Regular readers of my blog know that I believe buprenorphine is the most important development for treating addiction during my lifetime. At the same time, my own recovery from opioid dependence began over 20 years ago, long before the use of buprenorphine. I am grateful for the change in my perspective that occurred one desperate afternoon, when I first recognized the uselessness of ‘will power’ for stopping opioids. I was one of the lucky addicts who experienced a ‘spiritual awakening’— the realization that I could not recover through my own power, no matter my education or motivation.
I’ve searched, since then, for a scientific explanation of how acceptance of powerlessness and belief in a higher power removed, almost instantly, an obsession that I couldn’t control before that moment. I recognized the preciousness of my recovery as friends from treatment lost their sobriety. And I learned, at one point, that success in ‘traditional recovery’ requires lifelong attachment to meetings and step work.
Ten years later I was excited by the power of buprenorphine to induce remission of the same obsession. As patients on buprenorphine regained meaningful lives at a pace similar to those who practice traditional recovery, I realized that recovery from addiction and freedom from ‘character defects’ can stem from changes in thought, or from changes in neurochemistry. I realized that one approach isn’t more ‘natural’ than the other, and that both methods require lifelong efforts to prevent relapse to addictive behaviors. I wrote the following, several years ago, to explain what I was seeing.
Recovery in the era of buprenorphine
Most opioid addicts are familiar with Suboxone, a medication that erases cravings for opioids, and when used properly creates a state of remission from active addiction. My initial thoughts about Suboxone were influenced by my own experiences as an addict in traditional recovery. But that opinion has changed over the years, because of what I have seen and heard while treating over 700 patients with buprenorphine in my clinical practice.
Suboxone has opened a new frontier of treatment for opioid addiction, but arguments over the use of Suboxone split …
I recently heard parts of a lecture by a healthcare provider (not a psychiatrist), who was speaking to a group of general practitioners about psychiatry. She answered questions about the best approach for treating depression, anxiety, and other psychiatric disorders by relating anecdotes from her own experience and suggested by her favorite mentor. “Add a little of this, and if that doesn’t work, try adding some of that” she said. “Psych is all a gray area. You can be creative.”
Now THAT’S crazy. Her recommendations, sadly, will likely be followed in a number of actual patients. No wonder patients coming to treatment often have a distrust for psychiatry, or a sense of being a ‘guinea pig’ during earlier treatments for psychiatric conditions.
At some point over the past decade, we began using the term ‘evidence-based medicine.’ The term is likely over-used for marketing purposes, but the original concept of evidence-based medicine is of great value, particularly in psychiatry.
Medical scientists, i.e. practitioners who have training in conducting and interpreting scientific research, know the risks of letting personal experiences guide treatment approaches. They know that human beings have a natural tendency to assign greater importance to personal observation than to the experiences described by others, even if the personal observation involved one patient, no blinding, and no control group. Even people with advanced degrees, who recognize the value of blinded studies and appropriate control groups, tend to rationalize that they know, in THIS case, that their observations are valid.
Evidence-based medicine encourages practitioners to ignore their own experience, and to instead anchor practice patterns to those supported by peer-reviewed research. Practitioners should know the difference in predictive value for comments by a mentor, the findings in a case report, and the results of a large, prospective clinical trial. Practitioners should appreciate the perils of using their knowledge of basic science to extrapolate findings from one set of conditions, to a case where some variables differ.
These distinctions are especially important in an era where insurance companies increasingly try to influence treatment patterns. For example, there is considerable evidence that Abilify effectively augments the …
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?
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, …
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 …
In my last post, I wrote about the work-up of a patient who experiences symptoms similar to opioid withdrawal that start about an hour after each dose of Suboxone. We decided that the symptoms were signs of withdrawal—i.e. reduced activity of mu-opioid pathways—and that the symptoms were triggered by taking a daily dose of Suboxone (buprenorphine/naloxone).
Note that I wrote that the symptoms seemed to be caused by reduced mu activity, i.e. not necessarily by reduced mu-receptor binding. Endogenous opioid pathways are very complex. Decreased activity in opioid pathways may arise from decreased binding of agonist at the receptor, or from changes in a number of other chemical or neuronal pathways.
This diagram shows the processes that are triggered by mu-receptor binding in humans before and after opioid tolerance. The diagram only shows the complexity of processes within the neuron with opioid receptors; realize that each neuron 1. Has receptors for many other neurotransmitters as well, and 2. Receives input from thousands of other neurons. As we sort through possible causes of our patient’s symptoms, keep in mind the complexity of neural pathways.
While we are on the subject of complexity, the web site linked above is an incredible resource for those interested in biochemistry. The site includes diagrams of a number of metabolic pathways that describe how different molecules, including neurotransmitters, are manufactured by the human body. I encourage people to browse the site. You will gain insight into why the actions of substances are difficult to fully predict.
The withdrawal symptoms experienced by our patient might arise from dysfunction in any one of the many chemical pathways that affect opioid tone. But since a dose of Suboxone contains naloxone, a mu-receptor inverse agonist, it is possible, maybe even likely, that the naloxone is related to symptoms.
Naloxone is less lipid-soluble than buprenorphine and so only a small portion—about 3%– of a dose is absorbed through mucous membranes. The rest of the naloxone is swallowed, consciously or inadvertently, and eventually absorbed from the small intestine, to pass to the liver via the portal vein. …
I struggle with the length of my posts. I shoot for 1000 words—an amount of reading that most people can knock off in a typical trip to the bathroom— but I find it difficult to limit posts to that size. So as I have done in the past, I will break this post into a couple of sections. In the first, I’ll lay the groundwork for investigating symptoms of withdrawal in a patient taking buprenorphine. The second post will go into greater detail.
A patient recently contacted me to complain that he was experiencing withdrawal symptoms for several hours after each dose of Suboxone. I will describe my thought process, in case the description helps someone else experiencing similar symptoms.
My first decision point is whether or not the person is truly experiencing symptoms of withdrawal. Some people will misinterpret symptoms from excess opioid stimulation as withdrawal symptoms, for example. Nausea is a not-uncommon complaint among people taking buprenorphine, and patients often assume that nausea is the result of insufficient opioid activity, and so take higher doses of buprenorphine. But nausea is actually more common in opioid overdose than during opioid withdrawal, along with constipation, whereas withdrawal primarily causes diarrhea.
Pupil diameter is a good indicator of withdrawal vs. overdose; small or ‘pinpoint’ pupils suggest an excess of opioid activity, whereas withdrawal is associated with very large pupil diameter.
Other symptoms are also misinterpreted as withdrawal. Many opioid addicts develop a strong fear of withdrawal over years of using, and so ‘withdrawal’ is often the first thing to come to mind, during unpleasant symptoms. I also believe that the experience of withdrawal becomes learned in a way that allows the symptoms to re-occur after certain triggers. I remember an experience years ago, when I awoke from a dream experiencing significant withdrawal symptoms, even though I had not taken an opioid agent for years. I feel back asleep, and was grateful to find that the symptoms were gone, when I woke the second time.
People are angered by the notion that their symptoms have ‘psychological’ origins. But as …
The FDA recently released a Drug Safety Announcement regarding the use of codeine in young children after tonsillectomy/adenoidectomy surgery for obstructive sleep apnea. I was somewhat surprised to see a safety announcement on a medication that has been in use for decades, but the release underscores our improved knowledge of drug metabolism, and the broadening demographics of the United States.
Codeine has little activity at opioid receptors. The analgesic effects of codeine are actually caused by morphine, after the conversion of codeine to morphine at the liver. The conversion is catalyzed by an enzyme called CYP2D6, part of the cytochrome system of enzymes that are involved in the breakdown of a number of compounds.
I have written about the addictiveness of narcotic pain medications. People addicted to opioids often go to significant lengths to obtain prescriptions for narcotic pain relievers from healthcare practitioners. Emergency room physicians and nurses become aware of the efforts of ‘narcotic-seekers’, which range from faking pain symptoms or dental injuries to self-catheterization and instilling blood into the bladder to fake kidney stones. Distinguishing those with real pain from those who are addicted and not experiencing pain is a serious situation, but doctors roll their eyes at some of the more-typical presentations. One such situation is the patient who reports an ‘allergy’ to all of the weaker narcotics, and claims that ‘the only drug that works is (insert Dilaudid, morphine, oxycodone, or another potent opioid here).
Codeine is one drug that is commonly rejected as ‘ineffective’ as part of a request for something stronger. When I was a medical student, we assumed that requests for something other than codeine were disingenuous. But at some point, maybe 15 years ago, I remember reading an article that described the conversion of codeine to morphine by the liver. The article reported that the enzyme that performs the conversion exists in varying forms across the population, with some ethnic groups having more active forms of the enzyme than others. Some people have very low levels of CYP2D6, and therefore get very little analgesia from codeine. In …
I recently accepted a young man as a patient who was addicted to hydrocodone (the opioid in Vicodin), prompting a discussion about treatment options for someone who hasn’t been using very long, and who hasn’t pushed his tolerance all that high. Perhaps it will be informative to share my thought process when recommending or planning treatment in such cases.
In part one I’ll provide some background, and in a couple days I’ll follow up with a few more thoughts on the topic.
Most people who have struggled with opioids learn to pay attention to their tolerance level—i.e. the amount of opioid that must be taken each day to avoid withdrawal or to cause euphoria (the latter about 30% more than the former). For someone addicted to opioids, the goal is to have a tolerance of ‘zero’—meaning that there is no withdrawal, even if the person takes nothing.
That zero tolerance level serves as a goal, making having a high tolerance a bad thing, and pushing tolerance lower a good thing.
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 depression 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 depression, 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.
“Buprenorphine acts similar to opioid agonists in lower doses, with the same addictive potential as oxycodone or heroin. In higher doses—doses above 8 mg or 8000 micrograms per day—the ‘ceiling effect’ eliminates interest and cravings for the drug.”
I’m not sure I followed this. Can you explain more? What would you think about someone who is taking 1-2mg of Suboxone twice a day without a prescription, and says they want to stay on that dose once they find a prescriber? Are they better off on 8mg or more per day, or would it be ok for a prescriber to keep them at the lower dose? Is the answer the same if they hope to taper off the medication completely within a year (they don’t feel able to do this on their own right now, but hope to be able to when some life circumstances change). Thanks!
This gets a bit complicated, but I’ll do my best. A couple background issues; buprenorphine has a ‘ceiling’ to its effect, meaning that beyond a certain dose, increases in dose do not cause greater opioid effect. That is the mechanism for how buprenorphine blocks cravings.