Why We Shouldn't Blame Benzos

Sometimes I hear from well-meaning medical practitioners that methadone is unfairly maligned as it is blamed for so many deaths. Benzodiazepines, these doctors argue, are to blame for so many methadone poly-drug deaths. Benzodiazepines are the real killers. I don't buy it. While admittedly the dangers of combining benzodiazepines with methadone are well-known in the medical community, many people dependent on benzodiazepines continue to use them for years and years, without dying. In addition, benzodiazepines are highly addictive, and withdrawal can lead to fatal seizures. The New York Times recently reported:

"A majority of victims also used large quantities of alcohol or benzodiazepine sedatives but few would have died without an opioid as the primary culprit. 'You can take a lot of benzodiazepines without dying,' said Dr. Charles E. Inturrisi of Weill Cornell Medical Center, who said they strengthen the depressive effect of methadone."

What I am concerned about more than all the people using benzodiazepines, is all the doctors prescribing methadone to the people using benzodiazepines. A patient with a long-standing history of benzodiazepine use should not be started on methadone until the physician confirms the patient is benzodiazepine-free.

FDA Advisory: Respiratory Depression and Death

FDA Public Health Advisory: Methadone Use for Pain Control May Result in Death and Life-Threatening Changes in Breathing and Heart Beat

ADVISORY--FDA has received reports of death and life-threatening side effects in patients taking methadone. These deaths and life-threatening side effects have occurred in patients newly starting methadone for pain control and in patients who have switched to methadone after being treated for pain with other strong narcotic pain relievers. Methadone can cause slow or shallow breathing and dangerous changes in heart beat that may not be felt by the patient. Prescribing methadone is complex. Methadone should only be prescribed for patients with moderate to severe pain when their pain is not improved with other non-narcotic pain relievers. Pain relief from a dose of methadone lasts about 4 to 8 hours. However methadone stays in the body much longer—from 8 to 59 hours after it is taken. As a result, patients may feel the need for more pain relief before methadone is gone from the body. Methadone may build up in the body to a toxic level if it is taken too often, if the amount taken is too high, or if it is taken with certain other medicines or supplements.To prevent serious complications from methadone, health care professionals who prescribe methadone should read and carefully follow the methadone (Dolophine) prescribing information FDA is issuing this public health advisory to alert patients and their caregivers and health care professionals to the following important safety information:Patients should take methadone exactly as prescribed. Taking more methadone than prescribed can cause breathing to slow or stop and can cause death. A patient who does not experience good pain relief with the prescribed dose of methadone, should talk to his or her doctor. Patients taking methadone should not start or stop taking other medicines or dietary supplements without talking to their health care provider. Taking other medicines or dietary supplements may cause less pain relief. They may also cause a toxic buildup of methadone in the body leading to dangerous changes in breathing or heart beat that may cause death. Health care professionals and patients should be aware of the signs of methadone overdose. Signs of methadone overdose include trouble breathing or shallow breathing; extreme tiredness or sleepiness; blurred vision; inability to think, talk or walk normally; and feeling faint, dizzy or confused. If these signs occur, patients should get medical attention right away. FDA recently approved new prescribing information for methadone products approved for pain control. The information in the new prescribing information is based on a review of the scientific literature completed by FDA. A Medication Guide for patients is planned.

Zero Unintentional Deaths

The American Society of Anesthesiology has taken action regarding the increasing numbers of methadone deaths in the United States. And the ASA is a great organization to take such action: they count among their members people the common folk in America call "pain physicians." The ASA is engaged in an educational campaign entitled “Zero Unintentional Deaths” to reduce the number of accidental methadone deaths.
“Six Steps to Zero” highlights important rules for pain patients who are prescribed methadone:
1. Never take a prescription painkiller unless it is prescribed to you.
2. Do not take pain medicine with alcohol.
3. Do not take more doses than prescribed.
4. Use of other sedative or anti-anxiety medications can be dangerous.
5. Avoid using narcotic medications to facilitate sleep.
6. Lock up prescription painkillers.

I wish they had added this rule:

"If you get sleepy while taking methadone, call 911."

Many of my clients' families reported not understanding that drowsiness was a dangerous side effect of methadone, and remembering when their loved one retired to the bedroom to "sleep it off."
You can contact the ASA at Zero Unintentional Deaths c/o Life Source, 617 East 3900 South, Salt Lake City, UT 84106.

Phyllis Lile-King

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What Your Doctor May Not Know About Methadone

Frank's family called me a year ago after Frank went to a local hospital for a stomach ache. The physicians suspected an ulcer or a bleed and decided to keep him overnight. Frank had a history of back surgery and had been on 100 mg of morphine daily for a year. When Frank was admitted, he asked if he could make a call and get a family member to bring his morphine for his chronic back issue. The physician told Frank "no" and said they would take care of getting him the morphine from the hospital pharmacy. For whatever reason, Frank's gastroenterologist called in a neurologist to consult on getting Frank his morphine. The neurologist told Frank she was going to give Frank methadone instead of morphine-- that it was also an analgesic and would work like morphine. So the neurologist wrote an order for methadone 100 mg to replace Frank's 100 mg morphine. The mistake in the neurologist's conversion of morphine to methadone cost Frank his life. He went into respiratory depression within several hours, coded, was resuscitated and eventually transferred to ICU in a coma on a ventilator.
Phyllis Lile-King

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What is Respiratory Depression?

Methadone toxicity often manifests itself-- causing death by something called respiratory depression or central nervous system depression. Respiration is controlled principally through the part of the brain called the medullary respiratory center with peripheral input from chemoreceptors and other sources. We all understand that breathing is something that is involuntary-- like blinking ones eyes or beating one's heart. We don't "make ourselves breathe." Rather, chemoreceptors in the carotid arteries measure CO2 levels and transmit that information to the brain, which then directs the diaphragm and intercostals/lungs to "breathe." Thank goodness for this process. It would be difficult to sleep if we had to worry about making our bodies breathe. Opioids like methadone inhibit the chemoreceptors via mu opioid receptors and in the medulla via mu and delta receptors. While there are a number of neurotransmitters mediating the control of respiration, glutamate and GABA are the major excitatory and inhibitory neurotransmitters, respectively. So, a simpler way to understand this is to say that methadone interferes with the messages the chemoreceptors send to the brain. Methadone desensitizes the medulla, making the brain unaware of the need for the lungs to breathe. The result is respiratory depression. Families report that the son or daughter feels really sleepy, falls asleep and , the lucky families report that the child is difficult to awaken during the respiratory depression process. The unlucky mother tells me that she heard her son snoring heavily, and found him dead the next morning. Phyllis Lile-King

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Signs of Methadone Overdose

From the methadone hydrochloride package insert:

Deaths, cardiac and respiratory, have been reported during initiation and conversion of pain
patients to methadone treatment from treatment with other opioid agonists. It is critical to
understand the pharmacokinetics of methadone when converting patients from other opioids (see DOSAGE AND ADMINISTRATION). Particular vigilance is necessary during treatment
initiation, during conversion from one opioid to another, and during dose titration.
Respiratory depression is the chief hazard associated with methadone hydrochloride
administration. Methadone's peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects, particularly in the early dosing period. These characteristics can contribute to cases of iatrogenic overdose, particularly during treatment initiation and dose titration.

In addition, cases of QT interval prolongation and serious arrhythmia (torsades de pointes) have
been observed during treatment with methadone. Most cases involve patients being treated for
pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
Methadone treatment for analgesic therapy in patients with acute or chronic pain should only be
initiated if the potential analgesic or palliative care benefit of treatment with methadone is
considered and outweighs the risks.

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