1 NALTREXONE INDUCED DETOXIFICATION FROM OPIOIDS A METHOD OF ANTAGONIST INITIATED TREATMENT Opioid dependence is a devastating and frequently fatal medical condition. It is a manifestation of addictive disorder and characterized by denial and frequent violations of the morals, values and beliefs of the patient with the disease. A chilling question sometimes presented to the patient is, How many dead friends do you have? The response is often much more chilling. Since approximately 1986 we have employed a Naltrexone induced detoxification as the preferred method for detoxification from Opioids. The initial effort came from a sense of the difficulty that patients dependent on opioids presented when attempting abstinence based treatment, which was and is our orientation. These difficulties were exemplified by drug seeking as well as disruptive behavior and self focused irritability. The staff efforts required to deal with Opioid dependent patients were in excess of efforts required to deal with patients dependent upon alcohol, other sedative hypnotics or stimulants. Following some initial publications by Gold, et al related to the use of Clonidine to modify the symptoms of detoxification and following a review of a NIDA Monograph on Buprenorphine, we developed a protocol characterized by a brief stabilization on Buprenorphine followed by Naltrexone induced detoxification. The author has used this protocol in several facilities both freestanding and medical-surgical hospital based. This experience has informed an understanding of detoxification from Opioids. The success of the first few detoxifications was salutatory and possibly serendipitous in that there were dramatic results and the induced symptoms were easily manageable. As distinct from other Opioid addicts admitted to the facility, those who received the Naltrexone induced detoxification in fact, became indistinguishable in their group participation and enthusiasm for recovery within three to five days. Prior to this, Opioid addicts would typically be difficult for the majority of their stay in treatment and only be participatory in the last week or ten days of a four-week stay. Following Naltrexone induced detoxification, these patients were participatory and enthusiastic for the majority of their inpatient time. This experience of shortened detoxification and early enthusiastic participation in treatment has been consistent over the entire experience of using a Naltrexone induced protocol. The protocol has evolved over time. Figure 1 is a current order set provided to the nursing staff to initiate the process. When a change in staff has occurred or when the author has utilized a new facility there has been a significant learning curve for the nursing and support staff. However, this learning curve was relatively brief (several weeks) and, subsequently, nursing staff has competently handled the most difficult of presentations involving the physician in crisis management only at such times as the patient s response to the protocol was severe or unusual. From very early in this experience the facility used has been capable of lockdown if necessary. Earlier facilities were typically unlocked but could be locked if a particular patient s behavior required this response. This is mentioned because of the rather
2 Figure 1 ON ADMISSION IN ADDITION TO ROUTINE ADMIT ORDERS 1. Buprenorphine (Subutex) 2mg q2h prn pulse > 90, diastolic > 90, diaphoresis or restlessness. 2. Thorazine 50mg IM or PO Q6h prn nausea or vomiting or agitation. 3. Bentyl 20mg IM or PO Q6h prn cramping abdominal pain. 4. Zanaflex 8mg Q4h prn skeletal muscle cramps, diaphoresis, piloerection or signs or symptoms of opiate detoxification. 5. Imodium caps 2 Q6h prn diarrhea. 6. Seroquel 100mg PO qhs. Observe for orthostatic hypotension. 7. Catapres 0.1mg q1/2h prn pulse >80 up to 2.4mg/24 hrs. 8. Sandostatin 100mcg SC q4h prn nausea, vomiting or diarrhea. IF SEDATIVE AND/OR ALCOHOL DEPENDENCE ALSO PRESENT 1. Phenobarbital 90mg PO on admit and 6am, 2pm and 10pm 2. Phenobarbital 90mg PO q2h prn pulse >90, up to 4 prn doses in 24 hours. WHEN READY TO START DETOX (next morning, usually) 1. Xanax 2mg PO now. 2. Zanaflex 8mg PO now. 3. Bentyl 20mg IM now. 4. Thorazine 50mg IM now. 5. Sandostatin 100mcg SC now. 6. Imodium caps 2 now. 7. Buprenorphine 2mg SL now. 8. Naltrexone 150mg PO in ½ hour and 50mg qam. 9. DC Buprenorphine after above. 10. Catapres 0.2mg with first dose of Naltrexone and continue previous prn Catapres order. 11. Notify for pulse over 90 or diastolic over Xanax 2mg PO q2h prn agitation in next 12 hours only, up to four prn doses total. 13. DC all prn s 72 hours following first dose of Naltrexone.
3 consistent behavioral findings typical of induced Opioid detox. The patient responses over time, although with many individual examples of more severe and less severe reaction or difference in presentation, have been generally consistent. The initial process is stabilization on Buprenorphine, which may be for a period of 12 to 72 hours, depending on the potency, half-life and daily milligram dose of the Opioid that had been used. The rationale for a brief (12 hour) stabilization has been an idea that detoxification would be mild and easily manageable and the patient able to tolerate the procedure with reduced difficulty. This judgment has been based on the experience of detoxification in people who are young, healthy, have used Hydrocodone or Oxycodone compound tablets, Meperidine or Codeine. Generally such patients can be detoxified after orders written at the time of initial physician assessment, usually the day following admission, and this group of patients has not presented particular problems in management. A decision to stabilize a patient on Buprenorphine for up to72 hours would be based on medical comorbidities or the use of high doses of Opioids with a long halflife such as Methadone or high doses of sustained release Oxycodone. More recent experience would suggest that a high dose use history of Fentanyl might be best treated with a longer Buprenorphine stabilization also, although the understanding of this seems paradoxical because of the short half-life of Fentanyl. During the period of stabilization on Buprenorphine, as necessary (prn) medications are provided for the usual symptoms of detoxification, which includes antispasmodics, skeletal muscle relaxers, non-steroidal anti-inflammatory analgesics and Clonidine. At the time that induction to Naltrexone begins, the patient is preloaded with detoxification symptom specific medications as well as a mild dose of Alprazolam (2mg.) One-half hour later an initial dose of 150mg. of Naltrexone and a loading dose of Clonidine are provided by mouth. The emphasis to the nursing staff during the initial several hours of detoxification is that detoxification is best managed with frequent and liberal administration of Clonidine. A guideline is up to 0.1-mg. each one-half hour as symptoms persist up to a total daily dose of 2.4-mg. The provision of Clonidine is effective at these doses in relieving the majority of the symptoms of detoxification, however frequently induces orthostatic hypotension such that many patients require oneto-one staff attention during the first several hours. If the patient has been using high doses of Methadone or sustained release Oxycodone, a second dose of 100-mg. of Naltrexone is provided two hours after the initial dose. The typical symptoms of detoxification that are observed include marked restlessness with the patient moving about in bed and unable to remain still. Typically, patients are sedated enough that they appear to be sleeping fitfully. Occasionally, frank hallucinations occur in the context of pulse and blood pressure that is maintained at normal. The most disturbing symptoms that occur during detoxification are incontinence. This, of course, is disturbing to the dignity of the patient and difficult for the staff to deal with. Another disturbing symptom that occurs during this time is vomiting. Control of vomiting has rarely been difficult but often requires administration of injectable antiemetics, antispasmodics and non-specific anti-nausea medications as identified in Figure 1.
4 The length of expected physical symptoms of detoxification ranges from 3 24 hours. Most typically, patients have gotten through it or calm down within the first six hours. (A not very sensitive but descriptive language has developed among the staff to describe some of the observations. The author has typically received communications such as He s still flopping or he s done at times of ongoing medical symptoms or at completion of the severe symptoms of detoxification respectively.) When these symptoms resolve, the effect of sedatives administered usually result in a period of sleep that lasts 6 12 hours. During all stages of the protocol the patient is easily aroused and responds to verbal interaction although, occasionally, is obviously confused. The more informative experience, however, has been what follows the symptoms of physical detoxification. For the next hours the patient may have some residual mild symptoms of detoxification. Frequently these are muscle cramps, bone aches and sometimes rebound symptoms of a pain condition for which they were originally prescribed Opioids. Much more significantly, patients exhibit a period of anergy and anhedonia following awakening from their detoxification. This anergy and anhedonia lasts for 6 48 hours depending upon the drugs that have been used and idiosyncratic factors that have resisted clarification. Following the resolution of this period, the patients generally begin to feel well and even vigorous. During this period of returning physical improvement there is a period of irritability and agitation that can last another 6 72 hours depending upon the drug used, dose and idiosyncratic factors that have resisted clarification. Patients routinely describe this time as a time of intense craving and almost certain relapse. The significance is that these two stages of detoxification occur reliably and resonate with each patient s history of previous attempts at naturalistic detoxification over a much longer period of time. The physiology of these stages of detoxification certainly relate to the restoration of receptor and neurotransmitter equilibrium from the state of adaptation that occurs with daily Opioid use. It is the understanding of the author that these periods of sub-acute and post-acute withdrawal that reliably occur in the Naltrexone induced detoxifications also occur in attempts to achieve detoxification by taper or by sudden abstinence, however these stages take much longer without antagonist stimulation. A research question might be, Are these infrequently described and poorly understood sub-acute and post-acute withdrawal states responsible for the poor success rate in detoxification from Opioids? Another significant understanding informed by these observations is that these events will occur following induction of detoxification by any means. Specifically, in a setting where anesthesia-assisted rapid detoxification (Ultra Rapid Opioid Detoxification = UROD) is employed, the symptoms of detoxification would occur and would take as long no matter the dose of Naloxone or Naltrexone administered. The response observed during post-acute and sub-acute withdrawal states on an inpatient unit would predict that discharging a patient prior to the resolution of the anger/agitation/irritability stage would result in frantic attempts to relieve those symptoms by the use of Opioids. This may well explain the tragic results in some patients who have received anesthesia-assisted detoxification and certainly would explain the inability to successfully demonstrate improvement in terms of higher rates of
5 successful participation in abstinence-based treatment or in a lower rate of relapse to the use of opioids for UROD treated patients. As a result of the above experience, which has been accumulated in the treatment with this protocol of over 5,000 patients, the author would not suggest this protocol outside of a locked or potentially locked environment. Patients admitted for detoxification understand in advance that a 5 7 day hospitalization will follow their admission although a smooth experience might result in an earlier transition to a less intensive level of care. Patients are clearly informed that discussions of discharge prior to 72 hours following the administration of the first dose of Naltrexone will not occur. (Fortunately in our setting, should someone choose to leave anyway, law provides that they must request to leave in writing and the period of 72 hours may be utilized to determine if that patient requires involuntary treatment or may be safely discharged at the expiration of that 72 hours.) At issue is the experience of a high probability of relapse to the use of Opioids in the period of post-acute and sub-acute withdrawal. Detoxification from Opioids induced by Naltrexone is never easy and sometimes very uncomfortable. The rationale and justification for this protocol is the frequent fatality and rapid progression of addictive disorder in patients who use Opioids as their drug of choice as well as the great difficulty of completing detoxification through the post-acute phases. However, in the experience described there have been no fatalities within a month of discharge from the inpatient facility. There have been five transfers to the emergency room during detoxification. Two cases have resulted from over-sedation (earlier in the evolution of the protocol), in two cases there was intractable diarrhea with impending dehydration, and there was one case of aspiration pneumonia in a patient who vomited while unobserved. Two of these patients returned to the hospital for completion of the their detoxification and successfully entered abstinence-based treatment. Three of these patients declined the recommendation to return to the hospital. It will be important through retrospective records review, to attempt to determine if patients receiving Naltrexone induced detoxification were able to benefit from abstinence-based treatment at the same frequency and with the same success as patients with addictions to other drugs. If so, this would recommend criteria of completion of detoxification as a defined goal for Opioid addicts attempting abstinence-based treatment. Additionally, it would be important by the design of prospective trials to determine the efficacy of this intervention in the life history of persons with addictive disorder. Our experience has demonstrated that this is a safe protocol in the environment described above. Although critically important, the research questions have yet to be answered.