Archive for the ‘Overdose deaths’ Category

Benzodiazepines Associated with Increased Risk of Death

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Adults who use sleeping pills are more than three times more likely to die prematurely compared to matched controls that don’t use sleeping pills, according to a recent study. [1]

I’ve never been a fan of sleeping pills, even the newer, first-line “Z” medications: zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta). I’ve seen all of them cause more harm than good in my patients, but that’s not surprising, since I treat patients with addictions.
These newer sleeping medications are touted by many as being safer and less addictive than older medication like temazepam (Restoril), triazolam (Halcion) or clonazepam (Klonopin). However, all of the “Z” medications are Schedule IV controlled substances, just like their benzodiazepine predecessors. This means they all have roughly the same potential to cause addiction, despite some enthusiastic and misleading marketing done by some drug companies.

I know many people, without a history of addiction, can take sleeping pills without apparent problems, so I was surprised to read about this recent study. 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.

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).

Of note, eszopiclone (Lunesta) was associated with the highest risk of death. (This pill’s advertisement has a beautiful butterfly wafting in through an open window, and landing gently by a woman in bed, presumably helping her sleep. I guess the butterfly seemed like a better commercial symbol that the grim reaper.)

The use of hypnotic medications was also associated with an increased risk of cancer, and reached statistical significance in patients taking the most hypnotics. Lung, colon, and prostate cancers were significantly more likely to occur in these hypnotic medication users, as well as lymphoma.
The author 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.

Then in early 2014, a study done in the United Kingdom showed similarly increased mortality for patients prescribed anxiolytic and hypnotic medications. [2]

This second study was a retrospective matched control study, looking at all-cause mortality in patients prescribed these medications as compared to patients with no such prescriptions. Patients in the group prescribed benzodiazepines were more than three times more likely to die than matched controls. There was also a dose-response association; the higher the dose, the more likely the patient was to die. This study shows a correlation, but not necessarily causation. Perhaps sicker patients were prescribed the benzodiazepines in the first place.

We know benzodiazepines are associated with increased risk of auto accidents, increased risk of completed suicide, worsening of mood disorders like depression, increased risk of drug-induced dementia, and increased risk of daytime fatigue. Benzodiazepines are also associated with increased risk of cancer, falls, and pneumonia.

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.

So stay tuned. As time goes on, hopefully we’ll learn more about this correlation between benzodiazepines/hypnotics and death. Both of these studies are helpful because of their large size, and the author points out that 19 other studies have shown a relationship between hypnotics and increased risk for death.

1. BMJ Open2012;2:e000850 doi:10.1136/bmjopen-2012-000850
2. Weich et al, “Effect of anxiolytic and hypnotic drug prescriptions on mortality hazards: retrospective cohort study,” British Medical Journal, 2014

Naloxone Controversy

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It’s a misleading title, because most people support naloxone use. At this point…there’s not much controversy. Unless you live in Maine.

Their governor, Paul LePage, vetoed a bill, passed by their State House in 2013, that allowed naloxone to become more widely available. He called the life-saving medication and “escape,” and “An excuse to stay addicted.”

Naloxone is an escape in a way – an escape from death.

However, before learning about naloxone, I had some concerns too. For example, would having naloxone available for an overdose encourage people to use more illicit opioids? Would addicts be more likely to push then envelop of safety in the quest for the ultimate opioid high?

The answer appears to be no, at least according to some small studies. One of them was a study of intravenous heroin addicts in San Francisco, who received an eight-hour training in how to prevent heroin overdose, how to give CPR, and how to administer naloxone. [1]

These twenty-four study subjects were followed prospectively for six months. These addicts witnessed a total of twenty opioid overdoses. All of the overdose victims were said to be cyanotic, unresponsive, and have no respirations. The addicts in the study, who had received the eight hour training, administered naloxone to 75% of the overdose victims they encountered. They performed CPR on 80% of the overdose victims, and 95% of the overdose victims had one or the other of the two interventions performed. All of these overdose victims survived.

The study did not show an increase in the incidence of opioid overdose. In fact, the addicts in the study used less heroin over the study period, even though no part of the study was dedicated to encouraging the reduction of illicit opioid use or to entering addiction treatment.

Granted, the study participants had to be motivated in order to spend eight hours doing the training, so maybe they were already motivated to cut down or stop using drugs. But on the other hand, about half of these study subjects were homeless, a demographic many in our society would assume is poorly equipped or motivated to help anyone else. Yet they demonstrated a remarkable willingness and capability to help peers dying from overdoses.

Emergency medical services were called in only two of the overdoses. When study subjects were asked why they did not call emergency medical services, half said it was due to fear of police involvement and arrest. Twenty-five percent said no phone was available, and 25% said they didn’t see a need for EMS.

This information underscores the importance of Good Samaritan laws. In the broadest sense, Good Samaritan laws protect a person who tries to help another person from civil or criminal penalties.

Initially these laws were passed to protect doctors from being sued if they attempt to save the life of someone who is not a patient. For example, if I witness a man choking to death in a restaurant and I rush over to do the Heimlich maneuver, I can’t be sued if I break his ribs in my effort to get him to hack up the meatball wedged in his trachea.

Good Samaritan laws, as they apply to drug overdoses, give some degree of immunity to people who try to intervene to save another person’s life from drug overdose.

For example, in my state, our Good Samaritan law says if a person seeks medical assistance for an individual suffering from a drug overdose, that person will not be prosecuted for possession of less than one gram of cocaine or one gram of heroin. The bill has provisions for doctors to be able to prescribe naloxone to any person at risk of having an opioid-related overdose. Doctors can prescribe naloxone to the friends or family members of a person at risk for an overdose, even if that person is not a patient of the doctor. This is called third-party prescribing; the law hacks through red tape of previous regulations that said doctors could only prescribe naloxone for their own patients. And our Good Samaritan law says a private citizen can administer naloxone to an overdose victim, and so long as they use reasonable care, will be immune to civil or criminal liability.

Not all states allow third-party prescribing of naloxone or even Good Samaritan laws. Look on the map at the top of this blog, and if you live in a state that hasn’t yet passed these laws, write your congressmen. This is such an important issue, and naloxone needs to be more widely prescribed. (I don’t know why Maine is colored on the map as if they have naloxone laws).

Who should get a naloxone prescription? Opioid addicts should obviously receive kits, and the friends and family members of these addicts. I believe it should be considered for any patient prescribed opioids, including patients on opioids for chronic pain, and patients prescribed methadone or buprenorphine to treat opioid addiction.

Kits should certainly be provided for high-risk patients – opioid addicts recently released from jail or detox units.

I wish I could prescribe kits for all of my patients on methadone or buprenorphine now, but aside from the program where I work in Wilkes County, it’s not yet easily available.

But it will be soon. In April 2014, the FDA approved a commercially available naloxone auto-injector marketed under the name Evzio. This kit, which delivers .4mg of naloxone intramuscularly or subcutaneously, has both written and voice instructions. Each kit contains two doses, and it can be administered through clothing. This kit should be available in pharmacies this summer.

Until then, there are other options. Doctors can call a local pharmacy to see if they would be interested in making a kit for sale to patients. At a minimum, it would include one or two vials of naloxone, a needle and syringe, rubber gloves and alcohol wipes to cleanse skin prior to injecting. This would be a relatively cheap kit to make, but questions persist about who would pay for it: the patient, their health insurance company…
The Harm Reduction Coalition has been instrumental in providing intramuscular naloxone kits to anyone who wants one. They have contacted OTPs in my state to ask if they can hand out kits and other information, so that’s another possible source for a kit. If you are reading this article and want a naloxone kit for either yourself or a loved one, please contact either the Harm Reduction Coalition at: http://harmreduction.org
This wonderful organization does other good works besides distributing naloxone kits, and it’s worth checking out their website.

At the opioid treatment program where I work in Wilkes County, NC, Project Lazarus has paid all or part of the cost of intranasal naloxone kits for our patients who enter treatment. Thus far I know of three lives saved by these kits. None of them were our patients; our patients used their kits to save other people.

I’ve written about Project Lazarus before in my blog. This organization, founded by Reverend Fred Brason, has implemented ongoing measures that reduced the opioid overdose death rates not only in Wilkes County, but probably statewide as well. Other states have started programs modeled on Project Lazarus. You can go to this website for more information: http://projectlazarus.org I know that in the past, Project Lazarus has been willing to send a naloxone kit to anyone who has a need for it, so that’s another possible source for a kit.

I predict it will become easier to get relatively cheap naloxone kits from pharmacies everywhere as the momentum behind naloxone availability grows.

1. Seal et al, “Naloxone distribution and cardiopulmonary resuscitation training for injection drug users to prevent heroin overdose death: A pilot intervention study,” Journal of Urban Health, June 2005; 82(2): 303-311.

Project Lazarus in the Huffington Post

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In a nice article in the Huffington Post, Project Lazarus, located in Wilkes County, NC, was highlighted as an example of how a community can take action to prevent drug overdose deaths. Please check it out at: http://www.huffingtonpost.com/2014/03/05/project-lazarus_n_4889620.html?1394071210

Many people think Project Lazarus provides naloxone kits to reverse overdoses, and this is true, but they do much more than that. Project Lazarus has sponsored educational programs for doctors to learn to be more cautious when prescribing opioids, has sponsored medication take back days where old prescription meds can safely be disposed, and has worked with agencies and organizations across North Carolina and the nation to better inform doctors, law enforcement, and elected officials about what works to prevent drug overdose deaths.

Project Lazarus helped pass a Good Samaritan law North Carolina (see my post of April 20, 2013). Under this new law, a person who calls 911 to save another person’s life – or their own – won’t be prosecuted for minor drug possession, since they were trying to do the right thing and save a life by calling 911.

The Huffington Post article describes how the opioid overdose death rate has been falling in Wilkes County, while the overdose death rate in other parts of the country has been steadily rising. They credit Project Lazarus for this reduction in overdose deaths.

While I’m sure Project Lazarus has played a huge role in reducing overdose deaths not only in Wilkes County and the state of North Carolina, other factors have helped. Being an opioid addiction treatment provider, of course I believe availability of addiction treatment reduced deaths too.

Project Lazarus also supported the opening of an opioid treatment program in 2011, Mountain Health Solutions. Started by Dr. Elizabeth Stanton, this program initially offered only buprenorphine. As it grew, it became obvious some patients needed methadone treatment, so option became available by late 2011. Mountain Health Solutions was eventually purchased by CRC Health in 2012, and has continued to grow. Located in a small town, we have nearly four hundred patients.

I am honored to be the medical director at this program. It’s one on the best programs I’ve seen, and we work hard to keep improving our quality of care. Our program has done outreach -particularly in the medical community- to try to reduce the stigma of medication-assisted treatment. If you read my blog, you know this can be both a joy and a challenge.

Initially, Project Lazarus paid for an intranasal naloxone kit for every patient entering our opioid treatment program. Now since our patient census has risen, Project Lazarus still pays half of the $50 cost of the kits. The opioid treatment program pays the other half, out of a $33 admission charge for new patients. I feel lucky to be able to partner with Project Lazarus, as I’ve seen these kits save lives.

I know of four occasions when a naloxone kit saved a person’s life. Three of these four times, that person saved wasn’t even in treatment for opioid addiction.

Most recently, a parent used a kit to reverse an opioid overdose in a child who accidently ingested the parent’s medication. The parent called 911 and while waiting for EMS to arrive, used one of the two vials in the kit. The child partially woke, and started breathing better. Then EMS arrived and took the child to the hospital. This child survived a potentially fatal overdose and is back to normal with no lasting damage, thanks in part to that naloxone kit and a parent who knew how to use it.

Naloxone kits can be obtained much more cheaply, but contain Narcan vials, a more dilute form of naloxone that is meant to be injected. Those kits, which cost a few dollars, contain a syringe and needle instead of the Project Lazarus kit for nasal administration. Trying to inject naloxone into a vein is technically much more difficult than spraying the more concentrated form of naloxone up into the nose.

And unfortunately, a kit containing a needle and syringe would meet resistance from the public. I can imagine all sorts of angry phone calls to our opioid treatment program: “My son came to you people to get off the needle and you GAVE him a needle and syringe??” Politically, the public would more likely oppose distribution of a naloxone kit with a needle than a kit for intranasal use.

Fifty dollars for an intranasal naloxone kit to save a life is a pittance in the overall picture. Some insurance companies will cover these kits, as will Medicaid, but most of our patients have no insurance. They pay for their buprenorphine/methadone treatment out of their own pocket. Fifty dollars is a big sum for these patients.

I am blessed to work for an opioid treatment program that gets financial help from Project Lazarus for these kits. And I am very blessed to work for a for-profit company, CRC Health, which is willing to bear half the cost of the kits, since this comes out of their profits. Most opioid treatment programs do charge patients an admission fee, but unlike Mountain Health Solutions, don’t put that money towards buying a naloxone kits for their patients.

This is an example of the success that can happen when agencies work together toward a common goal.

Warning Warning Warning

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If you are still using heroin, or know someone using heroin, please heed this caution. SAMHSA (Substance Abuse and Mental Health Services Administration) sent out a notification last week, warning people that a deadly form of heroin is causing deaths in the Northeast.

Since the first of the year, thirty-none overdose deaths occurred in Pittsburgh and Rhode Island from heroin contaminate with fentanyl. Fentanyl is a powerful opioid, and kills opioid addicts accustomed to using heroin alone. Trends like these can spread rapidly, so if you are reading this and know someone who uses IV heroin, warn them about this deadly heroin.

When I first read SAMHSA’s notification, I wondered if I should put the warning on my blog. Being realistic, I know some addicts will think, “How can I get some of that? It sounds like good stuff!” That’s the insanity of addiction…people are dying from a variety of heroin and other addicts want to try the deadly substance, believing they can use without harm.

In the interest of harm reduction, I’m going to describe precautions that addicts, still in active addiction, can take to reduce the risk of overdose death. This information can be accessed at: http://harmreduction.org/wp-content/uploads/2011/12/getting-off-right.pdf

1. Don’t use alone. Use a buddy system, to have someone who can call 911 in case you stop breathing. Do the same for another addict. Obviously you shouldn’t inject at the same time. Stagger your injection times.
Many states now have Good Samaritan laws that protect the overdose victim and the person calling 911 for help, so that police don’t give criminal charges to people who do the right thing by calling for help for an overdose.
Take a class on how to give CPR so that you can revive a friend or acquaintance with an overdose while you wait on EMS to arrive.
2. Get a naloxone kit. I’ve blogged about how one patient saved his sister with a naloxone kit. These are easy to use and very effective. You can read more about these kits at the Project Lazarus website: http://projectlazarus.org/
3. Use new equipment. Many pharmacies sell needles and syringes without asking questions. Your addict friends probably can tell you which pharmacies are the most understanding.
Don’t use a needle and syringe more than once. Repeated use dulls the needle’s point and causes more damage to the vein and surrounding tissue. Don’t try to re-sharpen on a matchbook – frequently this can cause burrs on the needle point which can cause even more tissue damage.
4. Don’t share any equipment. Many people who wouldn’t think of sharing a needle still share cottons, cookers, or spoons, but hepatitis C and HIV can be transmitted by sharing any of this other equipment. If you have to share or re-use equipment, wash needle and syringe with cold water several times, then do the same again with bleach. Finally, wash out the bleach with cold water. This reduces the risk of transmitting HIV and Hepatitis C, but isn’t foolproof.
5. Use a tester shot. Since heroin varies widely in its potency, use small amount of the drug to assess its potency. You can always use more, but once it’s been injected you can’t use less. The New England overdose deaths described by SAMHSA may have been avoided if the addicts had used smaller tester shots instead of shooting up the usual amount.
6. Use clean cotton to filter the drug. Use cotton from a Q-tip or cotton ball; cigarette filters are not as safe because they contain glass particles.
7. Wash your hands thoroughly before preparing your shot, and clean the injection site with an alcohol wipe if possible. Don’t use lemon juice to help dissolve heroin, as it carries a contaminant that can cause a serous fungal infection.
8. Opioid overdoses are much more likely to occur in an addict who hasn’t used or has used less than usual for a few days, weeks, or longer. Overdose risks are much higher in people just getting out of jail and just getting out of a detox. Patients who have recently stopped using Suboxone or Subutex may be more likely to overdose if they resume their usual amount of IV opioids.
9. Don’t mix drugs. Many opioid overdoses occur with combinations of opioids and alcohol or benzodiazepines, though overdose can certainly occur with opioids alone.
10. Don’t inject an overdosed person with salt water, ice water, or a stimulant such as cocaine or crystal methamphetamine – these don’t work and may cause harm. Don’t put the person in an ice bath and don’t leave them alone. Call for help, and give mouth-to-mouth resuscitation if you can.

To people who believe I’m giving addicts permission to use, I’d like to remind them that addicts don’t care if someone gives them permission or not. If an addict wants to use, what other people think matters little. But giving people information about how to inject more safely may help keep the addict alive until she wants to get help.

The Harm Reduction Coalition has excellent information on its website: http://harmreduction.org

More about IRETA’s Guidelines for Benzodiazepines in OTPs

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This is a continuation of my last blog post about the IRETA (Institute for Research, Education & Training in Addictions) guidelines for management of benzodiazepine use in medication-assisted treatment of opioid addiction. You can read all of the guidelines at: http://ireta.org/sites/ireta.org/files/Best%20Practice%20Guidelines%20for%20BZDs%20in%20MAT%202013_0.pdf

Under the section of recommendations regarding addressing benzodiazepine use is found the following statement:
“Many people presenting to services have an extensive history of multiple substance dependence and all substance abuse, including benzodiazepines, should be actively addressed in treatment. People who have a history of benzodiazepine abuse should not be disallowed from receiving previously prescribed benzodiazepines, provided they are monitored carefully and have stopped the earlier abuse.”

The experts, after reviewing the best data, are saying that if a patient has abused benzos in the past, but isn’t abusing prescribed benzos now, it may be OK to continue benzos, with careful monitoring.

I don’t like this statement. It doesn’t conform to my present thoughts on the topic. I fear that the majority of patients with a history of benzodiazepine abuse or addiction will, sooner or later, revert back to problem use of the medication. That’s my anecdotal experience. Anecdotal experience is worth something, but data from clinical trials trumps anecdotal experience, and IRETA’s guidelines are based on both clinical trials and expert opinion.

So now I need to challenge my previously held views about benzos in the OTP. It’s unpleasant and uncomfortable to change a long-held view. But isn’t that what I ask of my patients? In the interest of science, I will re-consider my present opinion, but I won’t ignore the last part of the statement, which says careful monitoring needs to be done.

Careful monitoring includes, at a minimum, coordination of care between the OTP physician and the provider prescribing benzodiazepines, frequent benzodiazepine pill counts, and consulting the state’s prescription monitoring program regularly.

The IRETA guidelines say coordination of care is essential. The guidelines say that a patient who refuses to allow coordination of care between OTP physician and the physician prescribing sedative drugs may not be appropriate for treatment at an OTP with methadone/buprenorphine. The guidelines recommend the OTP physician get information on the patient’s diagnosis being treated with benzodiazepines and any observed misuse of the medication. The OTP doctor should also ask about the patient’s experience with non-benzo medications for the treatment of the patient’s disorder.

These are great ideas in a perfect world, but problematic in the real world.

Coordination of care is a term that’s batted around by non-physicians like a helium balloon, while in reality it’s as difficult as playing catch with anvils. Doctors, especially primary care doctors, are more pushed for time than ever. Many are at risk of losing their jobs if they don’t see enough patients per hour. (I know this because I was a primary care doctor before I fled the field for the more enjoyable addiction medicine.) Primary care doctors don’t want to spend valuable time on the phone talking to other doctors, especially if the other doctor works at “that clinic.”

I have found a few doctors in my area with whom I work well. I may not always agree with them, but I sense they are trying to do what’s best for their patients, and we can generally come to an agreement about the best plan of care.

And other doctors…not so much.

It’s not rare for my phone calls to prescribers of benzodiazepines to go unanswered. I’ve left up to four messages for one benzo-prescribing doctor at our local mental health clinic and have never received a return call. If we share a patient, I can’t coordinate care.

Even when I do get a call back, the conversation with the other provider is sometimes less than productive. The prescriber often says the patient is on Xanax because she has always been on Xanax, and there’s no clear diagnosis or plan of treatment for the underlying disorder. Prescriptions may be written twice a year with little discussion, with five refills. If non-benzo medications were prescribed in the past, the patient didn’t take them for very long before deciding that benzos were the only thing that worked for them. The doctor took this at face value and enthusiastically prescribed benzos ever since.

Sometimes I’ve suggested the doctor start a slow taper of the patient off benzos, if it’s clear the patient is misusing them. The doctor readily agrees with my suggestion, but month after month, on the prescription monitoring program website, I see the same amount of benzodiazepine being prescribed.

I’m not saying these are necessarily bad prescribers. I won’t call them doctors, because sometimes they’re also nurse practitioners or physician assistants. I do think many of them are pushovers, afraid of making patients angry by saying no. And some aren’t aware of best practice guidelines for prescribing benzodiazepines in general, even if the patient doesn’t have addiction.

Because I’ve worked in primary care, I know what happens. Benzo-seeking patients know which prescribers to go to, and they pester these providers incessantly until they are given the prescription they want. The providers, already pushed for time, give in to patient demands in order to get these patients the hell out of their office.

In my area, two or three prescribers are responsible for the majority of long-term benzodiazepine prescriptions. If I see a patient is on benzodiazepines, particularly alprazolam (Xanax) clonazepam (Klonopin) or diazepam (Valium), I can predict the prescriber. Addicts know who to go to; word gets around on the addict grapevine, an efficient mode for spreading news. I don’t feel I can coordinate care with these providers, even if I can talk to them about my concerns for a specific patient.

I agree with IRETA guidelines, but coordinating care with other prescribers isn’t always workable.

Getting back to the guidelines, later in the document is this important statement:

“Depending on capacity, it may be more appropriate for clinical settings to choose not to induct a person in MAT until benzodiazepine use has ceased and not manage a patient’s taper from benzodiazepines during MAT induction. This person may be more appropriate for inpatient detoxification.”

I heartily agree with this, and that’s what I’m doing at present. It’s much easier to get the taper from benzodiazepines done before MAT is started. Once the patient is on MAT, it’s nearly impossible – in my area – to find an affordable inpatient program that will accept patients on MAT, continue to dose them, and also treat the benzodiazepine or alcohol addiction. I hear from doctors in other states that they have inpatient programs willing to admit MAT patients with co-occurring benzo/alcohol addiction, and buprenorphine or methadone maintenance is continued during the admission. If I had that option available, I would use it.

IRETA guidelines say that patients with significant medical or psychiatric problems should be admitted to a hospital (or, I assume, medical detoxification units) for a benzodiazepines taper. Patients who have had benzodiazepine withdrawal seizures in the past also need to be hospitalized for a benzodiazepine taper, as should pregnant patients.

IRETA guidelines address induction of the dose of maintenance medication for patients taking benzodiazepines. Induction, usually considered to be the first several weeks of treatment, is the most dangerous time of treatment. Most overdose deaths happen during that time. As expected, the guidelines suggest using a lower starting dose of the methadone or buprenorphine in a patient with active benzodiazepine use, and daily observed dosing. The guidelines also say patients taking benzodiazepines who are starting MAT should not drive themselves to the facility each day until they have stabilized, and that they need to give permission for the program to call a relative if they come to the facility impaired. Impaired patients are not to be dosed, of course.

This section also recommends repeated attempts to talk with the patient about dose reduction of benzodiazepines and complete withdrawal from benzodiazepines at some point.

Under the section of IRETA guidelines addressing patient non-compliance with a taper agreement, they recommend trying to retain the patient in treatment if possible, but also say to eliminate take home doses so that the patient doses at the OTP facility each day. If the patient is misusing benzos to the degree that their safety is at risk, despite intensified psychosocial treatments, the patient may need to be referred to a non-MAT treatment for their opioid addiction.

I found interesting statements near the end of the IRETA guidelines, such as:
“Individuals who claim that “nothing else helps” should have a careful evaluation for addiction. Physicians should be aware that the subjective nature of anxiety allows for dishonest presentations of symptoms. The claim that “nothing else helps” is often a direct demand for benzodiazepines from the physician. A reasonable response is a trial of psychotherapy and medications without addictive potential.”

“Benzodiazepines should not be the first-line drug for any disorder.” And “Clinicians are advised not to use benzodiazepines to treat co-occurring psychiatric disorders.”

These statements illustrate the essence of the issue. Benzodiazepines have limited clinical indications. Use for more than three months has little benefit because of the quick development of tolerance to the anti-anxiety effect of the benzodiazepine. For that reason, they aren’t first-line drugs for anxiety disorders. And yet many prescribers take the “nothing else helps” statements at face value and prescribe benzodiazepines for years.

More statements about how to prescribe benzodiazepines from the IRETA guidelines:
“For people receiving methadone, physicians are advised to prescribe a benzodiazepine with a slow onset and long duration of action, at the lowest dose, and for the shortest duration possible.
Document education and treatment decisions during the initiation of benzodiazepines.
Avoid prescribing alprazolam to individuals receiving methadone.
Benzodiazepines with substantially lower abuse potential (e.g. oxazepam, clorazepate) are strongly preferred over benzodiazepines with a rapid onset, such as diazepam and alprazolam, which should be avoided because of their abuse potential.
Initiate short-term benzodiazepines with a prescription for no longer than one week.
For a short-course of treatment, the benzodiazepine prescription should be for less than one month.”
“Long-term maintenance of benzodiazepines is rarely indicated and should be avoided.
Providing a maintenance benzodiazepine dose in the context of MAT is to be considered a last-resort option after other alternatives have been exhausted.
One of the few who may benefit from a maintenance dose of benzodiazepine is a person who has long-term opioid and benzodiazepine abuse and is not able to stabilize on opioid substitution medication alone.”

These statements assure me that long-term benzodiazepine prescriptions are a bad idea for the majority of patients on medication-assisted treatment, but there may be some rare patients for whom it may be of benefit, though close monitoring is essential.

This is a controversial area. I appreciate IRETA’s time and effort in formulating these guidelines. I think they will be helpful as OTP doctors struggle to define a standard of treatment that is safe, yet not unduly restrictive for patients with serious mental health issues.

The Benzodiazepine Dilemma: New Guidelines for Opioid Treatment Programs from IRETA

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I’ve written about benzodiazepines before in this blog (See my post of November 3, 2012). I worry about overdose deaths and other complications in patients for whom I prescribe methadone who are also taking benzodiazepines, prescribed or illicit.

Now doctors at OTPs have help from the Institute for Research, Education and Training in Addiction (IRETA). This well-respected organization located in Pittsburgh, Pennsylvania just issued an evidence-based document titled, “Management of Benzodiazepines in Medication-Assisted Treatment.” You can access this document at IRETA’s website: http://ireta.org/

I love IRETA for tackling this subject. There’s much misinformation about the use of benzodiazepines, even for patients without addiction. But for patients with addiction, benzodiazepines can be deadly when combined with opioids including methadone and buprenorphine.

IRETA’s document first describes how and why these guidelines were created. Opioid treatment programs often have patients who also use benzodiazepines, both by prescription and illicitly. Physicians at OTPs have widely varying responses to these patients. Some programs have zero tolerance, meaning they won’t allow anyone on benzodiazepines to be in their opioid treatment program. Other physicians at OTPs actually prescribe benzodiazepines for their patients when they feel it’s clinically indicated. IRETA wanted to delve into actual scientific literature and consult a panel of experts for interpretation of that data. This IRETA document describes in detail how the literature search was done. It also goes into exhaustive detail about how each statement in the set of guidelines was vetted by experts.

This paper’s guidelines fall into seven categories:

General guidelines
Assessment for MAT
Addressing benzodiazepine use
MAT for patients with concurrent benzodiazepine use
Noncompliance with treatment agreement
Risk management/Impairment assessment
Special circumstances

Here are the general guidelines, taken directly from the document:

CNS depressant use is not an absolute contraindication for either methadone or buprenorphine, but is a reason for caution because of potential respiratory depression. Serious overdose and death may occur if MAT is administered in conjunction with benzodiazepines, sedatives, tranquilizers, anti-depressants, or alcohol.
People who use benzodiazepines, even if used as a part of long-term therapy, should be considered at risk for adverse drug reactions including overdose and death.
Many people presenting to services have an extensive history of multiple substance dependence and all substance abuse, including benzodiazepines, should be actively addressed in treatment. MAT should not generally be discontinued for persistent benzodiazepine abuse, but requires the implementation of risk management strategies.
Clinicians should ensure that every step of decision-making is clearly documented.
Clinicians would benefit from the development of a toolkit about the management of benzodiazepines in methadone treatment that includes videos and written materials for individuals in MAT.

Please note that under the third point of the general guidelines, it says patients shouldn’t be taken off MAT because of repeated benzo use, but need “risk management strategies.” That’s a little vague, but IRETA guidelines go into more detail later in the document.

IRETA’s second section of guidelines is about assessment for MAT. The guidelines say all of the usual things; for example, they say a doctor should do a complete evaluation of a patient presenting for treatment, as described in SAMHSA’s TIP (Treatment Improvement Protocol) 40 and 43. The evaluation should include the patient’s history of medical problems and history of all drug use, even over the counter medication. A mental status assessment and a drug screen should also be included.

Also under the assessment section, IRETA suggests adding patient education about the dangers of mixing benzos with methadone or buprenorphine. I like this idea, and I do something similar. When I ask about past drug use, I always warn patients about the potential bad outcome of mixing benzos and alcohol with the medication I’m going to prescribe, and I repeat the warning at the end of our interaction.

IRETA suggest doctors go farther, and give patients information not only about overdose risk, but also about the other problems benzodiazepines can cause. Benzodiazepines are associated with a greater risk of depression and suicide. Having a prescription for benzodiazepines doubles a patient’s risk for an auto accident, and increases the risk for other accidents, like falls. Taking a benzodiazepine prescription is associated with an increased risk for hip fracture.

The IRETA guidelines remind us that there is “Substantial and growing literature that suggests long term use of benzodiazepines (especially in large doses) leads to cognitive decline.” (page 16 of the report) the guidelines also say that benzodiazepines are associated with emotional blunting, and long-term sleep and mood disturbances. Even more relevant, studies show that patients on benzodiazepines have worse outcomes in medication-assisted treatment.

The third section of IRETA’s guidelines is about addressing benzodiazepine use. They say that a patient should be willing to address their benzo addiction. IRETA says that uncontrolled use of benzodiazepines is a contraindication to treatment with methadone or buprenorphine because of the “extremely high risk for adverse drug reaction involving overdose and/or death during the induction process.”

I’m in the “amen” corner for that one! But it’s hard for me to know which patients use benzos occasionally to help opioid withdrawal, and which patients use benzos heavily in an uncontrolled manner. Most patients, seeing me for admission to MAT, minimize their use of benzodiazepines, knowing it’s a big issue. If they’re getting benzodiazepine prescriptions in large amount from multiple doctors, I can see that on our state’s prescription monitoring program. If the patient is taking benzos illicitly, I may not have a way to know this. Information from family members and friends can sometimes help, if the patient will allow. Or family members and friends may be as heavily involved in addiction as the patient presenting for treatment.

The IRETA guidelines remind us that patients on long-term benzodiazepine therapy are at risk for adverse drug reactions which can include overdose and death. The guidelines say that central nervous system depressants are not absolutely contraindicated with methadone, but also put patients at risk for overdose and death. I assume at this point in the document, its authors are referring to other non-benzo central nervous system depressants like carisopradol (Soma), zolpidem (Ambien), and the other “z” sleep medications, and perhaps pregabalin (Lyrica).

IRETA’s benzodiazepine guidelines for OTPs are extensive, so I’m going to split my review of the contents over two blog entries. Stay tuned…or even better, go read them for yourself:

http://ireta.org/sites/ireta.org/files/Best%20Practice%20Guidelines%20for%20BZDs%20in%20MAT%202013_0.pdf

1. Thomas et al, “Benzodiazepine use and motor vehicle accidents. Systematic review of reported association.” Canadian Family Physician, 1998 April;44:799-808.
2. Smink et al, “The relationship between benzodiazepine use and traffic accidents: A systematic literature review.” CNS Drugs, 2010 Aug.24(8)6390653.

Really Scary: How to Die from Methadone

aaaaaaaaaaaaaascary

Here’s something really scary for Halloween.

Though methadone is a life-saving medication when used in the right way in the right patient at the right time, it can also be deadly. When methadone is used to treat opioid addiction, the first few weeks are the most dangerous. More than half of methadone drug overdose deaths occur during the first two weeks of treatment. The opioid treatment program physician is responsible for starting the methadone at the proper dose and increasing it in a proper way, but there are things the patient can do that increase the risk of overdose deaths. Here are a few of them:

1. Exaggerate your use of opioids to the doctor. Tell her you are accustomed to taking twice the amount that you actually use. You do this out of fear that you won’t get enough medication on the first day to keep you out of withdrawal, but the result may be that you get so much methadone that you don’t wake up.
2. Don’t tell your doctor about your benzodiazepine use. Even though you’ve been using two or three “ladder bars” per day, tell her you only used once last week, just to stave off opioid withdrawal. Assure her all of you drug screens will be negative for benzos, though you’re inwardly worried you won’t be able to stop taking Xanax. You tell this lie because you’re worried she would send you to a medical detox facility for benzos before accepting you into methadone treatment, and you don’t want to do that. Sadly, if you overdose and die from mixing methadone and benzo, you won’t have a chance to go to detox – or to see your children grow up.
3. Because the stupid doctor only started you on 20mg of methadone the first day, talk to drug buddies to see where you can buy extra methadone to supplement that dose. You are sure you’ll be in withdrawal, and can’t stand the thought of any discomfort. You don’t believe the doctor, who said your methadone blood level will increase each day even if you don’t go up on your dose, due to the very long action of methadone.
4. Since you know more than the doctor, drink alcohol with your methadone. You don’t believe that alcohol can kill you while you are on methadone, since alcohol is legal. After all, you don’t drink beer at the same time as your methadone dose, so you think it’s safe. Again, you don’t believe your doctor when she said alcohol later in the day is also dangerous, due to the very long action of methadone. What does she know? You are the expert on drugs.
5. You read on the internet that other people mix benzodiazepines and alcohol with methadone, and have not died. It must be true. Besides, you know your limits.

When I talk to patients about the dangers of overdose while on methadone, I hate to hear them say something like, “Don’t worry. I know my limits.” It gives me a shudder, because I remember the names of three patients who have said this to me…now all dead from drug overdoses.

Thanks to Dr. Payte for the inspiration.

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