Archive for the ‘Overdose deaths’ Category

The Benzo Conversation

Glass head full of pills

Not all of my patient interactions are easy. One of my colleagues, after reading my blog, remarked, “It sounds like you have really easy patients.” While that’s true for the most part, of course there are more difficult patients, as in any practice. Some patients, eager to get into treatment to stop opioid addiction, may not be at all ready to stop other drugs of addiction. That’s not a deal-breaker for me, unless those drugs could be fatal when mixed with methadone or buprenorphine. This means the use of alcohol, benzodiazepines, and sedatives of other kinds must be discussed in detail.

I’ve noticed a conversational merry-go-round that I call “the benzo conversation.” I’ve had versions of this conversation more times than I can remember.

This conversation occurs during my initial assessment of a new patient presenting for medication-assisted treatment. I always look on my state’s prescription monitoring program for each new patient on the day of admission. If they have prescriptions for benzodiazepines (like Xanax, Valium, or clonazepam), or other sedatives (Soma, Ambien, etc.) I need information about the pattern of use. Is my patient taking his prescribed daily dose? Is he then physically dependent on benzodiazepines? Is he selling them? Is he giving part of the prescription away, and taking the rest? Does he binge on benzos for the first few weeks of the month, and then run out for several weeks? Or is he bartering the benzos for opioids, and not taking any of them, despite filling a large prescription each month?

I really don’t care if the patient is breaking the law or not; I just want to get the complete picture of my patient’s health status.

Following is a typical conversation with a new patient whom I will call “Bob.”

Bob sought admission to our methadone maintenance treatment program for his opioid addiction. He had snorted pain pills for six years, and wanted help. He had little if any denial about his opioid addiction. He denied taking any prescription medications, saying he got all his opioids off the street, used no other drugs or medications, and had no other medical problems.

However, when I checked his name on my state’s controlled prescription monitoring program, he was filling a prescription for Xanax 2mg, ninety per month, from a local Dr. Feelgood. This prescription had been filled every month for the last four years. My patient’s admission urine drug screen also tested positive for benzodiazepines.

As part of my initial history and physical, I asked him about the Xanax prescription. I explained to Bob that benzos have the potential to cause a fatal overdose when mixed with opioids. I told him that benzos are especially risky with methadone, and I was concerned about his use of them.

Bob said, “Oh, I don’t use benzos now. I haven’t used Xanax for years.
“But you’ve been prescribed it every month and picked up the last prescription of ninety pills just two weeks ago.”
“Yes, but I don’t take them. I quit them long ago.”
“And you do have benzos in the urine sample you gave us.”
“Well, that’s probably from a little piece of Valium I used four days ago.”
“Ummm…, Valium’s also a benzo, in the same family as Xanax, so when you say you’ve stopped, that doesn’t make sense to me.…”
“As I told you, I don’t take benzos anymore.”
“But four days ago is pretty recent.”
“No,” he said, getting a little worked up. “As I’ve already told you, I stopped benzos years ago!”
“So what do you do with the Xanax pills you pick up at the pharmacy every month?”
“I don’t know. They’re in the house somewhere. But I don’t take them.”
“So you have…how many bottles do you have at home?”
“Bunches, I don’t know.”
I could tell I was annoying him, but this as an important clinical issue, so I pushed on.
“Would you be willing to bring all those bottles in tomorrow so the nurse can watch you dispose of them?”
He sighed deeply, annoyed by my questions. “Yes. I suppose I can. Now can I get my dose?”
“No, I’ll leave an order for you to be able to start tomorrow after you bring in the medication to dispose, since you tell me you haven’t taken them. I worry about a fatal overdose if methadone were combined with all that Xanax you have at home.”
Now he was mad. “I don’t have any Xanax at home! I’m not going to overdose! I know what I’m doing.”
“Will you give me permission to call the doctor prescribing the Xanax, so we can talk about your entry into treatment here? Maybe your doctor would be willing to taper your dose so that we can make it safer for you to be in treatment with us.”
“No! I don’t want everybody to know my business. My doctor is friends with my ex-wife and if she finds out I’m being treated for addiction, she’ll cause trouble. He can’t find out.”
“I’m sorry, but that’s a deal-breaker for me. I’m not going to prescribe methadone for you unless I can talk to your other doctor. It’s just too risky. All of your doctors need to know all medications that you’re on.”
“So you’re telling me to go back out there and use drugs? That I can’t get help unless my ex-wife finds out I’m an addict?” The veins in his neck were standing out.
“No. I’m not telling you to use drugs. I’m telling you…
“I want my money back, since I’m gonna have to go buy dope again ‘cause you won’t help me. It’s just not right. I came here to get help.” He stalked off toward the receptionist, where I heard him demanding his money back, despite the hour he spent with a counselor and the time spent with me in an evaluation. (For some reason, patients who don’t get admitted to the program don’t feel they should have to pay for their evaluation)

This was a difficult, tense conversation, and one I’ve had too many times to count. This patient wasn’t a bad guy, but he was not ready to address his benzodiazepine use. The outcome wasn’t what I’d hoped, and this patient didn’t come into treatment.

There’s no way I could know what this patient was doing with his benzodiazepine prescription. I couldn’t tell if this patient was telling the truth, in denial, or lying. Without being able to talk to his prescribing doctor, I wasn’t willing to start medication-assisted treatment. This didn’t mean he didn’t need treatment, only that perhaps a different form of treatment will be safer for him. I wish I could have given him information about other treatments, but he left too quickly and too angrily.

Sometimes patients tell me I’m violating their privacy by looking at their information on the prescription monitoring database. I tell them I don’t see it that was at all, since they are asking me to prescribe a medication that could have a fatal interaction with other medications. Not only is it my business, it’s my responsibility.

Some doctors would fault me for not admitting this patient despite his refusal to allow me to talk to his prescribing doctor, given the increased risk of death for patients in active opioid addiction who are not in any treatment. But I would feel terrible if I’d admitted this patient and he died during the first few weeks of a methadone/benzodiazepine overdose. Either way, there’s a lot at stake, and I feel stress about these decisions.

Durham, North Carolina: First in the South to Provide Naloxone to Departing Inmates

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The county jail’s addiction treatment program in Durham County, North Carolina, just started giving naloxone overdose prevention kits to inmates leaving their program.

This program, called STARR (Substance Abuse Treatment and Recidivism Reduction) consists of around 83 hours of group therapy, addiction treatment education, and weekly 12-step meetings. STARR participants are also taught how to respond to an overdose, and how to use naloxone. Inmates completing this program are also eligible to enter an additional voluntary four-week program known as GRAD. All graduating inmates are offered a naloxone kit.

At any one time, the STARR program has about 40 inmates in treatment.

Only three county jails in North Carolina offer addiction treatment services. Besides Durham County, Mecklenburg and Buncombe Counties have similar addiction treatment programs, but neither of the latter two offer naloxone kits. The development of education and prevention of overdose was achieved only after long efforts by the STARR program’s director, Randy Tucker, collaboration with the Harm Reduction Coalition.

Durham County is setting the right example for the rest of the nation.

It’s important to teach inmates with addiction how to avoid overdose. Inmates with addiction are at high risk for a fatal overdose during the first few weeks after their incarceration. While in jail, their tolerance has dropped. If they leave jail and relapse using the same amount as before they went to jail, an overdose is likely, particularly if they are using opioids.

Studies on all continents show this marked increase in overdose death among opioid addicts leaving incarceration. The degree of increased risk is debatable. Some sources say the risk is increased four-fold and others estimate a hundred-fold increase in overdose deaths risk, mostly within the first two weeks after leaving incarceration.

Last year, four people leaving the Durham County jail had fatal overdoses.

If the US treated addiction as the public health problem that it is, all state, county, and federal jails would provide naloxone upon dismissal from incarceration. (I won’t even get into the arguably more important issue of providing adequate addition treatment to inmates whose main problem is addiction). But we don’t do that in this country, still preferring to see addiction as bad behavior by deviants.

Ferguson, Missouri…Baltimore, Maryland…think how the attitudes and outlook of citizens could change, if jailers started handing out naloxone kits to departing arrestees.

Even without words, this action would go a long way toward giving arrestees the message that law enforcement saw their lives are valuable and worth saving.

Is Heroin the New Opana?

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From CDC data released 3/15

From CDC data released 3/15

The Center for Disease Control and Prevention (CDC) released new data last month showing a rapid rise in heroin overdose deaths. While total overdose deaths from opioids remained level for the past few years, deaths involving heroin escalated sharply.

The rate has tripled since 2010, and nearly quadrupled since 2000. Males have a four times higher rate than females with the highest rate seen in white males aged 18 to 44. All areas of the country had increased heroin overdose death rates, but the highest were seen in the Midwest, with the Northeast right behind them. The South, for a change, had the lowest rate of heroin deaths, after the West.

Those of us treating patients at OTPs knew heroin was moving into areas where pain pills once dominated, but I had no idea deaths had tripled in three years. That is appalling even to me, and I see appalling things all of the time. I can’t stress enough how bad this is.

Why is this happening? I’ve read and heard various opinions:

 Some people speculate that since marijuana became legal, that crop is less profitable to Mexican farmers, who switched to growing opium poppies. This is just a theory, though the timing supports the premise. I don’t know how it can be proved, short of taking surveys of Mexican farmers, which seems problematic and unlikely to happen.

 As we implemented measures to reduce the availability of prescription opioids, the price increased. Heroin is now cheaper than pain pills in many areas, and heroin’s purity has increased. Many addicts who can’t afford pain pills switch to heroin to prevent withdrawal. NIDA (National Institute for Drug Addiction) estimates one in fifteen people who use prescription opioids for non-medical reasons will try heroin at some point in their addiction.

Maybe that’s why the South still has the lowest heroin overdose death rates: we still have plenty of prescription opioid pain pills on the black market.

 With the increased purity, heroin can be snorted instead of injected. Many people start using heroin by snorting, feeling that’s safer than injection. It probably is safer, but addiction being what it is, many of these people end up injecting heroin at some point.

 Heroin has become more socially acceptable. In the past, heroin was considered a hard-core drug that was used by inner city minorities. Now that rural and suburban young adults are using heroin, it may have lost some of its reputation as a hazardous drug.

Most experts in the field agree that much of the increase in heroin use is an unintended consequence of decreasing the amount of illicit prescription opioids on the street. But we are doing the right thing by making prescription opioids less available. Physicians are less likely to overprescribe and that’s essential to the health of our nation.

Now it’s critical that we provide all opioid addicts with quick access to effective treatment, no matter where they live.

The face of heroin addiction has changed. It is no longer only inner-city minorities who are using and dying from heroin; now Midwestern young men from the suburbs and rural areas are the most likely to be using and dying from heroin.

In the past, when drug addiction was seen as a problem of the poor and down-trodden (in other words, inner-city minorities), the general public didn’t get too excited. But when addiction affected people in the middle classes, there was a public outcry. The Harrison Act of 1914 was passed due to public demand for stronger drug laws.

I think the same thing will happen now. Suburban parents will organize and demand solutions from elected officials for this wave of heroin addiction. Indeed, I think that’s already started to happen.

Let’s make sure a big part of the solution is effective treatment.

Let’s make treatment as easy to get as heroin.

Alcohol and Opioids (and Benzos) Don’t Mix!

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The Centers for Disease Control and Prevention (CDC) released a report in October of 2014 that analyzed data regarding the contribution of alcohol in opioid overdose deaths and in emergency department visits for opioid misuse. They also looked to see if alcohol was present in benzodiazepine overdose deaths, and emergency department visits related to benzodiazepine misuse. This information was gathered in 2010 by the Drug Abuse Warning System, (DAWN). [1]

The report found that alcohol was a contributing factor in at least twenty percent of the opioid overdose deaths. When they looked at emergency department visits for opioid misuse complications, alcohol was present in about eighteen percent of patients.

In other words, alcohol is a contributing factor in one-fifth of serious opioid overdoses deaths and near-overdoses.

The data was similar for alcohol combined with benzodiazepines; twenty percent of benzodiazepine-related deaths had alcohol present in the decedent’s body as a contributing factor. For emergency department visits related to benzodiazepine use, alcohol was present in over a fourth of these patients.

I don’t find this data to be surprising. If anything, I’d expect a higher percentage of decedents to have alcohol as a contributing factor to both opioid and benzodiazepine overdose deaths. Alcohol and benzos both act on the same type of brain receptors, and have the same sedative effect on the brain. They both also act of the portion of the brain that tells us to breathe while we are asleep. Since opioids have the same effect, particularly at higher doses, any combination of these three substances can result in death. The person goes to sleep, stops breathing, and dies.

Other bits of data in this report were interesting. For example, more men than women had alcohol as a contributing factor in opioid-related and benzodiazepine-related emergency department visits. That’s not a surprising finding, since men have a higher rate of binge-drinking than women.

In this study, older people were more likely to have used alcohol along with their opioid than younger people. Overdoses in people aged 40 to 59 had alcohol in around one-fourth of the deaths.

The study found people who used hydrocodone were more likely to consume alcohol. That’s an interesting finding. Maybe opioid addicts who have hydrocodone available, as compared to stronger opioids like oxycodone, tend to supplement with alcohol in order to boost the effect of the opioid. That’s merely conjecture on my part, but it’s based on conversations with opioid-addicted patients over the last ten years. Opioid-addicted patients will use anything to ease opioid withdrawal symptoms: alcohol, benzos, even cocaine or methamphetamine

For people who overdosed on benzodiazepines, twenty-eight percent were over age 60. There’s another good reason to avoid or reduce benzodiazepines in people over sixty.

I think this data shows we need to do a better job of educating patients not only of the danger of benzodiazepines and opioids mixed together, but that alcohol can be just as deadly with either benzodiazepines or opioids.

I really worry about my patients who drink alcohol while being prescribed either methadone or buprenorphine (Suboxone). Too many of my patients are cavalier about mixing alcohol with other drugs and medications. Many of them say they don’t see alcohol as a real problem, because they’ve been able to start and stop alcohol, unlike opioids. They say alcohol is legal, so what’s all the fuss? They say they don’t drink any more than their friends. Everybody drinks, don’t they?

No, they don’t. About thirty percent of the U.S. population doesn’t drink alcohol at all. Only fifty-six percent have had an alcoholic drink over the past month, which means nearly half of the people in this country haven’t had any alcohol over the last month.

One of my patients told me it was his right as an American to drink alcohol, and was angry at me when I told him of the dangers of mixing alcohol with methadone. I told him I didn’t know if drinking was a right or not; I was only telling him about how alcohol and drugs affect the body.

Sometimes I ask patients what they think about the warning label on their pill bottle that says, “Do not take with alcohol.” Some patients say they don’t believe warning labels because they’ve had alcohol with buprenorphine or other opioids before, and nothing bad happened. Some say they think the warning labels are put on all medicine bottles to protect the pharmacy from being sued.

Just because something has never happened before doesn’t mean it can’t or won’t happen in the future. Many factors can influence overdose risk, and it’s dangerous to assume an overdose can’t happen because it hasn’t happened before.

1. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6340a1.htm

Expanding Access to Buprenorphine

aaaabalance

My last blog post stimulated some lively debate, and I thought this topic deserved further discussion. However, I would like to ask commenters to talk about the issue and please refrain from mentioning specific names of previous commenters. Please and make your points in a thoughtful and respectful manner. Thanks for your cooperation.

Given our present epidemic of opioid addiction and opioid overdose deaths, authorities are considering lifting the 100-patient limit for physicians who prescribe buprenorphine from office-based settings. Some people in the addiction treatment field oppose expanding access to buprenorphine in the office setting, saying some of these patients don’t get the counseling that they need, but only medication. They say there aren’t enough regulations to prevent shady physicians from opening buprenorphine mills.

Experts on both sides of the debate make good points. It’s a tough topic, but let’s explore the issues further.

1. “You don’t provide enough counseling.”

Weirdly, this used to be a main complaint against OTPs, but now OTP personnel are directing the same complaint toward office-based buprenorphine physicians.

Is there any data to help us decide how much counseling is enough for opioid-addicted patients who are started on medication, either buprenorphine or methadone?

The POATS trial gives some information on this topic. (Weiss et al, 2010, http://ctndisseminationlibrary.org/protocols/ctn0030.htm )

POATS showed that opioid-addicted patients maintained on buprenorphine/naloxone were likely to reduce illicit opioid use during treatment with the medication, but most relapsed after being tapered off the medication at twelve weeks. So this part of the study supported keeping patients on medication longer, just like the older data with methadone for heroin users. No surprises so far.

Now comes the interesting part: POATS showed similar outcomes for patients getting standard medical management versus standard medical management plus fairly intense counseling. The group with added counseling didn’t do any better than the standard medical management group.

However, the standard medical management consisted of an hour-long first visit with the doctor, and a fifteen- to twenty- minute visit per week for the first four weeks, then every two weeks.
This may be more than an average buprenorphine doctor provides in real life. It’s a little more than I do for my office-based patients. My first visit with new patients is one hour, and usually I see them back in one week for a twenty-minute visit. But then, if they are doing well, I see them every two weeks, until the patient is established in counseling. After that, if all is going well, I cut down to monthly visits. I conclude that the average buprenorphine doctor may have to increase visit frequency to get the results seen in the POAT study.

The group with enhanced counseling treatment got 45 minutes with a counselor twice per week for the first four weeks, then twice per month. At present, patients of OTPs must have two counseling sessions per month, even at the beginning of treatment. Opioid clinic opponents say twice per month isn’t even close to enough counselling, and use this point as a reason to say opioid treatment programs deliver bad care.

The POAT study was relatively short. Twelve weeks may not be long enough to detect an improvement in patients getting enhanced counseling. We know life changes usually don’t happen quickly. Maybe it is unfair to say the counseling didn’t help, because the patients weren’t followed long enough.

Now let’s look at interim methadone. Interim methadone was proposed as an alternative to long waiting lists for patients to enter an opioid treatment program. People were concerned about the welfare of opioid addicts who wanted help, but had to wait for a treatment slot to open. Interim methadone is a short-term, simplified treatment where methadone medication is started for the opioid addict, until the patient can be admitted to an OTP. With interim methadone, some counseling given, but only for emergency situations. Drug screening is still done, but is more limited than for OTP patients. These interim patients can transition to a traditional opioid treatment program when a slot opens for them.

It appears that starting just methadone, with limited other services, still helps the patients. Studies show these patients are less likely to continue to use heroin, are less likely to commit crimes, and more likely to enter a full-service OTP when admission is offered. [1]

Would “interim buprenorphine” work as well? I don’t think there are any studies to give us data, but it seems logical that it would.

2. “Just apply to be an OTP”

Government officials have said that if office-based physicians wish to see more than one hundred buprenorphine patients, the physician should apply to become an opioid treatment center.

When I first read this suggestion, I laughed, because it sounded so silly to me. Well-intentioned though this statement might be, it starkly exposed a lack of knowledge of the average physician’s economic circumstances.

I don’t know many doctors like me who have the necessary capital to do this. Some professionals in the field estimate it takes starting capital of around a quarter of a million dollars. I’ve seen one OTP fold due to inadequate financial support and management, and another escape closure by a narrow margin. These days, it takes deep pockets to afford the eighteen to twenty-four month process to establish an OTP. Getting the certificate of need alone can take years. (Just look at Crossroad’s struggles to get a CON in Eastern Tennessee, an area with arguably more opioid addiction per capita than most other states!)

OTP sites must be approved by multiple agencies: the DEA, CSAT, SOTA, and local authorities to name a few. The pharmacy has to meet strict regulations, as do personnel. If you want to accept Medicaid, that’s another avalanche of regulation and paperwork.

I’m not saying it’s impossible for a physician to open an OTP, but I am saying that it would cost so much that most doctors who treat opioid addiction wouldn’t consider it. I could be wrong – maybe my colleagues are making a whole lot more than me…

3. “In it for the money.”

Experts in the field who work for opioid treatment programs oppose expansion of office-based treatment, saying doctors charge exorbitant fees for their patients. Sadly, in some cases, they are right. But many office-based doctors charge reasonable fees. If we allowed doctor to treat more than one hundred opioid-addicted patients at one time with buprenorphine, wouldn’t that reduce demand for services? And when demand decreases, shouldn’t cost of treatment drop too?

For example, let’s take a community where one buprenorphine doctor is price gouging, and charging $500 per month for only one doctor’s visit. The second buprenorphine doctor charges $250 per month for the same service plus addiction counseling. Both are at their one- hundred patient limit. If both were allowed to increase the number of their patients, wouldn’t the second, more reasonably-priced doctor get some of the more expensive doctor’s business?

Conversely, some advocates for office-based treatment say that opioid treatment programs are upset because they have lost money in recent years. They accuse organizations like AATOD of wanting to limit further expansion of office-based programs because it cuts into their business. With more access, more patients would abandon OTPs for these less restrictive programs

DATA 2000 changed the landscape of opioid addiction treatment. OTPs aren’t the only option for patients seeking treatment for their opioid addiction.

My point is, both OTPs and buprenorphine doctors can accuse the other group of being in it for the money. But as I pointed out in my last blog…no medical treatment in this country is free.

4. “My medication is better than your medication.”

Patients entering opioid addiction treatment often ask me, “Which is better, buprenorphine or methadone?” I say, “Both.” Each has its advantages, and I’ve discussed this in previous blog entries. Briefly, buprenorphine is safer, since there is a ceiling on its opioid effects, but it’s more expensive. Patients on buprenorphine also seem to leave treatment prematurely more often than methadone patients. This isn’t a good thing, since the majority of these patients relapse back to illicit opioid use.

Methadone, as a full opioid agonist, may be more difficult to taper off of, and maybe fewer patients leave treatment prematurely because of that feature. Methadone has been around for fifty years now, with a proven track record. It works, and it’s dirt cheap. Methadone does have more medication interactions, but those can usually be managed if all the patient’s doctors communicate with each other.

Buprenorphine isn’t strong enough for all opioid addicts. Because it’s a partial agonist, there’s a ceiling on its opioid effect. This property means it’s much safer than methadone, but it doesn’t work for everyone.

Buprenorphine is safer than methadone, which to me is its best quality. I’ve started hundreds of patients on buprenorphine and never had an induction death. Sadly, I cannot say the same of methadone. I am not saying overdose death is impossible with buprenorphine…I’m saying it’s much less likely, and that’s worth a lot to me.

Buprenorphine’s superior safety profile is one reason it was approved for use in an office setting. Methadone is riskier to prescribe from an office, because misuse and diversion is more likely to be fatal with this drug. That’s why buprenorphine has fewer restrictions on it. Neither medication is good or bad; the difference between the medications is pharmacologic, not moral.

Next week, I’ll describe my OTP, where we provide methadone, buprenorphine under the OTP license, and buprenorphine under my office-based license, all on the same premises. I think we’ve created a continuum of care that’s able to meet the needs of patients as their recovery evolves.

At our program, it’s not one program versus another. Difference patients need different things, and the same patient may need different things at different points in recovery.

1. Schwartz et al, “A Randomized Control Trial of Interim Methadone,” Archives of General Psychiatry, 2006

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.

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