Archive for the ‘comorbidity’ Category

COVID and Opioid Overdose Deaths





People in the U.S. are dying from more than just COVID. Opioid-related deaths have increased in nearly forty states this year, coinciding with the COVID pandemic. According to a recent New York Times article, opioid overdose deaths showed a slight drop in 2018, went up again somewhat in 2019, but in 2020 they have risen by around 13%. [3]

The article says the drop in opioid-related overdose death in 2018 reflected fewer prescription opioid pills available for misuse by people with opioid use disorder. Then by 2019 fentanyl was found at ever-increasing frequency and purity in heroin, causing the increase in overdose deaths.

An article by the AMA (American Medical Association) was released just last week, reporting similar findings nationwide. The AMA article says that at least forty states are reporting increases in opioid-related mortality, mostly due to fentanyl-containing drugs. [4]

My state of North Carolina has seen a jump in drug overdoses since March of this year, compared to last year.  According to our state’s Department of Health and Human Services, overdose visits to emergency departments from potentially addicting drugs increased to 1,454 in the month of June in 2020 statewide. This compares with 1,145 in June of 2019 [1]

Other states report similar news.  In a blog last month by Margaret Williams, M.D. says that in Franklin County, home to the state’s capitol of Columbus and to The Ohio State University (my medical school alma mater), during the first four months of 2020, overdose deaths were up by 50% compared to 2019. That’s a big jump. [2]

Why is this happening? In Dr. Williams’ blog, she cites some possible causes: increased financial stress from job loss during COVID and increased stress from social isolation could be a trigger for increased drug use. Boredom and loneliness could also be triggers for use. Then there’s the fearful stress of contracting the COVID virus. Since usual social networks have been interrupted, more people may be using drugs alone, with no one available to call for help or administer Narcan if they overdose.

I agree with Dr. Williams. When people with substance use disorders of all types experience stress, they tend to seek a chemical solution to alleviate that stress. More alcohol has been consumed in this country since the COVD pandemic hit, and so it makes sense that people who prefer opioids would seek to use more opioids when stressed.

It’s not just drug use that people use to alleviate stress. Think of the extra weight many people have gained, eating because they are bored, fearful, or lonely. We humans use drugs, food, sex, gambling, or other things to make us feel better when we have bad feelings. The COVID pandemic has exaggerated ordinary stress for most people.

Conversely, people with substance use disorders are often at higher risk for contracting COVID 19. If they are homeless, they may lack simple things like soap and water. Incarcerated people, the majority of whom have substance use disorders, are subjected to crowding and may lack personal protective gear.

People with substance use disorders may have higher rates of other chronic illnesses, like HIV and Hep C. Most people with substance use disorders smoke cigarettes, a risk factor for contracting COVID and for having more severe illness from COVID.

People with substance use disorders may have even more difficulty that usual accessing treatment services during the COVID pandemic. Despite the push for substance use disorder treatment facilities to remain open, some closed their doors to people at higher risk for COVID infection. For example, some have refused to take new patients directly from jail or prison, due to the increased risk of those patients for COVID>

During COVID, the AMA is asking state governors and state legislatures to remove barriers to treatment of opioid use disorder, specifically by allowing telemedicine to be used for admission and prescribing of life-saving medications. They also ask that other barriers such as prior authorizations for insurance coverage be removed. They ask states to remove barriers for patients with pain, such as dose caps, quantity limits, and refill restrictions. They advocate harm reduction strategies be implemented and supported, such as needle exchanges.

This is all commonsense stuff, not too different from what the addiction treatment field has been asking for years.

Except now, it’s more urgent.

Most providers I know have used telehealth to communicate with their patients. Even though I personally don’t like it as much as in-person visits, it has been a godsend. The technology isn’t perfect, and patients with poor connectivity have a harder time connecting with providers.

For the opioid treatment program, relaxation of the formerly strict take home regulations probably helped the most. We reduced crowding in our waiting room dramatically because of this. It also reduced wait times for patients when they do come in. We still are giving these extra take homes, which I expect will continue until the governor revokes the status of “State of emergency.” Most patients have been helped with the extra take homes, though a few weren’t able to manage their medication as well as we’d hoped. So far as I know, we haven’t had any deaths due to extra take homes, nor have I heard of this from any practitioners working in NC opioid treatment programs.

In other words, I don’t see any evidence that extra take home doses from opioid treatment programs are fueling the rise in opioid overdose deaths. I believe the increase is due to overall stress in the lives of people who use opioids who are not in treatment.



Methadone Induction: Be Careful

Graphic illustrating how methadone blood level rises over five days with no dose change




This blog is written with gratitude to Thomas Payte M.D., a leader in the field of Addiction Medicine, who passed away in 2019.  Many years ago, I listened to an ASAM (American Society of Addiction Medicine) lecture by Dr. Payte (on cassette tape, which shows how long ago this was) that changed the way I did methadone induction.

At the time I started working at an opioid treatment program, I felt much empathy for the patients suffering opioid withdrawal when I admitted them to treatment. With the best intentions, I wanted to help them get out of withdrawal as quickly as possible, so I started them at doses higher than I probably should have and increased their doses daily. The other physicians I worked with practiced in a similar way, so I thought that was the way it should be done.

We had patient induction deaths. I learned some things the hard way, but also started going to ASAM conferences and listening to ASAM lectures, which was when I had the good fortune to hear Tom Payte.

Decades later, I can’t be sure exactly what he said, but this is what I remember:

He cautioned that induction deaths were relatively rare but devastating. If we start every patient on 30mg, eventually a patient will die during induction. That shook me up, because not only was I starting patients on 30mg, quite often I was dividing their dose on Day 1 to get a total of 40mg. He said patients inherently metabolize methadone at very different rates, and sooner or later a slow metabolizer would arrive for induction, and rapid increases in dosing during induction would be fatal.

Dr. Payte wasn’t unsympathetic to patient misery in opioid withdrawal. He just reminded me that we must temper compassion with science.

Today, induction guidelines look very different from the way I was practicing back when I started. I have changed my induction practices a great deal over the years as I’ve learned more.

Physicians who work at opioid treatment programs have so much more information available now than when I started in this field. It’s so easy to get colleague input about problems: at a national level, there’s the PCSS system, which stands for Providers Clinical Support System, a system for providing information and even mentors for providers who would like them (

At our state level, the North Carolina Governor’s Institute has contracted with me and with Dr. Eric Morse, so that we can be available for questions from providers at any opioid treatment program in the state at any time.

Recently, at an organizational level, our Acadia programs in North Carolina arranged for a monthly phone call for physicians and physician extenders to discuss problems and concerns on a monthly phone call.

ASAM has all sorts of guidelines and position statements ( SAMHSA has publications to help physicians (

Because of all this help that’s available, there’s no reason for any provider working at an opioid treatment program in the U.S. to be ignorant of current methadone induction recommendations.

I recently blogged about ASAM’s newly updated guidelines for the treatment of opioid use disorders. In those guidelines, initial dose of methadone, “ranges from 10 to 30mg, with reassessment as clinically indicated (typically in 2 to 4 hours)…” and then goes on to say, “methadone…generally should not be increased every day.” The guidelines recommend methadone be increased no more than 10mg approximately every 5 days.

If you are a provider who is starting every patient at 30mg and then increasing the dose daily, stop it. You are going to have an overdose sooner or later.

And although these guidelines did say that benzodiazepine use should not be a reason to suspend or withhold treatment with methadone or buprenorphine, they did make it clear that use of sedative-hypnotics with these medications increases the risk of serious side effects.

In other words, we shouldn’t deny treatment to patients with a co-occurring benzodiazepine use disorder, but we can’t admit them and carry on like their risk is the same as other patients who aren’t on benzodiazepines. Consider lower methadone starting doses and consider slower rates of induction for these more fragile patients. Consider closer observation and more frequent drug screening

The provider has a lot more work to do when a patient is using benzodiazepines. First, that provider needs to figure out, if possible, how extensive that patient’s use is, and decide the appropriate setting for methadone induction. That may need to be at an inpatient facility.

Second, since benzodiazepine prescribing guidelines recommend these medications not be prescribed for longer than three months, except for end-of-life care, an ongoing prescription must be explained. The prescribers of benzodiazepines must be talked to. In my area, most of the benzodiazepines are prescribed by a handful of practitioners.  When I talk to these prescribers, they say the patient complains of anxiety, indicating they think this justifies ongoing benzodiazepines.

That’s not good enough. Benzodiazepines aren’t first-line medications for anxiety disorders. Like opioids did for pain, it appears benzodiazepines make people more anxious when they are used long-term. Benzodiazepines make post-traumatic stress disorder worse, and they complicate ordinary grief reactions. Yet many patients are prescribed benzodiazepines for these reasons.

Third, a plan must be formulated to reduce the risk for the patient. In most cases, this means a reduction in benzodiazepine use by some method. If the patient can control their use of benzos, their prescriber can gradually lower their dose. Most of the time the patient can come off benzodiazepines, or at least get by with much less of these medications. In the meantime, a more appropriate medication for anxiety can be started for better treatment of anxiety.

In many cases, the patient needs trauma-focused therapy to address old issues. Many, perhaps most, of our patients have experienced serious physical, sexual, or emotional trauma in their lives. Appropriate counseling and medication can be just as life-changing for patients as can treatment for their opioid use disorder.

Since alcohol is as big a risk as benzodiazepines, the same cautions during methadone induction need to be taken for patients with alcohol use disorders. Start with lower doses and increase more slowly.

More cautious induction must be considered for medically fragile patients: those with underlying pulmonary disease, lower body weight, those on multiple medications, and the “elderly” over fifty years old. And be sure to ask about opioid use over the preceding week. If a patient was admitted to a detoxification unit, or just got out of jail or a hospital, their opioid tolerance will be lower, and the patient needs a lower methadone starting dose.

If their admission drug screen is negative for opioids, stop for a moment to consider what this means. Does the patient really have opioid use disorder? Has the patient taken an opioid recently that doesn’t show on your drug screen? Or has the patient been unable to use opioids for the last several days? If the latter is true, consider a lower starting dose.

Don’t do cookie-cutter inductions. Carefully evaluate each new patient and gather all the data that you can, including history and physical, old records, the prescription monitoring program, and other treating physicians to help you make the best decisions possible. There will always be that pull…trying to get the patient out of opioid withdrawal so they can stop using dangerous illicit opioids….while trying to provide safe methadone induction.

I’ve written mostly about methadone induction because it’s much trickier than buprenorphine. Methadone is much less forgiving during induction than buprenorphine. With buprenorphine induction, just make sure you don’t start too soon and make your patient sick. At times I wish all my patients could do well on buprenorphine, but that’s not possible. We will never have one medication that works well for everyone. Many patients never feel right on buprenorphine, or it isn’t strong enough to treat their opioid use disorder.

I’m more cautious with methadone induction prescribing now than when I started many years ago. This is from a combination of experience and learning from experts. I strongly recommend the latter form of learning; it’s much less painful.

Complex Connections: Pain, Opioid Use, Suicide, and Opioid Use Disorder




Early this month, the New England Journal of Medicine published a review article about this topic. This article, titled, “Understanding Links among Opioid Use, Overdose, and Suicide,” summarized what we know so far about the twin epidemics of suicide and opioid use disorder. [1]

According to the authors, as unintentional opioid overdoses have risen over the past few decades, so have suicide rates, with both more than doubling from 2000 to 2017. We know that opioid use increases risk of unintentional overdose, but it’s been found that opioid use also increases the risk of suicide. People with opioid use disorders are more likely to commit suicide than people with other types of substance use disorders.

Why is this?

The article points out some specific pathways that cause vulnerability to overdose and suicide.

Pain causes changes in the brain that alters its reward system. We know patients with chronic pain are at increased risk for suicide, as well as riskier use of opioids. When opioids became more available at the turn of the century, due to efforts to treat pain more adequately, the average dose per capita increased seven-fold between 1997 and 2007. This availability increased the numbers of people who developed opioid use disorder, which is linked to both unintentional overdose and suicide. Higher doses of prescribed opioids are associated with higher risk for both unintentional overdose and suicide.

This article explained the two primary theories about the connection between increasing rates of both suicide and opioid overdose deaths.

The first theory says that both types of deaths are “deaths of despair,” meaning they occur in people whose general economic conditions are falling. Due to lack of opportunities, social isolation, legal problems and/or economic inequalities, people feel desperate, and look for ways to cope. Opioids dull emotional pain as well as physical pain, but according to this theory, also cause worse depression. This increases suicide risk and overdose risk. This theory is called the demand-focused hypothesis.

Or it could be the other way around, as the second theory explains: increased use of opioids causes decline in social function and increased risk of opioid use disorder, which may increase depression. This is called the supply-focused hypothesis. Studies that show increased suicide risk with higher doses of prescribed opioids would tend to support this hypothesis

To tell the difference, we need quality longitudinal studies to show which occurs first. We don’t have such studies, and we need them. The authors say it’s important to know which theory is more accurate, since public policy approaches to fix the problems would be different if one theory is more correct than the other.

Of course, sometimes we don’t know if a death in unintentional or suicide. Sometimes the people involved don’t even know. I’ve talked to many patients with opioid overdose history. When I’ve asked if it was a suicide attempt, they answer, “I don’t know. I just wanted to feel better. If I died, so be it.” How do we classify such an event?

For sure, opioid use disorder brings despair. Some of my patients tell me that they want to live, but they also want their painful struggle to stop. Since death would be one route of release, it becomes a more acceptable option. Hearing this magnifies the importance of getting patients into treatment.

Or maybe the person alters their description of the event, after they survived. If they admit to suicidal intent, they might fear an involuntary commitment to a psychiatric facility, which usually means enforced opioid withdrawal (at least in my area…in some states, psychiatric facilities do provide MAT), so they claim the incident was accidental.

There are shared risk factors for both types of deaths. Both suicide and overdose deaths are more than twice as likely to happen to men than women. White or Native American people have higher rates of both compared to black or Asian people, and highest rates are found in those in their middle years, 41-64.

All mental health conditions are related to higher risk of unintentional overdose, as well as increased risk of suicide. Risks of both events are even higher in people with both mental illness and opioid use disorder.

Knowing the profiles of people at highest risk, can we use that data to intervene and prevent both causes of death? Yes, if they can access help. These patients do the best when both opioid use disorder and mental disorders are addressed at the same time.

Many prescription monitoring programs use numerous factors to determine who is at highest risk for overdose death. Those patients could be given more attention, with detailed assessment and referral to appropriate treatment.

North Carolina added an overdose risk score to its prescription monitoring program recently. It needs fine-tuning, since scores are adjusted upward for factors not always under a patient’s control. For example, I had a patient who is prescribed two Suboxone 8mg films per day. Her pharmacy doesn’t always have them in stock, forcing her to go to other pharmacies. When she does this, her overdose risk score goes up, but it’s not due to anything my patient is doing. In fact, instead of getting discouraged and giving up, she does what she needs to do to stay in treatment. That should adjust her score downward, in my opinion. But the data collectors at the state level have no idea why she’s at multiple pharmacies and assume it’s risky behavior.

I was happy to see this article emphasized the importance of increasing access to medication-assisted treatment for patients with opioid use disorder as a life-saving measure. Of course, they also emphasized a combined approach to treatment, with inclusion of evidence-based forms of counseling.

This study addresses the dilemma of the patient with chronic pain. We know that higher opioid doses are associated with increased risk of overdose death, but we don’t have data that shows tapering that dose reduces the risk of overdose or of suicide. Many practitioners now advocate reduction of patients’ opioid doses to at, or below, the 90 mg MME (morphine milligram equivalents) recommended by the CDC (Center for Disease Control and Prevention) for reducing risk. Might such a reduction make pain worse and trigger suicidal intent? We don’t know.

Some patients on chronic opioids develop hyperalgesia, a condition where the body becomes more sensitive to pain due to adaptations from chronic opioid use. Often those patients feel better as opioids are tapered, but this is far from a universal experience for pain patients.

What I learned from this article was that while we know pain, opioid use, suicidality, and opioid overdose are linked, we are far from understanding precisely how one condition influences the others. So far, we have developed profiles of patients most likely to be at risk, and we should be talking to those patients, doing better assessments. Then we need to increase access to care using evidence-based treatments.

We see the best outcomes when mental illnesses are treated along with opioid use disorders.

  1. Bohnert et al., “Understanding Links among Opioid Use, Overdose, and Suicide,” New England Journal of Medicine, January 3, 2019, pp71-79.

Benzodiazepines: The Next Wave?




In the February 22, 2018 issue of the New England Journal of Medicine, Dr. Lembke and others wrote a perspective article about benzodiazepines, titled, “Our Other Prescription Drug Problem.”

The authors voiced concerns that amidst all the attention being given to opioid use disorders and opioid overdose deaths, we are ignoring the harms from overprescribed benzodiazepines. They felt it would be a tragedy if the present attention to opioid overuse and misuse led to more people being prescribed benzodiazepines, leading to a growing problem with this type of medication

While I am firmly in the amen corner on this one, I know physicians in my state have not ignored this problem. Since the South has the highest rate of benzodiazepine prescribing per capita of the U.S., [1] the opioid treatment program physicians frequently talk about how to reduce the overabundance of benzodiazepines, and the dangers they present to our patients.

We’ve seen the adverse events from benzodiazepines for more than ten years. The National Institute on Drug Abuse (NIDA) says deaths where benzodiazepines were involved quadrupled from 2002 to 2015. NIDA also says that when benzodiazepines are mixed with opioids, the risk of death increases ten-fold, and that three-fourths of all opioid overdose deaths also involve benzodiazepines. About two years ago, the FDA issued a black box warning about the overdose dangers from combining benzodiazepines with opioids.

As the Lembke article says, the number of people in the U.S. who were prescribed benzodiazepines increased 67% from 1996 to 2013. The quantity prescribed more than tripled over that time, indicating higher dose have been prescribed. In 2012, for every 100 adults in the U.S., 37.6 prescriptions for benzodiazepines were written. That’s an amazing – and scary – statistic.

It’s so bad in my area that Xanax functions as a form of currency. Forget bitcoin; Xanax works just like money. For example, it costs two Xanax 1mg pills to get someone to run you to the grocery store and back, assuming no other stops. That’s the going price. If you want to go to the hardware store too, you’d probably have to throw in another Xanax or clonazepam.

It’s a cultural thing. People feel like after they fill a prescription of Xanax or another benzodiazepine, it’s theirs to use as they wish. They can sell them, barter them, or even take them. People don’t even view this as wrong or illegal.

Most experts feel ordinary benzodiazepines are overused and prescribed for too long. Besides their risk when taken with opioids or other sedating drugs, and they have serious hazards when taken long-term. In a blog entry on September 1, 2014, I described a study published in the British Medical Journal that showed people who used sleeping pills died prematurely at a rate three times higher than controls who did not use sleeping pills, in a dose-related fashion. [2]

Studies show people on benzodiazepines (and other sedatives, like the “z” drugs like Ambien, Lunesta, and Sonata) were more likely to die from cancer and were more likely to have falls. Studies show an increased risk of dementia in patients who take these medications, though we can’t say for sure that it’s causal.

To make matters worse, analogues forms of some benzodiazepines are being made overseas in clandestine drug labs. Some are extremely potent. For example, an analogue of clonazepam is so potent that it needs to be dosed in micrograms rather than milligrams and can be bought online. We don’t know the magnitude of harm that could be caused by such drugs, because they are difficult to detect in urine drug screens.

I cringe when I encounter a patient who says, “I’ve been on my Xanax now for ten years. I can’t do without it.” Prescribing guidelines say these medications were never intended to be used long-term. They can be effective for a period of weeks to months, but daily use over three months isn’t recommended.

Certain providers seem to prescribe them for the flimsiest of reasons. I know this because when I request patient records, I see on a problem list: “Anxiety – continue clonazepam.” There’s no mention of other treatment that have been tried, no notation about any sort of counseling, which is very effective for some anxiety disorders. There’s no specification about the type of anxiety being treated. Sometimes benzodiazepines are used to treat depression, but since benzos are central nervous system depressants, they tend to worse depression. Sometimes benzodiazepines are prescribed for post-traumatic stress disorder, even though we know from VA studies that benzodiazepines tend to make PTSD worse. [3]

Other experts feel their positive aspects are overlooked, and that they are effective at relieving short-term anxiety, and at inducing sleep. As the Lembke article points out, benzodiazepines can be helpful when prescribed for less than one month, and when used intermittently. When used daily and for months, those benefits disappear, and the risks of benzodiazepines increase.

We aren’t the only country struggling with the negative effects of benzodiazepines. Other countries have attempted to mitigate the negative effects by putting prescribing guidelines into place for physicians to follow. As you will note, some of these countries have had guidelines in place for decades.




United Kingdom:


Several countries have adopted the guidelines written by the United Kingdom as their guidelines.

Several states and health organizations have taken on the challenge of writing benzodiazepine prescribing guidelines in the U.S.

Like the authors of the Lembke article, I too hope we see a push to use evidence-based data when prescribing benzodiazepines in the U.S.

  2. Weich et al, “Effect of anxiolytic and hypnotic drug prescriptions on mortality hazards: retrospective cohort study,” British Medical Journal, 2014

Older Patients at Opioid Treatment Programs, Part 2



Co-occurring medical issues complicate treatment of our patients at any age, but are more common in older (over fifty) patients.

Any of our older patients who report chest pain need an immediate workup for coronary artery disease (CAD). Since almost all our patients smoke or have smoked, CAD occurs frequently. Few of them know if they have high cholesterol or not, though most know if CAD has occurred in close family members, or if they have a personal history of diabetes or high blood pressure, which are other risk factors for CAD.

Some of our patients have used stimulants, which can cause certain types of heart disease including palpitations from cardiac arrhythmias. Long-term stimulant use can also cause cardiomyopathy, a disease that permanently weakens the heart muscle.

Methadone, but not buprenorphine, can cause a certain type of heart problem known as prolongation of the QT interval. To simplify, prolongation of the QT interval involves the electrical system of the heart. An extreme prolongation can put patients at risk for a potentially fatal heart rhythm problem. Patients with heart disease may need an EKG before and during methadone treatment to look for this specific problem. Minor heart ailments like mitral valve prolapse, or a murmur with no underlying structural problems may not be influenced by methadone at all. When in doubt, it’s easy to get an EKG.

Since my background is Internal Medicine, I feel comfortable reading and interpreting EKGs, as I did in primary care. I refer to cardiologists when there’s a problem. Most often, the cardiologists say that the benefit of methadone outweighs the risks of QT prolongation. That’s helpful, because my patients and I need information about the risk versus benefits of medication, to decide how to best move forward. Each patient is different, the patient must be part of the discussion of risk. Some patients don’t mind the extra risk, while others can be very bothered by it.

Respiratory problems can be made worse by methadone. Buprenorphine can also affect breathing, but to a lesser effect. However, almost always, these two medications reduce the overall risk of death when compared with uncontrolled use of illicit opioids in patients with respiratory problems.

The more severe the respiratory problem, the trickier methadone administration can be. Since opioids, including methadone and buprenorphine, can reduce respiratory drive, COPD with retention of carbon dioxide is one of the most worrisome conditions.

Patients who retain carbon dioxide have such severe obstructive lung disease, most often caused by cigarette smoking, that the patients have problems expelling carbon dioxide, a waste product of respiration. The CO2 accumulates, giving a chronically elevated level. This happens slowly, so that patients’ bodies make accommodations to keep the blood pH normal. Normal patients breathe faster when the body accumulates carbon dioxide, but patients with severe COPD can no longer do this. When respiratory depressants like opioids are used by these patients, there’s a danger that breathing will slow more, causing a potentially fatal build-up of carbon dioxide. In these fragile patients, it is best to use a much lower starting dose of methadone than usual, and to increase more slowly than usual. It’s also much more important to limit other sedative medications (like benzodiazepines, pregabalin, and others) that could further slow breathing.

Patients with kidney failure generally don’t need to have their dose adjusted. Methadone has no active metabolites, and is mostly metabolized by the liver. Less than one percent of the blood concentration of methadone is removed by dialysis, so the patient can dose daily as usual, with no adjustments needed after dialysis. However, the patient with end-stage kidney disease may be debilitated in general by their illness, so physicians need to be cautious when starting methadone, and follow the adage “start low, go slow” with dosing.

Methadone is stored in the liver and metabolized there, but it doesn’t harm the liver. However, if liver function is impaired, the metabolism of methadone may be slowed. This can cause a potentially fatal accumulation of this medication, so any patient with new-onset acute liver failure needs to be monitored more closely. In these patients, we may want to ask them to return to our OTP three hours after dosing, when the methadone level will be at its peak, to assess for sedation. Trough blood levels can be helpful in these patients too.

We used to worry that buprenorphine damaged the liver, and recommended patients with liver disease avoid buprenorphine. However, some big studies didn’t show any worsening of liver function in patients on buprenorphine, so again, the benefits outweigh the risks in most cases.

Two specific types of co-occurring medical problems challenge opioid treatment program staff regarding patient take home status: changes in mental status and mobility issues.

Let’s take mental status issues first.

Cognitive decline is always problematic with aging patients, and perhaps doubly so in patients with substance use disorders. Watching a patient who has done well on methadone for years become more forgetful and scattered in their thinking is so sad. Underlying causes vary. The decline could be due to a reversible cause, from onset of Alzheimer’s disease or other dementia, or other medical problems.

Because we see our patients so often, opioid treatment program staff – nurses, counselors, physicians, and physician extenders – may notice slight changes in cognitive function before their other medical care providers. It’s then up to us to convince patients to go to their primary care provider for a medical workup. We always hope a reversible cause will be found.

Medications can cause changes of mental status in our patients. The classic drugs of misuse have typical signs and symptoms, but sometimes mental impairment can be caused by other medications: toxic levels of anti-convulsants, bingeing on drugs like gabapentin, pregabalin or muscle relaxants, or interactions between medications. Benzodiazepines are infamous for causing mental slowness and even associated with increased risk of dementia.

Patients diagnosed with chronic mental decline, like that seen with dementia, are most difficult to manage. With these patients, take home doses are a quandary.

A patient with dementia may gradually lose the ability to manage take home doses appropriately. Sometimes our first clue that something’s wrong with a patient can be when they come to dose days earlier than they are supposed to. They are confused about what happened to their take home doses, or why they came back to the facility early.

This is such a dilemma. We don’t want the patient to feel as if we are punishing them by revoking take homes, but we can’t in good conscience allow them to walk out of our OTP with take homes if they can’t remember if they’ve dosed today. It’s a safety issue.

Patients with significant memory problems must come to the facility to dose every day, which can be a hardship. If their mental decline has been accompanied by physical decline, problems are compounded. Sometimes patients have dependable relatives living with them who can help them take their medications at the appropriate times, but that’s not always possible.

If patients’ illnesses worsen to the point they can no longer be taken care of at home, what do we do? How can we continue their care while in a nursing facility? That gets tricky. If the facility or a relative is willing to bring the patient each day, we can do that. If that’s not practical due to physical frailty, sometimes the nursing home is willing to dose our patients, but regulations say OTPs can only dispense medication to the patient for whom it is prescribed. That is, a relative or personnel from the nursing home can’t come to pick up the patient’s dose and take it to him, as can be done in a pharmacy.

Finding solutions which are practical and workable that don’t violate any OTP regulations can be problematic.

Even getting patients on methadone and buprenorphine into assisted living facilities can be complicated. Last month on the AT Forum website ( ), an article was referenced that recounted the difficulties of finding nursing facilities willing to accept patients on buprenorphine or methadone. [1]

This article said some facilities have policies against admitting patients being treated for opioid use disorder with buprenorphine or methadone. The article said this stance was probably based on a bias against MAT in favor of abstinence-based approaches to treating opioid use disorder. Some experts believe this is illegal, because it violates the Americans With Disabilities Act.

Mobility issues from falls, broken bones, orthopedic conditions, or recent surgeries sometimes collide with my assessment of the patient’s stability from opioid use disorder. What if a patient deemed too unstable (or too new to treatment) for anything other than one take home per week has a sudden medical issue that limits his mobility? This situation occurs more than you might imagine.

We used to be able to dose patients in their cars if it was difficult for them to walk into the facility. Now, the DEA opposes this, worrying a nurse carrying a dose of methadone to a car in our parking lot could be intercepted by someone with criminal intent. I agree this could happen, but the rare occasions when we’ve had to dose patients in their cars, we sent two staff: one nurse to carry and administer the medication, and a witness (usually the patient’s counselor) to witness it being given to our patient and no one else. This also protects our nurses against accusations they mishandled the dose in any way. But the DEA says we can no longer do this.

Some OTPs take a hard line and say if you can’t walk into the OTP, you are not appropriate for treatment. That seems unkind, particularly if a patient has done well with us in the past, and is now having a temporary medical issue limiting mobility.

I think the best approach is to get input from the patient’s physician and try to decide action that’s in the best interest of the patient.

First, I talk to the patient’s physician for specific recommendations of the patient’s mobility. Then I talk to the patient, usually with a counselor, and we ask about family members who could help the patient take extra take home doses as directed. We can ask for state and federal exceptions for extra take homes, so long as we do all we can to ensure patient safety, and describe the situation to officials, to give a better idea of our thought processes and safety concerns.

Sometimes I am surprised, and the other physician wants the patient to get up and walk around, particularly after surgery, for a better outcome. If that’s the case, no extra take homes need to be provided.

Some patients are so debilitated that being around other people presents a health hazard. We had a patient on heavy cancer chemotherapy. When her white blood cell count was extremely low, her doctor recommended she avoid crowds. This occurred during the height of cold and flu season last year, so we requested extra take homes for her, to keep her from having to come to our OTP and sit in a waiting room with other patients.

Her oncologist and I had to weigh the risk of extra take homes against the risk she could contract a simple viral illness that could kill her in her immune-suppressed state.

These types of situations will occur with frequently given the overall aging of the U.S. population, and the aging of patients on medication-assisted treatment. We need to remember this aging is a good thing – patients getting help with MAT are surviving, and living until old age



Avoiding Overdoses

August 31: Overdose Awareness Day




“I’m not gonna overdose. I know my limits.”

I really hate hearing these words. Usually patients say this in response to my concerns about their pattern of drug use while I’m prescribing methadone or buprenorphine. But many patients feel like they are the experts. They can’t imagine making a deadly mistake with their drug use. But I’ve heard this phrase, or something close to it, from at least five people who are now dead from overdoses.

I was reminded of this situation after reading an article in the latest issue of Journal of Addiction Medicine. Najman et al. wrote an article titled “When Knowledge and Experience Do Not Help: A Study of Nonfatal Drug Overdoses.”

The author of the study looked at nonfatal overdoses in Australia in 2013, where overdose deaths have risen steadily since 2007. In that country, unlike the U.S., heroin use is declining while pharmaceutical opioid misuse is rising.

This study looked at nonfatal overdoses in people who inject drugs. These people, identified by the needle and syringe exchange programs in Australia, were interviewed about the circumstances surrounding these overdoses, in order to get a better understanding of the risks. A total of 50 people were interviewed for this study.

Most of these people were male, middle-aged, single, and unemployed. Nearly all were smokers. Half had a diagnosis of liver disease and almost all reported a mental health diagnosis. Most injected pharmaceutical opioids, though some also injected heroin and methamphetamine. These were very experienced drug users, with an average of 21 years of intravenous drug use.

Surprisingly, more than half of the study subjects were in some form of treatment for substance use disorder. This finding is contrary to other studies, which have found being in treatment lowered the risk for overdose. Around 46% were in medication-assisted treatment with either methadone or buprenorphine. However, some of the overdoses happened on days that the person missed dosing for some reason, and substituted another opioid such as heroin or fentanyl. Thirty-two percent of study subjects dosed with either methadone or buprenorphine in the twenty-four hours prior to experiencing their overdose.

Most of these overdoses happened in private homes, and around half received some sort of folk remedy for overdose such as being slapped, put into cold water, or being shaken. Naloxone kits weren’t routinely being distributed at the time of this study.

When asked about the cause of their overdose, many the subjects said they were impaired by alcohol or benzodiazepines. Over half said they used benzodiazepines within twenty-four hours of their overdose. Of the 50 subjects, 64% said they had been prescribed anti-anxiety medications sometime in the year prior to overdose, and 38% said they’d been prescribed sleeping pills. Another 36% said they’d been prescribed some sort of tranquilizer in the year prior to overdose. I’m assuming many of the subjects were prescribed more than one of these groups of medications.

Alcohol was not as prominent as sedative medications as contributory cause of overdose; only 34% of subjects said they had some amount of alcohol in the twenty-four hours prior to their overdose.

Over a third of subjects had used fentanyl, a very powerful opioid, leading up to the overdose.

The authors of the study concluded that these experienced drug users were aware of common risks for overdose, yet drug intoxication from sedatives such as alcohol or benzodiazepines may have clouded the user’s thinking when injecting opioids. They also found that unexpected availability of drugs contributed to overdoses.

It’s an interesting study, and a little disturbing to me, particularly the data about overdoses in people who were enrolled in medication-assisted treatments. It does underline the importance of daily dosing of MAT, and the importance of avoiding alcohol and benzodiazepines in patients on MAT.

And if you didn’t know…August 31 is International Overdose Awareness Day.

Methadone Overdose Deaths: First Two Weeks



Methadone is a tricky drug to start, due to the narrow margin between therapeutic dose and fatal dose. Making it more difficult, people vary a great deal in the rate at which they metabolize methadone.  Some people have a methadone half -life as short as 15 hours, while others have half- lives as long as 60hours. The average is 22 hours. So even for people with a high tolerance to other opioids, increasing methadone too quickly can be deadly.

Methadone’s long half-life makes it good for a maintenance medication, since after stabilization, there’s not much fluctuation in the blood levels. However, the long half-life makes it more difficult to adjust the dose. The change I make in a patient’s dose today may not be fully experienced by the patient for five or more days.

The tolerance to the anti-pain effect of methadone builds faster than the tolerance to respiratory suppression, adding to the danger. When methadone is used inappropriately, patients may take more methadone to relieve pain, but by the time the pain is gone, they could easily have taken a methadone overdose.

All of this explains why the first two weeks of methadone maintenance treatment are the most dangerous. According to some studies, death rates for patients starting methadone at opioid treatment programs are actually higher during the first two weeks than when using illicit opioids. (1, 2)

Even so, it’s a risk worth taking, given the proven life-saving benefits of methadone (and buprenorphine) maintenance

Patient overdose during the first two weeks is a serious concern for doctors working at opioid treatment programs. We must do all we can to keep patients safe. It’s a fine line; if we start at too low of a dose or go up too slowly, we risk having our patients drop out of treatment. And if we increase the dose too quickly, it increases the risk of overdose…

The American Society of Addiction Medicine (ASAM) recently updated their methadone induction guidelines. In past years, doctors working at opioid treatment programs (OTPs) tended to start patients at 30-40mg and increase the dose rather quickly. Now, the expert ASAM panel recommends a starting dose of 10-30mg. If that dose isn’t sufficient to suppress withdrawal, a second dose can be given after three hours, so long as the total dose is not greater than 40mg. The expert panel recommends increasing the dose no more quickly than every five days, and no more than five milligrams at a time.

Some patients are more susceptible to overdose, and physicians should consider lower methadone starting doses for these people:

-Age over 60

-Using sedating drugs like benzodiazepines

-Regularly consume alcohol

-Are on prescription medications which can interact with methadone

-Medically fragile patients, for example patients with coronary artery disease, morbid obesity, -chronic obstructive pulmonary disease (COPD), or sleep apnea

-Have risk factors for prolonged QT interval, such as a recent heart attack, personal history of heart rhythm problems, or family history of heart disease

-Patients who have been abstinent from opioids for five or more days (e.g. recent incarceration, recent detoxification or hospitalization). These patients lose some of their tolerance and might be more prone to overdose with any opioid.


Interestingly, the degree of withdrawal that the patient has when entering treatment does not correlate with the dose of methadone they will need to get rid of withdrawal symptoms. In other words, one person in terrible withdrawal may need a smaller dose than another person with milder withdrawal. The degree of withdrawal that a patient feels is only partly due to opioid tolerance. Genetic makeup may be the reason why some people have more severe withdrawal than other people.

While I always ask my new patients how much opioid they have been using per day, that alone doesn’t determine methadone starting doses. There’s incomplete cross-tolerance between other opioids and methadone, meaning we can’t use the table of equianalgesic doses.

Last week I found an interesting article describing a large study of Canadian methadone patients, which will contribute even more to what we already know about risk during the first two weeks of methadone. This study showed which patient characteristics are associated with overdose death.

The study was done in Canada from 1994 until 2010, and covered over 43,000 patients enrolled in an opioid treatment program in those years. The study looked at all overdose deaths in this patient population and found 175 deaths deemed to be from opioids. These cases were matched with patients who entered treatment around the same time as the patient who died, creating a nested case-control study.

This study found, as expected, a higher degree of risk in the first few weeks on treatment. In this study, patients in the first two weeks of treatment were 16 times more likely to die in the first two weeks of treatment than any other time in treatment.

Psychotropic drugs were associated with a two-fold risk of overdose death overall, with antipsychotics associated with a 2.3-fold risk and benzodiazepines a 1.6-fold increased risk. Antidepressants were not associated with increased risk of overdose death. Alcohol use disorder diagnosis was also associated with a two-fold increase risk of overdose death.

Even more interesting, heart disease was associated with over five times increased risk of overdose death, and serious lung disorders (sleep apnea, COPD) were associated with a 1.7 times increase in overdose death.

This is a powerful study because it was so large.

This is information I can use. I’ve been stressing about patients whom I thought were at increased risk – those who use alcohol and benzodiazepines, and those with severe lung disease. While these patients are at higher risk, from this study it appears patients on anti-psychotics are at even higher risk. And I need to do a better job of getting patients to see primary care doctors, to screen for heart disease, which gave the highest risk of all.

As time goes on, I think we’ll get more information about which patients are at higher risk. Those patients need a higher degree of interaction with treatment center staff, and better coordination of care with mental health providers and primary care doctors. I know I plan to implement a system at the OTP where I work to make sure I see patients more often if they have the risk factors described.

Obviously any patient death is a terrible thing. Of course it’s worst for the family, but it also affects the treatment team. I feel badly for the families of those 175 patients in the Canadian study who died, but they gave us information that can hopefully help us provide better care for future patients.


  1. Caplehorn et al, “Mortality Associated with New South Wales Methadone Programs in 1994: Lives Lost and Saved,” Medical Journal of Australia, 1999 Feb 1;170(3):104-109
  2. Cousins et al, “Risks of drug-related mortality during periods of transition in methadone maintenance treatment: A cohort study,” Journal of Substance Abuse Treatment, October 2011, Vol 41(3); pp252-260.
  3. Leece et al, “Predictors of opioid-related death during methadone therapy,” Journal of Substance Abuse Treatment, Oct 2015,

Smoked Heroin Leads to Early Lung Disease










Heroin can be injected, snorted, or smoked. Researchers in England, noting an apparent increase in lung disease in people who smoke heroin, did a study that was just released late last year.

Walker et al, from Liverpool, England, studied 73 heroin smokers who had developed chronic obstructive pulmonary disease (COPD) symptoms before age 40. Researchers did pulmonary testing on these subjects and found significant abnormalities on pulmonary function tests, high-resolution CT scans, and oxygen diffusion capacity. (This last test shows how easily oxygen crosses from the lungs to the blood stream.)

These findings, building on other preliminary similar studies, shows that smoking heroin is associated with very early onset of COPD/emphysema.

Other studies have shown an associating between asthma attacks and smoked drugs, both with heroin and crack cocaine, but this study showed specific types are areas of lung changes which presumably are irreversible, in these very young patients. With cigarette smoking alone, significant COPD is rare before age 40, but all of these patients were younger than 40. Still, cigarette smoking could contribute to the severity of COPD.

Experts discussed the mechanism of lung damage in these heroin smokers. They postulated that heroin smokers tend to take deep breaths and hold the smoke in as long as possible, causing increased pressure in the thorax, which could cause or contribute to the lung damage.

Heroin smokers often put heroin on foil, then apply a heat source beneath and inhale the smoke. This is sometimes called “chasing the dragon.” Perhaps there’s something in the foil that when heated and inhaled, can cause lung disease. If that’s the case, then people who smoke pain pills could also be at risk for COPD from this practice.

Some experts point out that heroin burns at a much higher temperature than tobacco, and wonder if the higher temperature of the smoke causes this type of early lung damage.
For now we don’t know precisely why heroin smokers get early and probably irreversible lung damage, but physicians should be alert to this as a potential cause of early COPD, particularly in patients under age 40.

And here’s another good reason to stop using and get into recovery…

It’s That Time of Year! NSDUH is Here!


Data from the 2014 survey of NSDUH (National Survey on Drug Use and Health) was released this month, as it is every year, in time to celebrate National Recovery Month of September:

It’s mildly interesting reading; I saw no dramatic changes in the area of opioid addiction.

The number of non-medical users of prescription opioids remained roughly the same as last year, at 4.3 million people over the age of 12. That’s lower than in years 2001-2011. Overall, we may be seeing a slow trend downward. Also, there was a decline in users aged 18-25. Maybe current addicts are aging, and being counted in the next ago group 26 and older, but that next age group didn’t have a large increase this year or last. Maybe fewer youngsters are starting pain pill use, since they see the problems with opioid use in their older friends and acquaintances.

Heroin use is increasing, as has been discussed in this blog recently. However, according to NSDUH, though the total number of users increased, it only increased .1 percent. In total, an estimated 435,000 people over age 12 in the U.S. are current heroin users. I do suspect the upward trend will be more dramatic in future years, unfortunately.

The number of current marijuana users age 12 and older continued to gradually increase, with 22.2 million current users of marijuana and hashish. This is about 8.4% of the U.S. population over age 12. That number is not significantly higher than in 2013.

How accurate is NSDUH data? If anything, it likely underestimates the number of drug users. It surveys people living in households, at fixed addresses. It does not survey the homeless or those in jails, hospitals or other institutions. It also does not survey military personnel. People in some of these groups, particularly the homeless and the imprisoned, have high rates of drug addiction, so NSDUH is probably underestimating the prevalence of addiction.

However, this is the best yearly study we have available in the U.S.

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.