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AM. J. DRUG ALCOHOL ABUSE,6(3), pp. 345- 353 (1979)

Mortality Rates of Persons Entering Methadone Maintenance: A Seven-Year Study BARRY CONCOOL, M.D. HARRY SMITH, Ph.D. BARRY STIMMEL, M.D. Departments of Biostatistics and Medicine Mount Sinai School of Medicine of the City University of New York New York, New York 10039

ABSTRAm An analysis of all deaths occurring over a 79month period in patients enrolled in methadone maintenance (MM) revealed an overall mortality rate of 20/1,000. Over a similar period 510 persons were discharged from MM. Followup able to be performed in 80% revealed at least 22 deaths to have occurred subsequent to discharge. Survival curves calculated on the basis of these data indicate that even under the best possible assumption, age adjusted mortality rates of heroin addicts are not only above the national mean but are one and a half times that of the population in the community surrounding the clinic. None of the deaths could be directly attributed to methadone. Alcohol was prominent in 60% of a l l deaths, being responsible for 89% of medical deaths andpresent in 35% of violent deaths. These fmdings emphasize the persistent risk associated with heroin addiction as well as the role of alcoholism in the production of excessive mortality.

The life-style of illicit heroin users is associated with an impressive incidence of morbidity and mortality. Medical complications associated with illicit heroin use contribute toward mortality as does the prevalence of violent death through suicide or homicide [ 11 . Previous estimates with respect to death rates in heroin addicts range from 1 per 400 adults to 27 per 1,000 [2,3]. However, such estimates may be extremely misleading since the denominator, 345

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CONCOOL, SMITH, AND STIMMEL

the total number of heroin users in a specific area, is unknown. The expansion of treatment programs, most specifically methadone maintenance, has allowed large numbers of heroin addicts to enter rehabilitative therapy. All methadonerelated deaths are supposed to be reported to the Food and Drug Administration. The term “methadone related death,” however, is ambiguous and may not necessarily implicate methadone as a direct or indirect cause of death, indicating only that the deceased was in some point of his life a methadone uaer. Such reporting is incomplete, and mortality rates calculated on this basis are subject to large errors. The present study was undertaken to review a l l deaths occurring in individuals who had enrolled in a single methadone program over a 7-year period. An analysis of those deaths was performed in order to formulate mortality rates as well as parameters that may predispose to mortality in individuals participating in a methadone program both during and subsequent to discharge from therapy.

METHODS The initial population comprised all persons admitted for the first time to the Mount Sinai Methadone Maintenance and Aftercare Treatment Program (MMATP) between March 1969 and December 1976. The study population consisted of deceased individuals who were at one time registered in the MMATP. This group was divided into those patients who died while on methadone therapy (Group I) and those who were known to expire subsequent to discharge (Group 11). A control group of 80 patients was randomly selected from the entire clinic population utilizing a stratified randomization process in which the number of controls selected from a specific year was proportional to the number of deaths occurring that year (Group 111). These three cohorts were compared for possible signficant differences utilizing 34 demographic parameters. Deaths were classified as (1) violent, (2) accidental, (3) drug overdose, and (4) medical. In an effort to compare death rates within the MMATP to those of the community surrounding the clinic, mortality rate data were obtained from the New York City Department of Health Statistics for the East Harlem area for the years 1973, 1974, and 1975. Crude mortality rates as well as age adjusted mortality rates were obtained. Significant differences with respect to demographic characteristics were obtained by using Student’s t test and z test formats.

341

MORTALITY RATES AND METHADONE MAINTENANCE

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RESULTS A total of 1,156 persons were initially admitted t o the MMATP through June, 1976. Five hundred and ten persons were discharged during this period with follow-up obtained in 80%. The remaining 102 persons could not be located nor could any evidence be found in the Medical Examiner’s office concerning their demise. Of this population, 45 individuals died either while enrolled in or subsequent to discharge from the program, for a total death rate of 39 per 1,000. Twenty-three individuals expired while on the program (20/1,000) and at least 22 (19/1,000) expired subsequent to discharge. The classification of the 45 deaths is illustrated in Table 1. The largest number of deaths was due either to violence (38%) or medical complications (40%). Accidents (9%) and drug overdose (13%) were each responsible for the rest of the deaths. A comparison of cause of death between those patients whose deaths occurred while enrolled in the program and those whose deaths occurred after discharge did not reveal any significant differences. Within all four categories, alcoholism was present in 27 (60%) deaths (Table 2), being directly responsible for the 89% of all medical deaths and 35% of all deaths due to violence. A demographic comparison between control subjects and decedents (Tables 3 and 4) revealed significant differences with respect to (1) the presence of alcoholism 0 < 0.001), (2) age on admission G. < 0.001), (3) length of narcotic addiction @ < 0.001), and (4) solitary life style @ < 0.01). Persons who ceased had a mean age 8 years greater than the control population, an alcoholism rate twice as high, a greater history of drug addiction by 5.7 years, and were more likely to live alone. A comparison of total crude mortality rates by cause of death of those

Table 1. Cause of Deaths While enrolled Cause

Number %

Violent

8 1 3 11

34.8 4.3 13.0 47.8

23

100.0.

Accidental Drug overdose Medical Total

After discharge Number 5%

9 3 3 I 22

41.0 13.6 13.6 32.0 100.0

Total Number %

17 4 6 18 45

31.8 8.9 13.3 40.0 100.0

CONCOOL, SMITH, AND STIMMEL

348

Table 2. Classification of Alcoholism Related Deaths %

Number Violent

6

22.2

Medical

16 2 3 21

59.3 I .4 11.1 100.0

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Accidental Drug overdose Total

Table 3. Comparison of Selected Demographic Characteristics: Ethnicity and Social History Controls (n = 80) Number %

Controls (fl

= 45)

Number

%

Ethnicity : Hispanic Black Caucasian

49 26 5

61.2 32.5 6.3

21

14 4

60.0 31.1 8.9

Social history: Living alone Employed Excessive alcohol intake

13 31 24

16.3 38.0 30.0

12 16 21

26.1* 35.6 60.00**

*p < 0.01. **p < 0.001.

Table 4. Comparison of Selected Demographic Characteristics: Age, Drug History, and Education Controls

Decedents

Years

SD

Years

SD

Age

26.9

7.2

35.1

11.3'

Education

10.4 8.1 1.9

1.9 5.6 1.4

9.9 14.4 2.2

Duration of heroin addiction Duration of methadone maintenance

2.6 9.0** 1.6

*t = 4.95,p < 0.001. **t = 4.36,~ < 0.001.

enrolled at any time in the MMATP with that of the East Harlem population revealed a marked difference between the two groups (3911,000 vs 8.4/1,000). Significant differences were found to exist regardless as to cause of death in each group (Table 5) [S] . However, if one considers mortality rates using only deaths of persons while participating in the clinic, the crude mortality

349

MORTALITY RATES AND METHADONE MAINTENANCE Table 5. Mortality Rates (per 1000) MMATP vs East Harlem

~~

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MMATP Total mortality

39

Violent deaths

East Harlem 8.4*

15

0.36*

Accidental

3

0.23**

Alcoholism

16

Overdose *p p p

0.06' 0.13***

5

< 0.0001. < 0.05. < 0.003.

Table 6. Age-Adjusted Mortality Rates Comparing MMATP vs East Harlem Average number of deaths per year

Death rate per 1,000

Expected number of deaths

Age

Average populations per year

15-24

174

1

5 .I

145

2544

28 1

3

10.7

434

34

1

29.4

84 1

489

5

10.2

1420

MMA TP Clinic (I 9 73-19 76)

45-64

Totals

East Harlem (I 973-19 75)a 15-24

25,400

191

7.5

2544

40,s 16

307

7.6

45-64

28,611

498

11.4

94,527

996

10.5

Totals

aAge-adjusted death rate = 1,420194,527 = 15.0 per 1,000.

rate of 10.2/1,000 does not significantly differ from that of East Harlem (10.51 1,000). The age adjusted death rates, however, do differ with the MMATP mortality rate, being 1%times that of East Harlem (Table 6). It should be emphasized that the ethnicity of the clinic population differed somewhat from that of East Harlem with respect to the Hispanic population (58 vs 38%, respectively) and the Caucasian population (7 vs 29%) respectively). Survival curves of persons entering methadone maintenance using standard methods were calculated under four assumptions: (1) that no patients lost-tofollow-up died during the year lost, (2) that 10% of all patients lost-to-follow-up died in the year lost, (3) that 20% of all patients lost-to-follow-up died during the year lost, and (4) that 100% of the lost-to-follow-up patients died during the year lost. There are shown in Fig. 1. Based on the information derived from our

CONCOOL, SMITH, AND STIMMEL

35 0

.oo z

.80

0 Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by University of Auckland on 12/05/14 For personal use only.

I-

[L

0

.60

a

0

a .40

[L

.20 n

wO

2

4

6

8

10

12

14

16

YEARS A F T E R DIAGNOSIS*

--

Assume tnat of those lost to follow-up: A11 are alive 10%die per year 20% die per year .*.*..**..,... All are dead

* A s defined by entry into melhodone mointenonce

-1-1-

Fig. 1. Survival curves following entry into methadone maintenance.

ability to follow up on 80% of all patients admitted to the MMATP, the true survival curve should be somewhere between the 10 and 20% death curve. If so, the probability of surviving the eleventh year after entering the program having survived the first 10 is somewhere between 57 to 71% based on the 168 patients available with a 10-year follow-up.

DISCUSSION It has been extremely difficult to establish with any degree of accuracy mortality rates among heroin addicts. The seriousness of excess mortality in this population is real and can be emphasized by the fact that in New York City heroin was the single leading cause of death in young men between the ages of 13 and 35 during 1970 [4]. The New York City Register established an annual epidemiologic survey of all reported narcotic users in the city. Since 1968 the mortality rate has averaged 7/1,000 being somewhat higher in older heroin users [S] . The mortality rates calculated as a result of this Register, however, are incomplete since reporting is far from comprehensive and it is

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MORTALITY RATES AND METHADONE MAINTENANCE

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unclear as to whether all individuals reported had actually been addicted to heroin. Watterson et al. [6] have recently reviewed the death rate and causes of death among narcotic addicts in a community drug treatment program between 1970 and 1973. Their data reveal an overall death rate for the 3-year period to be 13/1,000. Forty percent of their deaths were related to violence with 33% related t o drug abuse and 27% to other or unknown causes. Not unexpectedly, deaths classified as “other” clustered most frequently in those patients over 30, being more than twice as prevalent than in the younger age groups. In a larger study sample of 10,988 persons followed in treatment for a 10-year period, Gearing [7] found the overall death rate to be 42/1,000. The overall mortality rate (20/1,000) of persons while enrolled in our MMATP was in between those previously reported. These differences are more apparent than real, reflecting the duration of the follow-up period in each study. The prevalence in the literature of increased mortality in men as compared to women was confirmed by our results (72 vs 27%). Although drug overdose was responsible for 13% of deaths, in no instance could methadone be implicated as a contributing agent. Alcoholism has been recognized as an increasingly prevalent condition among heroin addicts. Studies have revealed that 60 to 85% of persons entering treatment programs have been found to consume considerable quantities of alcohol during their periods of heroin dependency [8-11]. The use of alcohol in addition to narcotics may play an important role in chronic disease development and mortality. Cherubin et al., in a review of statistics of the Medical Examiner’s Office of the City of New York, found that almost 50% of persons succumbing to an acute fatal narcotic reaction had detectable levels of alcohol with levels greater than 0.10 g found in 25% [12]. The importance of alcoholism in narcotic addicts has been confirmed by other investigators [13, 141 , some of whom noted that at post-mortem examination alcoholic cirrhosis is more frequently found as a cause of hepatic disease in drug addiction than chronic viral hepatitis [15]. Haberman and Baden have reported heavy alcohol use to be the only factor differentiating a group of deceased narcotic addicts from a control group narcotic addicts with significant amounts of alcohol found in over 50% of violent deaths [16]. In their study those decedents with both alcoholism and narcotic addiction were in almost all cases primarily narcotic addicts rather than alcoholics. It is, therefore, not surprising that 24 of the 40 deaths (60%) in the current study were related in some way to alcoholism, with 14 of the 24 directly related to medical complications of this disease. These findings once again emphasize the need for increased knowledge and better management of the alcoholic narcotic addict.

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CONCOOL, SMITH, AND STIMMEL

Death rates of patients enrolled in our methadone program did not appear to differ from those who were subsequently discharged prior to death. This is in contrast to the findings of Roizin et al. [17] who noted the fatality of methadone maintenance patients to rise from 13 to 100 per 1,000 on release from or discontinuance of detoxification treatment. Once again, this discrepancy may be more apparent than real, since a complete follow up on all of our patients was not able to be obtained. It is quite possible that a proportion of those lost to follow up had ceased, which would result in findings similar to those reported by Roizin. The overall mortality rate of our patients was four times that of the East Harlem population, and represents a rate not seen in mortality statistics for the general United States population until beyond age 57 [18]. Crude annual mortality rates, however, did not differ between the MMATP and the East Harlem population in which the clinic resides. When adjustment for age was made, the mortality rates of persons while in treatment, although still 1% times that of East Harlem, was considerably less than the figure obtained utilizing overall mortality rates. Due to unavailability of comparative data regarding the East Harlem community, survival curves could only be calculated for the MMATP population. The absence of a complete numerator, however, of the total number of persons dying makes it difficult to make any firm statements about the long-term prognosis of heroin addicts. Even if one were to assume that the annual mortality rate of those lost to follow up was the same as those followed, longterm survival in this population is quite poor. It is of interest that in none of the deaths could methadone be implicated as a causative factor. These figures once again emphasize the risk with respect to medical complications of illicit drug use that persist even when a person is enrolled in therapy as well as the continuing hazard associated with persistent alcoholism.

REFERENCES [ 11 Baden, M., Homicide, suicide and accidental death among narcotic addicts, Human.

PUthOZ. 3~91-95(1972). [2] Dupont, R. L., Profile of a heroin epidemic, N. Engl. J. Med. 285:320-325 (1971). [ 3 ] Brewley, T. H., Ben-hie, O., and James, L. P., Morbidity and mortality from heroin dependence, Br. J. Addict. 1:725-732 (1968). (41 Halpern, M., Fatalities from narcotic addictions in New York City. Incidence, circumstance and pathologic findings, Hum. PurhoZ. 3:13-21 (1952). (51 Narcotic Register, New York City Department of Health, 377 Broadway, New York. (61 Watterson, O., Simpson, D. D., and Sells, S. B., Death rates and causs of death among opiate addicts in community drug treatment programs 1970-1973, Am. J. Drug AZcohol Abuse 2:99-111 (1975).

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[7] Gearing, F., Mortality rates and causes of death, in Final Report of 1977 of Columbia University School of Public Health, New York, 1977. [ 81 Simpson, D. D., Use of Alcohol by DARP Patients in lleatment of Drug Abuse 1969-1971 Admission (IBR Report Number 73-7),Texas Christian University, Fort Worth, 1973. [9] Stimmel, B., Vernace, S., and Tobias, H., Hepatic dysfunction in heroin addicts. The role of alcohol, J. Am. Med. Assoc. 222:811-812(1972). [lo] Brown, B. S., Kozel, N. J., and Meyers, M. B., et al., Use of alcohol by addict and nonaddict populations, Am. J. Psychiatry 130:599 (1 973). [ 111 Rosen, A., Ottenberg, D. S., and Barr, H. L., Patterns of previous abuse of alcohol in a group of hospitalized drug addicts, in Roceedings of the Fifth National Conference on Methadone Deatment, NAPAN, New York, 1973,p. 306. (12) Cherubin, C., McCusker, J., and Baden, M., The epidemicology of death in narcotic addicts, Am. J. Epidemicol. 96:ll-22(1972). [ 131 Keely, K. A., Kahn, P., and Keeler, M. H.,Alcohol and drug abuse: Causes of sudden death, South. Med. J. 69:8 (1974). [ 141 Nadler, J., Fumia, F., Cherubin, C., et al., Deaths of narcotic addicts in New York City in 1971: Those reported to be using methadone. Znt. J. Addict 10:135-147 (1975). [ 151 Force, E. E., and Millan, J. W., Liver disease in fatal narcotism. Role of chronic liver disease and alcohol consumption, Arch. Pathol. 47:166-169(1974). [ 161 Haberman, P. W., and Baden, M. M., Drinking, drugs and deaths, Znt. J. Addict. 9:761-773(1974). [ 171 Roizin, L., Halpern, M., Baden, M., et al., Methadone fatalities in heroin addicts, Prychiat. Q. 46:393410 (1972). [ 181 Statistical Abstract of the United States-1973, U.S. Government Printing Office, Bureau of the Census, Department of Commerce, Washington, D.C., 1973.

Mortality rates of persons entering methadone maintenance: a seven-year study.

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