Buprenorphine and the Medically Ill Patient
A 60-year-old man with a 15-year history of oxycodone dependence presented to a substance abuse detoxification program with acute withdrawal symptoms, including dilated pupils, nausea, vomiting, diarrhea, and hot and cold flashes. He reported his last opiate intake was 2 days earlier. He felt his addiction was out of control and he wanted treatment.
His medical history was notable for hypertension and a 30-year history of tobacco use (2 packs per day). He went to a local emergency department (ED) a month ago for a cough. No outside medical or prescription records were obtained prior to initiating treatment. On physical examination, abnormal findings included dilated pupils, elevated heart rate and blood pressure, hyperactive bowel sounds, and scattered wheezes and rhonchi bilaterally.
Per the treatment program's protocol, the patient received buprenorphine/naloxone (4.0 mg/1.0 mg) for opiate detoxification, first at 2:00 PM and then again at 4:00 PM. When the nurse checked on the patient at 7:00 PM, he was difficult to arouse and cyanotic with notable respiratory muscle retractions, a respiratory rate of 8 breaths per minute, and oxygen saturation of 67%.
The patient was transported to the nearest ED where he was diagnosed with acute opiate-induced respiratory distress complicated by pneumonia and chronic obstructive pulmonary disease. The ED staff obtained outside medical and pharmacy records, which indicated the patient was hospitalized with community-acquired pneumonia and chronic obstructive pulmonary disease at another hospital 3 weeks prior and was given a prescription for oral antibiotics and other medications, which he never picked up from his pharmacy. Fortunately, the patient made a full recovery after 4 days on the medicine ward and was then discharged back to the substance abuse unit.
The United States is currently experiencing an epidemic in opioid abuse and addiction fueled to a great extent by large increases in misuse of prescription opioid analgesics.(1) Since 1999, there has been a 300% increase in the sales of opioid pain medications. In 2010, more than 12 million (or 5% of) Americans aged 12 or older reported nonmedical use of prescription pain medications.(2) Coincident with the greater availability of these drugs, accidental deaths from overdoses have surged with 14,800 deaths in 2008—more than for heroin and cocaine combined. In 2009, there were 475,000 emergency department (ED) visits for adverse events related to misuse of opioid pain medications—a doubling of such events in only 5 years.(2) Visits to EDs as a result of toxicities related to opioid misuse increased by 134% from 2004 to 2010.(3) Drug-related adverse events occur at highest rates in those aged 65 and older with opioid pain relievers being one of the top five drug classes responsible for such occurrences.(3) The overuse and misuse/abuse of opioid analgesics has resulted in large numbers who develop opioid addiction. Opioid addiction is common in aging Americans who often have comorbid medical disorders and other co-occurring substance use and mental disorders. Treatment admissions for addiction to opioid pain medicines have increased fourfold between 1998 and 2008 (4), and the numbers of individuals seeking treatment for opioid dependence will continue to increase.
In the current clinical scenario, an older man with a long history of opioid analgesic dependence sought treatment at a substance abuse treatment program. There is no information on what triggered the man to seek treatment; we are only told that he had a history of hypertension, current symptoms consistent with opiate withdrawal, and that he had wheezing and rhonchi on pulmonary examination. Several issues need to be considered. First is the recognition that those with opioid dependence often have co-occurring illnesses that must be assessed and addressed in the treatment plan. In this case, it would be imperative to explore the underlying reasons for abnormal pulmonary findings, determine relevant medical history, prior treatment, and current treatment needs. Second, pharmacotherapy with opioid medications to treat opioid addiction requires that an evaluation occur prior to initiating opioid therapy. This evaluation must include a urine toxicology screen to confirm opioid use and to determine recent use of other substances that could impact clinical care—for example, if this patient were abusing alcohol and/or benzodiazepines, the administration of opioids might be complicated and represent greater risk to the patient.
Each consideration above is particularly relevant to decisions about the most appropriate substance abuse treatment for this individual. Several treatment options for opioid dependence should be considered in the context of joint decision-making with the patient: (i) use of an opioid medication for maintenance treatment without medical withdrawal (detoxification); (ii) medical withdrawal from opioids followed by use of an opioid antagonist medication to maintain abstinence; (iii) or medical withdrawal without ongoing pharmacotherapy for opioid dependence (the more common course with opioid withdrawal procedures). It is unclear why "detoxification" treatment (medical withdrawal) was selected for this patient. Medical withdrawal has been shown to have poor outcomes and high relapse rates in the year following this procedure regardless of the medication used for detoxification.(5,6) Treatment decisions should be based on current substance use disorder(s), prior treatments, and response to those treatments (including length of abstinence following treatment), and other comorbid medical and mental illness. Maintenance treatment without medical withdrawal might have been a more effective choice for a patient like the one in this case. Those with co-occurring medical and mental disorders may benefit from being opioid maintained rather than undergoing the mental and physical stress of detoxification.
If medical withdrawal is selected as the treatment for opioid addiction, there are multiple medication approaches to this procedure including methadone taper (which must be undertaken in a methadone maintenance program; i.e., specially regulated narcotic treatment programs) (5), clonidine (an alpha-adrenergic agonist approved for the treatment of hypertension that is also used to suppress some symptoms related to adrenergic excess that occurs in opiate withdrawal) administration (7), and buprenorphine taper. Buprenorphine is a mu-opioid receptor partial agonist that can be prescribed for the treatment of opioid addiction by physicians who meet federally specified criteria and/or have 8 hours of approved education in use of the drug and treatment of opioid dependence.(8)
This patient came to the substance abuse treatment program with medical illnesses in addition to opioid addiction and opioid withdrawal symptoms. The complicated medical picture could justify an inpatient hospitalization for the withdrawal procedure, where appropriate care and monitoring for both conditions could be rendered. It is notable that the patient developed opiate-induced respiratory distress following two standard doses of buprenorphine used for medical withdrawal. This is unusual. Because it is a mu-opioid receptor partial agonist, buprenorphine exhibits a ceiling effect with regard to respiratory depression.(9) Factors such as this patient's pre-existing chronic obstructive pulmonary disease (COPD), untreated pneumonia, and significant smoking history confer vulnerability to standard buprenorphine doses. Use of sedating drugs (e.g., antihistamines, benzodiazepines) and/or alcohol use, both associated with buprenorphine-related adverse drug events and deaths (10), additionally contribute to the risk of respiratory depression. When this risk is elevated, monitoring should be increased or the patient transferred to a higher level of care. Should treatment of respiratory depression be required, a naloxone infusion over several hours may be necessary due to the long half-life of buprenorphine.(11)
In a patient with a long history of opioid dependence and concurrent serious medical illness, other treatments can be considered once the detoxification is completed. For example, treatment with the opioid antagonist naltrexone (7,12) should be considered. Given high relapse rates for opioid withdrawal procedures without ongoing pharmacotherapy and psychosocial treatment, the use of an antagonist that can block the euphoria-producing effects of opioids should relapse occur may be an effective intervention to assist this individual with maintaining abstinence. Furthermore, the lack of opioid agonist effects with naltrexone will eliminate the potential for respiratory depression that might occur with other opioid therapies and which may be harmful to patients with COPD. Naltrexone is available as a tablet (50 mg given once daily, available as a generic) or as a once monthly injectable medication. It must not be administered to anyone who is currently physically dependent on opioids as it can precipitate opiate withdrawal. The presence of COPD is not a contraindication to medications with opioid agonist effects, but it does require close monitoring, a slow upward titration, use of the lowest possible dose to alleviate withdrawal and craving, and education of the patient about the risks of opioid therapy. Opioid therapies for treating this individual would include buprenorphine/naloxone (8) or methadone.(5) Methadone would require enrollment in a narcotic treatment program, which can be inconvenient for patients because of the need, at least in the early phase of treatment, to come to the clinic daily. Many methadone maintenance programs do not have embedded primary care so that substance abuse treatment must be received in one clinical setting and medical care in another. This too can be difficult for patients, and communication between programs can be challenging. On the other hand, buprenorphine/naloxone can be prescribed for treatment of opioid dependence from office-based practices by qualified physicians. This would allow one doctor to provide all of this patient's needed care, which can contribute to improved clinical outcomes.(8)
Any patient with opioid dependence must also receive psychosocial treatment in conjunction with any medication treatment. The diagnosis of opioid dependence is based on a constellation of aberrant behaviors associated with uncontrollable opioid abuse.(13) Medication will not impact these behaviors. Psychosocial treatment modalities, including group, individual, and family therapy, are equally important and employ evidence-based treatment approaches such as motivational enhancement therapy, cognitive-behavioral therapy, 12-Step programs, and/or contingency management therapy. Patients unwilling to participate in recommended psychosocial therapies may not be good candidates for opioid maintenance. Patients who drop out of psychosocial treatments need to be reevaluated for continued opioid therapy. Opioid dependence is a chronic, relapsing disease, and its treatment should be viewed similarly as that of any chronic disease that is likely to have periodic exacerbations (relapses). Opioid dependence requires ongoing assessment and increased treatment intensity as clinically indicated.
- All opioid-addicted individuals seeking substance abuse treatment must have a medical evaluation including a urine toxicology screen in order to determine the most appropriate treatment and level of care needed.
- Comorbid acute medical and/or mental illness is common in patients with an active substance use disorder. All of the disorders diagnosed in the patient should be addressed in the treatment plan. Medical, mental, and substance use disorders must receive treatment simultaneously.
- Opiate withdrawal symptoms can be treated with buprenorphine/naloxone, clonidine (an opioid antagonist), or methadone (the latter can only take place in a licensed narcotic treatment program). Choice of medication treatment for opioid dependence should be based on the assessment of the patient's clinical needs and safety issues.
- Drugs with opioid agonist effects may cause respiratory depression. The risk is increased in patients with pre-existing respiratory compromise and with some abused drugs (i.e., alcohol and benzodiazepines) that may have a synergistic interaction with the opioid agonist.
- Opioid pharmacotherapy alone is ineffective in treating opioid dependence (addiction). These medications should always be used in the context of ongoing psychosocial treatment.
Elinore F. McCance-Katz, MD, PhD Professor Department of Psychiatry University of California, San Francisco
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