Robert Averbuch, MD

Dr. Suryadevara is Assistant Professor, Department of Psychiatry, University of Florida, Gainesville, FL, and Assistant Professor, North Florida/South Georgia VAMC, Psychiatry, Gainesville, FL. Dr. Holbert is Assistant Professor, Department of Psychiatry, University of Florida, and Dr. Averbuch is Associate Professor, Department of Psychiatry, University of Florida.

The United States is currently in the midst of an opioid epidemic. The numbers are staggering: in 2016 there were 78 deaths per day from drug overdose, two-thirds of which involved opioids. Since 1999, deaths from opioid prescriptions have more than quadrupled.

As is often the case, the origins of this epidemic are multifactorial. Some overprescribing can be traced back to the health care profession’s efforts to recognize pain as the fifth vital sign, which compelled physicians to treat more aggressively. Some pharmaceutical companies may have also contributed to the problem through aggressive marketing of prescription opioids without proper emphasis on their addictive potential. Regardless of the cause, the problem is pervasive, affecting all socioeconomic groups and spheres of society.

While opioid use disorders are more common in younger patients, prevalence among the elderly is growing, and misuse poses unique risks in the geriatric population. From 1996 through 2010, the number of opioid prescriptions provided to older patients increased 9-fold. More alarming, 35% of patients aged older than 50 years with chronic pain reported misuse of their opioid prescriptions in the past 30 days.

 The hospitalization rate for geriatric misuse of opioids has quintupled in the past 20 years alone.

 Given the scope of the problem, federal and state governments have begun to implement new guidelines in prescribing opioids, but tighter regulations may intrude on individualized patient care and the benefits of opioid therapy in some patients. Whether these new policies are the best strategies remains to be seen.

Avoidance of iatrogenic addictions may be the first step in addressing the epidemic. Some situations are more straightforward. Most clinicians can distinguish which of the following fictional cases is an inappropriate use of opioids: a 78-year-old in hospice care for terminal lung cancer; a 65-year-old who underwent major surgery that morning; or a 68-year-old with a history of depression, anxiety, and chronic pain, and a urine drug screen positive for cocaine, opioids, and benzodiazepines (prescribed). Contrast that with more complex, typical clinical scenarios in which the distinction can be a real challenge.

Mr. X is a 66-year-old under hospice care for hepatocellular carcinoma, with a comorbid severe alcohol use disorder. Opioids were prescribed until his urine drug screen came back positive for marijuana and cocaine. Two days after opioid therapy was stopped, the patient was found dead due to a self-inflicted gunshot wound. Pain was determined to be a major contributing factor. This case highlights the importance of understanding the delicate balance between risks and benefits when prescribing opioids, and the unique role psychiatrists play in their use.

Opioids reduce the perception of pain and produce a sense of well-being by binding to opioid receptors (mu, delta, and kappa) distributed in the brain, spinal cord, and other peripheral tissues. When deeper brain regions are stimulated by opioids, drowsiness and respiratory depression ensue. Opioids are classified by their origin, mechanism of action, or potency. Based on their origins in nature, opium, morphine, and codeine are opiates. Semi-synthetics include hydromorphone, hydrocodone, oxycodone, and heroin. Completely synthetic opioids are manmade and include fentanyl, methadone, pethidine, levorphanol, tramadol, and dextro­propoxyphene. Based on their potency, codeine, hydrocodone, and oxycodone are considered mild opioids; morphine, meperidine, hydromorphone, fentanyl, and methadone are classified as major opioids. All are opioid agonists with the exception of buprenorphine, which is a partial agonist/antagonist.

Opioids are generally used for acute and chronic pain, active-phase cancer treatment, palliative care, and end-of-life care. The latter situations are relatively straightforward as the benefits are uniformly perceived to outweigh the risks. Standards for treatment of acute pain are similarly uniform among most physicians, with only minor variations. For treatment of nonmalignant chronic pain, there is far less agreement among providers. There are no clear data to support the long-term effectiveness of opioids in these conditions. Hence, guidelines have been established on when to initiate or continue treatment, selection of the proper opioid, dosage, duration of use, and when to discontinue therapy. These guidelines also outline how to conduct a thorough risk assessment and address potential pitfalls.

Opioids are also used for non-medicinal, recreational purposes. In the elderly, the line between use for physical and psychological well-being is often blurred, which complicates attempts to determine prevalence. Numbers vary for different countries and are based on different study results, further confounding the data. This variation in prescribing patterns could be a result of the inconsistent practice styles among physicians and a failure to adhere to the guidelines that aim at standardizing practice. The changing demographics of the elderly American population further influence the prevalence of substance use disorders.

The decision to prescribe opioids in the elderly requires careful consideration of the many pharmacokinetic changes associated with aging. Age-related changes include a decrease in hepatic blood flow and volume along with decreases in renal blood flow and the glomerular filtration rate. Depending on the opioid used, it is essential to estimate the creatinine clearance and hepatic function for appropriate dosing adjustments. Other age-related changes that may influence opioid levels include decreased rates of absorption and increased adipose tissue. Many comorbid medical conditions seen in the elderly can lower the serum albumin concentration, thereby increasing the free opioid concentration.

Additional risks include the potential for serious drug-drug interactions with opioids. The likelihood of such interactions is directly proportional to the number of medications prescribed and compounds the risk of serious adverse events such as respiratory suppression.

Elderly patients often take a number of medications, and the combination of polypharmacy-related drug interactions, pharmacokinetic changes seen with aging, and multiple comorbidities can make pain management particularly challenging. The management of pain in the long-term care setting poses an additional set of challenges. According to the American Geriatric Society, nearly 80% of elderly patients in long-term care settings have substantial pain, yet 25% do not receive any treatment.

Patients at the highest risk for inadequate pain control include members of racial and ethnic minority groups, women, the elderly, those with cognitive impairment, and those with terminal cancer. Persistent and undertreated chronic pain can lead to a variety of negative psychosocial and clinical consequences, including limitations in daily functioning, disruption in workplace productivity, stress in interpersonal relationships, and worsening medical conditions.

Non-opioid pharmacotherapy and non-pharmacological therapy are the preferred modalities of treatment for chronic pain. However, in the proper contexts, opioids can be a useful treatment option. They are most beneficial in the short term for acute injuries, including the management of pain postoperatively. Use should be time-limited, except in managing certain cancer-related pain syndromes and as a part of end-of-life care. Particularly in the elderly, appropriate precautions must be taken.

Obtaining a thorough history is the first step. Screen for a history of opioid use disorder or other addictive disorders, including nicotine use disorder and any family history of addiction. A complete psychosocial history, including current stressors, history of childhood abuse or neglect, legal problems, and interpersonal relationship stressors will help to identify high-risk opioid misusers. Comorbid depression and high levels of pain are additional risk factors for misuse of opioids in the elderly. Always screen for cognitive deficits and other psychiatric disorders. Depression and anxiety may increase the perception of pain and require a different approach to pain management altogether.

Be alert for certain findings on the mental status exam such as confusion or any other indicators of a clouded sensorium, disheveled or unkempt appearance, thought content preoccupied with opioids, and dramatic or exaggerated pain-related behaviors suggestive of drug-seeking. While doing a chart review or using prescription monitoring programs, look for doctor shopping and requests for early refills. Other red flags include patients’ keeping only the appointments related to pain management, a history of positive urine drug screens or refusal of such monitoring, losing pain prescriptions, and having multiple providers prescribing the same or similar classes of medications.

After a complete history and examination, if the decision is made to begin opioid therapy, a detailed list of all medical conditions, allergies, and medications-including over-the-counter and herbal remedies-must be obtained and regularly updated. Drug selection should be based on careful consideration of potency needs and individual patient characteristics. Before initiating therapy, realistic treatment goals should be set after careful consideration of pertinent risks and benefits.

Begin with low doses and gradual titration, monitoring regularly for adverse effects and drug-drug interactions (Table). Common adverse effects include constipation, dry mouth, tolerance, dependence, nausea, vomiting, drowsiness, confusion, and low blood pressure. Warn patients about the risk of withdrawal with abrupt discontinuation. Serious adverse effects include respiratory depression leading to death, especially when mixed with benzodiazepines or alcohol. The use of benzodiazepines is contraindicated in patients who are receiving opioid therapy.

Combining analgesics with different mechanisms, together with nonpharmaceutical pain management strategies, may improve outcomes and minimize the need for opioid dose escalations. With multiple states enacting laws to legalize marijuana for medical conditions, marijuana may be one remedy for the opioid crisis. Some studies have shown that the hospitalization rates related to opioid abuse and overdose have decreased significantly in the states that offer medical marijuana. However, we should caution that the evidence is still preliminary and in need of further review. Moreover, the availability of multiple preparations and potencies makes uniform recommendations a particular challenge.

When opioids are deemed appropriate for the treatment of pain, monitor use carefully and be vigilant for patient misuse. State-sponsored, prescription drug monitoring programs may be an invaluable tool. Should signs of misuse, abuse, or diversion emerge, clinicians are encouraged to avoid outright dismissals from treatment, opting instead for referrals or in-patient treatment of substance use disorders. Patients should be given the opportunity to choose either medication-assisted treatment with buprenorphine or methadone maintenance or naltrexone. These treatments are often coupled with behavioral therapies to help with addiction.

Patients who are taking opiates should also continue to be monitored for drug-drug interactions, particularly with anti-epileptics, antidepressants, and other drugs metabolized primarily by the cytochrome P-450 system. Opiates are also notorious precipitating factors for delirium, but there is no clear evidence that the risk varies based on the type of opiate used.

 If an opioid regimen proves ineffective, clinicians may rotate the opioids or change the formulation based on consideration of pharmacokinetics and metabolism. Urine drug screens are routinely employed to check for the presence of other illicit or contraindicated substances and to investigate suspicions of drug diversion.

There is no evidence to support the long-term use of opioids for the treatment of chronic pain in the elderly. Rather, there is extensive literature that shows possible harm from long-term opioid use. For acute pain management, 3 days of opioid treatment is sufficient. In rare cases, this may be extended to 7 days. Immediate-release formulations are preferred over long-acting preparations. In cases of longer-term opioid therapy, clear and measurable treatment goals should be established and monitored regularly.

Assessments should focus on overall functioning and activities of daily living. Progress should be reevaluated no less frequently than every 3 months, with appropriate consideration for the taper or discontinuation of therapy, particularly in the absence of clinically meaningful improvement. We cannot overemphasize that, particularly in the elderly, opioids are far more effective when accompanied by a comprehensive and multidisciplinary approach using psychological support, physical therapy, and other complementary therapies.

There are legitimate uses for opioids in the treatment of a variety of pain conditions. However, the significant risks associated with opioid prescription must be carefully weighed against the potential benefits. The alarming rise in fatalities seen with the current opioid epidemic provides a vivid illustration of this challenge.

Our “textbook” and real-world cases illustrate the application of prescribing recommendations. Based on these principles, most clinicians would feel justified prescribing opioids for the cases of the 78-year-old in hospice care for terminal lung cancer as well as the 66-year-old in hospice care for hepatocellular carcinoma. However, in the latter case, the patient’s comorbid substance use disorder as well as the evidence of misuse on drug screening provides a more complex, real-world scenario. Such cases require difficult clinical decisions-sometimes with untoward outcomes. It is our hope that understanding the guidelines, following the standards of care, and documenting the same will help clinicians provide better care to complex elderly patients.

The authors report no conflicts of interest concerning the subject matter of this article.

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