Directions for Use

30 March 2009 (Last Updated March 30th, 2009 18:30)

The leading cause of accidental death in one US state, the use of prescription drugs is a major concern. Erin Johnson, Kim A Bateman, Robert T Rolfs and Brian C Sauer of the Utah Department of Health explore the statistics and ways to prevent unintentional overdoses.

Directions for Use

Misuse of prescription drugs is second only to marijuana as the most prevalent drug problem in the US, as shown in the 2006 report 'Misuse of prescription drugs: Data from the 2002, 2003, and 2004 National Surveys on Drug Use and Health' (Colliver, Kroutil, Dai, & Gfroerer).

In Utah, the leading cause of accidental death is no longer from motor vehicle crashes. Since 2003, the leading cause of accidental death has been overdose from prescription drugs. Most of these deaths are related to prescription pain medications, such as oxycodone, hydrocodone, methadone and fentanyl. For the most part, these deaths are preventable. Based on research from the Utah Department of Health, a substantial part of the increase in deaths is attributable to patients receiving
legitimate prescriptions.

First to sound the alarm in Utah was Dr Todd Grey, chief medical examiner, who noticed an increase in poisoning deaths in autopsies done by his office, especially in patients taking methadone (a synthetic narcotic that is effective orally). Methadone is now being used more frequently as an inexpensive option for the relief of pain, although it has formerly been employed chiefly as a heroin substitute in the treatment of addiction.

Accidental death

In 2006 the Utah legislature passed HB 137 tasking the Utah Department of Health (UDOH) to study and remedy the causes of the problem. In response, the UDOH has assembled a diverse group to carry out this mandate.

"Since 2003, the leading cause of accidental death in Utah has been overdose from prescription drugs."

In 2007, the Medical Examiner investigated 467 overdose deaths related to drugs of any type. Of these, 62 decedents had strictly illicit drugs appear on the toxicology results while 317 had strictly non-illicit drugs in the toxicology results and 67 decedents had a combination of illicit and non-illicit drugs.

The mean age of people who died from a drug overdose in 2007 was 40 years old. The mean age of people who died strictly of non-illicit drugs was higher (39.5 years) than those who died of illicit drugs (34.9 years).

The individuals who died of strictly illicit drugs in 2007 were more frequently male (79%) than those who died of strictly non-illicit drugs (56% male). Non-illicit drug deaths occurred in 11 of the 12 health districts, showing that this is an urban and rural problem and that it is impacting most counties across the state.

A team of researchers in Utah investigated how many of the people who died of non-illicit opioid overdose received a prescription for the drug from a doctor. They were able to match records of the Medical Examiner with Utah's Controlled Substances Database (CSDB) for 1,234 patients who had died from non-intentional opioid poisonings.

In 483 (39%) of the accidental and unknown opioid poisoning deaths, illegal substances (such as cocaine, methamphetamine, and marijuana) were found during toxicology examination, and in 751 (61%) no illegal substances were found. In the first group, only 69 of the 483 (14%) decedents had at least one opioid dispensed where the supply would have ended within 30 days of death if the drug was used as prescribed.

In comparison, 431 of 751 (57%) of the non-illicit opioid decedents had at least one opioid dispensed where the supply would have ended within 30 days of death.

These results indicate that a substantial proportion of the individuals who died of prescription pain medication overdose had recently received at least one of the implicated opioids by prescription from a healthcare provider. This represents an opportunity for prevention by better educating patients and healthcare providers about the risks from these medications. Primary care providers had written most of these prescriptions, since they do most of the chronic pain management.

Preliminary results suggest that other specialities (such as orthopaedics, anaesthesiology and pain management) have a higher death rate per opioid prescription. The epidemic continues. About five chronic pain patients are dying each week, two of them shortly after visiting their physician.

Methadone concerns

Methadone is substantially over-represented in deaths compared to the number of prescriptions written. While it is important to understand the unique problems with methadone, it should not be forgotten that the majority of the deaths still come from the other opioids.

"About five chronic pain patients are dying each week, two of them shortly after visiting their physician."

Issues contributing to the increase in deaths include more prescriptions being written, but also a rise in the deaths per prescription, which may represent ever-greater participation in the practice of chronic pain management by relatively inexperienced physicians. Opioids are particularly dangerous in patients with (or at risk for) obstructive sleep apnea syndrome, although at higher doses, central sleep apnea also occurs even in lean patients, especially when opioids are combined with benzodiazepines.

Some of the unique problems with methadone are not fully understood by many prescribers, and are exacerbated by inaccurate information in common drug prescribing references and in opioid conversion tables. For example, the starting range for methadone in opioid naïve patients recommended in the package insert and many other commonly used sources allows for two to four times the safe dosage.

Because of unpredictable genetic differences among patients in the metabolism of methadone, the half-life of methadone can vary from 15 to 55 hours and longer. Since the duration of analgesia experienced by the patient averages only around four to six hours, toxic levels can build up over the first few days after initiation of methadone or changes in dosage.

A second problem is that methadone can cause serious dose-related cardiac conduction disturbances, including QT prolongation and Torsades de Pointes. This is made worse when the drug is combined with other QT-prolonging drugs such as many psychiatric and antimicrobial medications, which are often used in chronic pain patients. Also, deaths are occurring in patients in acute care settings such as in emergency care or post-operatively when long-acting narcotics are introduced to the management of short-term pain.

Role of doctors

To summarise the changes needed to make opioid prescribing safer in a memorable form, the following six guidelines for prescribing have been developed:

  1. Start low, go slow
  2. Obtain sleep studies for all patients on moderate or high doses of any long-acting opioid (morphine equivalent > 100mg or methadone > 50mg)
  3. Obtain EKGs before starting methadone, after 30 days of treatment, then annually. (Look for QT prolongation.) Also when increasing the dose to 100mg/day or combining with a QT prolonging drug
  4. Avoid sleep aids and benzodiazepines with opioids
  5. Avoid long-acting opioids in acute pain
  6. Educate patients/family about risk.

Tips for patients

The Utah Department of Health suggests six tips for patients to remember when being prescribed a prescription pain medication:

  1. Never take prescription medication that is not prescribed to you
  2. Never adjust your own doses
  3. Never mix with alcohol
  4. Taking sleep aids or anti-anxiety medications together with prescription pain medication can be dangerous. Always tell your healthcare provider about all medications you are taking from any source so that you avoid being prescribed a dangerous combination of drugs
  5. Keep your medications locked in a safe place to avoid misuse by others
  6. Dispose of any unused medications.
"Some of the unique problems with methadone are not fully understood by many prescribers."

The Utah Department of Health has developed a physician education intervention aimed at teaching physicians these key points about safe prescribing of opioids in order to reduce the death rate. The strategy has been to work with small groups of providers (eight to 20), using a didactic presentation coupled with exercises designed to change practice systems around chronic pain management including more effective use of the CSDB.

Depending on the degree of participation, participants can earn from 1.5 to 20 hours of CME credit. Presentations to larger groups are also planned. Utah Medical Insurance Association (UMIA) is also conducting physician education in safe opioid prescribing which has already reached over 500 physicians this year.

The Utah Department of Health has developed clinical guidelines on prescribing opioids, containing important recommendations for doctors to follow when prescribing opioids. It is hoped that these precautions being taken will lessen the incidence of accidental drug-related deaths throughout Utah and the US as a whole.

Summary of recommendations

Opioid treatment for acute pain

  1. Opioid medications should only be used for treatment of acute pain when the severity of the pain warrants that choice and after determining that other non-opioid pain medications or therapies will not provide adequate pain relief.
  2. When opioid medications are prescribed for treatment of acute pain, the number dispensed should be no more than the number of doses needed based on the usual duration of pain severe enough to require opioids for that condition.
  3. When opioid medications are prescribed for treatment of acute pain, the patient should be counselled to store the medications securely, to not share with others, and to dispose of medications properly when the pain has resolved in order to prevent non-medical use of the medications.
  4. Long duration-of-action opioids should not be used for treatment of acute pain, including post-operative pain, except in situations where monitoring and assessment for adverse effects can be conducted. Methadone is rarely if ever indicated for treatment of acute pain.
  5. The use of opioids should be re-evaluated carefully, including assessing the potential for abuse, if persistence of pain suggests the need to continue opioids beyond the anticipated time period of acute pain treatment for that condition.
"A substantial proportion of the individuals who died of prescription pain medication overdose had received at least one of the opioids from a healthcare provider."

Opioid treatment for chronic pain

  1. A comprehensive evaluation (including the pathophysiological causation, risk for abuse, and other co-morbid conditions) should be performed before initiating opioid treatment for chronic pain.
  2. Alternatives to opioid treatment should be tried (or adequate trial of such treatment by a previous provider documented) before initiating opioid treatment.
  3. The provider should screen for risk of abuse or addiction before initiating opioid treatment.
  4. When opioids are to be used for treatment of chronic pain, a written treatment plan should be established that includes measurable goals for reduction of pain and improvement of function.
  5. The patient should be informed of the risks and benefits and any conditions for continuation of opioid treatment, ideally using a written and signed treatment agreement.
  6. Opioid treatment for chronic pain should be initiated as a treatment trial, usually using short-acting opioid medications.
  7. Regular visits with evaluation of progress against goals should be scheduled during the period when the dose of opioids is being adjusted (titration period).
  8. Once a stable dose has been established (maintenance period), regular monitoring should be conducted at face-to-face visits during which treatment goals, analgesia, activity, adverse effects, and aberrant behaviours are monitored.
  9. Continuing opioid treatment after the treatment trial should be a deliberate decision that considers the risks and benefits of chronic opioid treatment for that patient. A second opinion or consult may be useful in making that decision.
  10. An opioid treatment trial should be discontinued if the goals are not met and opioid treatment should be discontinued at any point if adverse effects outweigh benefits or if dangerous or illegal behaviours are demonstrated.
  11. Clinicians treating patients with opioids for chronic pain should maintain records documenting the evaluation of the patient, treatment plan, discussion of risks and benefits, informed consent, treatments prescribed, results of treatment, and any aberrant behavior observed.
  12. Clinicians should consider consultation for patients with complex pain conditions, patients with serious co-morbidities including mental illness, patients who have a history or evidence of current drug addiction or abuse, or when the provider is not confident of his or her abilities to manage the treatment.
  13. Methadone should only be prescribed by clinicians who are familiar with its risks and appropriate use, and who are prepared to conduct the necessary careful monitoring.