Newborn Buprenorphine Abstinence: Get Real!

First Posted 2/6/2014
A few weeks ago I wrote about the differing standards of care for women who deliver babies while treated with buprenorphine for opioid dependence.  Some hospitals require newborns exposed to buprenorphine to stay in the neonatal ICU for arbitrary length of time.  Intravenous infusions of opioid agonists are given to infants whose first yawns or cries are interpreted as neonatal abstinence syndrome.  Other hospitals allow women on buprenorphine to take babies home at the regular schedule, allowing a natural taper from buprenorphine by breast-feeding.
Regardless of hospital policy, many women on buprenorphine enter into the delivery process with a sense of dread, knowing they are harshly judged by doctors and nurses.  Doctors warn women that their babies will suffer from withdrawal if they don’t taper off their medication before delivery.  And members of the media decry the selfishness of women treated for addiction who become pregnant, suggesting the more responsible expectant mothers would use ‘will power’ to avoid all substances.
Even while experts recommend that women treated for addiction stay on medication treatment regimens during pregnancy, society looks negatively on women who do the right thing.   A new mom on SuboxForum recently wrote about how horrible she felt, for putting her baby through such a difficult time.  But should women compliant with recommended treatment for opioid dependence feel so guilty?
Until 30 years ago or so, newborns having major surgery often received paralytic agents with little or no anesthesia or pain medication.  Surgeons and anesthesiologists did not think babies with heart anomalies would survive anesthetics, and saw no reason to anesthetize a brain that lacked a ‘record’ function.   Now, most babies having major surgery receive anesthesia.   But in many situations, non-medicated babies are simply restrained during procedures that would be painful in adults, ranging from awake intubation to circumcision to multiple attempts at IV access (the latter is required when doctors insist on treating neonatal abstinence with morphine infusions).
I did not enjoy working on newborns in those settings back in my anesthesia days, especially after having three children.  But there will always be times when anesthesia is too dangerous or impractical, leaving no choice but to tune out the baby’s cries and focus on safety.  In these cases, do babies experience pain?  We know that babies react to stimuli that adults would find painful, and generate stress responses to those stimuli.  But the answer to the question about pain is far more complicated than a simple ‘yes’ or ‘no.’
People having conscious sedation for colonoscopy, gastroscopy, or some emergency procedures (like reduction of a displaced fracture, emergency D and C, or insertion of a chest tube) often appear awake while appropriately sedated.  Patients who will later think that they were blissfully sleeping, in reality, carry on conversations and move about as directed on the OR table.  Depending on the anesthetic used, patients may react strongly to pain.  Patients who can’t be fully anesthetized because of the risk of aspiration or airway obstruction may yell out in response to the injection of local anesthetic, even when administered enough Versed and Ketamine to guarantee full amnesia.   They moan in pain throughout the procedure, and then thank their anesthesiologist for keeping them completely ‘asleep’.  Similar experiences are the norm in every GI suite across the country.
In this common scenario, do patients experience pain?  When someone sedated beyond the point of recall complains of discomfort, did the discomfort really happen?   Did the patient feel pain and then forget it?  How do we know?  Before my endoscopy, I knew that I would experience pain going forward in time.   But afterward, when I thought back about the procedure, it was a piece of cake.  Did I suffer?  Not at all.
Similar experiences occur in newborns.  Babies are not capable of remembering those first weeks or months.  One could argue that repeated discomfort creates brain pathways that lead to a heightened stress response in later years… but if that is true, how does the brain differentiate ‘normal’ pain experiences of the newborn from ‘abnormal’ pain?  The baby’s head is squeezed hard enough during delivery to change the shape of the skull.  That has to hurt… not to mention the discomfort of being squeezed inside a uterus during the last 4 weeks before delivery.  During delivery, the baby is transferred from a 37 degree uterus, where oxygen is delivered through the umbilical cord, to a bright, cold, environment where getting oxygen requires gasping for air, with every bit of strength.  Sounds traumatic to me!  During deliveries, babies sometimes experience dislocated shoulders and major nerve damage (shoulder dystocia).  Forceps or suction cups may be used to pull the baby, by the head, from the birth canal.
Newborns have immature nerve supply to the gut, so early peristalsis– the coordinated contracting that propels digestible material downstream in the fully developed intestine– creates cramping and ‘pain’ in infants (sometimes called ‘colic’).  Limb muscles are spastic, and the spasticity would likely be painful in an adult.  Choking or coughing on breast milk is a normal part of the newborn experience.
How does ‘withdrawal’ compare?  What is the worst part of withdrawal— diarrhea?  Cramping?  Body aches?  Anxiety?  Depression?  Compared to the normal experience of a newborn, how do these symptoms rate?  Babies do not feel embarrassed or ashamed of their condition.  They don’t feel guilty or remorseful.   And after raising children through, I don’t think a baby coming off buprenorphine could be more ‘depressed’ than other babies.  Can a baby who turns purple crying his lungs out, feel any worse?  Normal infants get pretty miserable at baseline!
Like most parents I have always been willing to put my life or discomfort before that of my kids, if that were possible.  I don’t lack empathy for babies experiencing pain.  But ‘to keep it real’, writing about those ‘poor babies going through withdrawal’ is an emotional response, not an accurate understanding of the newborn experience.
Most new moms torture themselves enough with fears about their mothering skills, without the medical profession piling on.

Killing the Suboxone Gift Horse with Naltrexone

First Posted 11/14/2013
I received an email update today with important news from the world of psychiatry and addiction.  The email highlighted a study from the October issue of Jama Psychiatry, entitled ‘A Randomized, Double-blind Evaluation of Buprenorphine Taper Duration in Primary Prescription Opioid Abusers’.  The study compared relapse rates in opioid addicts who were tapered off buprenorphine at different rates.  The study considered success as being free of opioid use and taking naltrexone, an orally-active opioid antagonist, after 12 weeks.  The study found that 50% of the people tapered off buprenorphine over 4 weeks were abstinent and taking naltrexone.  That compared to 21% and 17% of success in patients tapered over 1 or 2 weeks, respectively.
I’m sorry, but who cares?
Regular readers of my blog know my opinion about buprenorphine.  (Newcomers please note that by buprenorphine I mean buprenorphine, Suboxone, or Zubsolv, since they all work in identical fashion).  Most people who work in the addiction field agree that addiction is a life-long illness.  Most people who have worked in the field for a few years or more know that relapse is a common feature of opioid dependence.  I believe that anyone claiming to ‘cure’ opioid dependence through use of a plant, root, amino acid, vitamin, hypnosis, accu-pressure point, or 90-day program is either misinformed, pathologically optimistic, lying, or blinded by profit motives.
Opioid dependence is associated with a high rate of death and morbidity. Beyond buprenorphine, the only reliable intervention for treating opioid dependence is methadone maintenance, if ‘reliable’ is defined as ‘likely to be successful.’  I realize there are hundreds if not thousands of residential treatment facilities throughout the US that advertise ‘freedom from addiction’; some even offering freedom from ‘addiction’ to buprenorphine.  These claims are made, and apparently believed, even with one-year relapse rates greater than 90% in opioid addicts treated without medication.  In the real world of ‘Suboxone Talk Zone’, I have to burst a few bubbles about ‘sending someone to treatment.’    For opioid dependence, treatment without medication yields long-term sobriety in only a small minority of patients.
Yet many healthcare professionals continue to chase after the golden goose of abstinent recovery.  Makes me wonder if laetrile would still be around with better marketing!
Before buprenorphine, opioid dependence was an oft-fatal illness that in most people responded only to the administration of opioid agonists at frequent intervals, with no patient autonomy and the threat of discharge if anything prevented on-time arrival at the early-morning line-up.  In 2003, along came buprenorphine— a prescription medication with a reasonable generic cost (finally), with few or no long-term risks and tolerable side effects, that eliminates cravings and prevents illicit opioid use in 50% of an average study population of opioid addicts who are allowed to continue their medication.  So why, exactly, are we excited by the prospect of changing from buprenorphine to a medication that carries the risk of hepatic necrosis?
Are people on naltrexone better off than people taking buprenorphine?  One would hope so, given that 50%-83% of people in the current study went back to active using while trying to make the switch!  Patients on naltrexone still have the problem of blocked mu receptors during emergency surgery.  Having blocked opioid receptors is an even larger problem for many educated addicts than their doctors realize, that goes something like this: ‘I stopped opioid agonists, but now I have to block my endorphins too?!
Why not just keep stable buprenorphine patients on buprenorphine?
The argument for naltrexone over buprenorphine comes down to two issues.  The first is the quasi-spiritual attitude that people are in an inferior form of treatment if their mu receptors are bound by even a partial agonist—no matter that those receptors have developed complete tolerance to the agonist effects of the drug.
The second argument focuses on diversion.  Buprenorphine is sold on the street, particularly in areas where there are no doctors certified to prescribe the medication.  People divert buprenorphine in a number of ways, ranging from efforts to get high, to use ‘in between’, to attempts at self-treatment.  But should risk of diversion reduce the legitimate use of a medication that has saved thousands of lives? Is it logical to throw the bupe-baby out with the bath water when deaths from buprenorphine are less common than deaths from acetaminophen?
I expect that the risk of diversion decreases over time in patients treated with buprenorphine.  Patients in long-term, stable treatment are more likely  employed and insured, with less financial incentive to sell controlled substances and more to lose for doing so.  Most of my stable patients develop insight into the damage caused by addiction, and have no interest in getting someone else caught in the same trap.  Most of the patients I’ve treated over time have severed their connections with the using world.  And most of them are grateful for a second (or tenth) chance at life; grateful enough to avoid risking everything by selling drugs.
Even if diversion could be blamed, in part, on stable buprenorphine patients, why is addiction treated differently than other diseases?  Diversion of opioid agonists is a greater problem than diversion of buprenorphine, both by sheer volume and by the damage from diversion, yet the FDA just approved another potent mu agonist in Zohydro—a drug with far greater diversion potential than buprenorphine or Suboxone.  If diversion doesn’t disqualify the pain meds used for strained backs, bumps, and bruises, why should diversion derail one of the only effective treatments for a disease that is killing thousands of young people?  Heck, pseudoephedrine is sold from pharmacies with a signature; the dangers of methamphetamine didn’t eliminate our collective concern for people with stuffy noses!
If we take diversion out of the argument—for example by deciding that the 300-odd deaths from buprenorphine diversion don’t warrant removing an effective treatment for a disease that has become the leading cause of death in young adults— the push off buprenorphine makes little sense.  I suspect that the people advocating ‘progressing’ from buprenorphine to naltrexone do not envision patients treated indefinitely with naltrexone either, but rather see naltrexone patients as somehow ‘closer’ to abstinence than buprenorphine patients.  From a neurochemical standpoint, what is the difference between being fully tolerant to a partial agonist vs. taking an antagonist?  For relapse-prevention, advantage goes to buprenorphine, since ‘effective relapse’ to opioid agonists requires buprenorphine patients to first go through days of withdrawal.  Naltrexone patients on the other hand can miss the morning’s naltrexone, and later that night relapse using mu receptors that are even hyper-sensitive to agonists.
As for arguments that patients on buprenorphine are impaired, I would love to see my attorney-patients take part in THAT debate.  Concerns of impairment have come from poorly designed studies where buprenorphine groups consisted of patients with no tolerance to the medication. I suspect that medical reporters too often read the abstract and skim the ‘materials and methods’—let alone the statistics!
If ‘success’ consists of moving to naltrexone—a medication that many real-world addicts reject–   how long is naltrexone continued, and what happens when it is stopped?  Do people go back to heroin again?  If not, why not? The cycle of ‘use, treat, cease treatment, use, and repeat’ should be a black box warning on naltrexone— as soon as they finish stamping the warning on the steps of every residential treatment center.
I’ve been accused of being too long-winded.  The short version for those who skipped to the bottom:  buprenorphine-based medications offer an effective, tolerable, long-term treatment for a chronic, life-long disorder.  How many people will die in their quest—or their doctor’s quest—for ‘abstinent recovery’ with or without naltrexone?  Emphasis on naltrexone is just one more example of looking the gift horse of buprenorphine treatment in the mouth.
Sigmon SC, Dunn KE, Saulsgiver K, Patrick ME, Badger GJ, Heil SH, et al. A Randomized, Double-blind Evaluation of Buprenorphine Taper Duration in Primary Prescription Opioid Abusers. JAMA Psychiatry. Oct 23 2013;