AMER. J. DRUG & ALCOHOL ABUSE,2(34), pp. 379-390 (1975)
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Antagonist Study in St. Louis
S. PARWATIKAR, M.D., FRCP (C)
Clinical Assistant Professor of Psychiatry J. CRAWFORD
Research Psychologist C. UNVERDI, M.D. Clinical Assistant Professor of Psychiatry Missouri Institute of Psychiatry St. Louis, Missouri 63139
RATIONALE Because of the controversy surrounding methadone treatment, various alternative methods for treatment of heroin addiction have received attention. One such alternative is the use of a long-acting antagonist, such as naloxone (in high doses), cyclazocine, and naltrexone. The proponents of the antagonist treatment have relied heavily on the hypothesis introduced by Wikler [ I ] and Lindesmith [ 21. This method of treatment is more appealing than narcotic substitution because of (1) its use of a nonnarcotic and nonaddictive drug, and (2) its ability to block euphoric effects, aiding deconditioning of the needle/narcotic habit and relapse after withdrawal. Beginning in 1965, there has been considerable interest in antagonist drugs as a treatment alternative to narcotic addiction. Except for naloxone 379
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380
PARWATIKAR, CRAWFORD, AND UWERDI
in high doses, such antagonist drugs produce varying degrees of pharmacological actions other than the desired effect of blocking the opiate “high.” Such side effects include sensory distortions, insomnia, hallucinations, and drowsiness. For an antagonist to be clinically useful it must effectively block the opiate “high,” be long acting, be acceptable to the treatment population, and be economical in terms of administration and production. In a continuing search for a viable balance between the above described factors, Martin [ 31 proposed cyclazocine. Subsequently, this drug was submitted to clinical trial by Jaffe [4] and again by Freedman [51. The opiate high was successfully blocked, but some side effects were encountered. Despite these side effects, cyclazocine was adjudged as a drug of relative safety. Similar findings emerged from work with naltrexone, naloxone [61, oxilorphan, etc. Within this framework and under the auspices of the Missouri Institute of Psychiatry at the St. Louis State Hospital, an exploratory study of cyclazocine was undertaken in collaboration with other centers. The areas to be explored were: Side effects of cyclazocine. Its acceptability by heroin addicts. Physical and biochemical changes. Ability of the drug to inoculate the user Comparison of the retention rates of the (Cyclazocine Program) to the retention rates tenance program (Outpatient Clinic) and (2) (Archway).
against opiate usage. study population of (1) a methadone maina therapeutic community
METHOD Subjects were male, over 18 years of age without evidence of physical or mental abnormality, with positive criteria of narcotic addiction (withdrawal, history of addiction, positive urinalysis), and a desire to be drug free. Such subjects were recruited from the following populations: (1) those asking detoxification from a methadone program; (2) those obviously addicted who did not meet the criteria for methadone maintenance; and
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ANTAGONIST STUDY IN ST. LOUIS
38 1
(3) probationers and parolees who were not actively addicted, but who had a long history of addiction. Intake work-up included vital signs, physical examination, neurological and mental status, laboratory work-up (SMA 12), EKG, and a chest X-ray. Clients were cleared for placement, detoxified on methadone, held 2 days drug free, naloxone test administered, and started on cyclazocine. During induction a symptom check list’was used daily to document side effects. Later in the study the BPRS (Brief Psychiatric Rating Scale, Overall and Gorham) was added to the battery. A similar routine was used at the therapeutic community. All subjects were hospitalized. Induction was uniform. The initial dosage of 0.1 mg BID was gradually increased over 21 days to 4 mg O.D., and the subjects were discharged to outpatient status. Records were kept of (1) clinic attendance, (2) illicit drug usage, (3) recidivism to criminal activity, and (4) job placement. During the entire course of treatment, patients were extended vocational, individual, and group counseling on a regular basis. No attempts were made, however, to actively solicit subjects to attend outpatient clinics. After 3 to 6 months, a follow-up effort was mounted.
FINDINGS AND RESULTS Side Effects of Cyclazocine Two analyses were made: 1. An analysis of client flow within the program is embodied in Table 1. It indicates: a. Four patients started induction and were terminated prior to completion; two for visual and auditory hallucinations and two for irritability, sleeplessness, blurred vision, and poor concentration. b. Twenty-seven patients completed induction. 2. An analysis of side effects was compiled. It is presented below in “Symptom Check List Analysis.” Cyclazocine produces side effects but, in the main, these symptoms are transitory and easily tolerated.
PARWATIKAR, CRAWFORD, AND UNVERDl
382
Table 1. Treatment Course Statistics -~
~~
~~
~
~~
Cyclazocine Program A. Volunteered, rejected for medical reasons Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by University of Alberta on 12/29/14 For personal use only.
~
Left without meeting “success” criteria
Completed “success” criteria
6
B. Detoxified, started on induction, terminated for side effects or discomfort C. Volunteered, terminated for misbehavior or unwillingness t o remain in treatment
60
D. Completed induction, discharged to outpatient status, meeting success criteria
27
5
60
27
Archway
E. Patients remaining in therapeutic community 3 months, having complied with all community criteria of the setting F. Patients leaving the “drugfree” therapeutic community without medical advice
10
22
Outpatient Methadone Maintenance Clinic
G. Patients admitted to outpatient methadone maintenance program and continuing daily medication for 3 months, receiving weekly counseling
H. Patients leaving prior to the ninety-day success criterion
32 18
Other than the side effects noted in the Symptom Check List, no other complaint was noted. SYMPTOM CHECK LIST ANALYSIS
1. Approximately 80% of all patients experienced side effects. Of side effects noted, patients perceived 74% as mild, 18% as moderate, and 8% as severe.
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ANTAGONIST STUDY IN ST. LOUIS
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2. Drowsiness. Usually mild, was found in 80% of the patients. It usually appeared in 2 to 5 days and persisted for 3 or 4 days (when dosage was 0.4 t o 1.6 mg). 3. Increased Sex Drive. Approximately 80% of the patients reported a significant increase in their sexual drive. This symptom usually appeared on the third day and was persistent over time. One could argue that such a finding was somewhat related to the relative deprivation experienced by being confined to the ward. This does not appear t o be the case inasmuch as most of the patients reported increased libido after they were discharged and maintained on the drug. (The onset of this symptom usually occurred for a dosage of 0.4 t o 1.2 mg.) 4. Fullness in Head. Reported by approximately 20% of the patients. This symptom usually appeared when the dosage reached 0.8 mg, was mild, and persisted approximately 4 or 5 days. 5. Weakness, Blurred Vision, Muscle Cramps, and Difficulty in Concentration. These symptoms were experienced by 15%. Peculiarly, their courses appear parallel. Each of them appears at a dosage of 0.8 to 1.6 mg and persists for 3 or 4 days. 6. Abdominal Cramps, Itching, Sweating, Difficulties in Coordination, Running Nose, and Running Eyes. These symptoms appeared in 10% of the population and ran a course of 3 or 4 days; they appeared at a dosage of 1.2 mg. 7. Constipation. Reported by 20% of the patients. The onset and course of constipation was quite random. It usually appeared in conjunction with other symptoms, but it can be argued that the lack of exercise on a locked ward was contributory to this condition. It might thus be hazardous to accept constipation as a strong side effect without further study.
Acceptability by Heroin Addicts and Dropout Rate
Of the 32 who seriously tried the medication, 27 accepted it and were discharged to outpatient status where they were maintained. Twelve stopped taking the medication the first month, eight stopped medication the second, six in the third, and the final one shortly thereafter. Patients’ interviews by staff indicate that most patients can tolerate
384
PARWATIKAR, CRAWFORD, AND UNVERDI
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and will accept the medication once that they have accepted the principle underlying the antagonist treatment. The main difficulty appears t o be psychological, not physiological. This is supported by the fact that many patients continued t o take the medication for a limited time even after having left the hospital.
Physical and Biochemical Change In a review of the physicals and blood workups, nothing remarkable emerged. As is the usual in addict populations, liver profiles were somewhat elevated in terms of SGOT and LDH. Some VDRL false positives were encountered. Vital signs were taken on 1 1 patients at the same time of day by the same nurse over nine equally spaced time intervals. These intervals spanned the inducation period. Upon analysis of the data, induction on cyclazocine did not seem to have had any serious effect on blood pressure, pulse, respiration, nor temperature. In summary, other than the side-effects noted above, no physical or biochemical changes were noted.
Ability of the Drug to Inoculate the User Against Opiate Usage Patients’ reports t o staff indicate that after induction all patients experimented with drugs a t least once, some two or three times. Upon finding the “high” blocked, they either desisted or stopped the medication Cyclazocine appears to be effective in blocking the euphoria of heroin. This seems to be the case even for a heavy dose of street heroin. Obviously, no measurement of dosage level for a “street fix” is possible. Nevertheless, this view is warranted; several patients reported trying to “override” the medication by fixing 2 or 3 times in the space of an hour. From the foregoing it appears that as long as the patient continues on medication, he will be insulated from the use of narcotics. This is further supported by urinalysis data from outpatients. Such urine specimens remained negative during medication periods. Unfortunately, after dropout no further data are available.
ANTAGONIST STUDY IN ST. LOUIS
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To Compare the Retention Rates of the Cyclazocine Population CYC to the Retention Rates of (1) a Methadone Maintenance Program (OPC) and (2) a Therapeutic Community (TC)
1. By their respective natures, a drug-free therapeutic community, a methadone maintenance program, and an antagonist drug program are so inherently different that a common definition of success, generally appropriate to each, cannot be stated. Despite this, for the sake of comparison, success was defined individually for each: (a) Completion of inducation and being placed on an outpatient basis was considered successful in CYC. (b) Remaining in residence, displaying no criminal activity, and conforming to uniform criteria for abstinence during a 3-month period was defined in the TC as success. (c) Patients remaining in the treatment program for 3 months without inexcusable absence from medication, who met uniform criteria for abstinence, were considered “successful” in the OPC. Successful patients leaving the study program were considered as leaving “with medical advice” or WMA. Those leaving prior to meeting the criteria were deemed to have left “against medical advice” or AMA. 2. Using the above definitions, the three programs were compared. The results are embodied in Table 1. (a) In the CYC Program, 27 or 87 or 31% met the success criteria. (b) In the TC Prpgram, 10 of 32 or 31% met the success criteria. (c) In the OPC Program, 32 of 50 or 68% met the success criteria. Obviously, methadone retention is better; it is a narcotic substitution providing immediate gratification. On the other hand, no difference exists between CYC and TC. 3. Are their client characteristics predictive of treatment success? If there are, are they the same or different between program? Answering these questions would greatly facilitate treatment decision. To explore these question, each program was cast into two groups, WMA and AMA. Using sociodemographic data gathered from social histories and treatment records, these two groups were compared for each treatment modality. Some statistically significant findings emerged in each of the programs. Not surprisingly, these findings were similar across programs.
386
PARWATIKAR, CRAWFORD, AND UNVERDI
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Table 2 presents three rows of statistical results: CYC (cyclazocine), Archway, and methadone. Each row displays data on each of four variables: age of onset (AO), education level (EL), marital status (MS), and occupational clarity (OC). (a) In the CYC program it was found that the later the age of onset, the higher the educational level, the more accepting of occupational role, and the having of a viable heterosexual relationship (such as legal marriage o r an enduring common-law relationship), the more likely was the client t o remain in treatment. See Table 2. (On the basis of social histories, clients were classified as: i) those who drifted from job t o job and otherwise exhibited ambivalence in acceptance of an occupational role, ii) those who indicated a clear identification with a specific role, and iii) those not clearly assignable t o “a” or “b”.) See Table 2. (b) In the TC, as in the CYC, educational level and marital status differentiated WMA from AMA clients: age of onset and occupational role clarity did not. See Table 2. (c) As in Table 2, WMA methadone clients had a later age of onset, were more often married, and were more accepting of their occupational role than were AMA methadone clients. No difference was found on educational level. 4. In addition to the foregoing, two other findings merit attention: (a) In approximately 25% of the CYC and TC treatment records, nursing and counseling notes give evidence of depression. The onset of this depression did not seem associated with medication, but with a letdown following rising expectations on entering treatment. Patients seem t o accept treatment until they fail to make any real social progress. (b) The number of dirty urines in the CYC group was minimal as compared t o the TC group (3% as opposed to 12%).
SUMMARY AND CONCLUSIONS 1. Cyclazocine seems to be a safe drug with some side effects. Such effects as encountered appear t o be mild to moderate and transitory in nature.
AMA (mean) = 10.32 WMA (mean) = 10.13 t = .OO, df = 48 no difference
Outpatient WMA (mean) = 20.84 Methadone AMA (mean) = 17.96 Maintenance t = 3.23,df = 42 Clinic p < .003
WMA (mean) = 10.96 AMA (mean) = 9.98 t = 1.72,df=40 p < .05
AMA (mean) 9.84 WMA (mean) 1 1.04 t = 1.96, df = 30 p < .05
WMA (mean) = 21S O AMA (mean) = 18.60 t = 3.45,df= 26 p < .01
1
24
Single
< .01
< .02
p
< .05
p
14 22 28 xz = 5.41,df = 1
27 23 $ = 4.75,df= 1
11
Unclear 14
Clear WMA 18 AMA 4 Married AMA 6 WMA 21
Single 12
no difference
13
27
< .01
4 9 -
12
Unclear
Clear 5
p
WMA AMA
xz = O.O06,df=1
21 3 24
Single
23 x2 = 3.06,df= 1 p < .06
7 33 40
Unclear
Clients remaining on program more often display clear occupational role perception and acceptance Clear WMA 8 AMA 15
Occupational role clarity
xz = 15.5,df=1
Married AMA 0 WMA 5 5
p
34 25 xz = 7.16,df=1
AMA 23 WMA 11
Married
Married clients or clients maintaining a viable heterosexual relationship more often remain in program
Clients remaining in the program display higher educational levels
The later the age of onset, the more likely is the client to remain in program
AMA (mean) = 18.63 WMA (mean) = 18.88 t = .54, df = 30 no difference
Archway
Cyclazocine Program
Marital status
Educational level
Age of onset
Table 2. Retention: Treatment-Modality X Socialization Indicators
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4
W 00
5
0
9 r
v)
Z
13
.e
U
5
3
5
9
n
2 *
i2
PARWATIKAR, CRAWFORD, AND UNVERDI
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388
2. Patients seem to accept cyclazocine treatment at least as well as they accept TC treatment. Each patient reported challenging the drug and having found it an effective blocking agent t o the opiate “high.” 3. Other than the symptoms presented in the Symptom Check List, no physical or biochemical changes were noted. 4. As long as the client remained o n medication, he was insulated against narcotic use. The problem appears to be one of insuring taking of the medication. 5 . Dropout across treatment modalities appears the same except in the narcotic substitution program. Across all three modalities some crude correlates, predictive of remaining in treatment, have been isolated in this study. They are: educational level, marital status, age of onset, and clarity and acceptance of occupational role. Similar findings have been reported by Klienman [7] and Vaillant [81.
If the final objective of the treatment of narcotic addiction is keeping the person from getting “high,” then forced or coerced narcotic antagonist maintenance may serve as an answer. However, the etiology of addiction is of such a complex nature that treatment by curbing one’s own drug intake would be analogous to treating the neurotic by curbing or eliminating his impulsive, ritualistic activities. The drug-seeking personality is characterized by a need for immediate gratification even at the expense of future life stability. Antagonist drugs do not in themselves offer any alternative to this tendency. They merely prevent one mode of immediate gratification without offering any long-term alternative t o the estabished addict life style. Such alternatives must be fashioned out of daily learning provided by ancillary and supportive services, group support, etc. Such a program implemented at clinic level is not enough. An addict is easily swayed by peer pressure. The peer group is perceived by him as a strong subcultural element moving him to accept or reject ways of gratification, enhancing or limiting frustrations, and effecting the stresses of socialization. The more suggestible and vulnerable is the addict, the more he is influenced by his peer o r status groups. Accordingly, the antagonist drug functions t o insulate the individual against drug taking so that he can come and go without regressing to drugs. In this way he can explore
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ANTAGONIST STUDY IN ST. LOUIS
389
positive alternatives and relearn. On the other hand, the group has the complementary function of holding the patient in the social setting. At least once each day he will come under the social influence of this supportive pressure t o take his medication. He can go about his daily tasks, safe in the realization that he would waste both time and money seeking the immediate gratification of drugs. A final word: if the findings of this research mean anything, they indicate that the problem of drug addiction and rehabilitation are bottomed on inadequate and/or lack of socialization. No matter which treatment modality is chosen, if it is t o be successful, supportive therapy is essential. We must:
1. Get the family involved from the initial screening onward. 2. Encourage and reinforce a viable heterosexual relationship. 3. Marshal all manner of social and institutional support, including clergymen, neighbors, church groups, local tradesmen, employers, welfare agencies, and social workers. Each must extend the social support appropriate t o their particular relation to the resocialization of the client. 4. Provide access t o wholesome social activities in recreation, working, living, etc.
ACKNOWLEDGMENTS This research was supported by NIDA grant #HSM 42-72-116 and the Psychiatric Research Foundation of St. Louis.
REFERENCES [I] Wikler, A., Conditioning factors in opiate addiction and relapse, in Narcotics (D. M. Wilmer and G. G. Kasselbaum, eds.), McGraw-Hill, New York, 1965. [2] Lindesmith, A. R., Problems in social psychology of addiction in Narcotics (D. M. Wilmer and G. G. Kasselbaum, eds.), McGraw-Hill, New York, 1965. [3] Martin, W. R., Gorodetzky, C. W., and McClane, T. K., An experimental study in the treatment of narcotic addicts with cyclazocine, Clin. Pharmacol. 7’her. 7:455-465 (Jaunary 1966). [4] Jaffe, J . H., and Brill, L., Cyclazocine, a long acting narcotic antagonist; its voluntary acceptance as a treatment modality by narcotic abusers, Int. J. Addict. 1199-123(1966).
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PARWATIKAR, CRAWFORD, AND UNIVERDI
[ 5 ] Freedman, A. M., Fink, M.,Sharoff, R., and Zaks, A., Cyclazocine and methadone in narcotic addiction, J. Am. Med. Assoc. 202:119-I22 (1967). [6] Zaks, A., et al., Naloxone treatment of opiate dependence; a progress report, J. Am. Med. Assoc. 215:2108-2110 (1971). [7] Kleinman, P., Early age of onset of heroin addiction: A first investigation of some social determinants, Columbia University, 1974 (Paper Presented at the meeting of the Society for the Study of Social Problems, 1974, Montreal, Canada). [8] Vaillant, G., A twelve year followup of New York narcotic addicts. IV, Am. J. Psychiany 123(5):573-588 (November 1966).
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Antagonist Study in St. Louis
S. PARWATIKAR, M.D., FRCP (C)
Clinical Assistant Professor of Psychiatry J. CRAWFORD
Research Psychologist C. UNVERDI, M.D. Clinical Assistant Professor of Psychiatry Missouri Institute of Psychiatry St. Louis, Missouri 63139
RATIONALE Because of the controversy surrounding methadone treatment, various alternative methods for treatment of heroin addiction have received attention. One such alternative is the use of a long-acting antagonist, such as naloxone (in high doses), cyclazocine, and naltrexone. The proponents of the antagonist treatment have relied heavily on the hypothesis introduced by Wikler [ I ] and Lindesmith [ 21. This method of treatment is more appealing than narcotic substitution because of (1) its use of a nonnarcotic and nonaddictive drug, and (2) its ability to block euphoric effects, aiding deconditioning of the needle/narcotic habit and relapse after withdrawal. Beginning in 1965, there has been considerable interest in antagonist drugs as a treatment alternative to narcotic addiction. Except for naloxone 379
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380
PARWATIKAR, CRAWFORD, AND UWERDI
in high doses, such antagonist drugs produce varying degrees of pharmacological actions other than the desired effect of blocking the opiate “high.” Such side effects include sensory distortions, insomnia, hallucinations, and drowsiness. For an antagonist to be clinically useful it must effectively block the opiate “high,” be long acting, be acceptable to the treatment population, and be economical in terms of administration and production. In a continuing search for a viable balance between the above described factors, Martin [ 31 proposed cyclazocine. Subsequently, this drug was submitted to clinical trial by Jaffe [4] and again by Freedman [51. The opiate high was successfully blocked, but some side effects were encountered. Despite these side effects, cyclazocine was adjudged as a drug of relative safety. Similar findings emerged from work with naltrexone, naloxone [61, oxilorphan, etc. Within this framework and under the auspices of the Missouri Institute of Psychiatry at the St. Louis State Hospital, an exploratory study of cyclazocine was undertaken in collaboration with other centers. The areas to be explored were: Side effects of cyclazocine. Its acceptability by heroin addicts. Physical and biochemical changes. Ability of the drug to inoculate the user Comparison of the retention rates of the (Cyclazocine Program) to the retention rates tenance program (Outpatient Clinic) and (2) (Archway).
against opiate usage. study population of (1) a methadone maina therapeutic community
METHOD Subjects were male, over 18 years of age without evidence of physical or mental abnormality, with positive criteria of narcotic addiction (withdrawal, history of addiction, positive urinalysis), and a desire to be drug free. Such subjects were recruited from the following populations: (1) those asking detoxification from a methadone program; (2) those obviously addicted who did not meet the criteria for methadone maintenance; and
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ANTAGONIST STUDY IN ST. LOUIS
38 1
(3) probationers and parolees who were not actively addicted, but who had a long history of addiction. Intake work-up included vital signs, physical examination, neurological and mental status, laboratory work-up (SMA 12), EKG, and a chest X-ray. Clients were cleared for placement, detoxified on methadone, held 2 days drug free, naloxone test administered, and started on cyclazocine. During induction a symptom check list’was used daily to document side effects. Later in the study the BPRS (Brief Psychiatric Rating Scale, Overall and Gorham) was added to the battery. A similar routine was used at the therapeutic community. All subjects were hospitalized. Induction was uniform. The initial dosage of 0.1 mg BID was gradually increased over 21 days to 4 mg O.D., and the subjects were discharged to outpatient status. Records were kept of (1) clinic attendance, (2) illicit drug usage, (3) recidivism to criminal activity, and (4) job placement. During the entire course of treatment, patients were extended vocational, individual, and group counseling on a regular basis. No attempts were made, however, to actively solicit subjects to attend outpatient clinics. After 3 to 6 months, a follow-up effort was mounted.
FINDINGS AND RESULTS Side Effects of Cyclazocine Two analyses were made: 1. An analysis of client flow within the program is embodied in Table 1. It indicates: a. Four patients started induction and were terminated prior to completion; two for visual and auditory hallucinations and two for irritability, sleeplessness, blurred vision, and poor concentration. b. Twenty-seven patients completed induction. 2. An analysis of side effects was compiled. It is presented below in “Symptom Check List Analysis.” Cyclazocine produces side effects but, in the main, these symptoms are transitory and easily tolerated.
PARWATIKAR, CRAWFORD, AND UNVERDl
382
Table 1. Treatment Course Statistics -~
~~
~~
~
~~
Cyclazocine Program A. Volunteered, rejected for medical reasons Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by University of Alberta on 12/29/14 For personal use only.
~
Left without meeting “success” criteria
Completed “success” criteria
6
B. Detoxified, started on induction, terminated for side effects or discomfort C. Volunteered, terminated for misbehavior or unwillingness t o remain in treatment
60
D. Completed induction, discharged to outpatient status, meeting success criteria
27
5
60
27
Archway
E. Patients remaining in therapeutic community 3 months, having complied with all community criteria of the setting F. Patients leaving the “drugfree” therapeutic community without medical advice
10
22
Outpatient Methadone Maintenance Clinic
G. Patients admitted to outpatient methadone maintenance program and continuing daily medication for 3 months, receiving weekly counseling
H. Patients leaving prior to the ninety-day success criterion
32 18
Other than the side effects noted in the Symptom Check List, no other complaint was noted. SYMPTOM CHECK LIST ANALYSIS
1. Approximately 80% of all patients experienced side effects. Of side effects noted, patients perceived 74% as mild, 18% as moderate, and 8% as severe.
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ANTAGONIST STUDY IN ST. LOUIS
383
2. Drowsiness. Usually mild, was found in 80% of the patients. It usually appeared in 2 to 5 days and persisted for 3 or 4 days (when dosage was 0.4 t o 1.6 mg). 3. Increased Sex Drive. Approximately 80% of the patients reported a significant increase in their sexual drive. This symptom usually appeared on the third day and was persistent over time. One could argue that such a finding was somewhat related to the relative deprivation experienced by being confined to the ward. This does not appear t o be the case inasmuch as most of the patients reported increased libido after they were discharged and maintained on the drug. (The onset of this symptom usually occurred for a dosage of 0.4 t o 1.2 mg.) 4. Fullness in Head. Reported by approximately 20% of the patients. This symptom usually appeared when the dosage reached 0.8 mg, was mild, and persisted approximately 4 or 5 days. 5. Weakness, Blurred Vision, Muscle Cramps, and Difficulty in Concentration. These symptoms were experienced by 15%. Peculiarly, their courses appear parallel. Each of them appears at a dosage of 0.8 to 1.6 mg and persists for 3 or 4 days. 6. Abdominal Cramps, Itching, Sweating, Difficulties in Coordination, Running Nose, and Running Eyes. These symptoms appeared in 10% of the population and ran a course of 3 or 4 days; they appeared at a dosage of 1.2 mg. 7. Constipation. Reported by 20% of the patients. The onset and course of constipation was quite random. It usually appeared in conjunction with other symptoms, but it can be argued that the lack of exercise on a locked ward was contributory to this condition. It might thus be hazardous to accept constipation as a strong side effect without further study.
Acceptability by Heroin Addicts and Dropout Rate
Of the 32 who seriously tried the medication, 27 accepted it and were discharged to outpatient status where they were maintained. Twelve stopped taking the medication the first month, eight stopped medication the second, six in the third, and the final one shortly thereafter. Patients’ interviews by staff indicate that most patients can tolerate
384
PARWATIKAR, CRAWFORD, AND UNVERDI
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by University of Alberta on 12/29/14 For personal use only.
and will accept the medication once that they have accepted the principle underlying the antagonist treatment. The main difficulty appears t o be psychological, not physiological. This is supported by the fact that many patients continued t o take the medication for a limited time even after having left the hospital.
Physical and Biochemical Change In a review of the physicals and blood workups, nothing remarkable emerged. As is the usual in addict populations, liver profiles were somewhat elevated in terms of SGOT and LDH. Some VDRL false positives were encountered. Vital signs were taken on 1 1 patients at the same time of day by the same nurse over nine equally spaced time intervals. These intervals spanned the inducation period. Upon analysis of the data, induction on cyclazocine did not seem to have had any serious effect on blood pressure, pulse, respiration, nor temperature. In summary, other than the side-effects noted above, no physical or biochemical changes were noted.
Ability of the Drug to Inoculate the User Against Opiate Usage Patients’ reports t o staff indicate that after induction all patients experimented with drugs a t least once, some two or three times. Upon finding the “high” blocked, they either desisted or stopped the medication Cyclazocine appears to be effective in blocking the euphoria of heroin. This seems to be the case even for a heavy dose of street heroin. Obviously, no measurement of dosage level for a “street fix” is possible. Nevertheless, this view is warranted; several patients reported trying to “override” the medication by fixing 2 or 3 times in the space of an hour. From the foregoing it appears that as long as the patient continues on medication, he will be insulated from the use of narcotics. This is further supported by urinalysis data from outpatients. Such urine specimens remained negative during medication periods. Unfortunately, after dropout no further data are available.
ANTAGONIST STUDY IN ST. LOUIS
385
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To Compare the Retention Rates of the Cyclazocine Population CYC to the Retention Rates of (1) a Methadone Maintenance Program (OPC) and (2) a Therapeutic Community (TC)
1. By their respective natures, a drug-free therapeutic community, a methadone maintenance program, and an antagonist drug program are so inherently different that a common definition of success, generally appropriate to each, cannot be stated. Despite this, for the sake of comparison, success was defined individually for each: (a) Completion of inducation and being placed on an outpatient basis was considered successful in CYC. (b) Remaining in residence, displaying no criminal activity, and conforming to uniform criteria for abstinence during a 3-month period was defined in the TC as success. (c) Patients remaining in the treatment program for 3 months without inexcusable absence from medication, who met uniform criteria for abstinence, were considered “successful” in the OPC. Successful patients leaving the study program were considered as leaving “with medical advice” or WMA. Those leaving prior to meeting the criteria were deemed to have left “against medical advice” or AMA. 2. Using the above definitions, the three programs were compared. The results are embodied in Table 1. (a) In the CYC Program, 27 or 87 or 31% met the success criteria. (b) In the TC Prpgram, 10 of 32 or 31% met the success criteria. (c) In the OPC Program, 32 of 50 or 68% met the success criteria. Obviously, methadone retention is better; it is a narcotic substitution providing immediate gratification. On the other hand, no difference exists between CYC and TC. 3. Are their client characteristics predictive of treatment success? If there are, are they the same or different between program? Answering these questions would greatly facilitate treatment decision. To explore these question, each program was cast into two groups, WMA and AMA. Using sociodemographic data gathered from social histories and treatment records, these two groups were compared for each treatment modality. Some statistically significant findings emerged in each of the programs. Not surprisingly, these findings were similar across programs.
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Table 2 presents three rows of statistical results: CYC (cyclazocine), Archway, and methadone. Each row displays data on each of four variables: age of onset (AO), education level (EL), marital status (MS), and occupational clarity (OC). (a) In the CYC program it was found that the later the age of onset, the higher the educational level, the more accepting of occupational role, and the having of a viable heterosexual relationship (such as legal marriage o r an enduring common-law relationship), the more likely was the client t o remain in treatment. See Table 2. (On the basis of social histories, clients were classified as: i) those who drifted from job t o job and otherwise exhibited ambivalence in acceptance of an occupational role, ii) those who indicated a clear identification with a specific role, and iii) those not clearly assignable t o “a” or “b”.) See Table 2. (b) In the TC, as in the CYC, educational level and marital status differentiated WMA from AMA clients: age of onset and occupational role clarity did not. See Table 2. (c) As in Table 2, WMA methadone clients had a later age of onset, were more often married, and were more accepting of their occupational role than were AMA methadone clients. No difference was found on educational level. 4. In addition to the foregoing, two other findings merit attention: (a) In approximately 25% of the CYC and TC treatment records, nursing and counseling notes give evidence of depression. The onset of this depression did not seem associated with medication, but with a letdown following rising expectations on entering treatment. Patients seem t o accept treatment until they fail to make any real social progress. (b) The number of dirty urines in the CYC group was minimal as compared t o the TC group (3% as opposed to 12%).
SUMMARY AND CONCLUSIONS 1. Cyclazocine seems to be a safe drug with some side effects. Such effects as encountered appear t o be mild to moderate and transitory in nature.
AMA (mean) = 10.32 WMA (mean) = 10.13 t = .OO, df = 48 no difference
Outpatient WMA (mean) = 20.84 Methadone AMA (mean) = 17.96 Maintenance t = 3.23,df = 42 Clinic p < .003
WMA (mean) = 10.96 AMA (mean) = 9.98 t = 1.72,df=40 p < .05
AMA (mean) 9.84 WMA (mean) 1 1.04 t = 1.96, df = 30 p < .05
WMA (mean) = 21S O AMA (mean) = 18.60 t = 3.45,df= 26 p < .01
1
24
Single
< .01
< .02
p
< .05
p
14 22 28 xz = 5.41,df = 1
27 23 $ = 4.75,df= 1
11
Unclear 14
Clear WMA 18 AMA 4 Married AMA 6 WMA 21
Single 12
no difference
13
27
< .01
4 9 -
12
Unclear
Clear 5
p
WMA AMA
xz = O.O06,df=1
21 3 24
Single
23 x2 = 3.06,df= 1 p < .06
7 33 40
Unclear
Clients remaining on program more often display clear occupational role perception and acceptance Clear WMA 8 AMA 15
Occupational role clarity
xz = 15.5,df=1
Married AMA 0 WMA 5 5
p
34 25 xz = 7.16,df=1
AMA 23 WMA 11
Married
Married clients or clients maintaining a viable heterosexual relationship more often remain in program
Clients remaining in the program display higher educational levels
The later the age of onset, the more likely is the client to remain in program
AMA (mean) = 18.63 WMA (mean) = 18.88 t = .54, df = 30 no difference
Archway
Cyclazocine Program
Marital status
Educational level
Age of onset
Table 2. Retention: Treatment-Modality X Socialization Indicators
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W 00
5
0
9 r
v)
Z
13
.e
U
5
3
5
9
n
2 *
i2
PARWATIKAR, CRAWFORD, AND UNVERDI
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2. Patients seem to accept cyclazocine treatment at least as well as they accept TC treatment. Each patient reported challenging the drug and having found it an effective blocking agent t o the opiate “high.” 3. Other than the symptoms presented in the Symptom Check List, no physical or biochemical changes were noted. 4. As long as the client remained o n medication, he was insulated against narcotic use. The problem appears to be one of insuring taking of the medication. 5 . Dropout across treatment modalities appears the same except in the narcotic substitution program. Across all three modalities some crude correlates, predictive of remaining in treatment, have been isolated in this study. They are: educational level, marital status, age of onset, and clarity and acceptance of occupational role. Similar findings have been reported by Klienman [7] and Vaillant [81.
If the final objective of the treatment of narcotic addiction is keeping the person from getting “high,” then forced or coerced narcotic antagonist maintenance may serve as an answer. However, the etiology of addiction is of such a complex nature that treatment by curbing one’s own drug intake would be analogous to treating the neurotic by curbing or eliminating his impulsive, ritualistic activities. The drug-seeking personality is characterized by a need for immediate gratification even at the expense of future life stability. Antagonist drugs do not in themselves offer any alternative to this tendency. They merely prevent one mode of immediate gratification without offering any long-term alternative t o the estabished addict life style. Such alternatives must be fashioned out of daily learning provided by ancillary and supportive services, group support, etc. Such a program implemented at clinic level is not enough. An addict is easily swayed by peer pressure. The peer group is perceived by him as a strong subcultural element moving him to accept or reject ways of gratification, enhancing or limiting frustrations, and effecting the stresses of socialization. The more suggestible and vulnerable is the addict, the more he is influenced by his peer o r status groups. Accordingly, the antagonist drug functions t o insulate the individual against drug taking so that he can come and go without regressing to drugs. In this way he can explore
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ANTAGONIST STUDY IN ST. LOUIS
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positive alternatives and relearn. On the other hand, the group has the complementary function of holding the patient in the social setting. At least once each day he will come under the social influence of this supportive pressure t o take his medication. He can go about his daily tasks, safe in the realization that he would waste both time and money seeking the immediate gratification of drugs. A final word: if the findings of this research mean anything, they indicate that the problem of drug addiction and rehabilitation are bottomed on inadequate and/or lack of socialization. No matter which treatment modality is chosen, if it is t o be successful, supportive therapy is essential. We must:
1. Get the family involved from the initial screening onward. 2. Encourage and reinforce a viable heterosexual relationship. 3. Marshal all manner of social and institutional support, including clergymen, neighbors, church groups, local tradesmen, employers, welfare agencies, and social workers. Each must extend the social support appropriate t o their particular relation to the resocialization of the client. 4. Provide access t o wholesome social activities in recreation, working, living, etc.
ACKNOWLEDGMENTS This research was supported by NIDA grant #HSM 42-72-116 and the Psychiatric Research Foundation of St. Louis.
REFERENCES [I] Wikler, A., Conditioning factors in opiate addiction and relapse, in Narcotics (D. M. Wilmer and G. G. Kasselbaum, eds.), McGraw-Hill, New York, 1965. [2] Lindesmith, A. R., Problems in social psychology of addiction in Narcotics (D. M. Wilmer and G. G. Kasselbaum, eds.), McGraw-Hill, New York, 1965. [3] Martin, W. R., Gorodetzky, C. W., and McClane, T. K., An experimental study in the treatment of narcotic addicts with cyclazocine, Clin. Pharmacol. 7’her. 7:455-465 (Jaunary 1966). [4] Jaffe, J . H., and Brill, L., Cyclazocine, a long acting narcotic antagonist; its voluntary acceptance as a treatment modality by narcotic abusers, Int. J. Addict. 1199-123(1966).
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[ 5 ] Freedman, A. M., Fink, M.,Sharoff, R., and Zaks, A., Cyclazocine and methadone in narcotic addiction, J. Am. Med. Assoc. 202:119-I22 (1967). [6] Zaks, A., et al., Naloxone treatment of opiate dependence; a progress report, J. Am. Med. Assoc. 215:2108-2110 (1971). [7] Kleinman, P., Early age of onset of heroin addiction: A first investigation of some social determinants, Columbia University, 1974 (Paper Presented at the meeting of the Society for the Study of Social Problems, 1974, Montreal, Canada). [8] Vaillant, G., A twelve year followup of New York narcotic addicts. IV, Am. J. Psychiany 123(5):573-588 (November 1966).
