, if anything, than the exposure during pregnancy.  But mothers who are noncompliant, i.e. intermittently dosing with high-potency opioid agonists, could in theory expose their infants to levels of opioids higher than the infants’ opioid tolerance.  I did not find any reported associations between opioid use, SIDS, and breast feeding.

My take on the data is that the safest situation for any infant is to develop in the womb of a woman who is not drinking alcohol, smoking cigarettes, taking prescription medications, or using illicit opioids.  Out of all of these things, being compliant with a stable dose of buprenorphine or Suboxone likely carries the least amount of risk.  If there was certainty that pregnant women could remain free from opioids after stopping buprenorphine maintenance, then stopping buprenorphine during pregnancy would be a good idea.

But unfortunately, far more women PLAN to remain opioid-free after Suboxone, than actually remain opioid-free.  The intermittent use of illicit opioids, and the malnutrition, cigarette smoking, poor sleep, poverty, needle-sharing, and other risky behaviors that come with opioid dependence create the worst-case-scenario, making the stable use of Suboxone or buprenorphine far safer in comparison to ‘planned abstinence.’

As with everything, there is the world we want, and the world we live in.  I encourage women addicted to opioids to do all in their power to maintain compliance in a Suboxone/buprenorphine program.  I also encourage these women to look forward to a life of doing the ‘next right thing’ for their children— and cutting themselves some slack over taking buprenorphine.  Efforts to stop Suboxone would be better used to avoid alcohol, tobacco, and illicit substances, and to maintain appropriate prenatal care.

Baby’s room photo available from Shutterstock

We can now leave naloxone out of the discussion, and focus on the side effects of Suboxone that are caused by buprenorphine.

Side effects are symptoms caused by a given medication that are not part of the therapeutic benefit of that medication.  Whether a symptom is a side effect depends on the reason for taking the medication.  For example, decreased intestinal motility is the desired effect of opioids used to treat diarrhea, but a bothersome side effect when taking opioids for pain.  The term ‘side effect’ is not on the package insert for medication, the symptoms and actions instead referred to as ‘adverse reactions.’  Package inserts also have a section entitled ‘warnings and precautions’ where the most dangerous adverse reactions are listed.

Some medications have a ‘black box warning’ for adverse reactions that are particularly common or particularly dangerous, consisting of a frightening statement at the start of the package insert (enclosed, naturally, by a black box). Black box warnings in psychiatry include the warning for increased suicidal ideation in children and adolescents treated with antidepressants, and the increased risk of death in people with dementia treated with atypical antipsychotics.

Increased risk of cancer or mutations, and effects on fertility or fetal development, are listed in yet another section entitled ‘nonclinical toxicology.’  They are listed as ‘nonclinical’ because the events do not involve the intended physiologic system or pathway targeted by the medication.  For example, slowing of intestinal activity by opium is either treatment of diarrhea or unwanted constipation, but in either case the outcome is caused by actions of opioids at opioid receptors.  If the opium molecule happened to bind to DNA and cause cancer, the cancer would be nonclinical toxicology, not a side effect.  Carbamazepine decreases the excitability of neurons to prevent seizures, and the sedation caused by the slowing of neurons is considered an adverse reaction. Carbamazepine impairs fetal development through different actions, considered nonclinical toxicology.

All of these divisions can be picked apart so that division of symptoms to one category or another will appear arbitrary.  The system is not precise, by a long shot.  But it may be helpful to be aware that one person’s ‘adverse reactions’ are another person’s intended therapeutic effect.  Some people find the mood stabilizer quetiapine too sedating;  others find the sedation critical to a good night’s sleep.

Allergic reactions are yet another issue.  To put it simply, medication allergies are not something that the medication does to the body, but rather something that the body (the immune response) does to a medication—and the inflammatory fall-out from that reaction.  While the distinction sounds like splitting hairs, the true nature of a reaction can be important.  Nausea is a common adverse event from the action of opioids, used for pain control, at opioid receptors.  Through intellectual laziness, a patient with nausea from morphine in a hospital is often incorrectly labeled as having a morphine allergy. Because of the bureaucracy of modern medicine, the patient has had a very useful medication removed from the armamentarium of treatment options, in essence forever.  Analogous situations are ‘allergies’ to antibiotics like erythromycin.  Allergies tend to become worse with each medication exposure, whereas adverse reactions often go away over time.

Things actually get pretty simple from here. Buprenorphine, like other opioids, has a range of predictable effects that occur along the dosage spectrum— a spectrum that is relative to the person’s opioid tolerance.  Doses of buprenorphine low on the person’s tolerance spectrum fail to have the desired action of preventing withdrawal.  Doses that are close to a person’s tolerance level have the desired therapeutic effect, i.e. blocking withdrawal and a reduction in cravings for opioids.  Doses in this range commonly cause ‘ileus’, i.e. disruption of the normal movement of the intestine.  Ileus in turn causes a number of symptoms, including constipation, cramping, bloating, loss of appetite, and nausea.  Constipation can lead to increased intestinal pressure, leading to hemorrhoids or diverticular disease.

Apart from ileus, buprenorphine and all opioids have direct actions at the base of the brain, at the ‘area postrema’.  Actions at the area postrema cause nausea as an adverse reaction, or in other cases the desired therapeutic effect of induced vomiting.  Nausea is very common when doses of opioids are taken that are at the upper end of tolerance, making nausea particularly common with potent opioids like buprenorphine.  Impaired coordination, slow reflexes, sedation, slurred speech, and somnolence are also caused by strong opioid effects.  Combinations of these effects are obviously quite dangerous.

Opioids reduce the tone of the ‘gastroesophageal sphincter’, increasing the chance of acid reflux, heartburn, hoarseness, and theoretically even esophageal cancer in severe cases.

Cough suppression by opioids might be a therapeutic benefit, but can be an adverse reaction if gastric contents are aspirated into the lungs.

Opioids reduce the response of the brain’s respiratory centers to carbon dioxide, resulting in less drive to breathe.  Carbon dioxide level therefore goes up, and the rise in CO2 increases brain blood volume and in turn, intracranial pressure.  The increased brain pressure reduces the flow of fresh, oxygenated blood into the brain.  Because of this potentially-disastrous sequence of events, opioids must be used with caution in people with head injuries.

Respiratory depression is a common reason for overdose, but even that adverse event can be a desired therapeutic benefit in some cases, for example in patients who are on a ventilator and triggering the machine to cause hyperventilation.  Respiratory depression is even used therapeutically to reduce ‘air hunger’ in people at the end of their lives, to relieve suffering in patients and patients’ family members who are witnessing the death.

I realize that a simple list of side effects would have been easier to read, but like the proverb says about giving a man a fish, I’m hoping that running through the processes will help people figure out, for themselves, what their medications are doing.

What else…  pruritis or ‘itching’ is a common side effect of potent opioids, that doesn’t respond very well to the usual anti-itching treatments like diphenhydramine or steroids.  All common opioids except meperidine (Demerol) constrict pupils, which often makes daytime vision sharper, but impairs night vision by allowing less light to fall on the retina.

Opioids reduce immune function through a number of physiologic interactions, including the presence of opioid receptors on immune tissue. Opioids can have a range of effects on mood and mood disorders.  All opioids, including buprenorphine, have the potential to reduce testosterone levels in men, which in turn can affect mood, libido, and sexual performance.  Opioids alter the release of vasopressin, changing how much water is conserved by our kidneys—which in some people results in more trips to the bathroom at night.

Buprenorphine and other potent opioids interfere with the initiation of ‘micturition’, i.e peeing, particularly in men who are already struggling from an enlarged prostrate.

I know that I’m missing something, and I invite people to write and help me out.  I also realize, as I write this, that I don’t have a package-insert category for a particularly common worry about Suboxone, that it is hurting one’s teeth.  Such a reaction, were it found to be attributable to Suboxone, would probably be considered nonclinical toxicology, although a recent case report proposed that buprenorphine could increase cavities by reducing the immune response in teeth, which sounds more like an adverse reaction.  In either case, I’ve written about the lack of evidence for tooth damage from Suboxone, but the topic still appears on my forum now and then.

That’s all for now…

Depressed woman photo available from Shutterstock