Archive for the ‘Clonidine’ Category

Insomnia Medications for Patients in Medication-Assisted Treatment

aaaaaaaaaaaaasleep

In one of my recent blog entries, I talked about some simple measures that can help patients with insomnia, called sleep hygiene. Many times these methods can fix the problem, but other times, patients still can’t sleep well, which interferes with life. In these cases, medications may be of some help.

The “Z” medications
The “Z” group of medications includes zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta). These medications, which are not benzodiazepines, have been touted as being safer and less addictive than older benzodiazepines, like temazepam (Restoril), triazolam (Halcion) or clonazepam (Klonopin). However, the “Z” medications stimulate the same brain receptors as benzodiazepines, and are all Schedule IV controlled substances, just like benzodiazepines. This means they all have roughly the same potential to cause addiction, despite enthusiastic marketing by some drug companies.

I don’t prescribe the “Z” medications for patients on medication-assisted treatment with methadone or buprenorphine because they can cause overdose deaths in these patients. Also, these medications can give many patients with the disease of addiction the same impulse to misuse their medication. I’ve had patients develop problems with misuse and overuse of these medicines.

Trazadone
Many doctors, including me, have prescribed trazadone to help patients get and stay asleep. It’s an antidepressant, but daytime use has been limited due to drowsiness. In an effort to use this side effect for benefit, it’s often prescribed at bedtime to treat insomnia. But a recent study called this practice into question. In this study, trazadone was not found to be effective for methadone maintenance patients with insomnia. Test subjects were monitored with sleep study apparatus, and these subjects had no subjective or objective benefit from trazadone, either in initiating or staying asleep. [1]

Because trazadone can affect the QT interval, just like methadone, it’s possible these two drugs used together will dangerously prolong the QT interval. Also, both can cause sedation, also a concern. In view of this data, I have stopped recommending or prescribing it as an insomnia medication.

Quetiapine (Seroquel)
Quetiapine is in the group of medications known as atypical antipsychotics, and is indicated for the treatment of schizophrenia, the mania of bipolar disorder, and treatment-resistant depression. Because it is a sedating medication, many doctors prescribe it for treatment of insomnia, usually at low doses, around 25 to 100mg at bedtime.

Does it work? Two small studies, designed to see if the drug can help insomnia, showed conflicting results. One study showed significant improvement and the other showed no significant improvement.

Furthermore, this medication is not without side effects. At higher doses, used to treat bipolar disorder and schizophrenia, patients can develop diabetes and hyperlipidemia. But even at low doses, we see weight gain, restless legs, dizziness which can lead to night time falls, and dry mouth. There’s a risk, though likely small, of tardive dyskinesia with this drug. This is a serious movement disorder more commonly seen with the older antipsychotics like thorazine; patients on the atypical antipsychotics can also develop this potentially devastating disorder.

With little evidence to support its use, and potential serious side effects, I no longer initiate a prescription for quetiapine in a patient with insomnia. I do have some patients who’ve been started on this medication before they started seeing me. If they still feel it’s effective and I see no side effects, I’ll continue the medication. I make sure they get yearly lipid profiles done and recommend yearly screens for diabetes, and monitor for weight gain.

At addiction medicine conferences, I’ve heard doctors say that some of their patients misuse quetiapine. Personally, I think that must be unusual, and maybe these are patients in an experimental phase of addiction. I don’t see seasoned addicts using this medication to get high.

Ramelteon (Rozerem)
This medication, approved by the FDA for treatment of insomnia in 2005, isn’t addictive. It works by stimulating melatonin receptors and it helps patients get to sleep somewhat more effectively than placebo, but doesn’t help keep them asleep. Ramelteon doesn’t cause the rebound insomnia commonly seen after use of the “Z” medications, and has few clinically significant drug interactions. Last time I checked, it’s more expensive than many sleep medications, and many insurance companies demand a prior authorization before they’ll pay for it. I’ve had a few patients do well with this medication, so I like to prescribe it.

Melatonin
Once hoped to be the miracle treatment for insomnia, studies show that at best, melatonin is mildly more effective than placebo for the treatment of insomnia. Melatonin isn’t a prescription medication, and is sold by many manufacturers with little quality control. Since it is categorized as a dietary supplement, the FDA does not examine or approve these products. Since 2010, the FDA only requires that dietary supplements be made according to “good manufacturing practices,” and that companies make a consistent product, free of contamination, with accurate labeling. As I see it, that’s not much oversight and people take their chances with dietary supplements of any kind.

Diphenhydramine
More commonly known as Benadryl, many over-the-counter sleep medications contain this sedating anti-histamine. It can cause sedation in patients taking methadone, and should be avoided or used with caution. I’ve seen one methadone overdose death I believed was due to the interaction with methadone and diphenhydramine, though the patient had taken more than one 50mg diphenhydramine pill.

Otherwise, the medication is mildly to moderately effect at helping people get to sleep. Don’t take more than 50mg, because higher doses can have a reverse effect, and interfere with sleep.

Hydroxyzine (Vistaril) is another potentially sedating anti-histamine that is felt by some doctors to be safer than diphenhydramine, but I can’t find any data to support that view.

Other medications
Clonidine
I occasionally prescribe clonidine if I think my patient is having a degree of opioid withdrawal as the cause of insomnia. I’m talking about patients who wish to taper, not patients on maintenance. If a patient on maintenance has insomnia from withdrawal, it’s best to increase the dose of the maintenance medication.

Clonidine can help insomnia from withdrawal. Because this is a blood pressure medication, it can drop night-time blood pressure when taken for sleep. This can cause a patient to fall if they get up during the night. I caution patients that if they must get up at night, stand beside their bed for a few minutes to make sure they don’t feel dizzy. I usually prescribe a .1mg pill and have them take only one pill.

Gabapentin (Neurontin)
This anti-seizure medication is used for a little bit of everything, so why not insomnia? Officially, gabapentin is approved by the FDA for treating seizures and for the pain of post-herpetic neuralgia (that’s the pain that stays after a shingles outbreak). But doctors use gabapentin for fibromyalgia, insomnia, migraine headaches, bipolar disorder, and probably other conditions. According to Medscape’s drug interaction checker, gabapentin has no interaction with methadone or buprenorphine, but Epocrates’ drug interaction checker says use with caution with these medications due to possible daytime sedation.

Muscle relaxers
Some patients take these medications at bedtime for their sedating effect, but I don’t think there’s any evidence these medications are particularly effective.

Placebo
I include placebo as a reminder that about thirty percent of people will get benefit from a pill containing no medication. Our minds are powerful. (Parenthetically, I’m highly susceptible to suggestion. As a young adult, I got “drunk” on cider that I was told contained alcohol. I felt intoxicated, to the point of losing my balance and getting dizzy. But my friend had played a trick and there was no alcohol in this cider.) It’s difficult to know if a pill or potion for sleep works because it’s effective, or if it works because of the placebo effect. If you’ve found a medication that works, keep taking it, so long as it’s not doing any harm.

A recent study showed that adults who use sleeping pills are more than three times more likely to die prematurely compared to matched controls who didn’t use sleeping pills. This relatively large study looked at the medical records of over 10,000 patients who were prescribed hypnotics for sleep, and compared their outcomes to over 23,000 matched control patients, similar except the controls weren’t taking sleeping pills. The sleeping pills, also called “hypnotics” were associated with significant increases in mortality and significant increases in cancer incidence. [2]
The patients’ average age was 54, and they were followed for an average of 2.5 years. All were members of a large U.S. healthcare system in Pennsylvania. The data from the two groups were adjusted for age, gender, smoking status, prior cancer diagnoses, body mass index, ethnicity, and alcohol use.

Patients in the group taking prescribed hypnotics most frequently, defined as more than 132 doses per year, had over five times increased risk of dying than patients not taking hypnotics. Even the group of patients taking hypnotics relatively infrequently (up to 18 doses per year) had a three times higher risk of death. These differences were statistically significant. The medications in the study included all of the “Z” medications, as well as temazepam (Restoril), barbiturates, and the sedating antihistamines, such as diphenhydramine (Benadryl).

The author of this study estimated that hypnotic medications are associated with 320,000 to 507,000 deaths in the U.S. over the year 2010.
This study raises some important questions, since hypnotic drugs are the most commonly prescribed drugs in the U.S., with an estimated 6 to 10% of the population being prescribed these medications.

Sleep medicine doctors say that correlation doesn’t mean causation, and we shouldn’t jump to conclusions. One sleep specialist pointed out that the study didn’t control for psychiatric illness, which could be a significant factor. Additionally, patients who are prescribed sleeping medications may be sicker overall, in ways the study didn’t control, and therefore a generally less healthy group. This could distort study findings.

Other scientists say that sleeping pills could make sleep apnea worse, and cause deaths in that way. Obesity increases the risk of sleep apnea, and with more adults becoming obese, perhaps sleeping pills make apnea worse and these people die in their sleep. Other scientists say sleeping pills slow reflexes, and perhaps patients taking these medications are more likely to be involved in car accidents and other accidents, increasing their death rates.

As for my patients, many of whom are prescribed methadone or buprenorphine, the risk of drug interaction and overdose with the hypnotics usually outweighs all of the benefits, and I recommend that patients do not mix these two types of medications.

As a final bit of advice, I want to remind readers that other physical and mental health conditions can cause insomnia. It’s a good idea to see a primary care doctor to screen for these conditions, which can include sleep apnea, asthma, gastroesophagel reflux, hyperthyroidism, bipolar disorder, depression, and anxiety disorders. Sometimes patients need sleep studies to assess for sleep disorders.

1. Stein et al, “Trazadone for sleep disturbance during methadone maintenance: a double-blind, placebo-controlled trial,” Drug and Alcohol Depend., 2012, Jan 1;120(1-3):65-73
2. BMJ Open 2012;2:e000850 doi:10.1136/bmjopen-2012-000850

The Broken System

aaaaaaaaaaabrokennet

I’m feeling discouraged this week, due to a recent vivid display of my state’s broken mental health/substance abuse treatment system.

Details of this encounter have been changed to protect identities.

One of our former opioid treatment program patients returned to us, asking to be admitted again to methadone maintenance. In previous admissions, this patient struggled with repeated bouts of benzodiazepine addiction and had several near overdoses. He also had months at a time when he did relatively well, with little benzo use. I felt we were helping him – to some degree – until late last summer, when his condition worsened after his son died from an overdose. He was distraught and using all types of drugs in order to push away the pain of his loss. I became worried he would die of an overdose if we didn’t do something different. We really wanted him to go to inpatient care, because he’d become too sick for outpatient, medication-assisted treatment. He rejected this option and left treatment.

He was back last week, asking for help. He admitted to using a wide variety of drugs, including benzos, illicit methadone, cocaine, alcohol, and marijuana. He knew he was still grieving for his son, and he too had come to fear that he would die from his addiction. He was now ready to go to an inpatient residential treatment center. Even though we don’t offer that service, he came to us when he couldn’t find help anywhere else.

He’d already gone to our local hospital emergency department two days prior, asking for help, but he said he was turned away with no evaluation and no medication. Our patient told us the emergency department personnel told him he could be put on a waiting list for an inpatient program, and that it could take weeks for a bed to open up for him. Our patient left the emergency department feeling like personnel there didn’t care about what happened to him. He suspected they judged him as a bad person, not a sick person. He got no further referrals for treatment and wasn’t even offered clonidine, a blood pressure medication that can help with some of the opioid withdrawals.

Granted, our patient may be leaving out part of the story, or too sick to remember accurately. I know better than to take every patient report as completely accurate, but what this patient said had the ring of truth to it, and I tend to believe he gave an accurate account of his emergency department experience.

After this disappointment, he came to our program, saying he knew we did care about what happened to him. For the next five or more hours, our OTP counselor tried to get help for this patient.

First, she called our local management entity, or LME. This is a weird, non-descriptive term for local governmental agencies in North Carolina that contract with other mental organizations to provide care for any patient with substance abuse and/or mental health issues. LMEs are the safety net…but the net is broken.

The counselor called the LME and they offered to send a mobile crisis team. This is a grand term implying quick, on-site help for resolution of crises facing the service recipient. Service recipient is the new term for patient, by the way.

The mobile crisis management team consisted of a young woman with a bad attitude and little idea how to talk to patients who were sick and suffering. After an assessment of about forty-five minutes, which necessarily consisted of questions that we had already asked her, this mobile crisis management worker told our patient that he was in opioid withdrawal, and it was likely to get worse instead of better.

At this epiphany of the obvious, our patient thrust his face towards the worker and said sarcastically, “Ya think??” It was obvious our patient did not regard this revelation as particularly helpful. It was also obvious he had offended the worker, who angrily started to pack up her belongings. She said the only thing she had to recommend was going to the emergency room. When our patient informed her he had already gone there two days ago and no help had been forthcoming, the mobile crisis worker said that if he didn’t want to take her advice, she couldn’t make him. She said she could put on the list for a bed at an inpatient program, but it could take weeks for a bed to open. Then she left.

So…I was not at all impressed with the mobile crisis management team.

Our tenacious OTP counselor flew into action again, and called our favorite inpatient treatment program directly. This is a state-run program that’s also an opioid treatment program, named Walter B Jones ADATC (alcohol, drug addiction treatment center). It’s affectionately called “Walter B” by us. It’s the only inpatient program in the state that I know of that will admit patients with opioid addiction and keep them on their maintenance meds or start them on maintenance meds.

I felt that starting the patient on methadone as an inpatient, while benzodiazepine withdrawal was being managed, would be much safer. His mental health status could also be addressed, or at least begin to be addressed. A few weeks as an inpatient won’t fix everything, but it is a start, and the best option we could think of.

Walter B said they wouldn’t have a bed for at least a week, and that they needed an EKG and various labs prior to admission. This is because they don’t want to admit a medically unstable patient. Our patient would still have to go back to the hospital emergency department for the EKG and labs, since our OTP doesn’t have the capacity to do those. But our local emergency department sometimes refuses to do lab tests for inpatient admissions. I don’t know why, but I’m guessing it’s because most of these patients have no insurance, and the hospital assumes they’ll get stuck with the bill.

Next, our OTP counselor called a local detox facility. This facility does not “believe” in methadone maintenance and doesn’t even use buprenorphine to ease opioid withdrawal symptoms. But they do administer phenobarbital to help with benzodiazepine withdrawal, and they could perform the labs this patient needed for admission to Walter B. It wasn’t an ideal solution either, but an option.

No one answered the phone at this detox facility. The counselor left several voice mail messages, but didn’t get any calls back.

Frustrated but by no means willing to give up, our tenacious counselor called Project Lazarus. This is a program in Wilkes County that has received accolades for its work at preventing opioid addiction, overdose deaths, and promoting evidence-based treatments for opioid addicts. People who work at Project Lazarus have connections. They tend to know everybody in the treatment field, so they are often a valuable resource for us. One of their employees did know someone at the detox, and was able to call them through a back channel. That person finally called our counselor back.

Finally, a plan emerged. Our patient would go to this private detox that day or the next, where he could get the labs Walter B wanted. In a perfect world, our patient would leave the detox on the day a bed opens at Walter B. However, if that can’t be worked out, I will admit our patient to methadone as a stop-gap until the inpatient bed opens up. After treatment at Walter B., our OTP will accept him back into treatment and continue efforts to stabilize him.

This isn’t the best plan and it isn’t the safest plan. It’s piecemeal at best, and the plan could still fall through.

Ideally, our LME would contract with an agency that could do all of this for the patient. Ideally, detox beds could be offered on the same day the patient asks for help, with a seamless transition to inpatient treatment to continue patient stabilization. Inpatient treatment programs would offer patients medication-assisted treatment of opioid addiction or abstinence-based treatment and the patient could participate in the choice. Instead, most inpatient facilities don’t even mention the possibility of medication-assisted treatment, so there is no informed consent about which type of treatment is given.

If it took a dedicated and savvy counselor five hours and multiple phone calls to work out a plan for this patient, how would he have been able to access care on his own? Indeed, he did try to access care on his own, and failed to get timely help.

I wish all of the people who recommend inpatient abstinence-based treatment of patients with opioid addiction should be made to try to navigate our present labyrinth of care. This wasn’t even a non-insured person; he had Medicaid, and we still couldn’t find a bed for him.

I know our state has little money with which to treat mentally ill and addicted patients. Budgets for mental health and substance abuse treatments have been cut to the bone and then deeper. The public expects a safety net to appear without having to pay for it. The state-funded facilities do miraculous things with the little money that they have. But no one should have the misperception that our system of care is anything but broken.

Non-opioid 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. I’ve had many questions about these medications lately, so I thought a re-posting of this entry may be appropriate.

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. Obviously, compliance will be much better, 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.

One concern with the opioid antagonists described above is what to do 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 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

  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.

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.

Stop Buying and Selling Suboxone!

 It’s been longer than usual since my last post. That’s because I spent the last five days in Boca Raton, Florida, at the annual meeting of the American Academy of Addiction Psychiatry. I usually go to meetings of the American Society of Addiction Medicine, since I’ve been a member of that organization for seven or eight years. I’ve always thought of ASAM as more “medically -oriented” and AAAP as more “mentally-oriented” but this week I found that they’re similar. 

Anyway, I went to some great meetings and lectures.

 The most intriguing was “Buprenorphine 201.” In this meeting, we had a lecturer, but she functioned more as a moderator for many of the physicians as we exchanged ideas about how we prescribe buprenorphine for our addicted patients.

 One of the more interesting topics was if, when, and how to taper buprenorphine. Should physicians encourage patients who are doing well on buprenorphine to taper off of it at some point? All the research data shows high relapse rates for patients who taper off of it. But many patients insist on tapering, due to the stigma, cost, and inconvenience of being on this medication, so what’s the best way to do this?

 I heard several new ideas, like doing dose plateaus. This means that once you taper 25% of the total dose, stay on the new dose for a few months to make sure the patient has completely stabilized before pushing the dose down again. Then stay at that dose for months, and so on. Another doctor said to use clonidine to treat early withdrawal symptoms. Another doctor suggested using benztropine (Cogentin) to manage some of the symptoms of opioid withdrawal. This medication is usually given to help symptoms of Parkinson’s patients, and to help manage the side effects of anti-psychotic drugs.

 The two best ideas I heard were: 1-Taper the dose down to as low as possible, in the range of 2mg, and stay at that dose for a prolonged time, maybe months. The doctor and patient can decide to taper further after a very prolonged time. 2-Use the 2mg Suboxone film, and cut it to gradually lower the dose. 

We all agreed there is little research to guide us to decide when taper is appropriate, and how to do the taper. Much of what we decide depends on the characteristics of the patient and their desires.

 Several other things came out of this meeting. The most worrisome is the degree to which buprenorphine, brand name Suboxone, is being diverted to the black market. This is making the DEA rather cranky, and other law enforcement types are beginning to make noises, saying that Suboxone should be re-classified as a Schedule II controlled substance because of the frequency it’s seen on the black market. If that happens, it would be the end of the Suboxone program. The DATA 2000 law that made it permissible to treat opioid addiction in a doctor’s office says the drug must be scheduled III or IV. A schedule II drug wouldn’t be covered by DATA 2000.

 So let me say loud and clear: If you are buying Suboxone, selling Suboxone, or giving Suboxone to someone other than the person to whom it was prescribed… KNOCK IT OFF!!!

You could ruin a good program that offers opioid addicts an option that was illegal in this country until 2002.

 Let’s do all we can to keep this medication available for the addicts who want recovery.

Clonidine for Opioid Withdrawal

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 is 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 system that controls 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.

So how effective is clonidine? Most patients say that it helps somewhat, but they still feel withdrawal symptoms. My impression from what patients have described is that clonidine is mildly to moderately effective.

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 is more effective, and helps retain patients in detoxification, a necessary step prior to the more intense inpatient rehabilitation.

Follow

Get every new post delivered to your Inbox.

Join 755 other followers