Multimodality Treatment of Narcotic Addiction: Pharmacologic Therapies

2015

Narcotic substitution

The single therapy that has had the greatest impact on narcotic addiction appears to be methadone maintenance. Unlike drug-free approaches, it is acceptable to a large number of addicts (). It is medically safe, has minimal side effects and no toxicity when given to tolerant individuals, even for long periods of time (). Though the results of methadone treatment vary among programs, there is strong evidence that it provides a way to control narcotic addiction. Most patients who remain in methadone treatment have a marked decrease in heroin use, an increase in employment rates, and demonstrate improved personal adjustment (). At present there are approximately 80,000 people being treated with methadone in the United States (), but despite methadone’s wide applicability and effectiveness, it leaves much to be desired. It has been controversial since the beginning, and many aspects of methadone programs have been criticized ().

One problem has been an inability to demonstrate that methadone treatment increases the long term cure rate for addiction. This is a disappointment, as many had hoped that the social rehabilitation obtained via methadone maintenance would lay the groundwork for successful detoxification. In retrospect, this disappointment is probably natural and has precedents in other areas of medicine where new treatments are accompained by hopes which are not realized.

A second problem is the inability of methadone programs to attract and retain more addicts in treatment. Early experiences led to hopes that the majority of addicts within a given area could be enrolled and retained in programs. This has not happened. Enrollment usually includes much less than 50 percent of the addicts in any immediate area, and dropout rates are usually high (). Program variables may account for many of these difficulties, and improvements in program quality may produce better results. A rapid evaluation and prompt initiation of treatment is one such quality that may increase program retention ().

Another problem with methadone is diversion. Unless programs require daily attendance, “take home” doses must be given. A portion of these are almost always diverted. This may result in accidental ingestion of methadone by children or other nontolerant individuals, or in the sale of legitimately-prescribed methadone to other drug abusers (). On the other hand, the inconvenience of the requirement for daily attendance may reduce the attractiveness of treatment. Unfortunately, this may be particularly true for patients who are working and showing other indications of progress.

A fourth problem is that methadone is highly addicting, and some patients have complained that it is harder to detoxify from than heroin. This observation probably relates to dosage level and not to the drug itself (). Most street heroin is of low purity, and thus physical dependence is low (). Because of these differences, many patients being treated with methadone may develop a greater degree of physical dependence while receiving methadone than they had prior to entering treatment. This may be necessary in order for some addicts to benefit from methadone treatment, particularly in cases where high levels of tolerance are desirable, but it should iead to caution in prescribing high dosages.

In spite of these problems, however, it is probably accurate to say that prior to the development of methadone maintenance there was no outpatient treatment that could demonstrate positive results for significant numbers of addicts. Methadone treatment, though far from perfect, seems to have added an important and positive element to the treatment of narcotic addiction.

The current development of methadyl acetate (LAAM), a derivative of methadone that prevents withdrawal symptoms for forty-eight to seventy-two hours, shows promise for correcting the diversion problem. Currently this drug is in a developmental phase, but it is undergoing widespread clinical trials. LAAM (levo-alpha-acetylmethadol) has effects that are similar to methadone and appears to have no serious toxicity when used properly. Its major advantage is that people taking it need come to clinic only three times per week. This is especially beneficial for patients who must travel long distances and for those who have irregular schedules or who work long hours. It is also desirable from a public health standpoint because its use almost eliminates the need for take-home bottles. Some think that it also tends to lessen dependency on the clinic and is a step toward becoming drug free (). Studies done to date show that results for those who remain on LAAM compare favorably with those on methadone (). However, levo-alpha-acetylmethadol may be less acceptable to addicts than methadone, as initial dropout rates are higher (). This is difficult to evaluate because it is a new drug, and anxiety or other psychological factors related to its newness and investigative status probably influence some patients to discontinue it. If LAAM meets the safety and efficacy standards of the U.S. Food and Drug Administration (FDA) and is approved for general use, all clinics could use it, and most programs then would be in a position to offer patients either LAAM treatment three times per week or daily methadone. This system could lead to a marked reduction in methadone diversion and would be much easier for patients than coming to clinic for daily methadone treatments.

Propoxyphene napsylate, a drug with weak narcotic effects, has been tried with an eye to developing a maintenance drug that will produce less physical dependence than methadone. Propoxyphene can suppress abstinence symptoms in patients who have low degrees of physical dependence, and open clinical trials have shown that some addicts can be maintained on it (). However, double blind studies comparing low doses of methadone (maximum 36mg/day) with high doses of propoxyphene (maximum 1200 mg/day in divided doses) have shown that propoxyphene is not as well accepted as methadone. Preliminary data from these studies show that dropout rates and frequency of street drug use are considerably higher in patients maintained on propoxyphene. It seems that propoxyphene, therefore, is not as effective as metha-done for maintenance treatment (). Since a few patients do well on propoxyphene it might be useful as an alternative to methadone for selected patients who have low levels of physical dependence, who do not fulfill FDA requirements, or who want maintenance but are opposed to taking methadone. Detoxification from propoxyphene produces less discomfort than detoxification from methadone and therefore it may be useful as a transitional drug that can bridge the gap between a low dose of methadone and abstinence. At the present time, however, propoxyphene does not have FDA approval for the treatment of opiate addiction.

Detoxification

Detoxification has never resulted in very much social rehabilitation or long-term abstinence (), as patients usually relapse within the first two months after release from a detoxification program, sometimes even on the day of discharge. Many patients leave against medical advice before detoxification is finished (). Most patients in a three-week outpatient program relapse to illicit drug use before they stop receiving methadone. Behavior problems are common during detoxification, and patients can become very disruptive, with adverse effects on other patients and staff. Several investigators have found recently that more addicts complete detoxification with fewer behavior problems if they are permitted to alter their own dose within limits set by the treatment team (). This method should increase the short-term success of detoxification. Its long-term results may be improved by following it with narcotic antagonist treatment.

Narcotic antagonists

Antagonists have been used for many years to treat narcotic overdoses. Nalorphine was the first in clinical use, but it was used only with caution as it had agonistic as well as antagonistic effects. It was replaced by naloxone, an excellent antagonist with essentially no agonistic effects. Neither of these drugs is useful for the treatment of addiction per se, as they are short-acting and ineffective when given orally unless used in very high doses (). However, two antagonists, cyclazocine and naltrexone, have been developed recently for use in outpatient treatment programs. Both appear to be safe and effective when administered to detoxified addicts (). They are given orally and completely block or markedly attenuate the effects of narcotics for twenty-four to seventy-two hours (). Naltrexone is the superior drug, as it appears to have no agonistic effects other than occasional gastric irritation, and it is considerably longer acting (up to 72 hours). These drugs can be used as “insurance” against relapse, and they are effective in well-motivated patients. On the basis of favorable experience with antagonists in selected patients, some treatment programs are recommending that they be used for two to six months following detoxification.

Though antagonists are effective pharmacologically, their clinical usefulness for the majority of patients is uncertain. Most addicts are not interested in taking them, and most of those who start drop out within the first month (). Naltrexone produces no euphoria or physiological dependence, so it does not have an immediate reward, nor does it motivate patients to continue in order to prevent withdrawal symptoms as methadone does. Depot forms lasting 2 to 4 weeks are being developed, and they may result in more compliance with antagonist treatment. Some programs are experimenting with behavioral reinforcers that may encourage patients to stay in antagonist treatment longer.

Pharmacologic Treatments for Concurrent Psychiatric Problems.

Another area of current interest is the treatment of psychiatric problems that often accompany addiction. Some believe that psychiatric problems are a prerequisite for the development of addiction (). Others feel that narcotic addicts have minimal inherent psychopathology and that much of the psychopathology noted is a consequence rather than a cause of addiction (). Wherever the truth may lie, many studies and clinical observations indicate that addicts have an assortment of psychiatric disorders (). The degree of psychopathology is probably related to the addict’s cultural background. Those individuals who come from an environment where there are great social pressures against drug abuse are more likely to have serious psychiatric problems than are those coming from a background in which drug abuse is viewed less negatively ().

One common problem is depression (). There is considerable evidence that addicts have a higher incidence of depression than nonaddict peers. The depression, when present, is probably greatest at admission (), but it remains high even after stabilization on methadone. Some studies have shown that 20 to 40 percent of patients on methadone maintenance are depressed (). The depression is typically mild to moderate, and not the severe, psychomotor-retarded and delusional type seen on inpatient psychiatric units. If untreated, it may contribute to the severity of the addiction, since self-medication for depression (or other psychiatric problems) may be a reason that addicts relapse or continue to use drugs while being treated with methadone (). Effective antidepressant treatment may improve outcome, and two pilot studies have shown that depressed, methadone-treated addicts will respond to tricyclic antidepressants (). In one double blind study comparing doxepin with placebo, patients treated with methadone and doxepin had less anxiety, less depression, reported less drug craving and less amphetamine use than patients treated with methadone and placebo ().

Many addicts have significant anxiety and may request tranquilizers, especially diazepam and sedative hypnotics. Though these drugs are effective in reducing anxiety, there is considerable risk that they will be abused. Addicts not infrequently take 30-80 mg of diazepam in one dose and say that it creates a peaceful, euphoric sensation which they describe as a “high.” Continuous use of high doses of these drugs can produce physiological dependence; we have observed several instances of this, including three patients who had grand mal seizures after high dose diazepam was abruptly stopped (). Because of its frequent abuse by patients in drug treatment programs, diazepam should be prescribed with great caution. It is probably more appropriate to prescribe small amounts of oxazepam, chlordiazepoxide, doxepin, phenothiazines, or haloperidol for patients who request medication for anxiety. At least one of these usually works, and none has been noted to be abused by addicit patients to any significant degree.

Neuroleptics are useful for addicts with psychosis or borderline personality disorders. Psychoses probably are seen more commonly in patients who come from high socioeconomic groups (). Patients with these problems can be very disruptive to their families, employers, and the treatment program when they are overtly psychotic or when expressing intense affects such as anger or acute depression with suicidal behavior. Often, they can be treated by combining neuroleptics with methadone. Brief hospitalization may be necessary. We have been impressed by the ability of low doses of haloperidol to attentuate the intense outbursts of anger or aggression seen in paranoid schizophrenics and borderlines. It has been noted by clinicians for a long time that methadone aione appears to have some antipsychotic action (), but this is enhanced by adding haloperidol.

Another area of interest is the treatment of alcoholic narcotic addicts. Alcoholism has been reported in 20 to 80 percent of narcotic addicts (), and is a problem among patients on methadone maintenance. Some workers feel that methadone treatment increases the severity of alcoholism (). However, a recent study has shown that methadone neither increases nor decreases its severity (). Some pilot work has shown that disulfiram (Antabuse) can be used safely with methadone and may improve treatment outcome (). At present the Veterans Administration has started a collaborative project to study the effectiveness of disulfiram when used as an adjunct to methadone in the treatment of addicts who are also alcoholic.

Therapeutic Community

Some of the most intensive efforts to treat addiction have been made by therapeutic communities. These are iong term residential programs, some lasting for more than two years. They rely heavily on group therapy and use intense confrontation techniques. Selectivity in referral is essential in order to screen out those patients who cannot tolerate the anxiety that is generated. Studies have shown high rates of rehabilitation in patients who complete treatment in therapeutic communities (). Recent work has demonstrated that positive changes occur in patients who complete even a portion of the entire program and that those patients who stay longest tend to improve the most (). However, all studies of therapeutic communities are difficult to interpret because there are self-selection factors operating in those who enter and those who graduate. Controlled studies are needed to differentiate what part of outcome is due to treatment and what is due to patient factors. The practical and ethical problems inherent, in random assignment of patients to a therapeutic community or a methadone program make controlled studies of therapeutic communities difficult. They are four to five times more expensive per patient-year than methadone programs, and consequently their cost-effectiveness relative to methadone programs is an area that must be considered.

Outpatient, Psychotherapies Used With Methadone Maintenance

There is growing interest in studying the effect of outpatient psychotherapy when combined with methadone maintenance. Some feel that psychotherapy is one aspect of treatment which, if improved, wouid lead to better results (). Family therapy as an approach has been studied, and some preliminary results show that it can have a positive effect. In a controlled study completed recently in Philadelphia, a group receiving structural family therapy plus methadone did significantly better than control groups receiving only methadone and routine counselling. The family therapy patients detoxified more frequently and successfully and had higher rates of employment than controls (). At this time no other controlled studies of family therapy in addiction have been done, and more work in this area seems indicated.

Individual psychotherapy is another area to be explored. Traditional psychiatric and psychoanalytic teaching has indicated that analytically oriented psychotherapy is not appropriate for addicts (). However, clinicans with experience working in maintenance programs have expressed the belief that analytic psychotherapy or a modification of it may be helpful if used in addition to methadone. It is not clear what type of therapy is most applicable, but participants in a recent NIDA conference suggested that it should combine support, structure and self-expression (). No controlled studies on the effectiveness of psychotherapy have been done at this time, and positive results from psychotherapy studies could have a major impact on the organization and staffing patterns of methadone treatment programs.

 

Selections from the book: “The International Challenge of Drug Abuse”. Robert C. Petersen, Ph.D., editor. A monograph based on papers presented at the World Psychiatric Association 1977 meeting in Honolulu. Emphasis is on emerging patterns of drug use, international aspects of research, and therapeutic issues of particular interest worldwide. National Institute on Drug Abuse Research Monograph 19, 1978.