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Chemical Dependency Research Working Group |
J. Thomas Payte, M.D. is Chair of the American Society of Addiction Medicine (ASAM) Committee on Methadone Treatment, Editor of the Journal of Maintenance in the Addictions, Adjunct Instructor in Pharmacology at the University of Texas Health Science Center, and Founder and Medical Director of Drug Dependence Associates, a methadone maintenance treatment program in San Antonio, Texas.
Elizabeth Khuri, M.D. is Clinical Director of the Adolescent Development Program, Associate Professor of Public Health and Pediatrics at Cornell University Medical Center, and Associate Physician for The Rockefeller University in New York City.
Herman Joseph, Ph.D. is the Chair of the Chemical Dependency Research Working Group. He was a member of the original team at The Rockfeller University and has conducted research on methadone and addiction for the past 30 years.
Joycelyn Woods, M.A. is the Research Associate for the Chemical Dependency Research Working Group and Executive Vice President of the National Alliance of Methadone Advocates. Her background is in neuroscience and psychopharmacology.
* A version of this article has been submitted to the Journal of Maintenance in the Addictions for publication.
Opiate addiction and the most effective treatment for it, methadone maintenance, are not well understood within the medical profession. The reasons for this are complex and can be traced back to the Harrison Narcotic Act of 1914. Physicians were the first group to be persecuted by this legislation which did not consider opiate dependence a legitimate medical condition and forbade the prescribing of opiates solely for the purpose of maintaining dependence. At the time the majority of opiate-dependent persons were middle class women (housewives) and physicians or other medical professionals who had access to drugs. Nevertheless, many physicians attempted to pursue a humane course of medical treatment by continuing to prescribe their "necessary" narcotics. Authorities were determined to make an example of these mostly family doctors, so many physicians were arrested, imprisoned and lost their medical licenses and practices. It must be emphasized that these were not unscrupulous physicians, rather many were concerned about the patients they had treated for years.
Over the years, the medical profession's early experience with the Harrison Narcotic Act has evolved into the dictum "stay away from addicts" they are nothing but trouble and addiction is not a doctor's domain. By the 1930s, this attitude became prevalent in medical schools with physicians receiving little or no training in addiction, which remains to this day. The lack of training on addiction, drug dependence and prescribing medication for pain has resulted in much confusion among clinicians (Portenoy & Payne, 1992). Added to this confusion is the strict regulating of narcotic drugs whose main impact has been to cause the under prescribing of narcotic drugs for the relief of pain. Physicians have become concerned about addiction when prescribing for pain relief. Yet the fact is that when morphine is taken to relieve pain it rarely causes addiction. However, there is evidence that the medical profession is changing. Addiction treatment has recently become a subspecialty within the American Medical Association.
The unwarranted fear of addicts and the fear of prescribing opioid analgesics has been given a name, addictophobia. The education of physicians in the pharmacology of opioids and their ability to relieve pain, along with training in the basics of addiction, will help eliminate these attitudes. However, belief that addiction is a behavioral problem will no doubt persist until the biological causes are discovered and understood.
Tolerance is a pharmacologic property of all opioid drugs and is characterized by the need for increasing doses in order to maintain the original effects (Jaffe, 1985). Tolerance to the reinforcing effects of opioids, and the need to increase the dose in order to maintain the initial effects, is considered an important aspect of addiction. The belief that tolerance will develop to the analgesic effects of opiates in the opiate-naive patient and thus interfere with analgesic efficacy continues despite evidence to the contrary (World Health Organization, 1969). Studies have demonstrated that tolerance to the analgesic effects of opiates occurs only in patients with chronic and worsening pain (Foley, 1985; Twycross, 1983). Patients treated for prolonged periods with opiate drugs for nonmalignant pain fail to demonstrate the need for escalating doses in order to achieve pain relief (Portenoy & Foley, 1986; Portenoy, 1989).
Physical dependence is also a pharmacologic property and is defined solely by the abstinence syndrome or what is more commonly known as withdrawal (Jaffe, 1985). Much of the misunderstanding about physical dependence and addiction occurs because these terms are often erroneously used for one another. Physical dependence is a pharmacological property of all opioid drugs, as is tolerance while addiction is identified based on psychological or behavioral manifestations of the underlying disease.
Narcotic addiction as we know it, is characterized by drug craving, compulsive use, deviant behaviors and most commonly relapse after withdrawal from the drug. It is interesting to note that methadone has a significantly lower potential for abuse than heroin, morphine, etc., based on its slow onset of action with a relative lack of reinforcing effects. The term drug abuse is used to define any compulsive drug-taking behavior that is not within accepted societal or cultural mores. However, experts in the field are beginning to use this term less because of the moral implications, and prefer to use the term "drug use" in its place. It must be stressed that the behavior associated with compulsive drug taking is quite different from the behavior of a patient with a history of illicit drug use who requests medication to relieve pain.
It must be emphasized that it is unjustified for physicians to be reluctant to prescribe a sufficient dose of medication in order to relieve pain. Since medically caused addiction to opiates rarely occurs, their application to relieve pain should be pursued aggressively and early in order to promote health and healing. Furthermore, it is illogical for physicians to under prescribe opiate analgesics for patients suffering with the pain of terminal cancer or any other fatal condition for fear of addicting them. For these patients the focus should be on relieving the pain of the disease and dying and thus allowing them to live out their final days with their family and in comfort.
Methadone patients who are hospitalized with acute or chronic pain conditions are at high risk for receiving inadequate medication for relief of pain. There are several major reasons for this. First, many health professionals incorrectly believe that methadone patients will obtain pain relief from the methadone. Secondly, attitudes of the medical staff about illicit drug use may overwhelm the need to provide adequate pain relief and complaints from the patient are perceived as manipulations to receive opioids for other than pain relief. Another potential factor for under treatment is the failure of the medical staff to recognize the potential for tolerance in methadone-maintained patients. The result is that a large majority of methadone patients who have needed medication for pain relief did not receive an adequate dosage, or even any at all. As former drug users methadone patients often perceive the medical profession as unsympathetic and prejudiced based on earlier experiences. The rehabilitated methadone patient very often continues to be excluded by those responsible to provide comfort and relief. Whatever factors may contribute to the under treatment of methadone patients the end result is the undermining of the therapeutic alliance.
Some clinicians incorrectly assume that the methadone-maintained patient has no need for pain relief. Patients maintained on methadone have developed a tolerance or resistance to the narcotic, analgesic (pain killing) and tranquilizing properties of methadone. Consequently, they feel pain to the same degree as persons who are not maintained on methadone and need adequate doses of morphine or other narcotics to relieve acute and chronic episodes of pain.
These authors know of no studies that have evaluated the effects of tolerance and its potential in reducing the efficacy of analgesics (Portenoy & Payne, 1992). Several studies have found that the usual regimen used to provide pain relief for the non opiate tolerant patient can also be used to treat those maintained on methadone (Kantor, Cantor & Tom, 1980; Rubenstein, Spior, & Wolff, 1976). However, these studies did not assess directly the relief of pain, or evaluate the role of tolerance in achieving analgesia (Sawe, Hansen, Ginman et al, 1980). Since these factors were not considered these authors encourage clinicians to evaluate dosage in consultation with the patient in order to ascertain that adequate analgesia has been achieved for proper healing and health of the patient.
Some methadone patients who have been hospitalized for surgery have reported that their methadone doses were lowered in the hospital and as a result they experienced withdrawal symptoms while hospitalized (National Alliance of Methadone Advocates, Inc., 1994). Other reports have been received that some patients were even told to detoxify from methadone prior to surgery since it is incorrectly believed that methadone may interfere with analgesia or their health condition (Payte, 1994). In summary it must be emphasized that the opiate-dependent patient must be treated with the same dignity and respect as any other patient. When treated humanely and with compassion the opiate-dependent patient is no more difficult to treat than non dependent patients, although they may be a little more distinctive than the ordinary patient.
Methadone patients or opiate dependent individuals should never be given mixed opiate agonist/antagonist drugs as this will precipitate the abstinence syndrome and can cause serious problems. Commonly used drugs in this class include Talwin, Nubain and Stadol.
The methadone-maintained patient is easily treated for chronic pain. Physicians need not be concerned with those methadone patients maintained on a blockade dose of 80 mg/day or greater to feel any euphoric effects from short-acting narcotics (Dole, Nyswander & Kreek, 1966). The methadone will block it. Even lower doses of methadone will produce a partial blockade effect. It must be emphasized that in order to produce adequate analgesia in methadone patients short acting narcotics may have to be prescribed in higher doses and greater frequency than that needed for the opiate naive patient. Since, methadone patients at a blockade dose are protected from respiratory depression so the concern of the physician should be to achieve satisfactory analgesia.
Usually a sensitivity to narcotics can be determined through an interview with the patient and in these cases the initial dose of pain medication can be given in small increments while observing the patient until analgesia is achieved. Treating the methadone patient for pain on a blockade dose is easier than the patient whose dose only provides a partial blockade. Inadequate pain relief may result in the former illicit drug user to seek additional drugs for the relief of pain, thus placing them at a great risk of relapse. Illicit heroin and cocaine are readily available in urban and rural locales and therefore easy to obtain for hospitalized patients in pain.
Many former illicit drug users may be fearful of losing control and thus refuse any analgesia. First and foremost their request for no pain medication should be respected. However, in some patients eventually pain may overcome this fear and a request for pain medication may be made. Before this point is reached the clinician should discuss and make clear all the issues with the patient. Methadone patients receiving a blockade dose should be assured that their daily dose of methadone will block any euphoric effects of the drug and that analgesics will only produce relief of pain. Methadone patients on lower doses can similarly be advised of a partial blockade and that in all probability they will feel very little euphoria, if any at all from pain medication. Furthermore it should always be emphasized that analgesia for acute pain will probably only be necessary for a short time and that relief of pain is essential for a quick and healthy recovery. Some methadone patients may fear that their maintenance dose will have to be increased. Again these patients should be reassured that this problem has been studied and that an increase in their maintenance dose will not be necessary (Kantor, Cantor & Tom, 1980). Ultimately, the final decision should always rest with the patient, and the attending physician should make sure that these requests are respected.
There are several regimens that can be used with the methadone-maintained patient. None of these protocols have been demonstrated to be superior to the others, and physicians should rely on their own experience and observation, as well as listening to the patient. A common protocol and probably the easiest, is to continue the base line maintenance dose of methadone and supplement it with intermittent increments of a shorter-acting narcotic. Opiate-dependent individuals will metabolize narcotic analgesics faster and can rapidly develop tolerance to the analgesic effects of a short-acting narcotic and will probably require an increased dose and a more frequent dosing schedule (Kreek, 1983). The best advise to follow is that of the late Dr. Marie Nyswander who taught physicians to "listen to the patient."
Other regimens are somewhat problematic, but may be useful for some instances. One strategy is to increase dose of the long-acting narcotic, namely methadone, until the desired pain relief is achieved. In order to produce a sustained analgesia with methadone for a non opioid dependent patient, at least three doses per day are required. There is no advantage in using methadone for analgesia since the analgesic duration only lasts about four to six hours (Sawe, Hansen, Ginman et al, 1981). Methadone-maintained patients will quickly develop tolerance to the analgesic effects of methadone making this method only useful for short periods, if at all (Selwyn, 1992).
A final method is to completely abandon the long-acting narcotic methadone and institute a regimen to completely meet the needs of the patient's pain relief. Again another problem arises since short-acting opioids will probably be metabolized quicker in patients with a history of opioid drug use. They will rapidly metabolize short-acting opioids and develop tolerance to the analgesic properties faster thus making it difficult to achieve a maintenance dosage without development of some symptoms of the abstinence syndrome (Kreek, 1983).
Should these later two protocols be utilized and a problem occurs, such as the patient experiencing the beginning symptoms of the abstinence syndrome or analgesia is not achieved, the patient may perceive that they are being used to experiment on. No matter how erroneous this belief may be this attitude will undermine the ability to have a good therapeutic relationship with the patient. Persons with a history of drug use, as mentioned previously, have often had very bad experiences with the medical profession making them suspicious towards any clinician. Overcoming these attitudes is the art of medicine and they can be if the patient is treated with honesty, sincerity and dignity. Should it be necessary to choose any regimen that will either increase or decrease the maintenance dose of methadone it should be done in consultation with the physician treating the patient for their drug dependence.
For some conditions, especially abdominal surgery the methadone-maintained patient may need their medication administered via intra muscular (IM) injection. There is the illogical belief by physicians that methadone administered this way is stronger while in fact, "30 mg is 30 mg." Many hospitalized methadone patients requiring IM administration have reported that their daily dose was cut in half. This places these methadone patients at a distinct disadvantage. Methadone-maintained patients not receiving a blockade dose and especially those receiving 40 mg/day or less will begin to experience symptoms of the abstinence syndrome and will probably experience immediate discomfort within the 24-hour period. If these patients also require pain medication they will be experiencing pain and withdrawal symptoms simultaneously. Methadone patients on a blockade dose of 80 mg/day or greater will probably not experience any initial discomfort when their usual methadone dose is cut in half because it is administered IM, at least for awhile. As their methadone blood levels slowly drop these patients, formerly receiving a blockade dose of methadone (80 mg/day or more), are no longer protected against respiratory depression and, more importantly, the lower methadone dose of 40 mg/day may only partially block any euphoric effects of an opioid administered for relief of pain.
Perhaps the most cautious strategy when administering methadone IM is to administer half in the morning and half in the evening. Perhaps this is where the confusion began regarding the halving of the dose. A few methadone patients who are not taking a blockade dose above 80 mg/day and who are sensitive to methadone may experience an initial sedation when their medication is administered IM. It must be emphasized that every effort should be made to maintain a methadone patient on their usual maintenance dose which was prescribed by a physician experienced in addiction treatment. The methadone patient will be reassured if his maintenance dose is maintained promoting a therapeutic relationship and a healthy outcome. Many physicians are concerned about the unusually high doses required for methadone maintenance: doses that would normally cause respiratory depression and possibly even death in the non opiate tolerant patient. However, it cannot be over emphasized that doses over 80 mg/day are necessary for methadone to be effective and adequate in blocking drug craving and hunger. Once drug craving is controlled with an effective dose the methadone patient can live a relatively normal and stable life.
The care of patients who have a history of illicit drug use and are infected with HIV are of critical relevance when considering pain management. The complexity of the issues in treating these patients requires that the first step in their management should be a comprehensive assessment. First and foremost, all attempts should be made to obtain proper treatment for the illicit drug use. Clinicians not knowledgeable in addiction treatment should seek professional expertise when treating patients who are drug users. This will avoid acting-out behavior. Every effort should be made to assure these patients that an adequate maintenance dose of methadone will be given to them while they are hospitalized. Pain management for these patients may be difficult and require a greater frequency of monitoring. The use of a written contract which is kept in the medical record and defines the regimen and explicitly states the responsibilities of both the patient and the physician may be helpful in treating these patients.
Included in the contract should be the responsibilities of the patient after they are discharged from the hospital. The contract should have the methods used to renew prescriptions and the response to lost or stolen medication. One way to handle the problem of lost or stolen medication is to advise the patient in the contract that should this occur it will have to be reported to the police. The police report will have to be presented and placed in the patient's record before any replacement medication can be prescribed. Furthermore, it should be emphasized to the patient that medication will be replaced "only" once and therefore should only be used if the medication is truly lost or stolen. For patients who are not hospitalized or do not have a place to secure pain medication more creative protocols may have to be used. Certainly, one method is to only prescribe pain medication one day at a time. Such an arrangement could be made with a local pharmacy.
The methadone-maintained patient experiences normal pain and therefore needs adequate analgesic medication to relieve pain. At a blockade dose of 80 mg/day the methadone-maintained patient is protected from respiratory depression and will not experience drug craving or hunger or any euphoric effects of any short-acting opiates prescribed for relief of pain. Clinicians should not feel apprehensive about the large doses prescribed to methadone patients to treat drug dependence. Methadone will not interfere with the prescribing of opiates for analgesia. Detoxifying from methadone or any opiate is not recommended and can temporarily effect the health of the maintained individual. Perhaps the easiest protocol for pain management of the methadone patient is to prescribe adequate short-acting opiates while maintaining the maintenance dose of methadone. If it is necessary to change the maintenance dose of methadone it should be done in consultation with the patient and the clinician who is treating the patient for their drug dependence. If reasonable conditions of pain management are followed the methadone patient should be no different than any other patient treated for acute or chronic pain.
Dole, V.P., Nyswander, M.E. and Kreek, M.J. Narcotic blockade. Archives of Internal Medicine 1966 (October) 118: 304-309.
Foley, K.M. The treatment of cancer pain. New England Journal of Medicine 1985 313: 84-95.
Kantor, T.G.; Cantor, R. and Tom, E. A study of hospitalized surgical patients on methadone maintenance. Drug and Alcohol Dependence 1980 6: 163-173.
Jaffe, J.H. Drug addiction and drug abuse. In: Gilman, A.G.; Goodman, L.S.; Rall, T.W.; Murad, F. (eds), The Pharmacological Basis of Therapeutics (7th edition), p 532-581. New York: Macmillan Publishing Co., 1985.
Kreek, 1983 Health consequences associated with the use of methadone. In: Cooper, J.R.; Altman, F.; Brown, B.S.; Chzechowicz, D. (eds) Research on the Treatment of Narcotic Addiction, p 456-482. Treatment Research Monograph Series, DHHS no (ADM)83-1281. Rockville, MD: National Institute on Drug Abuse, 1983.
National Alliance of Methadone Advocates, Inc. Personal communication, 1994.
Payte, T. Personal communication, 1994.
Portenoy, R.K. and Foley, K.M. Chronic use of opioid analgesics in non-malignant pain: Report of 38 cases. Pain 1986 25: 171-186.
Portenoy, R.K. Opioid therapy in the management of chronic back pain. In: Tollison, C.D. (ed), Interdisciplinary Rehabilitation of Low Back Pain. Baltimore: Williams & Wilkins, 1989.
Portenoy, R.K. and Payne, R. Acute and chronic pain. In: Lowinson, J.H.; Ruiz, P.; Millman, R.B.; Langrod, J.G. (eds), Substance Abuse A Comprehensive Textbook (2nd edition), p 691-721. Baltimore: Williams & Wilkins, 1992.
Rubenstein, R.; Spiro, I and Wolff, W.I. Management of surgical problems in patients on methadone maintenance. American Journal of Surgery 1976 131: 566-569.
Sawe, J.; Hansen, J.; Ginman, C. et al. A patient-controlled dose regimen of methadone in chronic cancer pain. British Medical Journal 1981 282: 771-773.
Twycross, R.G. Clinical experience with diamorphine in advanced malignant disease. International Journal of Clinical Pharmacological Therapeutics and Toxicology 1974 9: 184-198.
World Health Organization. Technical Report No. 407. Expert Committee on Drug Dependence, 16th Report. Geneva: World Health Organization, 1969.
Dr. Gordon is currently Emeritus Professor of Psychology, State University of New York, College at Oswego, Oswego, N.Y. 13126.
In 1967 the initial investigation of the function potential of methadone maintained patients was begun. At the 4th National Methadone Conference Gordon, Warner and Henderson (1972) reported on their extensive study evaluating the "psychomotor and intellectual performance of ex-heroin addicts," who were the first to be maintained on methadone as part of their treatment for opiate addiction. The conclusions derived from those early studies showed that, receiving methadone as part of the treatment for heroin addiction did not have any adverse affects on either cognitive functioning or perceptual motor learning and performance. A later report (Gordon, 1973) summarized field and laboratory studies of the performance of ex-addicts maintained on methadone, from 1964 to 1972. This paper reviews both the earlier work as well as research by other investigators.
This review is divided into two major sections, Laboratory Studies and Field Studies. The laboratory studies included perceptual-motor, reaction-time and sustained attention tasks, as well as tests of cognitive and intellectual functioning. Field studies were primarily concerned with driving experiences of methadone patients as well as general assessments of job performance, compared with relevant control subjects. There were also one or two studies that assessed patient behavior on-the-job.
Prior to the studies to be reported on, only Isbell and colleagues (1948) had evaluated the effects of chronic administration of methadone in humans, which was conducted with institutionalized addicts to determine the addiction liability of methadone.
The Isbell study had indicated that methadone might have a detrimental effect on intelligence, therefore, one of the concerns of the early studies by Gordon et al (1972) was to examine intellectual functioning after patients were stabilized on maintenance doses of methadone. The results for 155 patients, whose initial maintenance dose ranged from 70-100 mg/day of methadone taken orally, did not show any departure from expected distributions of IQ scores found in the general population. An absence of cases in the lowest IQ categories was also noted.
Subsequently, Gordon and Lipset (1976) followed up on 30 of the 155 patients who had originally been tested for intellectual functioning, approximately 112 months later. When tested initially, these patients, had been maintained on an average of 79 mg of methadone, and on follow-up, the average daily dose was 69 mg. The tests used were alternate forms of the Wechsler Adult Intelligence Scale (WAIS). Twenty-five patients showed gains in IQ, one stayed the same, and four showed modest declines. Intellectual functioning in the follow-up, as in the original testing, was normal.
Later studies of cognitive functioning have arrived at similar conclusions. A study by Pugliese (1974) found no difference between age and education matched methadone patients and controls, when they were tested with the Wonderlic, a form of intelligence test. This study was concerned with the employability of methadone patients. A study by Lombardo (1974) also found that when educational level was taken into account methadone patients maintained on 50 or 80 mg per day showed IQs in the normal range.
A study concerned with memory processes by Grevert and colleagues (1977) found that methadone treatment had no effect on memory, in a study that compared memory performance prior to and after three months of treatment.
Studies of reaction-time measure decision time as well as motor response times, which are sensitive to drug effects. The first study by this writer (1970), compared 18 male and 9 female methadone patients stabilized on average daily doses of 100 mg, with matched drug-free recently detoxified heroin addicts, and college students. The task consisted of one simple and two more complex reaction-time (RT) tasks. Methadone patients, both male and female, were either equal to or superior to control subjects on two of the tasks, and on the most complex choice RT task.
Later, Gordon and Appel (1972) studied the RTs of methadone patients when they were 24 hours abstinent from their daily dose and compared their performance when they were one-hour post daily methadone dose. Again, overall results for male and female patients indicated no methadone effect, and RTs were either equal to or superior to relevant control subjects. One interesting finding in the latter study indicated that working patient's RTs were more rapid than those of nonworking patients.
Three additional studies (Chesher, 1985; Kelley, Welch & McKnelley, 1978; Rothenberg et. al., 1977) have appeared which reported on reaction-times of methadone patients in laboratory type tests of attention. Some evidence was found that indicated patients may respond more rapidly than controls.
Appel (1982) studied the performance of methadone patients on a continuous performance task, where responses were made to an unusual signal after subjects were required to ignore varying strings of regular signals. Different rates of signal presentation were used. Methadone patients did not differ from drug-free ex-addicts or opiate naive subjects. There were differences in response latencies among patients - working methadone patients performed better at the high signal rates, and had longer latencies and poorer accuracy at the low rates. Nonworking patients made more false positive errors at the high signal rate than the other groups.
Appel and Gordon (1976) used the digit symbol sub-test of the Wechsler Adult Intelligence Scale (WAIS) to study patients' abilities to follow a code in substituting digits for two-dimensional pictorial symbols in a paper and pencil speed test. Working patients did not differ from controls, but nonworking patients experienced poorer performance. No evidence was found that patients who spent the longest times in treatment (8 years) were any poorer than patients who had only been in treatment for 11 months.
Rothenberg et al (1977) has found that methadone patients had faster response times than controls, and that there was no difference in maintenance of attention between patients and other groups of subjects.
Isbell et al (1948) had indicated that methadone might slow some aspects of perceptual motor functioning. In early studies (Gordon, Warner & Henderson, 1972), perceptual-motor performance was measured by means of the rotary pursuit test (a task used to measure learning and performance in an eye-hand coordination task), over the period of a year or so. Patients exhibited normal functioning.
Moskowitz and Sharma (1979) reporting on skills performance of patients maintained on methadone for at least six months, concluded that patients failed to show impairment on the most obviously relevant skills performance tasks. These studies represent the most comprehensive evaluation of the performance of methadone patients found so far. A series of eight experiments on various sub-skills related to driving behavior were conducted. They included performance in a driving simulator in which patients and control subjects were subjected to a variety of experiences which required close attention and accurate responses. Tests were conducted just before and two hours after the daily methadone doses of both 60 mg and 80 mg of methadone. While two of the sub-tests gave evidence of a methadone effect, patients compensated by more rapid response times. Methadone is also mentioned in another report (Stapleton, Guthrie & Linnoila, 1986) as having an effect on eye movements, but an assessment of the consequences is lacking. Moscowitz and Sharma (1979) felt that the more rapid reaction-times shown by methadone patients, more than compensated for any potential oculomotor slowing. A final study undertaken by Kelley, Welch and McKnelley (1978) of various functional parameters, also failed to find any important evidence of negative impact on overall functional status.
An interesting study by Ho and Dole (1979) indicates that methadone-maintained persons do not differ from drug-free ex-heroin addicts in their perception of somatic pain, a finding of some significance in terms of functional status.
The general conclusion of available laboratory studies of methadone patients is that there does not appear to be any socially relevant barrier to their ability to perform a variety of tasks such as those found in industrial settings or in driving motor vehicles.
Field studies reviewed here have relevance to the question of functional capacity of persons maintained on methadone as part of their treatment for heroin addiction. A recent evaluation study of methadone treatment by Ball and Ross (1991), has found a general relationship between maintenance dose and cessation of heroin use. It appears that the critical dosage level is 71 mg of methadone per day. Those patients maintained on doses lower than 70 mg of methadone, are much more likely to use heroin. The finding implies that daily levels below 70 mg result in incomplete tolerance. This would lead to the suggestion that future studies of functional potential, take into account the methadone dose level needed to maintain tolerance.
The studies reported on below fall into two categories; studies of employability of methadone patients and reports of their performance as motor vehicle operators.
Two studies relate to employability (Double & Koenigsberg, 1977; Yankowitz & Randell, 1977). Both studies indicated that ex-heroin addicts maintained on methadone function quite well as skilled laborers and office workers. This matches the conclusions arrived at in an earlier study (Gordon & Lipset, 1976).
Driving motor vehicles is an area of considerable public concern, given the widespread misuse of alcohol and other drugs. An earlier review (Gordon, 1976) found that there was little cause for concern about narcotic use generally and specifically for methadone use, when it is used as a maintenance drug. Since the earlier review there are a number of additional reports that have appeared (Babst, Newman, Gordon & Warner, 1973; Blomberg & Preusser, 1974; Maddux, Williams & Ziegler, 1977; Moskowitz & Sharma, 1979; Stapleton, Guthrie & Linnoila, 1986). In these studies, methadone maintained individuals did not differ from age-matched non-drug users or abstinent ex-heroin addicts. The studies reported on both traffic violations and accidents, and report confirmation of interview data collected from patients, by means of the patients' actual motor vehicle driving records obtained from official sources. A recent review by Chesher (1985) finds that based on studies of skills related to driving, or based on epidemiological findings, narcotics, including methadone, generally do not appear to be a source of concern in road crashes.
The general conclusion of this reviewer is that there is considerable confidence in the fact that maintenance on methadone at appropriate dosage levels, as part of treatment for heroin addiction, has little if any affect on ability to function in any capacity for which the person is qualified.
The foregoing conclusion should not seem so surprising in view of the fact that even heroin addicts (Caplowitz, 1985) while using heroin, as well as those maintained on morphine as part of their treatment for heroin addiction (Waldorf, Orlick & Reinarman, 1974), were able to be gainfully employed and successful in a wide variety of positions.
Recently it was reported that large doses of opiates are being chronically administered to individuals suffering from otherwise intractable pain (New York Times, 1993). The use of opiates, in the manner reported, for pain management, not only relieves suffering, but enables affected individuals to function normally. The main disability they suffer is stigma for their presumed "addict" status.
The lesson the we learn from this, is that addictive behavior, is a construct that is biological in origin and modulated by social and behavioral factors. Narcotics per se can cause physical dependence, tolerance, and craving. However, the social context of a person's narcotic use and way of life determines the nature of addictive behavior. In conclusion, methadone patients who are either building or rebuilding their lives or who are functioning normally within the community are not "addicts" but medical patients being treated for a chronic condition.
The writer gratefully acknowledges the collaboration of his former students who participated as colleagues in many of the studies reported in this review: P. Appel, A. Ho, J. Lipset and A. Warner.
Appel, P.W. Sustained attention in methadone patients. International Journal of the Addictions 1982 17: 1313-1327.
Appel, P.W. and Gordon, N.B. Digit-symbol performance in methadone-treated ex-heroin addicts. American Journal of Psychiatry 1976 133: 1337-1340.
Babst, D.V.; Newman, S.; Gordon, N.B. and Warner. A. Driving record of methadone maintenance patients in News York State. NY State Narcotic Addiction Control Commission, 1974.
Ball, J.C. and Ross, A. The Effectiveness of Methadone Maintenance Treatment. New York: Springer-Verlag, 1991.
Blomberg, R.D. and Preusser, D.F. Narcotic use and driving behavior. Accident Annals and Prevention 1974 6: 23-32.
Caplowitz, D. The Working Addict. New York: Research Foundation, City University, 1974.
Chesher, G.B. The influence of analgesic drugs in road crashes. Accident Annals and Prevention 1985 17: 303-309.
Double, W.G. and Koenigsberg, L. Private employment and the ex-drug abuser: A practical approach. Journal of Psychedelic Drugs 1977 9: 51-58.
Gordon, N.B. Influence of narcotic drugs on highway safety. Accident Annals and Prevention 1976 8: 3-7.
Gordon, N.B. The functional status of the methadone maintained person. In: Simmons, L.R.S. and Gold, M.B., Discrimination and the Addict, p 101-121. Sage Publications, 1973.
Gordon, N.B. Reaction-times of methadone treated ex-heroin addicts. Psychopharmacologia 1970 16: 337-344.
Gordon, N.B. and Appel, P.A. Performance effectiveness in relation to methadone tolerance, p 425-427. In: Proceedings of the 4th National Conference on Methadone Treatment. New York: National Association for the Prevention of Addiction to Narcotics, 1972.
Gordon, N.B. and Lipset, J. Intellectual and functional status after almost ten years of methadone maintenance treatment. A paper presented at the American Psychological Association Convention. Washington, D.C., 1976.
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Ann Rosenberg, Ph.D. is the Director of Research at the Nassau County Office of Alcoholism and Substance Abuse Services, Long Island, New York.
Theorists such as Dole and Nyswander (1976), Goldstein (1972) and others have considered the possibility that there are physiological differences between opiate dependent and non-opiate dependent individuals. This study seeks to explore this possibility. Opiate dependent individuals may have a deficiency of endogenous opioids which they attempt to supplement by the use of opiates (Goldstein, 1976). The present research investigates the effect on attention that occurs by varying systemic levels of endorphins, the internal, or endogenous opioids.
In 1973 three laboratories found evidence of opioid receptors in vertebrate animals, with the highest concentration in the brain (Pert & Snyder, 1973; Simon, Hiller & Edelman, 1973; Terenius, 1973). Investigations followed that led to the discovery of naturally occurring, or endogenous, opioids, called endorphins that bind to these receptor sites (Goldstein, 1976; Hughes, Smith, Kosterlitz, Fothergill, Morgan & Morris, 1975; Terenius, 1975). Goldstein (1976) suggested that opioid receptors were related to emotional responses to pain.
A rich concentration of opioid receptor sites is located in the Locus Coeruleus (LC), an area of the brain that mediates attention (Kuhar, Pert & Snyder, 1973). Investigators found that applying morphine, or producing chemical lesions to the sites in the LC, interfered with the ability of the neurons to fire (Aghajanian, 1978; Pepper & Henderson, 1980; Arnsten, Segal, Loughlin & Roberts, 1981). Other investigators determined that the LC neurons responded selectively to complex, arousing stimuli (13). These studies indicate that the endorphin system plays a broader role than that of relaying information about pain and anxiety. It also plays a role in the processing of attentional information through the LC.
Implication that the endorphin system affects attentional mechanisms leads to questions regarding the effects on processing of simple and complex stimuli. Easterbrook (1959) has theorized that attention to a limited range of cues is preferable for certain tasks. Studies by Kahneman (1973) suggest that performance of a simple task requires limiting attention to a narrow range of cues, and conversely, the ability to attend to a wider range of cues facilitates performance on a complex task.
Naloxone and naltrexone are opiate antagonists; they block the ability of opiates to bind to the receptor sites, and inhibit the effects of opiates. The work of Arnsten (1981) and Arnsten et al (Arnsten, Segal, Loughlin & Roberts, 1981; Arnsten & Segal, 1979) suggests that naltrexone may operate to narrow the range of cues to which individuals attend. This may be desirable for performance on simple tasks, but inhibit performance on complex tasks. Gritz et al (1976) reported that naltrexone facilitated performance of opiate users on a simple task of selective attention. Appel and Gordon (1976) used a task of selective attention, the Digit Span sub-test of the Wechsler Adult Intelligence Score (WAIS), to compare subjects in methadone maintenance treatment with opiate-naive controls, and found no significant difference.
The above theories, discoveries and studies suggest that different levels of endogenous opioids should have an effect on the performance of simple and complex tasks of selective attention. Simply put, individuals with different levels of opioids in their system will respond differently to attentional cues. Opiate dependent individuals may have a deficiency of endogenous opioids (Goldstein, 1976). Treatment modalities for these individuals provide environments that affect systemic endorphins by controlling the use of exogenous opioids. Methadone maintenance treatment provides supplemental opiates, drug free residential treatment prohibits the ingestion of opiates, and treatment with naltrexone blocks the effect of both endogenous and exogenous opiates.
The present study investigates a model that states that: 1) the ability to respond to attentional cues is affected by endorphin levels, 2) this can be observed behaviorally when endorphin levels are manipulated, and 3) the nature of treatment for opiate dependency manipulates these levels.
The hypotheses are based on the theory that performance on tasks of selective attention is dependent on the systemic levels of endogenous opioids. If this is true, 1) methadone-maintained individuals and opiate-naive controls should respond similarly on simple and complex tasks of selective attention, because, though there may be a deficiency of endogenous opioids in this treatment population, methadone supplements this deficiency; 2) abstinent opiate-dependent individuals, who are not provided with opioid supplements should achieve lower scores on both simple and complex tasks of selective attention than scores achieved by both methadone treated individuals and by opiate-naive controls; and 3) if naltrexone does indeed help narrowly focus attention, individuals in naltrexone treatment should receive higher scores on simple tasks of selective attention than those of individuals in any of the other groups. However, because both endogenous and exogenous opioids are blocked, their scores on complex tasks should be lower than those of all other subjects. There should also be a greater difference in scores on both tasks within this group than those found in all the other groups.
Three groups consisted of subjects who were in treatment for opiate dependence. Group I consisted of 12 subjects in methadone maintenance treatment, Group II was made up of 12 subjects in treatment at a drug-free residential facility, and the eight subjects in Group III were in naltrexone treatment. Group IV was a control group made up of 12 opiate-naive subjects. All subjects were male and ranging in age from 21 to 44. All subjects were tested for near vision with the Nearpoint Rotochart. They were also tested with the Digit Symbol sub-test of the WAIS for the ability to distinguish and identify the numbers and symbols necessary for completing the various tasks, and to replicate the attentional task used by Appel and Gordon (1976).
Two forms of a paper and pencil Symbol Identification Test were developed by the investigator and evaluated for this research. They were used to evaluate performance on simple and complex tasks of selective attention. Both forms of the tests were administered in counterbalanced order.
The first set of hypotheses contended that there would be no significant differences in scores on both the simple and complex tasks between the methadone maintained subjects and the opiate-naive controls was supported by the data. These results are consistent with research suggesting that opioids are involved in mediating attention, and suggests the need for opiate-dependent individuals to receive supplementation.
The second set of hypothesis claimed that abstinent opiate users would have lower scores on simple and complex tasks of selective attention than methadone-maintained subjects and opiate-naive controls. Although the difference between the scores of the groups were not statistically significant, the results of all the comparisons were in the predicted direction.
The third set of hypotheses is based on the contention that naltrexone narrows the range of cues to which individuals attend by blocking the effects of endogenous opioids. Predictions are that individuals receiving treatment with naltrexone would have higher scores on simple tasks of selective attention than all other groups and lower scores on complex tasks than all other groups. It was also predicted that naltrexone treated subjects would show the greatest differences between scores of simple attentional tasks and scores on complex tasks. As before, all the results were in the predicted direction, but did not reach significance.
That there were no significant differences between groups overall served to confirm some hypotheses, specifically those that predicted similarities in function between methadone and control groups. But these results, at first glance, may be seen as weak in general, since differences that were found between the groups were not statistically significant.
On the other hand, it would be impossible to dismiss the hypotheses since the results were all in the predicted direction. A closer look at the differences between scores on the simple and complex tasks for all groups reveals consistently predicted trends. The absence of statistical significance may be due to an inadequate sample size. Increasing the number of subjects in each group may yield more significant results by differentiating discrete differences in attention between the groups.
The differences in attentional functioning sought in the present study may be more effectively measured with a combination of behavioral and physiological measures, specifically, highly demanding vigilance tasks combined with physiological measures of evoked potential at the brainstem and cortical levels.
The consistent trends revealed in this study not only prevent dismissal of the hypotheses and the theories that gave rise to them, but are actually indications that this is a fertile area for research. There are benefits in pursuing this investigation, not only for opiate dependent individuals, but also for individuals diagnosed with attentional deficits. Understanding the role of the endorphin, or endogenous opioid system in selective attention is an important step in helping to uncover the causes of some types of attentional deficits and in furthering the understanding of opiate dependency.
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