Alcohol dependence: disulfiram implants In 1949 the Donwood Institute in Toronto first undertook clinical trials of disulfiram (Antabuse) and began to explore a rationale for the integration of this drug into a multiphasic plan for the treatment of alcoholism. During the first few years the rationale for using disulfiram remained uncertain until a clinical role was identified that has remained relatively unchanged for more than 2 decades. My opinions concerning disulfiram implants are based on impressions gained from the oral administration of the drug to over 5000 patients. From the patient's standpoint the term "protective drug" is most appropriate. Caught in a progressively powerful dependence on alcohol in spite of an awareness of increasingly undesirable or dangerous consequences, the enlightened victim begins to appreciate that the greatest threat to his well-being is the dependence itself. The uncontrolled drinker may acquire this insight through the hard way of experience, or be fortunate enough to acquire it earlier by clinical instruction. In either case, recovery requires that the dependence be recognized and respected. It is important for patients and their associates to appreciate that the physical aspects of total dependence on alcohol, and on most other drugs, can be interrupted quickly and usually inactivated within a few days. To interrupt, reduce and inactivate psychologic dependence is quite another matter. Initiated as a reaction to personal and social situations, a dependence on alcohol in harmful quantities is reinforced and expanded as a coping mechanism by habituation. As the victim begins to be aware of alcohol-related problems, habitual dependence is soon reinforced by habitual defence of dependence. When eventually a break in tolerance for alcohol heralds the beginning of a general breakdown, depend-
ence on alcohol as a coping mechanism tective drug" could be visualized. accelerates in proportion to the decline Disulfiram can provide a chemical in stress tolerance. This helpless phase barrier between the habitual thought of uncontrolled dependence may ter- and the habitual act of drinking until minate in premature death from related this habitual process can decline illness, injury or suicide; in total sur- through lack of reinforcement. Clinical render to dependence with no further experience strongly indicates that the attempt to maintain family, occupa- process of decline and inactivation of tional or community status; or in an psychologic dependence on alcohol, appeal for help, so well expressed in initially taken in response to personal the first step of the Alcoholics Anon- desire or social custom, could continue ymous (AA) program. Defence of de- for 1 to 2 years or longer. pendence and resistance to treatment In 1935 AA first conclusively demmay be further augmented by a com- onstrated that some uncontrolled drinkplex of fears - of withdrawal, ab- ers could interrupt and inactivate their stinence, physicians, treatment, incar- dependence on alcohol. This was acceration, stigma and social rejection, complished within a special community among others. When to all of this is of their peers by adherence to the added the cumulative, deleterious ef- spiritual guidelines that determined fect on cognitive function of chronic their activities, goals and relationships. or recurrent intoxication with general Until that time the universal prejudice depression and associated malnutrition, and ignorance concerning the predicathe frightening experience of being ment of the uncontrolled drinker locked into an uncontrolled dependence sustained an attitude of pessimism and on alcohol becomes more understand- disinterest on the part of the clinical able. professions, and a rejecting, punitive My clinical respect for this power attitude by the community generally. of dependence grew with awareness of However, many who came in contact the complex of factors involved. Thirty with AA failed to become effectively years ago most patients reached, or involved with its program. came close to, the phase of surrender. In the early 1950s an industrial phyMandatory referrals designed to inter- sician in Michigan, Dr. Jack Jellema, rupt the progression of dependence who took a special interest in emwhile the defensive alibi systems were ployees with an alcohol problem, bestill intact were restricted to the occa- came especially concerned with those sional court order. However, it became who were not responding to his first apparent that the long-range objectives recommendation - involvement in the of treatment were the same in any fellowship of AA. In a personal comcase: to interrupt and inactivate psy- munication in 1956 he reported "I chologic dependence upon alcohol as decided to put them all on Antabuse, a coping mechanism, to achieve optimal and for the first time they were able repair of related problems - physical, to stay sober long enough to find out psychologic and social - and to ini- what AA was all about." The same tiate and support a program to im- could be said for many other forms prove health in all areas as the basis of therapy for the clinical management of a new, rewarding lifestyle with new, of dependence and its related problems. Although many patients have recoveffective coping mechanisms. With these therapeutic objectives in mind a ered from dependence on alcohol withspecific role for disulfiram as a "pro- out the help of protective drugs, the CMA JOURNAL/JUNE 18, 1977/VOL. 116 1333
special hazards of the first year, and particularly of the first 3 months, provide clinical justification for medical, psychologic and social support. Since new coping techniques are not firmly rooted in new habit patterns during the first 1 to 2 years, they must be maintained by conscious effort. After the patient has been introduced to one of the protective drugs and advised to accept all possible support throughout the hazardous transition period, the major responsibility for taking advantage of any or all support is transferred to the patient and his or her associates. This includes the decision about whether to continue taking disulfiram and for how long. A different orientation is required of patients whose dependence on alcohol resists all efforts at control. Patients who request disulfiram implants may be in this situation or may have a host of other reasons. Thus, careful assessment and screening are indicated in all referrals. In a review of the literature pertaining to the use of implanted disulfiram1 A. Wilson (associate professor and coordinator of psychiatric research, University of Manitoba) concluded: All reports of disulfiram implants conclude with at least mild optimism for the
technique as a therapeutic modality in the treatment of alcoholism. However, the criteria on which such optimism is based are often anecdotal and subjective. There is obviously a need for systematic research into two aspects of disulfiram implants the relative effectiveness of implants compared to no-implant controls, and the psychological effect of the surgical introduction of the implant. In addition, such parameters as size and duration of implant as a function of effectiveness should be studied, and the severity of DERs (disulfiram-ethanol reactions) and side effects with disulfiram implants systematically documented before the technique can be safely and effectively utilized. In addition to the study by Kline and Kingstone that is reported in this issue of the Journal (page 1382) two systematic studies have been conducted: Wilson, Davidson and White2'3 showed that in 40 disulfiram implant operations with 1 tablet at each of eight sites and 40 identical operations with a placebo consisting of 1.0 ml of physiologic saline at each of the eight sites, the periods of abstinence following each type of operation were practically identical. Furthermore, they demonstrated that, in either case, any operation is better than none. The 10 control subjects for the disulfiram implant and the 10 control subjects for the placebo were all drinking alcohol within 50
PHARMACCUTICALS
BELLEVILLE,ONTARIOK8N5E9 1334 CMA JOURNAL/JUNE 18, 1977/VOL. 116
days. The 40 subjects with disulfiram implants lasted an average of 210 days without alcohol, and the 40 subjects in the placebo group, 175 days. Wilson and colleagues also stated that when the patients with the sham operation began drinking, the pattern could not be differentiated from their previous drinking patterns, but among the patients with the real implant, reactions were generally severe enough to request help of their therapist again. From that point on most of them stopped drinking and maintained continued abstinence. Wilson and colleagues discovered a distinct difference between the DER produced by oral intake and that produced by the implant. After oral ingestion a full-blown reaction occurs quickly and usually lasts from 3 to 5 hours. With the implant the patient can drink from several days to a week, with a less severe, more gradual reaction of longer duration: "The patient gradually comes out of a flu-like illness after two or three days." This could have a bearing on the inability of Kline and Kingstone to substantiate a full-blown DER, and their conclusion that "pharmacologic actions appear to be minimal and the predominant benefits psychologic". The implanted tablets, in the view of Wilson and colleagues, may remain dormant and practically unabsorbed for up to 18 months unless the patient starts to drink. The resultant vasodilatation initiates greater blood supply and absorption. Thus, patients who drink may require another implant soon thereafter. This technique differs from that of Kline and Kingstone, who recommend repeat implants every 6 months. In summary, disulfiram can be an effective aid during the 18- to 24month period of decline and inactivation of psychologic dependence on alcohol, stabilization of new coping techniques, and awareness of new rewards from general improvement in health and social relations. For patients who resist all other efforts to bring their dependence under control I recommend disulfiram implants. The fact that 60% or more of the patients treated by Kline and Kingstone remained abstinent with the implant after failing to respond to oral therapy with disulfiram and other treatments is significant. The interruption of psychologic dependence by both the disulfiram and the placebo implants in the studies of Wilson and colleagues could mean that finally a therapeutic technique was used that was sufficiently impressive to compete with the complex mental processes sustaining the dependence. Their observation of reinforced motivation to stop drinking in implant patients
who experienced a DER is particularly notable in view of our clinical impressions of the time required to inactivate psychologic dependence. Since the danger to the patient from disulfiram implants is insignificant compared with the increasingly serious medical and social consequences of uncontrolled dependence on alcohol I strongly recommend continuation of controlled clinical studies of this therapeutic technique. Concerning the question, "the right treatment but the wrong drug?" asked by Kline and Kingstone in their paper, more research will be required to clan-
fy this issue; in the meantime there could be distinct advantages to being "locked into" psychologic rather than pharmacologic protection. R.G. BriL, MD
The Donwood Institute 175 Brentciffe 1.d. Toronto, Ont.
References 1. WILSON A: Disulfiram implantation in alcoholism treatment. A review. I Stud Alcohol 36: 555, 1975 2. WILSON A, DAVIDSON WJ, WHrra J: Disulfiram-ethanol reaction to implanted disulfiram. Can Psychiatr Assoc 1 21: 217, 1976 3. Idem: Disulfiram implantation: placebo, paychological deterrent, and pharmacological deterrent effects. Br I PsychIatry 129: 217, 1976
The vision of Wilder Penfield The legacy to neurology left by Wilder Penfield, as a set of papers in this issue of the Journal (pages 1365 to 1377) demonstrates, was incomparable and certainly immeasurable. But, while his contributions to the treatment of epilepsy and to our understanding of memory and speech mechanisms, for example, are unique in neurology, Penfield's legacy goes far beyond neurology or even medicine. A leader among Canadian physicians - Penfield was professor of neurology and neurosurgery at McGill University from 1934 to 1954 and president of the Royal College of Physicians and Surgeons of Canada from 1939 to* 1941 - he was greatly respected also by countless persons in many walks of life in numerous countries outside Canada. Penfield was a skilful and erudite neurosurgeon, but he was also a visionary, philosopher, educator and author. Penfield's legacy is for all rather than for neurologists alone. This is surely what he would have wanted. More than once Penfield quoted Kahlil Gibran's observation that "the vision of one man lends not its wings to another man". In that each of us sees only with his own perspective this is a valid observation, but it is not too difficult to gauge the compass of Penfield's wings of vision. Indeed we should try to understand Penfield's vision because his broad perspective has great value for us. As a neurosurgeon he probed the brain and charted new maps for others to follow, but it was his unique understanding of the human condition, especially in the realm of brain, mind and spirit, that permitted his fine mind to soar on steady wings of vision. Nor is the course of such a flight hard to follow; Penfield always
wrote simply and clearly. And at this moment in Canada's history his vision of what it means to be a Canadian must, without doubt, be made familiar to those who are truly concerned about the well-being of the nation we still call Canada. Penfield's work in neurosurgery led him to stimulate electrically the cerebral cortex to determine which areas could be safely removed together with the areas of scarring that he, following the path of Foerster in Germany, showed might. be epileptogenic. This work became an exploration into the human mind. It led Penfield to consider the age-old and still unanswered question of the relation between the brain and the mind. Stimulation of the interpretive cortex of the temporal lobe, for example, would "bring to mind" (as the saying has it) a memory of the past. As Penfield described this phenomenon in one woman, stimulation of the cortex would induce in her "seeing and hearing the same things that she heard and saw in some past strip of time"1 - even though, at the same time, she was aware that she was in fact in the operating room. To Penfield this experience was one of many examples of the operation of the mind; the underlying mechanism controlled, in part at least, the physiologic basis of the mind. The mystery of the mind, occupied Penfield increasingly, yet even he could do no more than speculate in reaching out for an explanation of the brainmind relation: No mechanism has been discovered that can force the mind to think, or the individual to believe, anything. The mind continues free. This is a statement I have long considered. I have made every effort
Cortisporin Otic Drops A leader in the field of otological therapy.
.Cortispori n * Otic Drops (Polymyxin B-Neomycin-Hydrocortisone) Sterile
INDICATIONS: External otitis, otitis media with perforated tympanic membrane, infections of mastoidectomy and fenestration cavities. GONTRAINDICATIONS: This product is contraindicated in tuberculous, fungal or viral lesions (herpes simplex, vaccinia and varicella) alsointhose individuals who have shown hypersensitivity to any of its components. CAUTION: This product should be used with care in cases of perforated ear drum and in long-standing cases. of chronic otitis media, because of the danger of ototoxicity. As with any antibiotic preparation, prolonged use may result in the overgrowth of non-susceptible organisms, including fungi. Appropriate measures should be taken if this occurs. DOSAGE: 3 or 4 drops in ear 3 to 4 times daily or more frequently in acute conditions if required. SUPPLIED: Each ml contains: polymyxin B sulfate 10,000 units, neomycin sulfate 5 mg, hydrocortisone 10 mg (1%) in sterile aqueous suspension. Available in 7 ml plastic dropper bottles. Also available: GORTISPORIN Ointment 3.5 g tube. Additional product information available on request.
Calmic Limited
. Montreal. Toronto
A Welicome Company
.Trade Mark
c 3020
CMA JOURNAL/JUNE 18, 1977/VOL. 116 1335
ence on alcohol as a coping mechanism tective drug" could be visualized. accelerates in proportion to the decline Disulfiram can provide a chemical in stress tolerance. This helpless phase barrier between the habitual thought of uncontrolled dependence may ter- and the habitual act of drinking until minate in premature death from related this habitual process can decline illness, injury or suicide; in total sur- through lack of reinforcement. Clinical render to dependence with no further experience strongly indicates that the attempt to maintain family, occupa- process of decline and inactivation of tional or community status; or in an psychologic dependence on alcohol, appeal for help, so well expressed in initially taken in response to personal the first step of the Alcoholics Anon- desire or social custom, could continue ymous (AA) program. Defence of de- for 1 to 2 years or longer. pendence and resistance to treatment In 1935 AA first conclusively demmay be further augmented by a com- onstrated that some uncontrolled drinkplex of fears - of withdrawal, ab- ers could interrupt and inactivate their stinence, physicians, treatment, incar- dependence on alcohol. This was acceration, stigma and social rejection, complished within a special community among others. When to all of this is of their peers by adherence to the added the cumulative, deleterious ef- spiritual guidelines that determined fect on cognitive function of chronic their activities, goals and relationships. or recurrent intoxication with general Until that time the universal prejudice depression and associated malnutrition, and ignorance concerning the predicathe frightening experience of being ment of the uncontrolled drinker locked into an uncontrolled dependence sustained an attitude of pessimism and on alcohol becomes more understand- disinterest on the part of the clinical able. professions, and a rejecting, punitive My clinical respect for this power attitude by the community generally. of dependence grew with awareness of However, many who came in contact the complex of factors involved. Thirty with AA failed to become effectively years ago most patients reached, or involved with its program. came close to, the phase of surrender. In the early 1950s an industrial phyMandatory referrals designed to inter- sician in Michigan, Dr. Jack Jellema, rupt the progression of dependence who took a special interest in emwhile the defensive alibi systems were ployees with an alcohol problem, bestill intact were restricted to the occa- came especially concerned with those sional court order. However, it became who were not responding to his first apparent that the long-range objectives recommendation - involvement in the of treatment were the same in any fellowship of AA. In a personal comcase: to interrupt and inactivate psy- munication in 1956 he reported "I chologic dependence upon alcohol as decided to put them all on Antabuse, a coping mechanism, to achieve optimal and for the first time they were able repair of related problems - physical, to stay sober long enough to find out psychologic and social - and to ini- what AA was all about." The same tiate and support a program to im- could be said for many other forms prove health in all areas as the basis of therapy for the clinical management of a new, rewarding lifestyle with new, of dependence and its related problems. Although many patients have recoveffective coping mechanisms. With these therapeutic objectives in mind a ered from dependence on alcohol withspecific role for disulfiram as a "pro- out the help of protective drugs, the CMA JOURNAL/JUNE 18, 1977/VOL. 116 1333
special hazards of the first year, and particularly of the first 3 months, provide clinical justification for medical, psychologic and social support. Since new coping techniques are not firmly rooted in new habit patterns during the first 1 to 2 years, they must be maintained by conscious effort. After the patient has been introduced to one of the protective drugs and advised to accept all possible support throughout the hazardous transition period, the major responsibility for taking advantage of any or all support is transferred to the patient and his or her associates. This includes the decision about whether to continue taking disulfiram and for how long. A different orientation is required of patients whose dependence on alcohol resists all efforts at control. Patients who request disulfiram implants may be in this situation or may have a host of other reasons. Thus, careful assessment and screening are indicated in all referrals. In a review of the literature pertaining to the use of implanted disulfiram1 A. Wilson (associate professor and coordinator of psychiatric research, University of Manitoba) concluded: All reports of disulfiram implants conclude with at least mild optimism for the
technique as a therapeutic modality in the treatment of alcoholism. However, the criteria on which such optimism is based are often anecdotal and subjective. There is obviously a need for systematic research into two aspects of disulfiram implants the relative effectiveness of implants compared to no-implant controls, and the psychological effect of the surgical introduction of the implant. In addition, such parameters as size and duration of implant as a function of effectiveness should be studied, and the severity of DERs (disulfiram-ethanol reactions) and side effects with disulfiram implants systematically documented before the technique can be safely and effectively utilized. In addition to the study by Kline and Kingstone that is reported in this issue of the Journal (page 1382) two systematic studies have been conducted: Wilson, Davidson and White2'3 showed that in 40 disulfiram implant operations with 1 tablet at each of eight sites and 40 identical operations with a placebo consisting of 1.0 ml of physiologic saline at each of the eight sites, the periods of abstinence following each type of operation were practically identical. Furthermore, they demonstrated that, in either case, any operation is better than none. The 10 control subjects for the disulfiram implant and the 10 control subjects for the placebo were all drinking alcohol within 50
PHARMACCUTICALS
BELLEVILLE,ONTARIOK8N5E9 1334 CMA JOURNAL/JUNE 18, 1977/VOL. 116
days. The 40 subjects with disulfiram implants lasted an average of 210 days without alcohol, and the 40 subjects in the placebo group, 175 days. Wilson and colleagues also stated that when the patients with the sham operation began drinking, the pattern could not be differentiated from their previous drinking patterns, but among the patients with the real implant, reactions were generally severe enough to request help of their therapist again. From that point on most of them stopped drinking and maintained continued abstinence. Wilson and colleagues discovered a distinct difference between the DER produced by oral intake and that produced by the implant. After oral ingestion a full-blown reaction occurs quickly and usually lasts from 3 to 5 hours. With the implant the patient can drink from several days to a week, with a less severe, more gradual reaction of longer duration: "The patient gradually comes out of a flu-like illness after two or three days." This could have a bearing on the inability of Kline and Kingstone to substantiate a full-blown DER, and their conclusion that "pharmacologic actions appear to be minimal and the predominant benefits psychologic". The implanted tablets, in the view of Wilson and colleagues, may remain dormant and practically unabsorbed for up to 18 months unless the patient starts to drink. The resultant vasodilatation initiates greater blood supply and absorption. Thus, patients who drink may require another implant soon thereafter. This technique differs from that of Kline and Kingstone, who recommend repeat implants every 6 months. In summary, disulfiram can be an effective aid during the 18- to 24month period of decline and inactivation of psychologic dependence on alcohol, stabilization of new coping techniques, and awareness of new rewards from general improvement in health and social relations. For patients who resist all other efforts to bring their dependence under control I recommend disulfiram implants. The fact that 60% or more of the patients treated by Kline and Kingstone remained abstinent with the implant after failing to respond to oral therapy with disulfiram and other treatments is significant. The interruption of psychologic dependence by both the disulfiram and the placebo implants in the studies of Wilson and colleagues could mean that finally a therapeutic technique was used that was sufficiently impressive to compete with the complex mental processes sustaining the dependence. Their observation of reinforced motivation to stop drinking in implant patients
who experienced a DER is particularly notable in view of our clinical impressions of the time required to inactivate psychologic dependence. Since the danger to the patient from disulfiram implants is insignificant compared with the increasingly serious medical and social consequences of uncontrolled dependence on alcohol I strongly recommend continuation of controlled clinical studies of this therapeutic technique. Concerning the question, "the right treatment but the wrong drug?" asked by Kline and Kingstone in their paper, more research will be required to clan-
fy this issue; in the meantime there could be distinct advantages to being "locked into" psychologic rather than pharmacologic protection. R.G. BriL, MD
The Donwood Institute 175 Brentciffe 1.d. Toronto, Ont.
References 1. WILSON A: Disulfiram implantation in alcoholism treatment. A review. I Stud Alcohol 36: 555, 1975 2. WILSON A, DAVIDSON WJ, WHrra J: Disulfiram-ethanol reaction to implanted disulfiram. Can Psychiatr Assoc 1 21: 217, 1976 3. Idem: Disulfiram implantation: placebo, paychological deterrent, and pharmacological deterrent effects. Br I PsychIatry 129: 217, 1976
The vision of Wilder Penfield The legacy to neurology left by Wilder Penfield, as a set of papers in this issue of the Journal (pages 1365 to 1377) demonstrates, was incomparable and certainly immeasurable. But, while his contributions to the treatment of epilepsy and to our understanding of memory and speech mechanisms, for example, are unique in neurology, Penfield's legacy goes far beyond neurology or even medicine. A leader among Canadian physicians - Penfield was professor of neurology and neurosurgery at McGill University from 1934 to 1954 and president of the Royal College of Physicians and Surgeons of Canada from 1939 to* 1941 - he was greatly respected also by countless persons in many walks of life in numerous countries outside Canada. Penfield was a skilful and erudite neurosurgeon, but he was also a visionary, philosopher, educator and author. Penfield's legacy is for all rather than for neurologists alone. This is surely what he would have wanted. More than once Penfield quoted Kahlil Gibran's observation that "the vision of one man lends not its wings to another man". In that each of us sees only with his own perspective this is a valid observation, but it is not too difficult to gauge the compass of Penfield's wings of vision. Indeed we should try to understand Penfield's vision because his broad perspective has great value for us. As a neurosurgeon he probed the brain and charted new maps for others to follow, but it was his unique understanding of the human condition, especially in the realm of brain, mind and spirit, that permitted his fine mind to soar on steady wings of vision. Nor is the course of such a flight hard to follow; Penfield always
wrote simply and clearly. And at this moment in Canada's history his vision of what it means to be a Canadian must, without doubt, be made familiar to those who are truly concerned about the well-being of the nation we still call Canada. Penfield's work in neurosurgery led him to stimulate electrically the cerebral cortex to determine which areas could be safely removed together with the areas of scarring that he, following the path of Foerster in Germany, showed might. be epileptogenic. This work became an exploration into the human mind. It led Penfield to consider the age-old and still unanswered question of the relation between the brain and the mind. Stimulation of the interpretive cortex of the temporal lobe, for example, would "bring to mind" (as the saying has it) a memory of the past. As Penfield described this phenomenon in one woman, stimulation of the cortex would induce in her "seeing and hearing the same things that she heard and saw in some past strip of time"1 - even though, at the same time, she was aware that she was in fact in the operating room. To Penfield this experience was one of many examples of the operation of the mind; the underlying mechanism controlled, in part at least, the physiologic basis of the mind. The mystery of the mind, occupied Penfield increasingly, yet even he could do no more than speculate in reaching out for an explanation of the brainmind relation: No mechanism has been discovered that can force the mind to think, or the individual to believe, anything. The mind continues free. This is a statement I have long considered. I have made every effort
Cortisporin Otic Drops A leader in the field of otological therapy.
.Cortispori n * Otic Drops (Polymyxin B-Neomycin-Hydrocortisone) Sterile
INDICATIONS: External otitis, otitis media with perforated tympanic membrane, infections of mastoidectomy and fenestration cavities. GONTRAINDICATIONS: This product is contraindicated in tuberculous, fungal or viral lesions (herpes simplex, vaccinia and varicella) alsointhose individuals who have shown hypersensitivity to any of its components. CAUTION: This product should be used with care in cases of perforated ear drum and in long-standing cases. of chronic otitis media, because of the danger of ototoxicity. As with any antibiotic preparation, prolonged use may result in the overgrowth of non-susceptible organisms, including fungi. Appropriate measures should be taken if this occurs. DOSAGE: 3 or 4 drops in ear 3 to 4 times daily or more frequently in acute conditions if required. SUPPLIED: Each ml contains: polymyxin B sulfate 10,000 units, neomycin sulfate 5 mg, hydrocortisone 10 mg (1%) in sterile aqueous suspension. Available in 7 ml plastic dropper bottles. Also available: GORTISPORIN Ointment 3.5 g tube. Additional product information available on request.
Calmic Limited
. Montreal. Toronto
A Welicome Company
.Trade Mark
c 3020
CMA JOURNAL/JUNE 18, 1977/VOL. 116 1335
