RAPID OPIATE

DETOXIFICATION

AND NALTREXONE INDUCTION

UNDER GENERAL ANAESTHESIA

Dr Mark Greenberg MD and Peter Garber MD are using Rapid Opiate Detoxification in Canada. We suggest those in North and South America access their Web site www.endaddiction.com to evaluate their program.

 Puget Sound Rapid Opioid Detoxification Consultants

A BOLD NEW

STRATEGY FOR AUSTRALIA

 1.

INTRODUCTION

This paper is in response to the urgent call by members of the community (Peter Hollingworth, Archbishop of Queensland 1997) who have not been able to reach a clear view on the present alarming Heroin (Gabor D Kelen M.D,1996) increase in Australia and, Australian usage of the traditional method of Methadone maintenance, which to date has been unable to decrease Heroin addiction.

METHADONE

It appears that a number of factors limit methadone effectiveness (Rettig, Richard A, 1995) e.g. the multiple health and social problems of methadone maintenance patients and the variability in the quality of treatment programs. Side effects and the more difficult detoxification that’s required is not attractive to a particular client group (Bob Aldred 21 August 1997).

DETOX

One important factor in Detox is that the patients "fear of withdrawal does perpetuate dependency" (Dr Jim Flack,1997) Ultra-rapid detox is a painless way of withdrawal for heroin addicts, this is clinically very significant. "For the late stage narcotic patient, fear of the pain from withdrawal can be the single factor that continues their dependency. They are so overwhelmingly frightened of the pain of detox.

NALTREXONE

Juan Jose Legarda and Michael Gossop (1994) procedure for detoxification using naltrexone after sedation with midazolan, after detoxification (12hours) patients were discharged without withdrawal symptoms. An intriguing feature of this procedure is that the addict is sedated during withdrawal and therefore does not consciously experience any symptoms of opiate withdrawal. Fears and anxieties about withdrawal my deter some addicts from seeking treatment and such factors can also increase the level of distress experienced during withdrawal (Phillips,Gossop and Bradley,1986). The prospects of avoiding having to experience any withdrawal symptoms may make the procedure described in this paper non-threatening to addicts. Many addicts on this trial expressed their enthusiasm for this aspect of the treatment. (Page 93).

Dr David L Simon’s (1997)procedure shows that when withdrawal is maximally hastened, it is necessary to mask the symptoms of withdrawal with general anaesthesia in order to maintain a humane and compassionate treatment. All methods of rapid detoxification without anaesthesia have caused increased withdrawal symptoms. Rapid opioid detoxification under general anaesthesia can be safely performed by adhering to the current standards of practice of modern anaesthesia care. This requires the participation of qualified anaesthesia care providers.

The minimal monitoring standards for a general anaesthetic should be utilized:electrocardiography, continual blood pressure measurement, pulse oximetry, capnography and the ability to monitor temperature. Modern anaesthesia in qualified hands is very safe. Heroin abuse, left untreated, itself carries a great risk for morbidity and mortality (page 115). The dropout rate for detoxification using anaesthesia is lower, and this should be taken into account when determining overall cost effectiveness.

2.

In addition, maintenance with p.o. naltrexone as is instituted as part of the continuum of care following rapid opioid detoxification is much cheaper than methadone maintenance. Naltrexone is a "non-scheduled" drug with no potential for abuse. Therefore, it can be obtained with a prescription at any pharmacy. Methadone on the other hand, is a highly regulated scheduled narcotic.(page 117).

The efficacy of rapid opioid detoxification under anaesthesia followed by naltrexone maintenance and psychotherapy has the potential to be the most efficacious opioid abuse treatment. Firstly, the detoxification process is 100% effective in that every one who undergoes general anaesthesia become detoxified. There are no reports of dropout from treatment during anaesthesia, so, resources are maximally utilized in this procedure. Secondly, there are unsubstantiated claims that 80% of those treated with rapid opioid detoxification using naltrexone and anaesthesia are abstinent from opioid abuse six months after treatment. Furthermore, cerra et al. reported in 1995 that about 80% of patients detoxified with naltrexone (without anaesthesia) and followed up , were abstinent from drug abuse six months after treatment (page 116,117).

Maintenance of the patients using naltrexone pills orally have three important effects; one, they cause a decreased craving for narcotics; two, they tend to make the effects of heroin ineffective; and three, over time they reverse the chemical changes in the brain caused by heroin; eventually, the pills are discontinued, these three effects make it much easier to undergo effective counselling after detoxification. The one day detoxification procedure followed by oral pills and psychosocial support have proven to be extremely effective 75%-80% of addicts do not use heroin 6 months after this kind of therapy program according to published reports; 100% of patients are reported to effectively undergo the "sleep therapy" procedure.(Jean Krajicek Bartek (1996)

It is important to understand that naltrexone competes with opioid (narcotics) for opioid receptor sites in the brain to prevent narcotics binding with opioid receptors. This action blocks euphoria, analgesia, and other physiologic effects of narcotics, if taken. Naltrexone can also displace narcotics already occupying these specific opioid receptor sites. It must be understood that therapy with naltrexone is unlike methadone maintenance therapy, which substitutes a long-acting orally active opioid (an opioid agonist) for heroin.

Medication for long-term or maintenance treatment (e.g. methadone or naltrexone) are usually evaluated for overall effectiveness and are measured by many researchers using the addiction severity index(ASI) for all measurements. The ASI is a structured clinical interview that can be administered in 30min., it produces a10 point problem severity ratings in each of 6 areas.

RECOMMENDATIONS

That the Federal Department of Health and the Queensland Alcohol, Tobacco and other Drug Services branch of the Health Department, evaluate the following Detox and Rehabilitation Centres for the best practices using the Ultra Rapid Opiate Detoxification and Naltrexone Induction under General Anaesthesia.

3.

Dr Lance Gooberman

US Detox Center

Merchantville, New Jersey 08109 USA

Tel +001-609-663-4447 Fax +001-609-488-6380

Dr David L Simon

Medical Director

Nutmeg Intensive Rehabilitation Center

359 Merrow Road

Tolland Connecticut 06084 USA

Tel (860-5447    email@2nutmeg.com

http://www.2nutmeg.com

Dr Juan Jose Legarda

Cita Centro de Investigacion y Tratamiento

Psicologicos;

Avda. Ediardo Dato.

34 50 A, Seville 41005 Spain.

Dr Colin Brewer

The Stapleford Centre

25A Eccheston Street

London SWIW 9NP

Tel +44(0) 171-730-7176 Fax +44(0)171 730-3409

e-mail: cb@stap-cen.demon.co.uk  

http://www.staplefordcentre.co.uk

Dr Andre Waismann

Megama Institute Ltd

50 Basel Street

Herzliya Pituah, 46646

Tel + 972-9-9548424, Tel + 972-9-9548423 Fax + 972 .9. 9548422

email Dr Andre Waismann : contact@megama.com

Dr George O'Neil M.B.,B.S.,C.O.G.,Dip. Diagnostic Ultrasound

Australian Medical Procedures Research Foundation

65 Townshend Road 

Subiaco

West Australia 6008

Tel (08) 9381 6960 Fax (08) 9388 7073

e-mail: gomedic@wantree.com.au

Addiction Medical Group Inc. (AMGI)

Darryl Ballin MD

dballin@ix.netcom.com

http://amgionline.com

PRESENTED AT THE 4TH INTERNATIONAL THE ROYAL CONFERENCE SOCIETY OF MEDICINE LONDON 9TH JANUARY 1998

Authors: Dr James Fellows-Smith, Dr George O'Neil Dr Garry Hulse

An observational analysis of the first 100 heroin addicts treated with Naltrexone in Western Australia

The preliminary finding of 268 heroin addicts referred to an out patient programme of rapid detoxification and relapse prevention using Naltrexone in Western Australia are discussed. Of the first 100 patients treated at 11 to 16 weeks 93% remained on the programme. 60% continued to take 25-50mg Naltrexone orally per day, 33 had relapsed. 15% had relapsed for a short period (<2 weeks) and 12% had relapsed for a longer period (>2 weeks) where treatment was interrupted. 6% showed satisfactory benefit yet had relapsed and were awaiting re- treatment. 1% ceased early after detoxification land had not relapsed. 6% had returned to full original use of Methadone or heroin.

Re-treatments were virtually routine (33%). High retention rates on the programme were attributed to the use of psychoeducative approach with the involvement of family members supervising ongoing treatment and a rapid response (,,24 hours) to requests for retreatment. Detoxification periods as short as 12 hours were included although most patients were encouraged to detox for as long as they could tolerate. No patients required intensive care hospital admissions for their treatments. The protocols established are discussed.

OBJECTIVE

The use of oral Naltrexone to extinguish craving and opiate seeking behaviour relies heavily on patient compliance. Relapse associated with poor patient compliance with Naltrexone has been estimated at between 23% and 63% at three to six weeks after starting treatment (Gonzales et al, 1988). In contrast retention in treatment on Methadone maintenance programmes may be as high as 83% at 6 months (Ward et al, 1994) with consequent reduction in heroin use, crime, injection related risk behaviours and premature mortality. As at September 1993 there were 13386 individuals maintained on Methadone in Australia whereas only 40 patients have been treated with Naltrexone since the Australian Therapeutic Goods Administration rejected an application to market the drug in 1985. There are however advantages to using an antagonist drug for maintenance treatment. Methadone does not preclude continue opiate use which is estimated as high as 67% with some studies, neither does it prevent possible overdose as Naltrexone (Williamson et al, 1997). Due to inclusion criteria that involve only those that have well established heroin addiction. Methadone maintenance only reaches 20 to 25% of the addict population. Furthermore, withdrawal from Methadone con be difficult and of those that are successful the majority return to using herbs as before. Rapid detoxification has been shown to be feasible and cost effective in opiate addiction (O’Connor et al, 1995). It is postulated that the severity and duration of withdrawal symptoms is related to compensatory changes to the microcirculation (Yang et al., 1994) which are medicated according to occupation of opiate receptor sites as opposed to opiate levels in the plasma per se. In support of this the accelerated withdrawal symptoms induced by a slow intravenous injection of 300mcg of Naloxone are not observed in the same subject treated one hour later with a larger 800mcg of the same drug. Protocols for rapid out patient detoxification include displacement of opiate molecules from their receptor sites with Naloxone and attenuation of the withdrawal symptoms with Clonidine (Brewer et al, 1993) prior to starting Naltrexone treatment. There is a high prevalence of heroin abuse in Perth (ref). This may be due to its close proximity to South East Asia. At the time of starting this treatment in June, 1997 there were a record number of deaths from heroin overdose and a nine month waiting period for Methadone treatment (ref). From June to November 1997 there were 210 patients treated with Naltrexone under a special application for each patient. This paper describes the preliminary findings of the first 100 patients treated with Naltrexone in Western Australia.

PRIVATE METHOD

The treatment was provided in a private practice setting funded by Medicare and staffed, largely by volunteers. Most patients sought help-directly after hearing about the programme from other opiate abusers or were referred from other agencies such as the Alcohol and Drug Authority.

Patients were treated in an outpatient setting by an obstetrician with an interest in pharmacology and a psychiatrist. The therapy team comprised a social worker and a network of psychologists, family members, carers and volunteers. Regular contact with patients to monitor recovery and compliance was made in person or by telephone. As the Naltrexone medication was in short supply patients were requested to pick up the treatment from the practice on a weekly basis. Patients who failed to do so were vigorously followed up and in the case of relapse encouraged to undergo retreatment. The presence of intercurrent physical and psychiatric illness, including dependence on other substances was attended to. Psychological intervention to assist relapse prevention included a rational recovery programme that was cognitively based Wilkinson and Saunders et al, 1995) and/or a Narcotics Anonymous approach. Families of addicts were instructed on how to monitor and administer the Naltrexone. Family therapy was offered, where appropriate using a psychoeducative approach. A Naloxone challenge test was performed prior to starting Naltrexone. Two treatments of Naloxone were given one hour apart in high risk patients who had used heroin until the day of treatment. After an initial dose of 1-300 micrograms of Naloxone was given slowly intravenously patients were asked to report any significant withdrawal symptoms. The symptoms were observed to progress in sequence from the nose to the eyes followed by muscle cramps and gastrointestinal pain according to the severity of the withdrawal. In most individuals the symptoms could be quickly alleviated with withdrawal medication that included Clonidine 0.15mg orally, octreotide 0.1 mg subcutaneously, Ondansetron 4mg intravenously and diazepam ]5mg orally. A second dose of Naloxone 800 micrograms given quickly intravenously was observed not to bring on withdrawal in the majority of cases. Having achieved a rapid negative response to a Naloxone challenge test, Naltrexone 2m91hr for six doses was given. The following day Naltrexone 2m91hour was given for a further ten doses while withdrawal symptoms were controlled with the withdrawal medication. Having achieved rapid detoxification patients were instructed to take Naltrexone 25-50mglday orally.

PRIVATE RESULTS

The retention rate of patients on the program was 93% for the first 100 patients at 11 - 16 weeks. From July to November 1997 there were 268 patients reviewed of which 210 patients had been successfully detoxified and started on Naltrexone. An observational analysis of the first 100 patients identified the following groups. Group 1 continuous uninterrupted daily use 60%. Group 2 Short episode (,,2 weeks) where treatment was interrupted 15%. Group 3 longer episode (, 2 weeks) were treatment was interrupted 12%. Group 4 Benefited from Naltrexone, had ceased treatment and were awaiting re-treatment 6%. Group 5 Detoxified with Naltrexone, had ceased treatment but had not relapsed 1%. Group 6 Returned to recreational use on ceasing Naltrexone 0%. Group 7 Returned to full original use of Methadone or heroin after ceasing Naltrexone 6%. High retention rates of the current treatment are likely largely attributable to three clinics policies. Firstly, the clinic encouraged involvement of family members or other opiate free salient others to supervise Naltrexone administration. For entry into the programme the patients needed to attend with a carer, preferably a family member, who could supervise daily consumption of Naltrexone.

DISCUSSION

Naltrexone treatment was commenced on a service base rather than as a planned clinical study. Despite this we were able to make clinical observations to help improve future treatment protocols. Retention on the treatment was high 93% at 11 - 16 weeks. Retention rates as high as 92% at six months have been reported (Washton et cl, 1984) in a study of 129 addicts who were in jeopardy of losing employment or liberty such as business executives, physicians and health care professionals.' The present study did not attempt to exclude patients who may have had a poor prognosis on the basis of demography or intercurrent illness. Retreatments were virtually routine (33% of patients). When patients become non compliant and returned to opiate abuse they were encouraged to view the situation as a potential learning experience (Prochaska and Di Clemente, (1982) and not as an episode of failure. Emphasis was placed on flexibility with an early response (,,24 hours) to requests for retreatment. Due consideration was made to constraints of time, private health cover, public hospitals waiting periods and family resources. Previous studies have found no apparent relationship between attrition rates and trial design with respect to inpatient verses outpatient treatment, use of Naloxone Challenge tests, use of Clonidine detoxification or length of opiate free period prior to commencement of Naltrexone treatment. Our treatment experience points to the benefits of involving relatives or other informal carers. The family often provided useful information about the patient and their addiction, this facilitated treatment plans in which the families played a prominent role in helping to supervise medication, encourage participation in rehabilitation programmes and generally provided an environment conducive to promoting recovery. The crucial role of carers in maintaining compliance was recognised. Optimal collaboration with the families relied on a tolerance attitude especially toward cultural differences both inside and outside the family.

For entry into the programme the patients needed to attend with a corer who could supervise the treatment preferably a family member. The relatives relationship to the patient was reformed as not only familial but also as corer (Szmukleir et al, 1997). As such they were given information regarding opiate addiction and its treatment on a need to know basis (O'Neil, 1997). A psychoeducative approach has been shown to be effective in reducing relapse in schizophrenia and offer potential for better family coping and a diminution in their distress (Bloch et al., 1995). Comparison between the use of dopamine antagonists in the case of psychosis and opiate antagonists in opiate addiction may also help develop pharrnacotherapy with recent interest in the use of depot preparation of Naltrexone to improve compliance. Since starting this study the use of Naloxone in ambulances has been sanctioned to combat the rising number of deaths from heroin overdose in Western Australia. It is estimated that a single 50mg dose of Naltrexone can block several grams of street heroin from producing intoxication. Due to the long half life of Naltrexone (10 hours) addicts may have to wait three days before being able to feel the effects of opiates again. This may be particularly beneficial for those with poor impulse control however caution needs to be exercised for those likely to require opiates for analgesia. The availability of an effective treatment may help to shift societal Attitudes away from those of the criminal justice system towards awareness of addiction as a treatable medical condition. One token of this is the exchange of the stigmata of intravenous injection for the medic alert badge.

REFERENCES

1. Bloch S, Szmukler G, Herrman H. Counselling caregivers of relatives with schizophrenia: theses, interventions and corers. Family process 1995;34:413-25.

2. Brewer C, editor. Naltrexone in the prevention of relapse and opiate detoxification. Treatment options in addiction. London: Gaskell, 1993.

3. Gonzales J, Brogden R. Naltrexone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of aped dependence. 1988.

4. O'Connor PG, Waugh ME, Carroll KM, Rounsaville BJ, Diagkogiannis IA, Schottenfeld RS. Primary care-based ambulatory aped detoxification: the results of a clinical trial. Journal of General Internal Medicine 1995; 10:255-60.

5. O'Neill G. How to care for patients with heroin addiction. Australian Medical Procedures Research Foundation, Subiaco, Western Australia.

6. Prochaska JO, DiClemente CW. Transtheoretical therapy: toward a more integrative model of change. Psychotherapy: theory, research and practice 1982; 19:288-96.

7 Szmukleir G, Bloch 5. Family involvement in the care of people with psychoses: an ethical argument. Br J Psych 1997;171:401-5.

8. Ward J, Mattick R, Hall W. The effectiveness of Methadone maintenance treatment. An overview. Drug and Alcohol Review 1994;13:327-36.

9. Washton AM, Pottash AC, Gold MS. Successful use of Naltrexone in addicted physicians and business executives. Advances in alcohol and substance abuse 4 1997.

10. Williamson PA, Foreman KJ, White IM, Anderson G. Methadone-related overdose deaths in South Australia, 1984-1994. How safe is Methadone prescribing? Medical Journal of Australia 1997; M: 302- 305.

11. Wilkinson C, Saunders B. Perspectives on Addiction: Making Sense of the Issues. William Mongomery Pty Ltd., Perth, WA.

12. Yang D, Zhang 1, li Y Observation of nailfold microcirculation in 220 heroin addicts. Chinese bulletin on drug dependence 1994;2:172.

13. Ginzberg. . 1986. 14. Kleber, Kosten. . 1984.

15. O'Brien, Green stein, Mint, Woody. . 1975.

16. Osborne, Grey, Reznikoff. . 1986.

17 Garcia-Alonso, Gutierraz, San, Bedate, Forteza- Rei, Rodriguez-Artalejo, et al. . 1989. 18. Thomas. . 1976.

4.

Using the following criteria to see which centres is most efficient.

1. Pre Detox evaluation to identify indicators of good prognosis of opiate dependent patients who would benefit from (UROD) treatment.

2. The most safe and cost effective method for Ultra Rapid Opiate Detoxification and Naltrexone induction under general anaesthesia.

3. Maintenance/Rehabilitation/Evaluation of clinical outcomes/Follow-up/Urinalysis. Recognising that what happens to patients after detoxification is often more important than what happens during it.

REFERENCES

1. Aldred Bob,Esecutive Officer, Queensland Alcohol and Drug Foundation, (Courier Mail 21 August 1997.

2. Bartek K Jean Dr. New Findings support Pharmacological Interventions in Addiction; Naltrexone and Revia (Journal of Addictions, Nursing Vol 8, Number 1, 1996).

3. Brewer C. Accelerated opioid withdrawal and naltrexone induction in one day. Proceeding of International Congress on Alcohol, other drugs and the Family. (Nov 1988, Sydney, Australia).

4. Flack Jim, Director Chemical Dependency Services, Methodist Hospital, Texas (Paper by Aaron Howard on (UROD).

5. Gabor D Kelon MD. Testimony before National Security, International Affairs, and Criminal Justice Sub-committee of the Government Reform and oversight Committee. (19 September, 1996) Heroin Epidemic: Public Health and Emergency Medical Care Issues.

6. Gerstein, D R and Harwood, H J (Eds.) 1990. Treating drug problems. Volume 1. A study of the evolution, effectiveness, and financing of public and private drug treatment systems (Vol.1)) Washington, D.C: National Academy Press.

7. Goodman and Gelman’s, Eight Edition, Chapter 21 Opioid, Antagonists pp.514-517.

8. Gooberman LL. Presentation at the American Society of Addiction Medicine, 17th Annual Medical-Scientific Conference, Atlanta Georgia, 1996.

9. Goths Medical Pharmacology, twelfth edition, Chapter 29, Narcotic, Antagonists. Pp331-333.

10. Herman BH, Czechowicz D,NIDA, Scientific Report of Ultra Rapid Detoxification with Anaesthesia (UROD): Opinion of the consultants and criteria relating to evaluating the safety and efficacy of UROD, February 23, 1996.

11. Hollingworth Peter, The Sunday Mail, 10 August 1997.

12. Juan Jose Legards, Michael Gossop, A 24-Hour in-patient detoxification treatment for Heroin addicts: A preliminary investigation, Drug and Alcohol Dependence 35 (1994) 91-93.

13. Lerner G Arturo, Gelkopf Makc, Sigal Mircer, Oyffe Igor; Indicators of good prognosis in naltrexone treatment: A five-year prospective study. Addiction Research 1997 Vol.4 pp 385-391.

14. Messick Jm,Mackenzie RA, Nugent M. Anaesthesia at Remote Locations. Anaesthesia, third edition, RD Miller, Editor, 1990;pp2081-85.

15. Nutmeg Intensive Rehabilitation, P.C.c. 1996-1997. 359 Merrow Road, Suite B, Tolland Connecticut. 06084.

16. Rankin, Review of the effectiveness of Methadone Maintenance Treatment and Analysis of St Mary’s Clinic, Sydney. Rankin Judy and Mattick, Richard P, 1997. NDARC Technical Report No.45, University of New South Wales.

17. Rettig. Richard A; Adam Varmolinsky (eds.). Federal Regulation of Methdone Treatment. Washington DC: National Academy Press. 1995.

18. Sarwicki T. The Miracle Cure?. A revolutionary-and highly controversial treatment for heroin addiction is achieving astounding success in Israel, and is now set to go overseas. The Jerusalem Report, July 13, pp 20-21.

19. Simon L David. Rapid Opioid Detoxification using Opioid Antagonists: History, Theory and State of the Art. Journal of Addictive Diseases. Vol. 16 (1) 1997.103-122.

20. Weiner W. Chapter 9. Drugs that inhibit adrenergic nerves and block adrenergic receptors. Goodman and Gilman’s. The Pharmacological Basis of Therapeutics. Sixth Edition 19809. MacMillan Publishing. Pp202-4.

21. White Paper of ONDCP. Treatment Protocol effectiveness study. Treatment Protocol Effectiveness Study. Pp 297-303,1996.

22. World Health Organization (1992). The ICD-IO classification of mental and behavioural disorders: Clinical descriptions and diagnostic guidelines. Geneva Author.