Archive for the ‘Naltrexone’ Category

Opioid Blockers: Do They Take All the Fun Out of Life?

According to an interesting article in the most recent copy of the American Journal on Addictions, the answer appears to be, “No,” at least for some people. (1)

 This article described a study where researchers asked patients on the extended-release opioid blocker naltrexone to rate the amount of pleasure they obtained from things like eating good food, sex, and exercise. These patients were on naltrexone for the treatment of alcoholism, but of course, the information may be helpful for opioid addicts who are treated with opioid blockers to prevent relapse back to opioid use. The subjects were asked to rate, on a scale of 1 to 5, the amount of pleasure they obtained from activities such as sex, eating good food, exercise, talking with friends, and other usually enjoyable things in life. A score of 1 meant they felt no pleasure at all, and 5 meant they felt much pleasure.

 The good news is that pleasure scores for these patients were relatively high. For example, the average score for pleasure from eating good food was 4.14, out of a possible 5. For listening to music, it was 4.00 out of 5. For sex, it was 3.92. For drinking alcohol, it was only 2.57 out of 5, which supports the use of this medication for alcoholics.

 In summary, the study found that subjects on extended-release naltrexone still experienced a good amount of pleasure from life.

 There were limitations to this study, however. We don’t have a pre-naltrexone baseline for these patients. In other words, we know pleasure ratings were fairly high while on naltrexone, but it’s possible these subjects had even higher pleasure scores before naltrexone. Also, there was no placebo control in the study. Maybe people getting pretend, or sham, treatments would have had higher pleasure scores, but we don’t know. 

In my mind, the biggest weakness was that the study enrolled 187 patients, but only 74 completed the intended survey. That means about 60% of the subjects dropped out of treatment, and the article doesn’t say why they dropped out. Maybe the drop-outs were the ones to feel a lack of pleasure in their lives from being on naltrexone, and the ones who stayed on it didn’t have this same side effect. If so, this would obviously skew the results.

 But even with these admitted weaknesses, and even though the study was paid for by the company that manufactures the sustained-release naltrexone (Vivitrol), this article gives hope that Vivitrol may work for opioid addiction. It may help prevent relapses, without interfering with life’s pleasures. And we need every tool we can get to fight addiction.

  1. 1.      O’Brien, Charles; Gastfriend, David; Forman, Robert; Schweizer, Edward; Pettinati, Helen, Long-Term Opioid Blockade and Hedonic Response: Preliminary Data from Two Open-Label Extension Studies with Extended-Release Naltrexone, American Journal on Addictions, Vol. 20 (2), March/April 2011, pp106-112.

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 New OxyContin Formulation

Over the last three weeks, at least five of the opioid addicts I’ve admitted to treatment said they wanted help because they couldn’t abuse the new form of OxyContin.

 And I say: Hallelujah! It’s about time!!

 This new tablet, approved by the FDA in April of this year, appeared recently on the black markets of this area, replacing the older, more easily abused OxyContin. The new tablet is bioequivalent to the older tablet, meaning the same amount of oxycodone, the active ingredient, is available to the body when swallowed whole, as it’s meant to be. In other words, the same amount of pain reliever is given to the body. However, it’s more difficult to crush for the purpose of snorting or injecting, because it turns into a gummy ball.

Purdue Pharma, the drug company that makes OxyContin, admits this new formulation isn’t abuse-proof, but hopes it will be more resistant to abuse.

The patients I’ve talked to say the new tablet is a big disappointment. One patient, who usually chews her pill to get a faster high, said it was like trying to chew a jelly bean. Other patients said they could crush the tablet, but got a kind of gelatinous mess that was impossible to snort or inject.

 For pain relief, the opioid in OxyContin lasts much longer when it’s taken as directed and swallowed whole. Addicts prefer to crush and snort or inject because of the quick high they feel with this route of administration. But when used in this way, it leaves the body faster, and the addict usually needs to find more opioid within six to eight hours to avoid withdrawal.

Before I applaud Purdue Pharma for this change, my cynical mind asks a few questions: Why didn’t the company make this change earlier?

In 2002, a Purdue Pharma representative testified before congress, saying that the company was working on a re-formulation of OxyContin, to make it harder to use intravenously. This representative said they expected to have the re-formulated pill on the market within a few years. (1)  But it took eight more years.

Sterling, the drug company that makes Talwin, another opioid pain medication, was able to re-formulate their drug within a few years when they discovered it was being abused frequently. This was in the 1980s, when, presumably, medication technology wasn’t as advanced as today. Sterling added naloxone, an opioid blocker that’s inactive when taken by mouth, but puts an addict into withdrawal when it’s crushed and injected. It worked great. Talwin isn’t a commonly abused drug.

 I’m assuming that Purdue Pharma holds the patent for this new formulation that makes their tablet gummy when crushed. Purdue probably teaches its sales staff to market the new OxyContin as a safer option than older versions, perhaps available in cheaper generics. So did they wait to re-formulate until their patent was ready to expire? I don’t know, but time will tell.

At any rate, this drug is now just a little bit safer, for now. People with addictions are often clever and creative. I won’t be surprised if soon there’s a way to defeat this new technology.

Just think what addicted people could do, if they directed their talent and intelligence in ways that would help and not hurt them. There would be no stopping them.

1. United States Senate. Congressional hearing of the Committee on Health, Education, Labor, and Pensions, on Examining the Effects of the Painkiller OxyContin, 107th Congress, Second Session, February, 2002.

Naltrexone to Treat Opioid Addiction

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. They also remove opioids from the receptors, so if antagonists are given to an actively using opioid addict, the addict will become sick with immediate withdrawal. This is called “precipitated withdrawal” because it was caused, or precipitated, by a medication.

Naltrexone is the most common oral opioid blocker that is used. 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 start. Because it is a blocker, 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, then increased to the full dose, for better tolerability.

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 illicit 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 career 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 is 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 ensured, unless the addict wants to dig the pellets out to be rid of the blocking drug.

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.

Sometimes people get confused, and think that this drug will alleviate opioid cravings. It doesn’t. Sadly, those cravings are still present, but opioid blockers can be an added bit of insurance against an opioid relapse.

Rapid Detox: Detoxification under anesthesia

It sounds great. It should work. Go to sleep under anesthesia, and wake up drug-free. The appeal of this idea is obvious: the addict doesn’t have to go through any painful withdrawal. While the patient is under anesthesia, the opioid antagonist drug naloxone (or one similar) is given, putting the body into withdrawal. Hours later, the patient is brought out of anesthesia, and according to treatment centers that do this type of treatment, the patient has no further withdrawal.
However, it’s more complicated than that. Several studies show that post-procedure symptoms of nausea, vomiting, and insomnia can continue for days afterward, and the outcomes for patients aren’t any better with this treatment than with the usual inpatient buprenorphine taper. (1) Plus, ultrarapid detox costs much more; in many places the procedure costs tens of thousands of dollars. (2)
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! Many proponents of rapid detox exaggerate and inflate success rates in this way. But studies show that at one year, success rates with rapid detox under anesthesia compared to detox with a short course of buprenorphine are equal – equally dismal, that is, with only 20% of the addicts still abstinent from all opioids. (3)
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 that 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 20% chance that of abstinence at one year after the procedure, that addict will still be introduced to the idea of addiction treatment, and possibly more willing to participate in another form of treatment.
References:
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 80% had relapsed back to opioid use at the six month follow up. Drug and Alcohol Dependence, 1998; 52(3) 243-250.