Archive for the ‘Rapid Detox’ Category

Medications to treat Opioid Addiction

    This blog entry describes medications (other than methadone and buprenorphine) that treat opioid dependency. None of these medications are opioid stimulating drugs, and therefore have no potential for addiction.

 Clonidine

     Clonidine has been used for decades as a blood pressure medication. It’s cheap and effective, but has some unpleasant side effects: sedation, dry mouth, and constipation. Because newer blood pressure medications have fewer side effects, clonidine is used less today than in the past to treat high blood pressure. However, it’s at least moderately effective at treating many of the symptoms of opioid withdrawal.

     Among many other places in the central nervous system, opioids act on a part of the brain called the locus ceruleus. The locus ceruleus, which in Latin means the “blue place,” is part of the autonomic nervous system. When locus ceruleus neurons are stimulated, norepinephrine is released into the brain, and this causes overall stimulation of the brain. Opioids slow the firing of these neurons in the locus ceruleus, reducing the release of norepinephrine. When the body gets opioids regularly from an outside source, the locus ceruleus makes adjustments, to make up for extra opioids. Then, if the supply of opioids is suddenly stopped, the locus ceruleus becomes unbalanced, and releases an overabundance of norepinephrine. The heart rate and blood pressure increase, along with other symptoms: runny nose, yawning, tearing of the eyes, diarrhea, and nausea.

     Since clonidine works by calming the locus ceruleus, clonidine reduces many of these unpleasant opioid withdrawal symptoms, though it rarely eliminates all withdrawal symptoms. In the past, when it was the only medication available for opioid withdrawal management, patients rarely stayed at a detox facility long enough to complete their withdrawal. It was difficult to retain the addict in treatment. Now, most state-of-the-art detoxification units use Suboxone to ease withdrawal symptoms because it’s more effective, and helps retain patients in detoxification, a necessary step prior to the more intense inpatient rehabilitation.

 Opioid antagonists (blockers)

     Opioid antagonists are drugs that firmly attach to the opioid receptors, but don’t activate these receptors. Antagonists prevent other opioids from reaching and activating the receptors. Antagonists remove opioids from the receptors, so if antagonists are given to an actively using opioid addict, the addict will become sick with withdrawal. This is called “precipitated withdrawal” because it was caused, or precipitated, by a medication.

     Naltrexone is the most commonly used oral opioid blocker. It’s taken orally, in pill form. It’s started after an opioid addict has completed opioid withdrawal. It can be a difficult medication to take, because it may also block endorphins, our own naturally made opioids. Some patients complain of headache, muscle aches, and fatigue while taking naltrexone. Many times these unpleasant symptoms will subside, with more time on the medication. The medication can be started at a half dose for the first week or so, and then increased to the full dose. Most patients tolerate this better.

     Naltrexone has been used in this country mainly for relapse prevention, particularly for addicted professionals. Many professionals, such as doctors and pharmacists, who have been treated for opioid addiction, are started on naltrexone when they return to work. These professionals may need to work around opioids, and if they relapse while taking naltrexone, the opioids will have no effect. The antagonist thus serves as extra insurance against a relapse. Many licensing boards for impaired professionals insist they take naltrexone as a condition of being allowed to return to work in their fields.

     Naltrexone works well, but only if the patient takes it every day.  If the addict “forgets” to take her dose for one or two days, it’s then possible for her to get high from ingested opioids. Because of this, the medication is also available in an implantable form. Pellets containing naltrexone are placed just under the skin and the medication is released into the body over three months. With this method, compliance is obviously higher, since the addict would have to dig the pellets out to be rid of the blocking drug. Not many centers place these pellets, so access to this treatment may involve some travel.

     A long-acting, monthly injection of this drug has just been approved for the treatment of opioid addiction. It’s marketed under the brand name Vivitrol, and it’s also used for alcohol addiction.

     Obviously, compliance with naltrexone will be much better with this method, because after it’s injected, there’s no turning back. Studies are ongoing to see what the success rate will be with this easier option.

Unfortunately, the injection is quite a bit more expensive than the daily pills. Another concern with the opioid antagonists described above is pain control. What if the patient is in a bad accident, and needs opioid pain medications, or needs surgery? Most patients will have to be admitted to the hospital, with close monitoring, because it takes large doses of opioids to override the effect of these opioid blockers. Pain control is obviously more complicated in such a situation.

     Naloxone is the intravenous form of an opioid antagonist, better known by its brand name Narcan. It’s injected to rapidly reverse the effects of opioids. Emergency workers often carry Narcan with them to use if they encounter a person who has overdosed with opioids. This medication can be life-saving, but it also puts the opioid addict into immediate withdrawal. 

Detoxification under anesthesia

     Because of the fear that many opioid addicts have of opioid withdrawal symptoms, some treatment programs have used a method of inducing physical withdrawal while the patient is under anesthesia.

     With rapid or ultra-rapid detoxification, the patient is first given some type of general anesthesia, and then given doses of an intravenous opioid antagonist like naloxone. The naloxone puts the patient’s body into withdrawal, but since he’s unconscious, he won’t be aware of it. Hours later, the patient is brought out of anesthesia. Proponents of this method of detoxification say that the patient has no further withdrawal once he is out of anesthesia. However, several studies show significant post-procedure symptoms, with nausea, vomiting, and insomnia. These symptoms can continue for days after the procedure. (1)

      This method appeals to many addicts because it’s advertised to be quick and painless. However, most evidence shows patient outcomes using rapid or ultra-rapid detoxification have the same results as techniques using buprenorphine to transition off of opioids and onto naltrexone. (2) Plus, ultrarapid detox costs much more. In many places, the procedure costs tens of thousands of dollars. This method also has the added risks of general anesthesia.

     Treatment centers that perform rapid detox advertise claims of “100%” success, speaking of numbers of patients that complete treatment.  But if the patient is under anesthesia, of course 100% will complete the treatment. They aren’t going anywhere, since they are unconscious. Many proponents of rapid detox exaggerate and inflate success rates in this way. However, most studies show that at one year, success rates with rapid detox under anesthesia, compared to detox with a short course of buprenorphine are equal. They’re equally dismal, with only twenty percent of the addicts still abstinent from all opioids.

     Most reputable treatment centers no longer use this expensive, and relatively riskier, method of detoxification under general anesthesia. Since the studies don’t show greater abstinence rates with this method, it’s difficult to justify its expense and risk. (2)

     However, there may be some patients for whom this is an acceptable treatment. Perhaps if ultra-rapid detox is the only treatment option that an addict is willing to try, the potential benefits may outweigh risks, since we know continued active addiction is very risky. This method of detox may be most successful with a very motivated addict who, for whatever reason, has a deadline they want to meet for detoxification. Even though there’s less than a twenty percent chance that he will be off opioids at one year after the procedure, that addict  will still be introduced to the idea of  addiction treatment

 End notes:

  1. Singh j, Ultra-rapid opioid detoxification: Current status and controversies, Journal of Postgraduate Medicine 2004; 50:227-232.
  2. Collins ED, Kleber HD, Whittington RA, Heitler NE, Anesthesia-assisted vs buprenorphine- or clonidine-assisted heroin detoxification and naltrexone induction: A randomized trial, Journal of the American Medical Association, 2005; 294 (8) 903-913.
  3. Cucchia AT, Monnat M, et.al; Ultra-rapid opiate detoxification using deep sedation with oral midazolam: short and long-term results. The authors conclude that patients still had withdrawal symptoms after the detoxification procedure, and withy percent had relapsed back to opioid use at the six month follow up. Drug and Alcohol Dependence, 1998; 52(3) 243-250.

The Pain Management Movement

 In the late 1990’s, organizations like the American Pain Society and the American Academy of Pain Management declared that doctors in the U.S. were doing a lousy job of treating pain, and were under-prescribing opioid pain medications, due to a misguided fear of causing addiction. As a result, there was a national push to treat pain more aggressively. Some states even passed pain initiatives, mandating treatment for pain. Lawsuits were brought against doctors who didn’t adequately treat pain. The Joint Commission on the Accreditation of Healthcare Organizations (JACHO), the organization that inspects hospitals to assess their quality of care, made the patient’s level of pain the “fifth vital sign,” after body temperature, blood pressure, heart rate, and respiratory rate. Pain management specialists encouraged more liberal prescribing of pain medication. These experts told their primary care colleagues that the chance of developing addiction from opioids prescribed for pain was about one percent.

With these limited facts, the pain management movement was off and running. Many pain management specialists, some of whom were paid speakers for the drug companies that manufactured powerful opioid pain medications, spoke at seminars about the relative safety of opioids, used long term for chronic pain. Pain management specialists taught these views to small town family practice and general medicine doctors, who were relatively inexperienced in the treatment of either pain or addiction.

The problem was…the specialists were wrong.

These specialists, in their well-intentioned enthusiasm to relieve suffering, used flawed data when reciting the risk for addiction. The one percent figure came from a study looking at patients treated in the hospital for acute pain, which is quite different from treating outpatients with chronic non cancer pain. (1) In other words, they compared apples to oranges.

To many addiction specialists, an addiction risk of only one percent seemed improbable, since the general population has an addiction risk estimated from six to twelve percent. Surely, being prescribed pain pills would not lessen the risk for addiction. Yet the one percent figure was often cited by many pain management professionals, as well as by the representatives of the drug companies selling strong opioids. 

Some pain management specialists even took a scolding tone when they spoke of some primary care physicians’ reluctance to prescribe strong opioids. They often muddied the waters, and grouped patients with cancer pain, acute pain, and chronic non-cancer pain together, and spoke of them as one group. This can feel insulting to doctors who, though reluctant to prescribe opioids endlessly for a patient with chronic non cancer pain, are adamant about treating end-of-life cancer pain aggressively with opioids. No compassionate physician limits opioids for patients with cancer pain or with acute, short term pain. However, chronic non-cancer pain is different, with different outcomes than acute pain or cancer pain.

 We didn’t learn from history, or we would have learned that when many people have access to opioids, many will develop addiction.  We are scientifically more advanced than one hundred years ago, but we still have the same reward pathway in the brain. The human organism hasn’t changed physiologically. The present epidemic of opioid addiction is reminiscent of the early part of the twentieth century, just after the Bayer drug company released heroin, which for a short period of time was sold without a prescription, before physicians recognized that over prescription of opioids caused iatrogenic addiction.

 Few pain patients intended to become addicted. Some addicted people blame their doctors for causing their opioid addiction, but most doctors were conscientiously trying to treat the pain reported by their patient, and the pain management experts had told these doctors the risk of addiction was so low they didn’t have to worry about it.

Certainly many patients made bad choices to misuse their medications, either from curiosity or peer influence, pushing them farther over the line into addiction. Patients need to recognize their own contribution to their addiction. But with opioid addiction, as the disease progresses, the addict loses the power of choice that he once had. If the addict is fortunate enough to have a moment of clarity, before the disease progresses too far, he may be able to stop on his own, without treatment.

 By their very nature, opioids produce pleasure. Any time doctors prescribe something that causes pleasure, we should expect addiction to occur. Some people, for whatever reason, feel more pleasure than others when they take opioids, and seem to be at higher risk for addiction. As discussed in previous chapters, genetics, environment, and individual factors all influence this risk.

Opioids treat pain – both physical and emotional. Many of the neuronal pathways in the brain for sensing and experiencing pain are the same for both physical and psychological pain. For example, the brain pathways activated when you drop a hammer on your toe are much the same as when you have to tell your spouse you spent the rent money while gambling. Opioids make both types of pain better. Chronic pain patients with psychological illnesses are at increased risk for inappropriate use of their pain medications.

 In a recent study, the rate of developing true opioid addiction in patients taking opioids for chronic pain was found to be increased fourfold over the risk of non-medicated people. (2) Instead of a one percent incidence, as estimated by pain medicine specialists in the past, it now appears eighteen to forty-five percent of patients maintained long-term on opioids develop true addiction, not mere physical dependency. (3) If this information had been available in the late 1990’s, doctors may have taken more precautions when they prescribed strong opioids for chronic pain.

 Researchers have identified the risk factors for addiction among patients who take opioids long-term (more than three months) for chronic pain. Studies now show that a personal past history of addiction is the strongest predictor of future problems with addiction, as would be expected.  A patient with a family history of addiction is also at increased risk for addiction, as are patients with psychiatric illness of any kind, and younger patients. (4)

However, at the height of the pain control movement, there were no good studies of the addiction risk when opioids were used for more than three months. The little information that did exist was misused, resulting in an incredible underestimation of the risk of addiction in patients with chronic pain, who were treated with opioid medications for more than three months.

 With the momentum of the movement for better control of pain, both acute and chronic, the number of prescriptions for opioid pain pills increased dramatically. In the years from 1997 through 2006, prescription sales of hydrocodone increased 244%, while oxycodone increased 732% during that same time period. Prescription sales for methadone increased a staggering 1177%. (5)

It’s not just patients who are at risk for abuse and addiction. The increased amount of opioids being prescribed meant there was more opioid available to be diverted to the black market. When an addicting drug is made more available, it will be misused more often.

  1. Porter and Jick, New England Journal of Medicine, 302 (2) (Jan. 10, 1980) p. 123.
  2. Michael F. Fleming, Stacey L. Balousek, Cynthia L. Klessig, et al. “Substance Use Disorders in a Primary Care Sample Receiving Daily Opioid Therapy,” Journal of Pain, 207; Vol. 8, issue 7: 573-582.
  3. 7. Steven Passik M.D., Journal of Pain and Symptom Management, Vol. 21 No. 5, (May 2001), pp.359 – 360.
  4. Chou, R, Fanciullo, G, Fine, P, et. al., “Opioid Treatment Guidelines: Clinical guidelines for the use of Chronic Opioid Therapy in chronic, non-cancer pain.” The Journal of Pain, 2009, Vol. 10, No. 2. pp. 113-130

5. Andrea Trescott, MD, Stanford Helm, MD, el. al., “Opioids in the Management of Chronic Non-cancer Pain: An Update of American Society of the Interventional Pain Physicians’ Guidelines,” Pain Physician 2008: Opioids Special Issue: 11:S5 – S 62.