Treatment of opioid dependent individuals. Setting Up a Buprenorphine Clinic One Year Later 111 & THEIR TREATMENT DISORDERS

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1 Setting Up a Buprenorphine Clinic One Year Later Krishna Balachandra, MD* and Ismene Petrakis, MD Original Article 111 Abstract Buprenorphine is a new FDA-approved medication for treating opioid dependence. There has been little described about the practical aspects of setting up such a practice or clinic. This article describes the practical aspects of using buprenorphine in an outpatient setting based on the one-year experience of a clinic which is housed within a busy outpatient substance abuse clinic in a Veterans Hospital setting. The spectrum of treatment from induction to maintenance and stabilization and, when appropriate, discharge as well as other treatment challenges is discussed. Overall both patients and staff report a positive experience. The purpose of describing this process is to encourage those practitioners that are considering starting buprenorphine clinics to do so. This in turn will make this pharmacotherapeutic option for patients with opioid addiction more widely available. Key Words: disulfiram, naltrexone, alcoholism, comorbidity, treatment (Addict Disord Their Treatment 2005;4: ) Treatment of opioid dependent individuals requires a comprehensive approach. Methadone maintenance treatment has been the gold standard and, under current federal regulations, can only be prescribed in carefully regulated opioid treatment programs. For the first time in nearly a hundred years, physicians in the United States have the opportunity to treat opioid dependent individuals with Food and Drug Administration (FDA) approved medications in the office or clinical settings. Buprenorphine is a new FDA approved medication for treating opioid dependence. It is a semi-synthetic opioid derived from thebaine, an alkaloid of the poppy Papaver Somniferum. It is a partial agonist at the mu receptor and an antagonist at the kappa receptor. Since first synthesized in 1973, it has been used in a number of countries as maintenance for opioid dependent individuals. 1 Numerous studies have established its safety and efficacy by comparing it to methadone. 2 4 Since approval in the US in 2002, there are two currently available preparations to treat opioid dependence: buprenorphine alone (Subutex Ò ) and buprenorphine combined with naloxone (Suboxone Ò ). In 2003 a consensus conference was held to discuss its use in office based treatment of opioid dependent individuals, and the consensus statements have begun to appear in the literature. 5,6 Understandably, there has been much excitement about the possibility of treating opioid dependent individuals in the office or clinical settings. Basic information about new legislation, pharmacology, and clinical guidelines have been described elsewhere. 7,8 Unfortunately, there has been little described about the practical aspects of setting up such a practice or clinic. In fact, clinicians may be reluctant to set up such a clinic; and in a recent national survey of psychiatrists, nearly 80% were not comfortable in prescribing office based opioid agonist therapy to opioid dependent patients. 9 We describe the use of buprenorphine in a clinical setting based on our 1-year experience from implementing and operating a buprenorphine clinic in the hopes other practitioners could learn from our experience and be encouraged to set up their own clinic. THE SETTING The site for this buprenorphine clinic is in a Veterans Administration Medical Center *Addiction Psychiatry Fellow, Yale University Veterans Administration Healthcare System #116A, West Haven, CT and Associate Professor of Psychiatry, Yale University Veterans Administration Healthcare System #116A, West Haven, CT. Reprints: Ismene Petrakis, MD, Yale University Veterans Administration Healthcare System #116A, 950 Campbell Avenue, #116-A West Haven, CT ( ismene.petrakis@yale.edu). Copyright Ó 2005 by Lippincott Williams & Wilkins

2 112 Balachandra and Petrakis (VAMC) in a general hospital setting. Our site, VA Connecticut Healthcare System, West Haven campus, is located in West Haven, CT. Approximately 53,000 veterans are cared for through this hospital, the associated outreach clinics, and an affiliated local community care center. It is also one of the main teaching hospitals affiliated with Yale University School of Medicine, and therefore the site of research and a training site for general psychiatric residents and advanced addiction psychiatry residents. The clinic itself was set up within the Substance Abuse Treatment Program, an outpatient program offering a range of substance abuse services. These include an ambulatory detoxification clinic, an intensive day rehabilitation program, a general outpatient service, a methadone maintenance clinic, and a specialty dual diagnosis clinic. The VAMC uses a paperless electronic medical chart that contains the patient s entire history, and prescriptions are also electronically written and medications are then dispensed on site by the VA pharmacy. VA Connecticut Healthcare is also the site of the VA VISN I (New England) Mental Illness Clinical Research Center (MIRECC), a federallyfunded grant that supports research, clinical, and educational endeavors in the treatment of veterans with substance use disorders. The buprenorphine clinic was first developed as a clinical initiative of this MIRECC. THE BUPRENORPHINE CLINIC Ó 2005 Lippincott Williams & Wilkins The actual set up of this clinic was modeled on a psychiatric medication clinic group, in which patients come for appointments during a specified weekly block of time but at varying frequency depending on clinical need (weekly, biweekly, monthly, etc), sign in during clinic hours, and are briefly seen by a psychiatrist to review medications, write renewal medications, and make other medication changes as needed. The buprenorphine clinic is located in clinic offices located within the general Substance Abuse Treatment Program. This was by design, to be physically apart from the methadone maintenance clinic, which is located in another building within the campus of VA Connecticut Healthcare System. Buprenorphine clinic hours are a specified 2 hours per week, but patients with work schedules that conflict can be accommodated during other days or times. The Buprenorphine Clinic has 3 parttime attending psychiatrists, an advanced addiction psychiatry resident, and two clinicians. Each staff member spends no more than 1 2 hours per week on this clinic, and has a clinical caseload commensurate with other clinicians within the clinic. There are more staff members than clinically needed because the staff involved in the clinic have each volunteered to participate in this clinic to gain experience with buprenorphine. The non-md staff members coordinate clinical care with the individual s primary substance abuse clinician and also help with psychosocial referral if indicated. The MD staff members evaluate the patients during clinic visits and write the prescriptions. Since this is a relatively new clinic, a team meeting is held for 15 minutes before patients are seen to review patients and treatment plans, new referrals, and other administrative issues. Prescriptions are written during or after the patient is seen in the clinic by the psychiatrists who are eligible to write for buprenorphine. No formal advertising has been undertaken for the clinic, and patients are most often referred from ambulatory outpatient detoxification but also from self-referrals and from clinicians within the substance abuse treatment program. Following referral, a comprehensive assessment is conducted including a complete medical and psychiatric interview, physical examination, mental status evaluation, and laboratory testing. In the medical history, current symptoms, past illnesses including risk for HIV, hepatitis, and tuberculosis, immunization history, medications, and allergies are reviewed. The psychiatric evaluation consists of assessing both substance abuse and comorbid psychiatric conditions. The admission criteria are reviewed in Table 1.

3 TABLE 1. Admission Criteria for Buprenorphine Clinic 1. Diagnosis of opioid dependence and current opioid use 2. No contraindications for treatment (eg, allergy to buprenorphine) 3. Agreement to clinic contract 4. Ability to provide informed consent 5. Not currently taking benzodiazepines Overall the attitude is a rather liberal one and only under the most exceptional circumstances are patients denied entry. Examples include a history of diversion or administrative discharge from other opioid agonist maintenance programs. The other exception to this is the presence of recent use of benzodiazepines. Given the reports in the literature of patient deaths when combining high doses of benzodiazepines and buprenorphine, 10 patients with benzodiazepine abuse were excluded. In addition to the usual criteria for buprenorphine treatment, the VAMC requires that buprenorphine maintenance be limited to those patients who do not have timely access to methadone maintenance and must be referred for psychosocial treatment. All patients within the Buprenorphine Clinic are also assigned to a clinician within the general Substance Abuse Treatment Program. Borrowing from a methadone maintenance model, this clinic also included a behavioral contract for admission. The contract was designed to deal with potential behavioral Setting Up a Buprenorphine Clinic problems commonly associated with patients treated in methadone maintenance clinics and addresses issues related to the protection of staff from violence or threats, adherence to clinic appointments and treatment, the potential for diversion of medication, and the use of illicit substances. This contract is summarized in Table 2. While buprenorphine comes in two formulations, the buprenorphine/naloxone combination (Suboxone Ò ) is used in all phases of treatment within our clinic. INDUCTION This is a critical component of buprenorphine treatment. In our setting, induction was conducted in the ambulatory detoxification clinic. Ideally, patients being induced are in early stages of withdrawal or abstinent from opioids. Patients are first educated to understand the partial agonist effect of buprenorphine and about the ceiling effect of the medication. Further, patients are educated about sublingual administration and to refrain from swallowing or parentral use. The initial dose is based on individual patient circumstances but 4 mg/1 mg is the usual starting dose. Patients are monitored for vital signs and for signs of withdrawal using the Clinical Opiate Withdrawal Scale (COWS). 11 Additional doses can be given, with a maximum of 8 mg buprenorphine the first day. After the first day, patients are seen on a daily basis and given take home doses. In most cases, after 1 week 113 TABLE 2. Buprenorphine Clinic Contract Maintenance Phase Clinic hours are 10:00 12:00 on Mondays. If the patient arrives outside the clinic hours, s/he may have to wait another business day to be seen. No make-up doses will be given. Patients are expected to keep all appointments with their clinicians and their psychiatrist. Discharge Criteria Relapse into illegal substance use or frequently missed appointments will result in closer monitoring (eg, three times/week urine toxicology). Continued use of illicit drugs may lead to discontinuation of buprenorphine and/or referral to methadone clinic. Administrative discharge may result from diversion, violence, repeat illicit substance or alcohol use, falsified urine samples and/or multiple missed appointments.

4 114 Balachandra and Petrakis of induction, when patients clearly are able to tolerate the medication, patients are seen in the regular Buprenorphine Clinic. STABILIZATION AND MAINTENANCE After induction, patients are assessed weekly in the clinic with weekly urine toxicology and assessment by a physician. The dose is titrated based on the patient s self reported craving, presence or absence of illicit drug use, and ability to tolerate side effects, to a maximum dosage of 32 mg/8 mg. All patients are expected to continue with regular appointments with their assigned clinician in the general Substance Abuse Treatment Program. With compliance, clean urine toxicology, and improvement in functioning, patients are eligible to be seen biweekly. If patients relapse to drug use or have difficulty with regular appointments, they may be asked to present more frequently for urine monitoring or may be referred to more intensive behavioral treatments. Patients who fail treatment, defined as those who continue with drug use despite other interventions, can be referred to methadone maintenance or to other higher levels of care (eg, residential treatment). DISCUSSION Ó 2005 Lippincott Williams & Wilkins Buprenorphine provides new hope for the treatment of opioid dependent patients in the office or clinic settings. Based on our 1-year experience, the overall treatment has been a relatively positive experience for patients and treaters, and this experience is congruent with that reported by other countries where buprenorphine is available. 12,13 While this clinic is located in a general substance abuse clinic within a general hospital, the ease with which the clinic runs suggests that even for office-based practitioners, it would be feasible to prescribe buprenorphine. However, there are challenges in treating patients with opioid dependence with buprenorphine, particularly in the office setting. These include the practical aspects of induction, dealing with behavioral problems including illicit drug use, and the need for availability of more intensive treatment programs for individuals who fail treatment. Induction may be the first challenge. First of all, patients need to be educated to understand the unique pharmacology of buprenorphine and the rationale for the induction process. Second, a clinic setting where nursing monitoring is possible is ideal. Clearly our setting has many available resources, including an ambulatory detoxification clinic with nurses who can evaluate patients over time. Given the potential time consuming requirement of slowly titrating the medication and observing, induction centers have been proposed. 5,6 For clinicians in an officebased setting, internists offices may be more conducive to initiating buprenorphine, particularly if the office setting has adequate support staff who can monitor patients after the first medication dose is administered. For other physicians without the support staff, having the patient wait for a few hours in the waiting room may be a realistic, albeit less attractive, alternative. As expected, once patients are started on the medication, other administrative and behavioral problems have arisen. Patients in our clinic have missed appointments, lost medications, and been reluctant to follow through on psychosocial recommendations. These are similar to challenges faced in general substance abuse clinics and in methadone maintenance programs, and the solutions employed in those settings are certainly applicable in buprenorphine treatment. 14 Firm limit setting, therapeutic contracts, and behavioral interventions are concepts with which a prescriber must become familiar. Nevertheless, the most problematic behavioral problems associated with methadone maintenance clinics have been largely absent. There have been no instances of patient threats, patients have not demanded medications at unscheduled times or in other

5 Setting Up a Buprenorphine Clinic settings (like the emergency department), and patients have not made requests for benzodiazepines or other medications with abuse liability. There are no known instances of diversion, although one patient did report losing a prescription on 2 occasions. In these instances, urine screens were sent for buprenorphine levels, but unfortunately the unreliability of these tests made it difficult to use this in a clinically meaningful way. The biggest challenge faced in our clinic has been the problem of non-opioid drug abuse, most commonly cocaine. This is similar to problems faced in methadone maintenance clinics. 15 While our behavioral contract states that there will be behavioral consequences for other drug use, the staff have not uniformly agreed on what consequences are appropriate. Some staff favor more strict behavioral limits, similar to those enforced in methadone clinics where repeated positive urine toxicology screens positive for cocaine may lead to discharge. The rationale for this is that if strict limits are not upheld, patients will take this as permission to continue to use other drugs. Others have favored a more lenient approach, consistent with a harm reduction model. 16 In our experience, several patients were referred to the methadone maintenance clinic for continued cocaine and marijuana use, with surprisingly good results. This suggests that, unfortunately, buprenorphine may not be ideal for all opioid dependent patients. Those with persistent opioid cravings and the inability to adhere to clinic rules may be referred to methadone maintenance programs. It must be noted that a setting like the VAMC has certain advantages in terms of availability of psychosocial resources. Our multidisciplinary team model facilitates comprehensive treatment planning and treating each patient on an individual basis. Clinicians not only have the chance to discuss cases but also provide coverage during absences and stay up to date on relevant literature. Our particular site also has a methadone maintenance program and several affiliated residential programs, where patients can be referred. The office-based clinician may have to determine what resources are available in his/her community, and use community supports such as Narcotics Anonymous. Overall, both our patients and staff have found this an overwhelmingly positive experience. Patients report that buprenorphine is preferable to methadone in that it controls cravings without producing a high. The staff have been impressed with how well many patients do, and the more worrisome behavioral problems have not arisen. In fact, with more experience, our clinic will likely allow patients to be seen even less frequently, making this method of treatment more cost effective than methadone maintenance. 17 We hope that our experience will encourage practitioners that are considering starting buprenorphine clinics to do so, with minimal burden on clinical staff in providing an important new option for patients with opioid addiction. ACKNOWLEDGMENTS The authors thank Winsome Mellers, MSW, Isabel Rathbone, MD, Louis Trevisan, MD, Rachel Alpert, MSW, and Dennis Wigg. This work was funded in part by the VAfunded VISN I Mental Illness Research and Clinical Center (MIRECC, principal investigator is Bruce Rounsaville). REFERENCES 1. Cowan A, Lewis JW, Macfarlane IR. Agonist and antagonist properties of buprenorphine, a new antinociceptive agent. Br J Pharmacol. 1977;60: Barnett PG, Rodgers JH, Bloch DA. A meta-analysis comparing buprenorphine to methadone for treatment of opiate dependence. Addiction. 2001;96: Mattick RP, Kimber J, Breen C, et al. Buprenorphine Maintenance Versus Placebo or Methadone Maintenance Versus Placebo or Methadone Maintenance for Opioid Dependence. Cochrane Database Systems Review, (CD002207). 4. West SL, O Neal KK, Graham CW. A meta-analysis comparing the effectiveness of buprenorphine and methadone. J Subst Abuse. 2000;12:

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