As emphasized above, mere withdrawal from the morphine-like agent does not constitute complete treatment of the drug-dependent patient. Further definitive treatment is almost always required.

Ambulatory Treatment-Ambulatory (outpatient) withdrawal is extremely difficult. Except in experienced hands and with careful screening and selection of patients, it is not generally successful. Many complicating factors can be present pointing to the need for continuing professional supervision and care. Among such factors are a high degree of reliance upon the drug and intense craving for it, the fear of suffering any symptoms of acute withdrawal, low tolerance for any type of tension or stress, and personality malfunction with its adverse effect on proper self-administration of the drug.

Ambulatory withdrawal is sometimes feasible in patients whose general health is good and whose drug dependence is of moderate degree, and where adequate social support and control of the dispensing of the medication can be achieved. Even in these instances, however, the patient should be seen daily by the physician. This will permit continuing evaluation of the physical and psychological status of the patient, and determination of the dose schedule of methadone for that day. It also will permit the administration of any additional chemotherapy or other medical treatment that is indicated. The patient should not be given written prescriptions for self-procurement and self-administration of methadone tablets. Liquid, non-injectable methadone should be administered orally and directly to the patient by the physician or his aide, and the patient should be observed while he takes the medication. If more than a single dose per day is required, methadone should be dispensed only in a quantity that will serve to meet withdrawal requirements for the ensuing 24 hours. The same considerations regarding stabilization and gradual withdraw from methadone as were discussed in the section on Hospital Treatment are applicable here. Ambulatory treatment of the withdrawal syndrome should be accomplished within three weeks.

If the administration of methadone, including both stabilization and its gradual withdrawal, goes beyond three weeks, it is considered to be methadone maintenance.

Adequate and accurate patient records are essential. Each patient's clinical file should include results of complete medical history and physical examination plus notations of the rationale for the institution of ambulatory treatment of the withdrawal syndrome. These records should also document each visit to the office, clinical observations, and daily dose of methadone administered. Such treatment should be terminated immediately if additional supplies of morphine like drugs are being procured by the patient, or if the prearranged schedule of withdrawal is not being followed. Urine testing should be utilized to determine whether other narcotic drugs are being taken by the patient during the course of withdrawal treatment. If there is concomitant physical illness. hospitalization is almost always indicated in order to accomplish the withdrawal treatment properly.

There will be an exceptional situation (e.g. illness, travel) where circumstances will prevent the patient from making daily visits to the treating physician. In these instances, it is justifiable for the physician to dispense to the patient a few days' supply of liquid, non-injectable methadone, with specific written instructions concerning the withdrawal dose schedule to be followed during the intervening period. Wherever possible, the drug supply should be in the custody of a responsible third party. Specific notation should be made in the patient's record of the reasons for giving an ambulatory supply, plus the quantity of methadone dispensed.

In those cases of mixed drug dependence of morphine-type and barbituratealcohol type, ambulatory treatment of the withdrawal syndrome should not be attempted. Hospitalization is always required.

With ambulatory treatment, as with hospital treatment, the physician has the responsibility of arranging for the patient's aftercare following withdrawal. Repeated withdrawal at short intervals with methadone substitution constitute maintenance.

PREGNANCY AND THE WITHDRAWAL SYNDROME

A drug-dependent woman who is pregnant should undergo withdrawal treatment prior to delivery.

If there is insufficient time to accomplish withdrawal before delivery, the physician should maintain the woman on the required dose of methadone during confinement and delivery, and treat for withdrawal after delivery. The physician also should be alert for signs of drug dependence in the new-born, and treat the infant for withdrawal.

DEFINITIVE TREATMENT

Vital to the successful treatment of the drug dependent person is the relationship that develops between the physician and his patient. Winning the trust, confidence and respect of the patient constitutes the first task to be accomplished. Confidentiality is essential. Even implied threats of reporting to police officials, of cross-examining in search of source of drug supplies, or of alerting parents and family, except under extreme emergency conditions, may destroy the trust required for continuing therapy.

The physician must demonstrate an active interest in the patient and become allied with him in his struggles. The physician must identify and acknowledge positive aspects of the patient's personality and behavior, so that the patient does not look upon him as just another critical member of the "establishment." Drug dependent persons have been lectured to and scolded, often for years, by parents, spouses, friends, employers, probation officers; they are hypersensitive to criticism, which has come to signify rejection. Careful choice of words is required in establishing communication and in avoiding an implication of condescension or hostility.

The most critical therapeutic efforts begin when the patient has completed withdrawal and the intensive observation period, and is ready to leave the hospital or ambulatory program and return to his community. Continuing contact and help are essential at this point. If such help is not forthcoming, relapse to the use of drugs can be expected. An adequate aftercare program is vital to the patient. Supportive social, vocational, counseling and educational services should be provided as needed. Such services can help the patient adjust to a drug-abstinent status, learn new skills, find a job and utilize leisure time constructively. They can make it possible for him to improve his life style in other ways,as well as assist in resolving financial and family problems.

Physicians should play an important role in the mobilization of social and economic resources for aftercare on a community-wide basis and in providing supervision and follow-up treatment. It is, additionally, the physician's responsibility to his patient to assure that contact with such services is made. Another resource in many communities which the physician can utilize with some drug-dependent patients is the self-help group. Among the more well-known groups are Synanon, Narcotics Anonymous, Day Top Village, Gateway House, Odyssey House and Phoenix House. Such groups now function in most metropolitan areas, and the physician should familiarize himself with their programs. Evaluation of them will determine which, if any, may be suitable for each of his patients.

It is thus unrealistic to believe that the physician's role in the treatment of the drug-dependent patient ends when withdrawal from the drug has been completed, even if there are no general medical or surgical problems that would otherwise require outpatient follow-up care and treatment. In many respects, withdrawal is just the beginning.

Mr. ROGERS. What about new drugs to treat addiction? Is this promising?

Dr. SEEVERS. You mean as a substitute for methadone, or any kinds of new drugs?

Mr. ROGERS. Yes.

Dr. SEEVERS. Well, the most interesting research phase at the present time involves drugs which we call "antagonists" which act exactly opposite to methadone.

In other words, if a person takes an antagonist regularly, and if he were to take heroin he would get no effect. In other words, this acts to prevent the effects of heroin or any other narcotic.

We have some very excellent ones. The only trouble is, they lack the proper physical qualities to be long-acting. We have one drug known as naloxone which, if given to a person will completely prevent the effects of heroin for a matter of hours. There is considerable research being carried on at the present time to try to make a longacting derivative of this, so that taken once a day, or once every third day or something like this, we could have a complete blockade of the

action of any heroin, so if they took the drug they wouldn't get any effect. This is a most fruitful area of research.

Mr. ROGERS. Who is doing most of that?

Dr. SEEVERS. Part of this is being carried on under contract. Some of the pharmaceutical houses are working on this particular program. I think it should be expanded greatly.

Mr. ROGERS. So, it needs funding in this area?

Dr. SEEVERS. I think it needs funding very badly. It is probably technically possible to solve this problem in a relatively short time. You asked about a solution. If any solution is apparent at the present time where money could be used, this, in my opinion, offers the best

Mr. ROGERS. So you don't have the problem that you do with methadone.

Dr. SEEVERS. It is not addictive in its own right, and it completely prevents the effects of heroin or any other narcotic.

Now, I am sure that Dr. Jaffe has been involved in this program, and I am sure that one of the large areas in which he will see that money is spent is in development of this program technically.

Mr. ROGERS. Are you familiar with the drug perse, p-e-r-s-e, I believe it is spelled.

Dr. SEEVERS. Is that this antimony compound? This drug has not been tested properly, and I see no evidence to support that it is going to be of any value. The only thing that is claimed for it is that it prevents the individual from having withdrawal signs when you take the drug off. This is not really a problem. It doesn't prevent the continued use, which is our major problem.

Mr. ROGERS. Would you let us have something for the record on the drugs that AMA thinks may have merit?

Dr. SEEVERS. I will see that you get that.

Mr. ROGERS. And about the state of the art that it would appear that we are in now, and if you have a suggested funding level, I think it would be helpful for the committee to have that suggested level of funding.

(The following information was received for the record:)

DRUGS THAT HAVE MERIT IN COMBATING HEROIN ADDICTION

(1) Methadone

(2) Acetylmethadol

(3) Naloxone

(4) Nalorphine

(5) Levallorphan

(6) Cyclorphan

(7) Cyclazocine

(8) Pentazocine

(9) Derivatives of the above substances

Methadone prevents the response to heroin and stabilizes the individual. It helps the heroin dependent person to achieve social if not medical rehabilitation (see attached guidelines for proper medical practice with methadone). It can cause addiction. Acetylmethadol acts in the same fashion as methadone but it carries its effect for 2 to 3 days rather than the 1 day effect of methadone. It is currently undergoing trial to determine toxically effects on long term use. Naloxone can accomplish complete blocking of heroin action. It has no potential for physical dependence. It is short acting and high doses are needed frequently. It is also costly.

1

TREATMENT OF MORPHINE-TYPE DEPENDENCE BY WITHDRAWAL METHODS 1

GENERAL CONSIDERATIONS

This method of treatment of the patient with drug-dependence of the morphinetype sould have the combined goal of abstinence, resolution of general medical and psychiatric problems, and social rehabilitation. The initial step in this treatment procedure is withdrawal from the dependence-producing drug (detoxification). The physician also should seek consultation, or make referrals, when needed to obtain the psychiatric and other medical evaluation necessary for instiuting additional specific treatment measures. Furthermore, sociological studies and assessment by competent professionals will point to those living problems requiring continuing attention and help as part of the patient's social rehabilitation.

These various efforts are viewed as being parts of a single therapeutic continuum, individualized for the particular patient, and aimed at accomplishing the stated therapeutic goals. Mere withdrawal does not constitute complete treatment of the drug-dependent patient. It is the further responsibility of the treating physician to assure that his patient establishes an active working contact with an aftercare facility so that complete treatment of his drug dependence may be implemented.

Abrupt, untreated, complete withdrawal ("cold turkey") as routine "treatment" is inhumane, unnecessary and distinctly contraindicated, even the patient is in jail. When abstinence symptoms are not severe, withdrawal can be accomplished with little difficulty. In such instances, mild sedation or administration of tranquilizers, together with the kind and reassuring presence and attention of medical and other personnel, provide adequate support. Where substitutive therapy is indicated to treat the withdrawal syndrome in patients with any substantial degree of physical dependence, the drug of choice, at this time, is methadone.

Methadone is qualitatively similar to other morphine-like drugs, such as heroin and hydromorphone (Dilaudid), in most of its pharmacological actions, (e.g., analgesia, gastrointestinal and cardiovascular effects), tolerance and physical dependence development. It also has mutual cross-tolerance and cross-dependence with other morphine-like drugs. However, it differs significantly in its timecourse action. There is prolongation of action, with large oral doses especially, increasing the drug's oral effectiveness. Intravenous methadone, on the other hand, has a duration of action of only a few hours, like that of other morphine-like drugs.

The rationale for methadone therapy is that its substitution for the drug of dependence is pharmacologically complete, thus permitting the original drug to be eliminated from the body in a few days without the appearance of withdrawal symptoms or signs. Abrupt withdrawal of methadone after substitution reveals a relatively mild methadone abstinence syndrome.

DESCRIPTION OF THE WITHDRAWAL SYNDROME

The character and severity of the withdrawal symptoms that appear when a morphine-like drug is sudenly discontinued depend upon many factors, including the particular drug, the total daily dose used, the interval between doses, the duration of use, and the health and personality of the patient. There is a fairly direct correlation between the severity of withdrawal symptoms and the intensity of physical dependence. The general course of the syndrome and the severity of symptoms will also be affected by the psychological or symbolic meaning of withdrawal, coupled with the factors of anticipatory anxiety and stress tolerance of the individual patient.

It is helpful to view the total clinical picture of the withdrawal syndrome as made up of "purposive symptoms," (i.e., those which are goal-oriented, highly dependent on the observer and environment, and directed at getting more drug) and "non-purposive symptoms," (i.e., those which are not goal-oriented and relatively independent of the observer and of the patient's will and the environment.) The purposive phenomena, including complaints, pleas, demands, manipulations and symptom mimicking, are as varied as the psychodynamics, psychopa

This is an amplication by the AMA Council on Mental Health and Committee on Alcoholism and Drug Denendence of the section "Treatment of Morphine-Type Dependence by Withdrawal Methods" in "Narcotics and Medical Practice" (JAMA 218(4): 581-582 (Oct. 25, 1971).)