BRIEF REPORTS Ambulatory Opiate Detoxification and Primary Care: A Role for the Primary Care Physician PATRICK G. O'CONNOR, MD, MPH, MARTIN E. WAUGH, DO, RICHARD S. SCHOTTENFELD, MD, IOANNIS A. DIAKOGIANNIS, MD, BRUCE J. ROUNSAVILLE, MD To d e t e r m i n e the f e a s i b i l i t y o f p r i n t a r y care.based ambulat o r y opiate ~ f l c a t i o n (.401)) a n d a n o p t i m a l regimen, t h e a u t h o r s c o n d u c t e d a p i l o t study o f AOD in a m e d i c a l clinic c o m p a r i n g t w o r e g i m e n ~ c l o n i d i n e a n d c l o n i d i n e plus naltrexone. Sixty-two opiate addicts who bad been r e f e r r e d f o r A OD h a d the f o l l o w i n g features: m e a n age w a s 34 years, 75% w e r e male, 74% used cocaine, a n d 64% s h a r e d needles. Initially, 4 0 p a t i e n t s selected cionidine, 22 c l o n i d t n e / n a l t r e x o n e . The g r o u p s ( c l o n t d i n e a n d clonid i n e / m a i r e x o n e ) were similar in baseline f e a t u r e s , including: c r a v i n g scores ( 4 4 / 1 0 0 vs. 4 2 / 1 0 0 ) a n d withd r a w a l scores ( 2 0 / 7 2 vs. 17/72). Overai~ 61% ( 3 8 / 6 2 ) o f initial AOOs were stw.cessfu~ i n c l u d i n g 43% ( 1 7 / 4 0 ) o f those u s i n g c l o n i d i n e a n d 9 5 % ( 2 1 / 2 2 ) o f those u s i n g clonidtne/naltrexone (p < 0.0001). Of 45 patients who ultimately completed AOD, 78% ( 3 5 / 4 5 ) r e m a i n e d i n treatm e n t f o r a t least o n e month. Key w o r d s : s u b s t a n c e abuse;

op/o/d addiction,. ~

w/thdrawal syndrome; addic-

tiom detoxiflcatiom ciontdine; naltrexo~. J Gm¢ l~-.'~w~q MED 1992;7:532- 534. INTRAVENOUS DRUGUSERSc o m m o n l y present to primary

care physicians with complications of drug use, including acute heroin withdrawal. Opioid withdrawal poses challenging dilemmas for physicians. The prescription of opioids to treat withdrawal may contribute to continued addiction and is illegal, v3 In addition, many communities have limited drug abuse treatment resources. Physicians may find themselves unable to h e l p these patients. Two protocols for opioid detoxification have b e e n d e v e l o p e d that may be suitable for the primary care setting: clonidine and clonidine plus naltrexone. 4-7 Both methods have shown success rates from 31% to 86%, although c l o n i d i n e / n a l t r e x o n e is thought to be more effective and has the advantage of shortening the course of withdrawal .8 While both methods have b e e n studied in drug treatment settings, neither m e t h o d has b e e n evaluated in a primary care setting. We decided to

Received from the Departments of Medicine and Psychiatry, Yale University School of Medicine, New Haven, Connecticut. Presented at the annual meeting of the Society of General Internal Medicine, Arlington, Virginia, May 2 - 4 , 1990. Supported by NIDA Grant: "AIDS Outreach Demonstration Proje c t " (#5R18DA05758). Address correspondence and reprint requests to Dr. O'Connor: Yale University School of Medicine, IE-61, SHM, 333 Cedar Street, New Haven, CT 06510,

532

perform a study of clonidine vs. c l o n i d i n e / n a l t r e x o n e to answer the following questions: 1) Can opioid detoxification be p e r f o r m e d effectively and safely in a primary care setting? and 2) Which protocol is more effective? Here w e report data for the first 62 patients w h o c o m p l e t e d our pilot study.

METHODS Patients were recruited through a NIDA-funded AIDS Community Outreach Project in New Haven, CT, primarily through the use of a medical van that canvassed high-risk neighborhoods. Other recruitment activities included institutional- (hospitals, welfare offices, probation offices) and storefront (project headquarters)-based outreach. Patients meeting o u r inclusion criteria were intravenous drug users w h o were not in treatment and were addicted to opioids. Patients also n e e d e d to be able to c o m p l y with outpatient detoxification and be willing to enter a relapse-prevention program following detoxification. Our exclusion criteria were: pregnancy, a history of adverse reactions t o the study medications, and significant medical or psychiatric conditions that w e r e felt to p r e c l u d e these methods. Excluded patients w e r e referred to other drug treatment programs. Detoxification was p e r f o r m e d free of charge at the Central Medical Unit, a freestanding medical clinic that provides primary care services to substance users in treatment. Following detoxification, patients were referred for relapse prevention to a nearby outpatient program for naltrexone maintenance and counseling. Assessments done on admission i n c l u d e d a medical evaluation, laboratory studies, and drug addiction evaluation. Our withdrawal symptom scale, w h i c h contained ratings (from 0 to 3) of 24 symptoms of opioid withdrawal, was used to measure withdrawal severity. 9 Opioid craving was measured using a visual analog scale. Two protocols were offered to patients, w h o selected their own treatments (Table 1). Clonidine detoxification was designed to last u p to 12 days, clonidine/naltrexone u p to 5 days. Specific aspects of each protocol were explained to patients, including the time

JOURNALOFGENERALINTERNALMEDIONE, Volume 7

commitment needed and the features of withdrawal that could be expected from each regimen. For example, the clonidine/naltrexone protocol necessitated that patients be willing to spend up to eight hours in the clinic on day 1. After the regimens were discussed, patients selected their own protocols. Patients in both groups were given oxazepam ( 1 5 - 30 mg every six hours as needed) as adjuvant therapy to treat muscle cramps and insomnia. Nonnarcotic analgesics and antiemetics were also available if needed. Successful detoxification was defined as the ability to begin patients on blocking doses of naltrexone (50 mg), and successful referral to relapse prevention. Successful initiation of relapse prevention was defined as participation in treatment for one month.

RESULTS Seventy patients were evaluated, and eight were e x c l u d e d - - t w o for pregnancy, two for medical problems (asthma, seizure disorder), one for psychiatric problems (depression), and three for other reasons (e.g., no show). Thus, 62 patients were enrolled in this study. Clonidine was selected by 40 patients and clonidine/naltrexone by 22. Patients in the two treatment groups were similar in terms of mean age (34 vs. 35 TABLE 1

Treatment Protocols for Ambulatory Opiate Detoxification* Clonidine: up to 12 days Day I

Clonidine, 0 . 1 - 0 . 2 mg po q4h, up to 1.0 mg

Days 2 - 7

Clonidone, O. 1 - 0 . 2 mg po q4h, up to 1.2 mg on days 2 - 4 , then taper

Days 8 - 1 2

Initiation of naltrexone and referral to relapse prevention

Ctonidine/naltrexone: up to 5 days Day l~r:

S33

TABLE Z

Treatment Outcomes of Ambulatory Opioid Detoxification Success (%)

Failure

Total

Acute detoxil~cation Clonidine (n = 40) *Clonidine/naltrexone (n = 22) TOTAL

17 (43%) 21 (95%) 38 (61%)

23 1 24

40 22 62

Relapse prevention (1 month) Clonidine (n = 17) tCIonidine/naltrexone (n = 28) TOTAL

13 (76%) 22 (79%) 35 (78%)

4 6 10

17 28 45

*X 2 = 16.8, p < 0.0001. tlndudes seven patients who initially failed on cionidine and attempted a "second chance" detoxification using clonidine/naltrexone.

years), gender (76% vs. 77% male), educational level (38% vs. 45% high school graduates), and employment status (50% vs. 45% employed). Seventy percent of clonidine and 55% of clonidine/naltrexone patients reported needle sharing. The groups also were similar in two important clinical features of w i t h d r a w a l - - t h e craving score ( 4 4 / 1 0 0 vs. 4 2 / 1 0 0 ) and the withdrawal symptom score ( 2 0 / 7 2 vs. 17/72). Treatment outcomes are shown in Table 2. The overall success rate for initial detoxification was 61%. Forty-three percent of the clonidine patients and 95% of the clonidine/naltrexone patients were successful. Seventy-six percent of clonidine and 79% of clonidine/ naltrexone patients who completed detoxification remained in relapse prevention for at least one month. The overall success rate for these 45 patients was 78%. We noted one significant complication. One patient was treated with intravenous fluids (2 L) during a clonidine detoxification for symptomatic hypotension, which developed in the setting of acute viral gastroenteritis.

DISCUSSION Oonidine: O. 1 - 0.2 po q4h, up to 1.2 mg Naltrexone: 12.5 mg po at 11:00 AM

Day 2

Clonidine: O. 1 - 0 . 2 po q4h, up to 1.2 mg Naltrexone: 25 mg po at 10:00 AM

Days 3 - 5

Clonidine: O. 1 - 0 . 2 po q4h, taper Naltrexone: 50 mg po at 10:00 AM Referral to relapse prevention

Adjuvant medications(both groups):

(September~October), 1992

Oxazepam ( 1 5 - 3 0 mg po q6h) Nonnarcotic analgesics (e.g., ibuprofen) Antiemetics (e.g., prochlorperazine)

*All patients were seen daily in the clinic. t Patients were given a preload of oxazepam ( 3 0 - 60 rag) and clonidine ( 0 . 2 - 0 . 4 rag) prior to receiving their 11:00 AM dose of naltrexone on day I and patients remained in the clinic until 5:00 PM to be monitored for withdrawal.

While primary care physicians are familiar with the use of methadone for managing inpatients going through heroin withdrawal, this approach is not applicable to outpatients, in part because of legal restrictions. 3 The clonidine and clonidine/naltrexone protocols were designed to be practical approaches to the detoxification of opioid addicts in a primary care setting. Clonidine is one of the first nonopioids identified as efficacious in managing opioid withdrawal. 1° Prior studies have suggested success rates ranging from 36% for heroin withdrawal to 80% for methadone withdrawal. Clonidine works by suppressing autonomically mediated signs and symptoms of withdrawal. Although the prescription of benzodiazepines to opiate-dependent patients is controversial because of their abuse potential, short-term use is warranted to treat with-

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O'Connor eta/., AMBULATORYOPIATEDETOXIFICATIONAND PRIMARYCARE

drawal symptoms less effectively suppressed by clonidine (e.g.; muscle cramps, insomnia, and restlessness), n Generally, oxazepam requirements in the present study were highest on the high withdrawalsymptoms days (e.g., day 1 for the clonidine/naltrexone group). Patients infrequently n e e d e d more than 120 mg over a 24-hour period and typically n e e d e d it only for sleep by day 5 of detoxification. The n e w e r " r a p i d " detoxification m e t h o d using clonidine/naltrexone was developed to shorten the course of withdrawal and improve success rates. Initially used for inpatients, the clonidine/naltrexone detoxification has been successfully utilized in an outpatient drug abuse treatment setting with acceptable patient tolerance and considerable success, s. 9 In this study we demonstrate that both methods may be generalizable to primary care settings, giving primary care physicians a potentially greater role in initiating drug abuse treatment. In this pilot study w e e x p e r i e n c e d a significant overall rate of success (61%), and the clonidine/naltrexone protocol was more successful than clonidine only (9 5% vs. 4 3%). This may indicate the greater effectiveness of a shorter, more intensive approach that resuits in detoxification within five days instead of 12 days. In addition, more highly motivated patients may have selected clonidine/naltrexone. Other aspects of this pilot study deserve comment. While both regimens were well tolerated, we recomm e n d careful b l o o d pressure monitoring during detoxification. A limitation of the clonidine/naltrexone is the need to monitor patients for eight hours (day 1) due to the potential severity of withdrawal that can ensue after the first administration of naltrexone. Although this may last only two to three hours, it does necessitate the dedication of staff time and space. Further research and experience will be n e e d e d before the c l o n i d i n e / naltrexone regimen can be routinely r e c o m m e n d e d for primary care settings. Both methods are limited by the need for adequate social support so that patients m a y b e

transported to and from detoxification. Finally, providers w h o wish to perform ambulatory opiate detoxification need to understand that detoxification represents only the initial step in the treatment of drug addiction. Thus, ongoing drug abuse treatment services (e.g., naltrexone treatment, relapse prevention groups) need to be part of the overall treatment plan. In conclusion, ambulatory opioid detoxification can be performed effectively and safely in a primary care setting. While clonidine/naltrexone initially may be more effective than clonidine alone, patients successfully detoxified with b o t h methods meet with the same success at one-month follow-up.

REFERENCES 1. JaffeJH. Drug addiction and drug abuse. In: Gillman AG, Rail TW, Nies AS, Taylor P (eds). The pharmacologic basis of therapeutics, eighth edition. Elmsford, NY: Pergamon Press, 1990;522. 2. Tennant FS, Uelman GF. Prescribing narcotics to habitual and addicted narcotic users: medical and legal guidelines in Californ/a and other Western states. WestJ Med. 1980;133:539-45. 3. Methadone: rules and regulation. The Federal Register. 1989;54:8954. 4. Charney DS, Steruberg DE, Kleber HD, et al. The clinical use of clonidine in abrupt withdrawal from methadone. Arch Gen Psychiatry. 1981;38:1273-7. 5. Jasinski DR, Johnson RE, Kocher TR. Clonidine in morphine withdrawal. Arch Gen Psychiatry. 1985;42:1063-6. 6. RiordanCE, Kleber HD. Rapid opiate detoxificationwith clonidine and naltrexone. Lancet. 1980;i: 1070-80. 7. Charuey DS, Heninger GR, K/eber HD. The combined use of clonidine and naltrexone as a rapid, safe, and effectivetreatment of abrupt withdrawal from methadone. Am J Psychiatry 1986;143:831-7. 8. Kleber HD, Topazian M, GaspariJ, Riordan CE, KostenT. Clonidine and naltrexone in the outpatient treatment of heroin withdrawal. AmJ Drug AlcoholAbuse. 1987; 12:1-17. 9. Vining E, Kosten TR, Kleber HD. Clinical utility of rapid clonidine-naltrexone detoxification for opioid abusers. Br J Addict. 1988;83:567-75. 10. Washton AM. Clonidine for opiate detoxification: outpatient clinical trial. AmJ Psychiatry. 1980;130:1121-2. 11. Jasinski DR, Johnson RE, Kocher TR. Clonidine in morphine withdrawal. Differential effects on signs and symptoms. Arch Gen Psychiatry. 1985;42:1063-6.