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.

1. https://www.injuryfreenc.ncdhhs.gov/DataSurveillance/StatewideOverdoseSurveillanceReports/OpioidOverdoseEDVisitsMonthlyReports/MedDrugOverdosewithPotentialforDependency-EDVisits-June2020.pdf
2. https://wexnermedical.osu.edu/blog/why-are-overdose-deaths-surging-amid-covid-19
3. https://www.nytimes.com/interactive/2020/07/15/upshot/drug-overdose-deaths.html?smid=em-share
4. https://www.ama-assn.org/system/files/2020-08/issue-brief-increases-in-opioid-related-overdose.pdf

 

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 (https://pcssnow.org/)

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 (asam.org). SAMHSA has publications to help physicians (https://store.samhsa.gov/)

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.

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…

Insomnia

Insomnia is defined as a sleep disorder which makes it difficult to get to sleep or stay asleep. Insomnia can come & go for periods of time, or can be a chronic problem. Not sleeping well can make us less able to handle the stresses of the next day, and can severely affect the quality of our lives.

Insomnia afflicts many patients in recovery, including those on medication assisted treatment with buprenorphine and methadone. Insomnia can occur for many reasons: the brain may be adjusting to life without the chemical ups & downs of addicted life, or because the patient had insomnia even before the addiction started. Physical health problems (chronic pain, thyroid disease, and menopause to name but a few) can cause insomnia or make it worse, as can mental illnesses like anxiety and mood disorders.

Active addiction can destroy normal sleep-wake cycles. Addictive chemicals disrupt the structure and function of the brain, and often people in active addiction become accustomed to passing out rather than falling asleep. It can be difficult to re-learn how to get to sleep naturally.

Many U.S. citizens, and not only addicts, have become “chemical copers.” We have the idea that every problem can and should be fixed with medication. But with insomnia, sleep hygiene is the best first option, and medication can be used if sleep hygiene doesn’t work.

Sleep hygiene, which sounds it means washing behind your ears at bedtime, really refers to habits that help us get satisfactory sleep. Most are common sense ideas, and they can really make a big difference. Here are some of these ideas:

1. Go to bed at the same time and wake at the same time every day, even on weekends.
If it’s at all possible, don’t go to bed later or sleep later on weekend days. Get your body into the habit of keeping a regular sleep/wake cycle. You will fall asleep more easily with a fixed bed time.
Besides making your feel better because you’ll get more regular sleep, this practice has other benefits. For example, people with migraine and tension headaches have fewer pain episodes with regular sleep/wake times. Keeping regular sleeping hours is also highly recommended for patients with bipolar disorder, as it can help with mood swings.

2. Avoid caffeine late in the day. For some people, drinking caffeine in the late afternoon can affect them up to six hours later. To be sure, cut off caffeine at least eight hours before you want to sleep. Caffeine doesn’t affect everyone to this degree, but unless you know for sure, try to limit late-day caffeine. If you consume energy drinks, consider cutting back or stopping them.

3. Make sure your bed is comfortable and your room as free from distractions as possible. Pets and rowdy bed partners may need to sleep in other areas. Make sure the room temperature is conducive to sleep and there’s no noise or light that may interrupt sleep. Keeping the television on for background noise isn’t a good idea and can prevent you from getting to the deeper levels of sleep.

4. Don’t set your alarm for earlier than you need to. Many of us like to do this so we can hit snooze a few times. However, the most beneficial sleep, REM sleep, comes at the end of the night, and we are depriving ourselves of REM sleep by hitting the snooze button a few times before getting out of bed for good.

5. Have a bedtime ritual. Have things you do each night before going to bed that relax you and put you in a mindset to sleep. This could be a series of ablutions like brushing your teeth, flossing, or taking a warm bath. Other people may prefer doing prayer or meditation to quiet the mind, or reading.

6. Don’t nap during the day to catch up on sleep. More than anything else, napping will keep you from sleeping at night.

This is a tough one for me, since napping has long been one of my hobbies. Because I think of a good nap as one of life’s great joys, on some days I’m willing to risk not being able to get to sleep at night and take the nap anyway.

7. Don’t use alcohol to help you sleep. While alcohol does cause faster sleep onset, it also shortens the sleep cycle, causing us to wake earlier, and robs us of the important REM sleep. Over long term, alcohol can greatly interfere with your sleep cycle.

8. Only use your bed for sleep. OK, for sex too. But don’t live in your bed so that you become accustomed to eating, watching television, and working on the computer in bed. Your mind should associate bed with sleep, and not these waking activities.

9. Exercise each day. More than most other suggestions, this one can help you more than you expect. Even a small amount of exercise can have surprisingly good benefits. Don’t exercise too close to bedtime, since exercise can have a stimulating effect.

Sometimes people in early recovery find they want to sleep more than usual. This can be part of your physical recovery, and I think it’s best to listen to your body and allow yourself extra sleep time without feeling guilty. However, some mood disorders also make people want to “take to the bed” during times of stress and negative emotion. This latter situation may need medication if it continues or interferes with your life.

If you try all these sleep hygiene measures and you still can’t sleep, talk to your doctor about a safe medication for sleep. I’ll write more about medications in a later blog.

Is Impotence on the Rise in Opioid Users?

According to a recent study, long-acting opioids are nearly five times more likely to suppress testosterone levels than short-acting opioids.

Over the last few years, we’ve seen a surge in data that couples opioid use with lowered male testosterone levels. We know the use of opioids can lead to hypogonadism, a condition of lowered sex hormone production. In males, lowered testosterone levels can lead to fatigue, depression, and even osteoporosis and obesity. Some studies suggest this hypogonadism is also associated with lowered pain tolerance.

In previous studies, opioid users were lumped together, but this recent study compared the testosterone levels of patients taking long-acting opioids with patients taking short acting opioids.

Dr. Andrea Rubinstein presented data at the annual American Academy of Pain Medicine meeting. Her study compared 81 male patients taking opioids for at least three months. Those in the long-acting opioid group included patients prescribed methadone, buprenorphine (Subutex, Suboxone), sustained-release medications in patch form, such as morphine and fentanyl, and sustained-release medications like OxyContin (taken whole as intended with the coating not removed). These patients were compared with those on short acting opioid like immediate-release oxycodone and hydrocodone.

The patients on the long acting opioid were nearly five times more likely to have low testosterone levels than patients on the short acting opioids. The age of the patient and the total daily dose did not appear to affect the risk of low testosterone.

It’s possible that short acting opioids give more fluctuation in serum opioid levels, and thus less likely to suppress hormonal function.

This is not great news for those of us who treat opioid addiction. We use long-acting opioids like methadone and buprenorphine precisely because they are long-acting, and give a steady blood levels. Their long action in the body means they can be dosed once a day (usually) and still relieve all opioid withdrawal symptoms. The relief from opioid withdrawal frees the patient to focus on making important life changes. With short-acting opioids, most addicts feel a euphoric high, followed several hours later by withdrawal. This drives them to seek opioid drugs as often as every six hours. It’s hard to maintain a normal life when seeking pursuing opioids three or four times per day. Simply staying out of withdrawal becomes the opioid addict’s full time job. Short acting opioids may be better for my patients’ testosterone levels, but not good for their disease off addiction.

So what should I do with this data about hypogonadism in my practice?

I think I should be more diligent about monitoring my patients for symptoms of low libido. It’s important to ask male patients about sexual difficulties because sometimes they are embarrassed to mention them. If patients have no symptoms of hypogonadism, they probably don’t need further testing. If patients do have symptoms, I’ll ask them to see their family doctors for a work-up, because that’s something that can’t be treated at the opioid treatment programs where I work. Testosterone can be supplemented with gel or intramuscular injections, and testosterone levels need to be monitored, as well as cholesterol levels.

I’ve had previous patients who object to testosterone supplementation because they felt they were treating a side effect from one medication with a second medication. While this is true, the only other option is tapering off methadone or buprenorphine, or cutting down their dose. This also has risks, as opioid addiction is a life-threatening illness. If a patient wants completely off medication, he should have an inpatient treatment lined up as soon as his dose is low enough for admission.

What about women on medication-assisted treatments with low sex drive? Women weren’t included in this study, but yes, we know their hormones are also affected by opioids. Testosterone may help women recover their sex drive, but it has serious side effects and hasn’t been proven to be safe in the long term for women. For females who report sexual dysfunction on long-acting opioids, I will continue to refer them to their gynecologists.

As usual, the benefits of long-acting opioids must be balanced against their risks.

Opioid Use and Prostate Health

I found an interesting article in a recently published issue of the Journal of Addiction Medicine, Vol 7 (1) pages 58-65. This article describes the effect of opioids on PSA (prostate specific antigen) scores.

PSA is an enzyme normally found in low levels in the blood of men with healthy prostates. It’s elevated in a variety of prostate diseases. Notably, it’s elevated in men with prostate cancer, but it can also be elevated from other ailments that cause inflammation of the prostate.

Routine screening of men through checking the PSA levels is controversial, and some experts say routine screening of PSA leads to unnecessary prostate biopsies. They also say screening doesn’t reduce deaths from prostate cancer. However, many men specifically ask for PSA screening, and many doctors still check the PSA levels as part of a routine physical. PSA levels can be followed after a patient has been treated for prostate cancer, and elevated levels can mean a recurrence of the cancer.

In this study of Iranian men, male opioid addicts had 28% lower PSA levels than subjects that didn’t use opioids.

We already know that opioid use is associated with lower serum testosterone levels, so the authors of the study postulated that lower testosterone levels lead to lower PSA levels, but this was not the case, at least in this group of men. There was no correlation between serum testosterone levels and PSA levels in this study, so it did not appear that testosterone levels caused the lowered PSA levels.

Since prostate biopsies are performed on men with elevated PSAs the study authors were concerned that in opioid addicts, their lower PSA levels will fall below the threshold for biopsy. This could mean cancers could be missed in opioid users that might be detected in non-opioid users. Therefore, prostate cancers may not be detected in opioid addicts until the cancer is more advanced.

Indeed, in this study, more the men on opioids who were diagnosed with prostate cancer during the study period had higher grade prostate cancer than the men not on opioids who were diagnosed with prostate cancer during the study period.

This study suggests that for men on long-term opioids, PSA cut-offs should be lowered when deciding if the patient needs an evaluation for possible prostate cancer.

Comorbidity

Today I had the pleasure of talking to a group of therapists and mental health professionals about my favorite topic in medicine: the treatment of opioid addiction with methadone and buprenorphine. I’ll blather on about that topic as long as anyone’s willing to listen.

 

Today’s listeners asked some great questions. They asked questions not only about opioid addiction, but also about the overlap between addiction and mental illness. These questions are crucial in the treatment of both disorders, because they occur together so frequently. When both types of disease occur in the same patient, we call this “comorbidity,” or “dual diagnosis,” or “co-occuring disorders.”

Addicted patients are twice as likely as non-addicted patients to have mental illnesses such as mood disorders, anxiety disorders, schizophrenia, and attention-deficit hyperactivity disorder. The converse is also true: patients with mental illness diagnoses are twice as likely to have an addictive illness in addition to their mental illness.

Why is this? Is there a common factor underlying both types of disorders? Does one cause the other? For years, doctors and therapists have argued about this, and there are still no definite answers. However, why these diseases occur together isn’t as important as how to treat them most effectively.

We know patients get the best results when both diseases are treated at the same time, preferably under the same roof. That’s not always easy, but it’s the ideal.

To further complicate treatment, many times drug addiction causes the same symptoms as mental illness. For example, a person intoxicated on methamphetamine can look just like someone in the manic phase of bipolar disorder, or even schizophrenia. Another example can be seen in heavy drinkers, who are often depressed from the effects of alcohol, a depressant.

I rely on several methods to help me decide if drug use, abuse, or addiction is mimicking mental illness. First, I try to get information about what a patient was like during periods of abstinence from all drugs. If all of the mental illness symptoms went away during abstinence, it’s less likely that there’s an underlying mental illness. However, if the patient was still suffering with significant symptoms of mental illness even during a period of abstinence from drugs, the patient probably has a second diagnosis.

 I ask about family history of mental illness, because if relatives have been diagnosed with these disorders, it’s more likely that the patient I’m treating will have mental illness in addition to addiction.

I ask my patient which started first, the symptoms of mental disorder or drug use? Often, symptoms of mental illness and drug use both started around the same time, at late adolescence/early adulthood, so that history may not be helpful.

Here’s an example of a case I saw recently: (identifying details have been changed):

A 24 year old female saw me in my office as a new patient. She wanted to be considered for my Suboxone program. She gave a history of illicit drug use for four years, and had used opioids daily for a year and a half, snorting up to 200mg of hydrocodone or oxycodone per day. She used marijuana three times a week, usually two cigarettes per day. She denied use of benzodiazepines or alcohol, and said her father was an alcoholic. She used cocaine heavily in the past, but stopped using it three years ago because of its expense, by that time, she preferred opioids. She acknowledged recent use of methamphetamine three or four days ago, and said she snorted methamphetamine when she couldn’t find any opioids, only to stave off withdrawal. Her answers about frequency and amount of methamphetamine used were vague and evasive, so I was unsure of her exact history.

When I asked about her mood, she said she was depressed because of all the bad things that were happening as a result of her addiction: she was broke, her boyfriend just broke up with her (he was her drug using buddy) and her family wasn’t loaning her any money, so she was in withdrawal much of the time. She denied any period of abstinence from drugs since she started using at age 15. Family history was significant for a maternal aunt with severe bipolar disorder, requiring psychiatric hospitalization on multiple occasions.

Her exam was worrisome for a very low body weight. At 5’6” she weighed 103lbs. (she denied any symptoms of eating disorders) She was tense, pleasant, intelligent, and well-spoken. She fidgeted in her chair to an extreme amount. She was in florid opioid withdrawal, with wide pupils that were briskly reactive, obvious runny nose, frequent yawning, sweating, and goose bumps visible on her upper arms.

Her mother, who paid for her treatment, came to the appointment with her. My patient gave me permission to talk with her mother, who had quite a bit to add to the story. Mom said her daughter often seemed paranoid, and last weekend she stayed awake all night on Saturday, peering out one window after another, and checking repeatedly to make sure they were locked. My patient’s weird behavior kept the family awake all night. My patient also claimed to be able to hear people talking just outside the windows, and was sure the government meant to take her from her family for a nefarious reason. The patient’s mother said this last weekend was the most severe paranoid behavior she had seen in her daughter, but she had seen similar conduct in the past.

At this point, I thought there was a good chance we were dealing with more than just addiction. I considered bipolar disorder with psychotic features to be the most likely diagnosis, or schizophrenia. I hoped her use of methamphetamine caused these worrisome symptoms, since she shouldn’t have them once she stopped use of the drug and got out of opioid withdrawal.

With this new information, I changed my treatment recommendation, and thought an inpatient admission to a detoxification unit was most appropriate. Her psychiatric status could be closely observed, and she could be started on Suboxone. If the psychotic features resolved, great. If not, she could be started on appropriate medications, be stabilized and then come see me after she was discharged. I could maintain her on Suboxone after she was stabilized.

It was a great idea, but unworkable. The detoxification unit wanted a chunk of money up front, before admission, and she didn’t have that kind of money. It was also beyond her mother’s financial capability.

The patient pleaded with me to start on Suboxone. She believed all would be well if only she could get out of opioid withdrawal. I had my doubts, but agreed to prescribe one week of medication with telephone contact. Her mother agreed to call me or take her daughter to the psychiatric emergency room if her mood or behavior deteriorated.

One week later, a calm, smiling young lady entered my office. She had gained seven pounds in one week, and was no longer restless. The change was remarkable. Her mom came with her and said she hadn’t seen any more paranoid behavior. Her mother started to cry, saying, “I have my daughter back.” I was thrilled at the improvement. I adjusted her Suboxone dose slightly, and made sure she had her first session with the addiction counselor in my office.

I’ve seen her every week for the past month. She goes to three Narcotics Anonymous meetings per week, which is fewer than I’d like, but at least she’s going. She’s met with the licensed addiction counselor in my office each week. She’s had negative urine drug screens for the past three weeks and continues to gain weight. She says her mood is good, and she just went back to work.

For now, I don’t see evidence on mental disorder, but I’ll keep watching for problems.

To learn more about the comorbidity of addiction and mental disorders, go to this free report:

http://drugabuse.gov/researchreports/comorbidity/