Ultra-high Dose Opioid Therapy: Uncommon and Declining, But Still Needed
There is a small, but tragic, group of chronic pain patients who require high or ultra-high daily doses of opioids. We have previously defined high dose as 200 mg per day and ultra-high dose as 1,000 mg per day of morphine equivalents.1 On the surface, the use of high opioid doses may appear controversial, but on close examination of various state medical board regulations, and even proposals to change FDA opioid labeling,2 there is no attempt to restrict or deny the use of ultra-high dose opioid therapy in needy patients.3,4 In fact, leeway is made for this outlier group if there is documentation that standard dosages and modalities have failed. Put another way, no party wants to leave patients in severe pain and suffering because of dosage restrictions. They just don’t want “unneedy” or “illegitimate” patients to receive high-dose opioid therapy.
At the outset, I want to emphasize that no physician should attempt high, much less ultra-high, dose opioid therapy unless the physician is experienced with this form of therapy because it has potential risks and hazards—endocrine complications are essentially universal with high-dose opioid therapy. That said, I would like to encourage interested pain practitioners to learn to prescribe high and ultra-high opioid doses when they are indicated and necessary to save a patient from suffering a bed-bound existence, or early death. Every community needs such a physician to provide ultra-high dose opioid therapy so these uncommon but needy patients don’t have to endure unthinkable misery. Table 1, will help calculate which dosage group to apply to patients.
The goal of this article is two-fold: First, to describe some apparent trends and emphasize that current standards for opioid pain treatment are adequate to validate the need for ultra-high dose opioid therapy.3,5 The second goal is to lay out some of the methods and procedures I personally use to ensure efficacy, safety, and prevention of overdoses and diversion in patients who require ultra-high dosages of opioids.
Need for High Dose Is Declining
The need for ultra-high dose opioid therapy, based on referrals to my clinic and discussions with other pain practitioners, appears to be declining. There are three main reasons for this decline. First, in the not too distant past, too often pain treatment was delayed, which allowed peripheral pain to become centralized. More recently, early intervention with aggressive pain treatment after surgery, trauma, or illness has been one of the biggest factors in the reduction of chronic pain. Second, some practitioners preferentially prescribed the most potent opioids (such as fentanyl and oxycodone), which drove up tolerance to the pain-relieving effect of the opioid too rapidly. Better education about proper opioid prescribing has led to a decline in these practices. The third reason for the decline is that many non-opioid therapies have been developed that reduce the need for opioids. These include neuropathic agents, electromagnetic devices, spinal interventions with corticoid injections, and hormonal agents. For example, a patient who complains of severe pain today, in contrast to some years ago, will more likely be started on non-opioid measures that keep opioid dosages in a lower range.
Standards and Guidelines
In 1998, the Federation of State Medical Boards created and published model guidelines for the use of controlled substances for the treatment of pain.5 These guidelines, which are summarized in Table 2, have endured and they are as applicable today as in 1998. Although various states may have slight variations in standards and guidelines (as do some professional organizations), they don’t deviate much from the 1998 model.1,3 Physicians who prescribe ultra-high dose opioids must closely follow these guidelines.5
Why Ultra-high Dose Opioid Therapy Is Still Needed
There are some forms of pain—just as there are forms of conditions such as hypertension, diabetes, and schizophrenia—that are appropriately called malignant or catastrophic.6 These are the outliers from the norm. Patients with these tragic conditions, just as some pain patients, cannot survive and function without competent, caring help, and high dosages of medication. If left untreated, severe centralized intractable pain not only causes a total bed-bound suffering state, but may contribute to early death. The mechanisms of death in severe pain patients are known to include cardiac arrhythmia, malnutrition, adrenal failure, and sepsis.7 Sometimes pain patients are found dead in bed or on the toilet and are falsely diagnosed as an overdose death.
Unfortunately, patients who require ultra-high dose opioid therapy often have seen too many practitioners who have attempted too many treatments that have failed to help. Practitioners often are afraid of ultra-high dose opioid therapy, so they try all kinds of treatments that may be detrimental and brutal to the patient. For example, I have been referred patients with spine conditions who have received between 25 and 50 interventional corticoid procedures of which none provided more than a few hours or days of relief. Multiple spinal surgeries are sometimes attempted because practitioners don’t want to embark on ultra-high dose opioid therapy. A review of my last 15 referrals in preparation for this paper revealed that the number of prescription medicines taken by each patient ranged from 6 to 15. Polypharmacy is not a substitute for directed opioid therapy. A delay of ultra-high dose opioid therapy may result in a patient’s pain becoming uncontrolled, resulting in detrimental immunologic, hormonal, and neurologic damage.6
Each community, therefore, needs a subspecialist or a referral and evaluation mechanism to get these patients the help they need. For example, a primary care physician or interventionalist pain practitioner may wish to help follow an ultra-high dose opioid patient if there is a physician they can consult with who is familiar with ultra-high dose opioid care. The important point is not to ignore these patients just because they are complicated and need extraordinary long-term treatment.
Long-term Care And Monitoring
It is doubtful that ultra-high dose opioid patients can ever be opioid-free, unless cures are found for centralized pain. They can, however, develop a quality of life and function quite well. These patients will need to be seen and monitored regularly to determine that opioids are not impairing their quality of life. Simple tests to measure blood pressure, pulse rate, and observation of ambulation and alertness usually are sufficient at each visit. Too high of an opioid dosage lowers blood pressure and pulse rate and too low of a dose allows pain to raise the blood pressure and pulse rate.7