Archive for the ‘medical treatment of methadone patients’ Category

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 (http://atforum.com ), 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

  1. https://www.statnews.com/2018/04/17/nursing-homes-addiction-treatment/

 

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Medication-assisted Treatment in An Aging Population

 

 

Patients prescribed medication-assisted treatments with buprenorphine, methadone, and naltrexone are getting older…as we all are. This is wonderful, because it means our patients are surviving, making it to old age. Methadone has been prescribed for the longest of the three, so we tend to see more older patients on it.

Aging in our patients can present specific challenges; research literature shows high rates of physical and psychological illness in opioid users in general, meaning as this population ages, we can expect to see even more co-occurring illnesses.

When looking for information about aging MAT patients, I was appalled to see a journal article define “older adult” as those fifty and above. I’ve always thought of “older” as being, well, older than me. I’m no longer pushing fifty – I’ve been pulling it behind me for nearly seven years, so I felt a little resentful on behalf of my patients.

Anyway, the article was titled “Older Adults Prescribed Methadone for Opiate Replacement Therapy: A Literature Review,” and the author said that the U.S. had 1.7 million people over age 50 in 2000 who needed substance abuse treatment. That number is expected to rise to 4.4 million by 2020. [1]

This article said the numbers of patients over 50 years old who are on MAT is expected to rise, and this group of patients has special needs. They say these patients tend to age more quickly (physiologically) due to past lifestyle.

I see that in my patients. Around 90% are smokers, and cigarettes cause a whole host of medical issues. Some patients have had poor dietary habits since childhood, from a combination of factors. Many patients haven’t had the time or energy for self-care, prior to entering recovery, and this takes a toll.

A New York study of older OTP patients on methadone [2] sampled 156 patients enrolled in OTPs. Twenty-nine percent were age 55 or older (45 patients) These patients, as compared with their younger counterparts, were significantly more likely to have been in treatment longer, less likely to be using heroin currently, but more likely to have an alcohol use disorder.

The older patients were less likely to be impulsive or hostile, but more likely to have chronic medical problems and more likely to be on medications for those problems. Older patients were more likely to be on more liberal take home schedules, due to less illicit drug use compared to younger patients. Despite having more chronic medical issues, older patients’ scores on life satisfaction scales weren’t different from younger patients.

Improving the health of our older OTP patients is a challenge, and I have a few suggestions to help.

Get them to a primary care provider. Some OTPs are fortunate enough to be able to offer primary care to their patients. That’s wonderful, but if, like me, you work at an OTP that can’t do that, patients will need to be referred. This should be easy, but it’s not, at least in some areas of this country My patients tell me when they call for an appointment as a new patient, they are told they can’t be accepted if they have a history of substance use disorder or treatment for chronic pain. They say they’ve called all the practices in the area and none will accept them.

Could this be exaggeration by patients? Maybe, but I’ve heard this over and over. Some patients say the receptionist who answers the phone takes their name and birthdate, then calls back to say they can’t be accepted. The patients think it’s because the prospective physician sees they have past histories of filling controlled substances on North Carolina’s prescription monitoring program. I hear the same things from patients with private insurance, Medicaid, and self-pay.

I’ve never heard any physician to admit to doing this, since it would unethical, and probably also a violation of the Americans With Disabilities Act.

Federally Qualified Health Centers (FQHCs) will take these patients. We have a center that does an excellent job with our patients; however, it’s an hour’s drive away. Some patients have difficulty getting transportation for that distance.

Medicaid patients should be assigned to a doctor or practice, and it’s printed on their Medicaid card.

Health maintenance can’t be neglected.  

Often a patient says something to the effect of, “I didn’t expect to live this long. I never thought of doing those things.” This is called a “sense of foreshortened future,” meaning the person senses he will not live to an old age and is destined to die young. It’s seen in people who have experienced trauma in their lives and can be a symptom of post-traumatic stress disorder (PTSD). But now here he is, over 50, and not accustomed to taking care of himself.

And yes, it also means that rite of passing age 50: the screening colonoscopy.

Our patients need routine PAP smears, mammograms, prostate exams, and vaccinations. They need their blood pressure and cholesterol profiles checked when appropriate. We need to encourage our patients to keep up with these simple measures.

After patients get into recovery, it takes time and effort to adjust thinking, and accept the idea that good self-care can extend the quality and length of life.

Opioid treatment programs, like all other medical practices, should keep an updated medication list and updated problem list.

That should be easy to accomplish, but at my OTP, our present software system has no provision to document this essential information. I’m left to figure it out with paper charts, which isn’t ideal, but workable. But I can only see that data if I’m in the office with the chart in front of me.

Methadone has interactions with many medications. The list is long, and difficult to remember, so I use a smart phone app that will tell me about drug interactions. There are many out there: Epocrates and Medscape are but a few. If you work in an OTP, get this phone app. It will save you time and effort.

See complicated patients more often.

This applies to older patients, but also to younger ones if they have a complicated medical history. Sometimes it’s hard to convince patients they need to see me if they are doing well. Particularly if they have their own doctor, and they are doing fine, why should they waste their time? Of course, I think it’s time well-spent, but I understand their thinking. I delay seeing my doctor too. Life is hectic and that’s never at the top of my list.

I’ve started “warning” new patients with more than a few medical issues that I will want them to see me every 3 months. We can flag this in our computer system, along with flagging when they will be due for a yearly physical.

I count diseases like heart disease, diabetes, COPD/emphysema/asthma, and other chronic conditions as complicating illnesses. There are dozens of others, and I also count chronic mental illnesses, even though they are treated by psychiatrists. Many of those medications can have interactions with methadone, making it prudent to see these patients more often.

More than anything else, keep talking to patients about quitting smoking. Smoking-related illness is the number one killer of people in recovery. It’s not easy, but keep encouraging and supporting them. My state has a quitline to help anyone wanting to quit at: https://www.quitnow.net/Program/This is sponsored by the American Cancer Society, for no cost to the patients.

In my next blog, I’ll talk about some of the most challenging co-occurring problems in my patients: deteriorating cognitive function and limited mobility.

  1.  Doukas et al., and published in Addiction and Preventive Medicine, February 10, 2017.
  2. Rajaratnam et al., Journal of Opioid Management, 2009 5(1), pp 27-37.

 

Methadone Overdose Deaths: First Two Weeks

Methadone

 

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

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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…

Insomnia Medications for Patients in Medication-Assisted Treatment

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Insomnia Medications for Patients in Medication-Assisted Treatment

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A recent study showed that adults who use sleeping pills are more than three times more likely to die prematurely compared to matched controls who didn’t use sleeping pills.

This relatively large study looked at the medical records of over 10,000 patients who were prescribed hypnotics for sleep, and compared their outcomes to over 23,000 matched control patients, similar except the controls weren’t taking sleeping pills. The sleeping pills, also called “hypnotics” were associated with significant increases in mortality and significant increases in cancer incidence. [2]

The patients’ average age was 54, and they were followed for an average of 2.5 years. All were members of a large U.S. healthcare system in Pennsylvania. The data from the two groups were adjusted for age, gender, smoking status, prior cancer diagnoses, body mass index, ethnicity, and alcohol use.

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

The author of this study estimated that hypnotic medications are associated with 320,000 to 507,000 deaths in the U.S. over the year 2010.

This study raises some important questions, since hypnotic drugs are the most commonly prescribed drugs in the U.S., with an estimated 6 to 10% of the population being prescribed these medications.
Sleep medicine doctors say that correlation doesn’t mean causation, and we shouldn’t jump to conclusions. One sleep specialist pointed out that the study didn’t control for psychiatric illness, which could be a significant factor. Additionally, patients who are prescribed sleeping medications may be sicker overall, in ways the study didn’t control, and therefore a generally less healthy group. This could distort study findings.

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

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

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

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