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Annals New York Academy of Sciences, 1982. V.398 pp 44-53

METHADONE AND OPIATE DRUGS: PSYCHOTROPIC EFFECT AND SELF-MEDICATION

Gerald J. McKenna

Department of Psychiatry
Veterans Administration Medical Center, Brentwood
Los Angeles, California 90073

Department of Psychiatry
University of California, Los Angeles School of Medicine
Los Angeles, California 90024

The concept of drug use as self-medication has been extant for many years but has received considerably more attention in the last decade. This, of course, coincides with the influx of large numbers of mental health professionals into the drug dependence field and renewed efforts to explain the phenomena of drug use and to better understand the complex nature of drug dependence. Attempts have been made to provide a unifying theory of drug dependence, and individual investigator have approached the problem from one or another theoretical viewpoint, each providing a partial explanation for drug dependence.

Wikler in his 1953 paper, "Psychiatric Aspects of Drug Addiction,"1 discussed a multi-etiological basis of "drug addiction" and three formulations of the psychiatric aspects of drug addiction. He notes several different groups using narcotic drugs for differing reasons: "neurotic individuals" seeking relief from anxiety; "psychopaths" seeking a state of elation; "normal individuals" seeking relief from physical pain; and "psychotic individuals" seeking relief from depressive feelings. Since this paper is particularly concerned with this latter group, who seem to use narcotic drugs (in this case, methadone) in the self-treatment of various psychotic symptoms, it will be useful to review some of the relevant literature prior to and subsequent to our initial observations in 1973. Many of the earlier clinical observations on the antipsychotic actions of morphine and methadone have later been more firmly founded in pharmacologic theory with the discovery and investigation of the actions of endorphins. This will be briefly discussed later in this paper and is being more thoroughly discussed in other presentations at this conference.

In a 1971 paper, "The Psychotic Heroin Addict,"2 Wellisch et al. cite Nyswander’s writing3 that opiates had been used in Europe to treat manic depressive psychosis and melancholia prior to the introduction of neuroleptic drugs. Other have provided anecdotal reports3 of similarly using morphine to attempt symptomatic control of severe psychotic symptoms in an age when the psychopharmacologic armamentarium of psychiatry contained only a few drugs, including opiates, barbiturates, and other sedatives such as chloral hydrate. These drugs were used to initially calm very disturbed patients but were not used in an ongoing manner to control psychotic symptoms.

Wellisch et al.2 report that in treating over 1500 patients in their drug detoxification section: "among these patients have been numerous individuals who were using heroin for its tranquillising and ‘antipsychotic’ properties." They cite Chein’s finding5 of 22 out of 52 addicts studied were psychotic or borderline psychotic. They also report on several patients who effectively used heroin as self-medication for psychotic symptoms. They describe a pattern "of many cases in which overtly psychotic individuals remained ambulatory and functional on self-maintained dosages of heroin, only to have their psychoses become overt during of shortly after withdrawal." At the end of their paper they state, "it is our clinical opinion that methadone possesses little, if any, antipsychotic effect, unlike morphine or heroin." It has been our observation, as will be discussed later, that methadone does possess powerful antipsychotic effects.

Other authors in the early ‘70s described the action of methadone and other narcotics on certain affective states. Both Wurmser6 and Khantzian7 reported the calming effects that methadone appeared to exert on rage and aggression in patients on methadone maintenance.

In 1978 Verebey et al.8 reviewed the work on the existence and possible functioning of endorphins in the brain. Linking these with the pharmacologic properties of opioid drugs, they suggested possible uses of these drugs in treating mental illness. They suggest using methadone as the primary pharmacologic agent in treating selected schizophrenics and others with a psychotic disorder who cannot be treated with the usual neuroleptics because of severe side effects or certain medical conditions. We will return to this important paper and concept later in the discussion since it does appear to have clinical relevance despite some obvious drawbacks.

Also in 1978, Berken et al.9 describe a woman who had been unresponsive to a variety of treatments, including ECT, neuroleptics, antidepressants, minor tranquillizers, and psychotherapy. When all treatment attempts seemed to have failed she was induced onto methadone maintenance. This treatment better controlled her "rage" than other treatments. They also note the calming effects of methadone on other patients "with a history of rage, current aggressive rage, or repressed rage who joined the program…."

There are a number of other articles in the literature describing various psychopathological disorders in patients on methadone maintenance.10-20 These articles illustrate the complexities of patients on methadone maintenance and the various mental disorders that either precede or accompany drug dependence in these individuals

Case Examples

In three separate methadone maintenance programs we have observed patients who had first used opioid drugs, primarily heroin, to self-treat pre-psychotic and psychotic symptoms. When they were later on methadone maintenance, this drug served a similar purpose. Several case examples are presented here from a 1973 study conducted to the Boston City Hospital Drug Treatment Program. They will illustrate both the Mental Disorders and the Personality Disorders that often are present simultaneously in such patients.

Method. The three patients were followed clinically for 2 years to 5 years in the Drug Treatment Program and inpatient psychiatric unit of Boston City Hospital. Their charts were extensively reviewed, the staff having contact with them over the years were interviewed, and the patients themselves were extensively interviewed by this author. Concurrence of diagnostic impressions was obtained by independent reviews and interviews by at least two other psychiatrists using the DSM-II diagnostic criteria in use then. We shall later retrospectively review these patients using DSM-III criteria.

Case 1

Al was a 30-year-old divorced man born of Eastern European parentage in a Boston industrial suburb. His father was a heavy drinker and often frequent fights between his parents and remembers being terrified of his father’s outbursts of temper. He felt intimidated by his father and avoided him whenever possible. His first few years of school appeared satisfactory and he formed friendships without difficulty. As he progressed in grade school, though, he experienced a significant change in his peer relationships. He felt scapegoated and ineffective in dealing with the "class leaders." He became increasingly defensive yet continued trying to please his adversaries and maintain a relationship with them. When he transferred to high school, he associated with children of ethnically different backgrounds, which met with parental disapproval. He again found himself feeling inferior and involved in relationships similar to those he had experienced in grammar school. Shortly thereafter he began associating exclusively with black students.

In retrospect he feels that he was identifying with those looked down upon by peers of his own ethnic background. Temporarily he felt better about himself, began dating black girls, but was finally jilted by one black girlfriend with a subsequent plunge in his self-esteem. Having failed at all his attempts to form meaningful relationships within any group, he now became fascinated with the idea of becoming a "dope fiend." He read extensively about drug addiction, told peers he was addicted and even marked his arms with pinpricks to validate his charade.

He first used heroin in 1955 after joining the Air Force; he experienced a euphoria he had not previously known, felt good about himself for the first time in his memory and thereafter sought narcotics on weekend passes. During the next ten years he became progressively more involved with narcotics (mainly paregoric and dilaudid), had frequent arrests and hospitalisations, but continued drug-seeking behaviour when not in confinement. He experienced periods of euphoria alternating with depression when not using narcotics, but had no definite psychotic episodes. He began methadone maintenance in 1968 and in July 1970 made his first attempt at detoxification. It was noted during the hospitalisation that he experienced mood swings varying from elation with flight of ideas, to profound depression. He completed detoxification and was discharged in September 1970/ He began using heroin almost immediately and subsequently reentered the methadone maintenance program. From 1970 until 1972 he remained on methadone maintenance and seemed stable during that time.

In February 1972 he was hospitalised for detoxification from 150 mg of methadone. He was detoxified over the next three weeks. When his methadone dose had been decreased to 30 mg, he noted the onset of feelings of elation. These progressed through stages of increased energy, loquaciousness, flight of ideas, and finally the paranoid delusion that he was a prophet sent to save the world, and he felt endowed with extraordinary powers. His psychosis exacerbated following total withdrawal from methadone and he was transferred to the general psychiatry unit and started on thorazine, which was increased to 1600mg per day. He remained on this dose for 1 months and hypomania decreased somewhat. His flight of ideas and delusions of grandeur continued, although abated. It was decided that his past history and present symptomatology represented a manic-depressive psychosis and he began treatment with lithium carbonate. Lithium successful interrupted his hypomania but he felt increasingly depressed, spontaneously stopped taking lithium after two months and entered a deep depression. Al describes this period as the worst in his life. He suffered assaults of suicidal ideas and felt that some uncontrollable force inside of him was driving him to suicide. There were times when he felt a similar urge to homicide. Panicked by his depression and preoccupation with death he sought relief by taking street thorazine, heroin, and large amounts of alcohol. For a period of two months he was lost to follow-up but returned to the unit in July and was reinduced to 110mg methadone maintenance and 150mg amitryptyline daily with a gradual decrease in depressive symptoms and subsequently discontinued the amitryptyline but remained on methadone.

In late 1972 Al was slowly detoxified from methadone at his request and begun on lithium carbonate 1800mg per day. He did well for the next 8 months and was able to remain free of other drug use. He later left the region with the plan to continue on lithium.

Case 2

John is a 33-year-old divorced white male born in a working class town near Boston. He had a mild physical deformity at birth which limited his later ability to compete with his peers in athletics or other strenuous exercise. His father, a physical fitness and athletic buff, rejected John because of his lack of physical ability. John recalls a "miserable" early life, felt he was the weakest in any group, and was scapegoated in early childhood and during hes school years. He was given nicknames such as "dumbo" and "buck teeth," and chronically felt humiliated in peer interactions.

His parents divorced when John was five years old; he lived with his mother after that and has had little contact with his father since. He describes his mother as "naive," having Old World ideas, and restricting his physical activities. Neither parent had a drug or alcohol problem.

John did well scholastically in grammar school but was always unpopular. He avoided close relationships and says, "If I got close to someone, I’d end up getting stabbed in the back."

By the eighth grade he "changed tactics" and turned to crime. He says, "I felt I couldn’t get anywhere with my classmates so I took to breaking and entering; I was getting recognition for getting into trouble."

In high school he was absent from classes most of the time, was arrested in 1954 and sent to a juvenile reformatory. Following his release one year later he entered a local trade school and did well scholastically. Nevertheless he remembers feeling chronically anxious and agitated and says, "I just couldn’t sit still." These feelings progressed, reaching a peak in late high school. He began drinking heavily and using marijuana but felt these drugs did nothing for him. In 1958 he first tried morphine and stated later that "it calmed me down, everything looked beautiful, and I had a new energy." He relates that the morphine changed his relationship with people, allowing him to be now talkative and able to share his feelings.

From 1958 to 1964 he continued a life of searching for opiates. When he was not using the drugs he had a recurrence of previous feelings of anxiety and depression. He began using street methadone in 1964, felt more controlled with this drug than with other opiates, and stopped using morphine and heroin. He was married in 1964, but divorced in 1966. The relationship was functioning as long as he continued methadone, but when he began self-detoxifying, the relationship began to disintegrate. He attempted self-treatment with barbiturates, tranquillizers, and amphetamines, but could not control his feelings of depression. When his wife left him, John returned to using street methadone, supplementing his dose with Valium. His depression cleared, but as he raised his daily dose of methadone beyond 150mg per day he experienced feelings of uncontrollable anger and paranoia. He sought psychiatric treatment, was detoxified rapidly on a psychiatric ward, experienced an initial withdrawal reaction, and then entered a progressive depression. Three weeks after detoxification he attempted suicide by hanging himself from a rafter in his room.

For the next five years John was in the methadone maintenance program with three inpatient hospitalizations for detoxification at his request. He was never able to become methadone-free without experiencing symptoms of anxiety and severe depression. He was finally placed on a combination of methadone and amitryptline, and Valium, which appeared to stabilize him fairly well.

It should be pointed out that at various times it was suggested to John that he be treated with tranquillizers and antidepressants alone, but he refused. He felt that he has tried various combinations of tranquillizers on his own but feels the need to continue using opiates, and whenever he is not in a formal drug treatment program he returns to opiate use with the attendant problems of procuring drugs on the street.

Case 3

Simon was born in Boston in 1946. His parents divorced when he was an infant and he spent the first two years of his life in an orphanage.

He was placed in his grandparents’ home at age two, and had a distant relationship with them. He recalls being embarrassed by his grandmother in front of his friends because he was enuretic. His grandparents kept his mother’s identity secret; though she lived nearby and frequently visited, Simon was told that she was his older sister.

He did well in grammar school, appeared to socialize normally until the fourth grade when the family moved to avoid contact between Simon and his mother. He began a difficult period of adjustment at school, had frequent fights and missed his mother, the person with whom he had the closest relationship. When he was in the sixth grade, his mother found out his whereabouts and there ensued a struggle for the next several years between the mother and grandparents over custody of the child. He discovered his mother’s identity at age 13 and went to live with her. His mother and stepfather drank heavily; following a fight between Simon and his stepfather, he was forced to return to his grandparents. For the next year he was constantly in trouble, engaging in car theft, breaking and entering, and drinking heavily. He was sent on court order to live on a farm in Maine and remained there for two years, described as the best in his life. He returned to live with his grandparents for some unclear reason, but was unhappy and soon returned to criminal activity. He attended three different high schools while back in Boston, was expelled from each, and labelled as a troublemaker.

At age 15 he was introduced to drugs by an addict he met while in a juvenile detention centre. Upon his release from the centre he obtained dilaudid from a physician and intravenously used an opiate for the first time. He says, "I really liked the way it made me feel, there wasn’t a problem in the world; it supplemented all the love I had missed."

He continued to use, supporting his habit by breaking and entering, robbing drug stores, stealing prescriptions, writing bad cheques, and using stolen credit cards. From 1960 to 1968 his life was dominated by drug seeking, frequent arrests and jail sentences, a disastrous stint in the Marine Corps, and an equally disastrous marriage to avoid a jail sentence. In 1968 he began methadone maintenance in Boston and was injecting up to 300mg of take-home and street methadone tablets each day.

In 1970 he was first admitted to the general psychiatry service for detoxification. He remained on the ward for five months and describes the experience as "the worst detoxification ever." He was detoxified over a six-week period and shortly thereafter underwent a psychotic decompensation. He experienced auditory hallucinations and paranoid delusions. He was treated with stelazine, artane and psychotherapy, with symptomatic improvement. He was discharged on stelazine but was lost to follow-up. According to Simon he stopped the phenothiazines after six weeks. His psychosis returned and he began using methadone. In 1971 he again began methadone maintenance treatment. In the succeeding two years Simon make one more attempt at detoxification and again developed symptoms of a paranoid psychosis which lasted for seven months. He was then reinduced onto 60mg per day of methadone with subsequent clearing of his psychotic symptoms.

These three patients each meet the DSM-III diagnostic criteria for an Axis I diagnosis of Substance Use Disorder, Opioid Dependence, and the latter two cases meet the criteria for the Axis II diagnosis of Antisocial Personality. The fist case meets some of the criteria for Antisocial Personality and could be given the Axis II designation Antisocial Traits. In addition and central to our theme, case 1 meets the criteria for Bipolar Disorder, Mixed; case 2, the criteria for Major Depression, Recurrent; and case 3, the criteria for Schizophrenic Disorder, Paranoid Type.

Reviewing these histories reveals some interesting phenomena. Each patient actively searched for a drug that would relieve dysphoric symptoms and found that opioid drugs accomplished this better than other classes of drugs. Interestingly, none of these patients spoke of using drugs in order to achieve a euphoric state. Their use of opiates was intended to help them lead quasi-normal lives. In each case, methadone had a definite psychotropic effect. The methadone was more effective in relieving the symptoms of Bipolar Disorder and Schizophrenic Disorder than in relieving the symptoms of the Major Depression. This is consistent with the reports of the high incidence of depression among patients on methadone alone.10,11 In fact, the second case presented had more relief of depressive symptoms than would be expected by eventually necessitated tricyclic treatment along with methadone.

In the Cambridge Hospital Drug Treatment Program we conducted retrospective and concurrent chart reviews for patients on the program beginning July 1971 and ending September 1974. Patients with histories and/or diagnoses of a psychotic disorder were reviewed in detail. Staff familiar with the patients were interviewed and, when possible, patients were interviewed. With the exception of one month, there was always at least one patient with a psychotic diagnosis in the methadone maintenance program, and at most times approximately 10% of the patients had a history of non-drug-related psychosis. The two most common diagnoses were Schizophrenic Disorder and Borderline Personality Disorder with psychotic decompensation.

We are currently reviewing patients on methadone maintenance in the Drug Treatment Program of the Veterans Administration Medical Center Brentwood. Preliminary findings again point to a small but consistent percentage of patients with histories of psychotic disorder. Though we do not yet know, we anticipate finding that some of these used opiates as self-medication for their psychotic disorders.

Discussion

Clinical evidence has been presented supporting the concept that opioid drugs are used by some individuals to self-treat dysphoric psychological symptoms. Evidence shows that methadone appears to reduce symptoms usually associated with psychotic disorders. A 1980 report by Judd et al. dismisses this notion. They report on six patients, five of whom were not receiving neuroleptics, who were administered 10 mg intramuscular methadone or placebo. Described results include negative schizophrenic symptomatology, such as emotional withdrawal, motor retardation, and blunted affect. They conclude that "methadone HCl does not exert a specific antipsychotic effect in schizophrenic patients but instead accentuates emotional withdrawal and decreases motor activity. These results may well be due to the single-dose design which does not replicate the homeostatic effect of longer term methadone or neuroleptic treatment.

While the early observations of the psychotropic effects of methadone and other opioid drugs were clinical, there appears to be mounting theoretical evidence to give further credence to the clinical observations and clinical theory. Most of the theoretical advances have occurred because of the intensive work that has been done since the discovery of the endorphins. The existence of these endogenous opioid peptides has opened the horizons of new research in the biochemical basis of schizophrenic disorders and should ultimately impact significantly on our understanding of the mechanisms involved in opioid drug dependence.

In 1977 and 1978 Gold et al.22, 23 reported on the dopamine-blocking action of methadone as evidenced by the increase in serum prolactin following administration of methadone. They point out that neuroleptic agents such as haloperidol inhibit the enzyme dopamine-stimulated adenylate cyclase. Methadone and other opioid drugs apparently do the same. They postulate that for this reason "opiate agonists may be antipsychotic in man." Kleber and Gold in 1978 documented well the various uses of psychotropic drugs in the treatment of narcotics addicts on methadone maintenance. The administered lithium carbonate to a group of patients on methadone maintenance with a history of recurrent depression but no history of manic or hypomanic episodes. The allowed the patients to decrease their methadone dose while on the lithium trial and found that the methadone dose decreased significantly (p0.01) during the trial. They provide support for the hypothesis that methadone is antipsychotic and antimanic and suggest an endorphin hypothesis for the mechanism of action of lithium. They also document the use of neuroleptics in schizophrenic patients maintained on methadone as a result of their opiate dependence. The state, "With the recent developments in opiate receptor and peptide identification reexamined clinical data suggest that opiate receptor activity and opiates may be psychotomimetic and antipsychotic respectively." The antipsychotic properties of methadone are hypothesized on the basis of opiate agonist receptor activity, i.e., interference with the postsynaptic action of dopamine, the mechanisms espoused for the antipsychotic actions of traditional neuroleptic drugs.

In 1978 Verebey et al. suggested the therapeutic uses of opioid drugs in the treatment of certain mental disorders. They advocated the use of methadone particularly in the treatment of selected schizophrenic patients, while cognizant of the disparate results of various researcher in determining the role of the endorphins in the etiology of schizophrenia, a controversy that still exists. They suggested candidates for treatment with methadone, including patients with schizophrenic disorders who have been unresponsive to treatment with traditional neuroleptics, those with especially aggressive behaviour unresponsive to neuroleptics, and those with early tardive dyskinesia who cannot discontinue neuroleptic treatment without serious psychotic deterioration. We echo those recommendations today and support their trial recommendations. The most serious argument against such use relates to the political polarisation surrounding methadone and the introduction of an addicting drug in the the treatment of nonaddicted schizophrenic patients.

In addressing both the arguments for and against using methadone or l-acetylmethadol in the treatment of certain "treatment resistant" patients with schizophrenic or bipolar disorders, there are a number of considerations. First, there are a number of patients at every centre who do not respond to any dose of neuroleptic drug. These patients daily continue to suffer from the symptoms of the disorder, without apparent hope of relief. Treatment with opioid agonists might result in symptomatic relief and the possibility of a more normal existence. They would become dependent on the opioid drug, but that might well be preferable to experiencing unabated psychotic symptoms with their attendant dysfunction. There again, the personality traits so often associated with drug-dependent individuals may not develop since the associated behaviours have no need to exist. The experience with large numbers of opiate-dependent servicemen returning from Viet Nam has certainly destroyed the myth that opioid dependence is necessarily connected with further opioid dependence or related behavioural characteristics.

The argument that opioid drugs have antipsychotic properties but do not produce the disabling complications of tardive dyskinesia has been questioned. In a 1980 article by Wasserman and Yahr,25 choreic movements in a patient on methadone maintenance were reported. They logically conclude that if methadone blocks the postsynaptic dopamine receptor in a manner similar to the neuroleptics, there may develop supersensitivity of the striatal dopamine receptor resulting in the subsequent development of choreic and, presumably, other pseudo-parkinson symptoms in patients on methadone maintenance. This possibility must be carefully examined. The authors correctly point out that it took many years of continuous use of neuroleptics before the serious complication of tardive dyskinesia was discovered and that the same phenomenon may be true of methadone treatment. This prospect should not, however, preclude the use of opioid drugs on a trial basis for the treatment of neuroleptic-resistant patients with schizophrenic disorders. It may also be feasible and desirable to use opioid drugs in the treatment of certain depressive disorders, as described by Kleber,24 or in the treatment of certain patients with Bipolar Disorder who have developed nephropathy or other serous complications of lithium carbonate treatment.

Conclusion

Evidence has been presented to support the hypothesis that some opiate dependent individuals use opioid drugs to self-treat prepsychotic and psychotic symptoms. These symptoms were later alleviated by methadone maintenance treatment. Tis has been observed in three methadone maintenance programs with which we have been involved and has been reported anecdotally by many other professionals involved in methadone maintenance programs. The theoretical basis of these clinical observations has been discussed. The conclusion that methadone does act as a psychotropic drug is presented and recommendations that methadone or longer acting opiate agonists be used on a trial basis in the treatment of certain patients with psychotic disorders is made.

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