Opiate-Dependent Patients on a Waiting List for Methadone Maintenance Treatment Are at High Risk for Mortality Until Treatment Entry

ORIGINAL RESEARCH

Einat Peles, PhD, Shaul Schreiber, MD, and Miriam Adelson, MD

piate addiction is a chronic relapsing disorder. Opiate ad- Objectives: In 2002, our methadone maintenance treatment (MMT) O dicts usually experience several trials and failures of in- clinic reached full capacity and admission to treatment was delayed stitutional and self-detoxification and withdrawal during their for >1 year. In order to evaluate possible impact of the waiting list on long addiction “career” before they apply and start chronic mortality risk of the registered patients, we compared survival after substitution treatment, which is the best treatment for opiate the first 2 years, and long-term survival since registration between addiction, namely methadone maintenance treatment (MMT) admitted and not admitted to our MMT (or other treatment facilities) (NIH consensus statement, 1997). It is not clear whether or and to those who admitted immediately, before the establishment of not the timing for acceptance to treatment is of any impor- the waiting list in 2002. tance when they finally do seek MMT. Methods: A total of 608 patients registered between 2002 and 2009. As MMT is a chronic treatment and resources are lim- Their vital statistics were obtained from the Israeli National Registry ited, a waiting list may be needed. Does the need to wait (October 2010). for months and even for more than a year before entry to Results: Of the total 608, 366 registrants (60.2%) were admitted to MMT make any difference with respect to their outcome? any treatment (194 [53%] to our MMT, 162 [44.3%] to other MMTs Does it matter how long they have to wait? The results of and 10 [2.7%] to other facilities) and 242 (39.8%) were not admitted studies that looked at the relation between the waiting period anywhere. Nonadmission to treatment when it became available was before admission to treatment and treatment outcome were, due to inability to contact the patient (116, 47.9%), self-reported however, inconsistent (Addenbrooke and Rathod, 1990; Stark drug discontinuation (44, 18.2%), refusal to follow regulations (39, et al., 1990; Bell et al., 1994; Best et al., 2002; Claus and Kindleberger, 2002; ). Chun et al. (2008) discussed the impor- 16.1%), imprisonment (27, 11.2%), violent behavior (1, 0.4%), death tance of timely treatment access for this population (Grahan (13, 5.4%), and other (2, 0.8%). The mortality rate (available among et al., 1995; Rosenbaum, 1995; Kaplan and Johri, 2000) and 583) during the 2 years on the waiting list was higher (5.0/100 person concluded that longer waiting periods decrease the likelihood years) for the 225 nonadmitted applicants than for the 358 admitted of treatment entry (Stark et al., 1990; Festinger et al., 1995; < (0.42/100 person years, P 0.0005) and those who were admitted Hser et al., 1998; Donovan et al., 2001). In a survey among with no delay before 2002 (2.1/100 person years). The long-term opioid users and specialist services that explored what needed survival between those 3 groups did not differ significantly. improvement in MMT clinics in New Zealand, both patients Conclusions: Opiate addicts are at high risk for mortality during pro- and clinicians rated the waiting list as having high priority longed waiting periods for admission to MMT, indicating an urgent (Deering et al., 2011). need for immediate expansion of MMT availability. Our MMT clinic was established in 1993 and reached Key Words: methadone maintenance treatment, mortality, waiting its full capacity at the end of 2002. Since then, addicts who wished to receive treatment were put on a waiting list (with list the exception of pregnant women and HIV [human immun- (J Addict Med 2013;7: 177–182) odeficiency virus] patients). The mean waiting period during 2002 and 2009 was 1.2 year. We hypothesized that the waiting time is a problem that may hamper the prognosis of some of these individuals, and thus, those who are eventually accepted From Dr Miriam and Sheldon G. Adelson Clinic for Drug Abuse, Treatment may be actually a selective group (with a better prognosis) and Research (EP, SS and MA) and the Department of Psychiatry (SS), than those who were not accepted to any treatment. To address Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. this, we first compared (Peles et al., 2012) outcome (retention) Received for publication October 12, 2012; accepted January 14, 2013. between a historical cohort group (admitted between 1993 and The authors declare no conflicts of interest. 2002) without delay and the latest group (admitted since 2002) Send correspondence and reprint requests to Einat Peles, PhD, Henrietta Szold that had been on a waiting list. The latter group presented a Street, Tel Aviv, 64924 Israel. E-mail: [email protected]. better retention rate, which could have been attributed to their Copyright C 2013 American Society of Addiction Medicine ISSN: 1932-0620/13/0703-0177 being relatively older and self-referred, both well-known inde- DOI: 10.1097/ADM.0b013e318287cfc9 pendent predictors of better retention. r J Addict Med Volume 7, Number 3, May/June 2013 177

Still, a question that remained unsolved was about out- Cause of Death come of those who registered but were not admitted to treat- The cause of death was taken from each patient’s chart ment. In the current study, we now evaluated the 2-year survival or from the national population registry (coded according to of all opiate addicts who registered to our MMT clinic, from the International Classification of Diseases, Tenth Revision)as time of registration to our MMT clinic to determine whether described elsewhere (Peles et al., 2010). the delay to treatment initiation plays an important role in the survival of this population. Specifically, we compared mortal- Statistical Analyses ity rate between those who registered and were admitted to Data analyses were performed by using SPSS version 17 any treatment (either to our MMT program or to any other (SPSS Inc., Chicago, Ill). The 2-year survival was calculated facility throughout the country) and those who registered for from the date of registration until the registrant died or 2 years but did not manage to get any treatment. Mortality rate of the since registration, using Kaplan-Meier survival analyses (re- historical cohort group of patients admitted immediately with sults given as mean and 95% confidence interval [95% CI]). no need to wait (before the initiation of the waiting list) served The log-rank test was used to test for statistical significance. as another comparison group. The mortality rate per person year (py) was calculated by di- viding the number of deaths by the number of follow-up years METHODS from registration for first admission to MMT until death or 2 years since registration. Statistical significance is reported us- Characteristics of the Patients and the Clinic ing the Fisher exact test for rates (number of deaths/py). These The study was approved by the institutional review board calculations were done using WINPEPI (PEPI-for-Windows) (Helsinki committee) at our medical center [05-217]. A total computer programs for epidemiologists (copyright Abramson of 608 opiate addicts were registered on the waiting list to the JH, 2009,Version 9.7). Survival and mortality rate were also Adelson MMT Clinic between January 2002 and June 2009 calculated for follow-up up to 9 years. Comparisons of con- and followed-up until October 2010. They were all 18 years tinuous variable differences between all the groups were done or older and addicted to heroin (Diagnostic and Statistical using analysis of variance and categorical variables using the Manual of Mental Disorders, Fourth Edition, Text Revision). chi-square or Fisher exact tests. Patients who were pregnant, HIV positive, or special cases (eg, severe illness) were excluded from the current study because RESULTS they were admitted without delay. While registering and being put on the waiting list, the Waiting Time and Rates of Admission addicts were informed exactly why no place was available A total of 608 opiate addicts registered for our MMT at the time and they were advised to look for other possibly clinic from January 2002 until June 2009. By October 2010, 194 (31.9%) of them had been admitted to our MMT. The available facilities in the meantime. They were provided with ± descriptive details of other facilities in the region, and with mean waiting time was 1.2 0.9 years. The mean waiting the fax number of the relevant department at the Ministry of time by year of admission increased from 0.6 years in 2003 Health. to 1.9 years in 2010 (Fig. 1), whereas 90% of the registrants Vacancies in our MMT program are due to patients drop- waited for more than 6 months and 50% for more than 1 year. ping out mostly for severe misconduct, jail, or death. The pace The mean waiting time did not differ significantly by year of is usually about one patient each week. When this occurs, registration (Table 1). the clinic contacts the consecutive candidates highest on the A total of 366 patients were admitted to any treatment waiting list until there is a response. This usually involves an (Table 2). Specifically, 53% were admitted to our MMT, 44.3% average of 3 ± 1.2 contacts (range: 1-10). We also checked 10 other MMT clinics throughout Israel to determine whether our registrants had been entered into their 2.0 program. Of the 470 patients who admitted to the Adelson MMT clinic between 1993 and 2002, 400 who were non- 1.5 HIV and nonpregnant women served as a control group (early cohort). 1.0 1.94

1.34 1.3 1.2 1.29 1.3 Duration (years) 0.5 1 Mortality 0.6 Vital statistics on the 608 registered candidates were 0.0 retrieved in October 2010 from the Israel National Population 2003 2004 2005 2006 2007 2008 2009 2010 Registry that records all deaths in the country. Information Year of Admission on 25 of them could not be found because of a missing or incorrect identiﬁcation numbers, leaving a total of 583 (95.9%) FIGURE 1. Mean duration of waiting time from registra- of the registrants for mortality studies. Of the early cohort tion until acceptance into methadone maintenance treatment control group, vital information was available for 394 of the (MMT) by year of admission to MMT among 194 patients who 400 patients. were admitted to our MMT clinic.

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Copyright © 2013 American Society of Addiction Medicine. Unauthorized reproduction of this article is prohibited. r J Addict Med Volume 7, Number 3, May/June 2013 Risk for Mortality on a Waiting List for Methadone Maintenance

TABLE 1. Rate of Admission to Our Methadone Maintenance TABLE 3. Cause of Death After up to 2 Years Since Registration Treatment (MMT) and Length of Waiting Time Before Admis- by Registrants Who Did or Did Not Receive Any Treatment sion by Year of Registration Received No Received Any Admitted Clinic full Cause of Death Treatment Treatment Early Cohort Registration Total n(%) Waiting Time, y capacity All causes N = 21 N = 3N= 17 Ye a r n = 608 194 (31.9) 1.2 ± 0.9 Patients, n Overdose 1 4 2002 26 14 (53.8) 1.6 ± 1.9 300 Trauma 3 1 2003 119 41 (34.4) 1.2 ± 1.1 300 Cancer 2 1 4 2004 105 30 (28.6) 1.7 ± 1.0 300 Heart diseases/CVA 1 1 2005 68 19 (27.9) 1.2 ± 0.7 300 HCV/B -related 1 2 2006 108 32 (29.6) 1.1 ± 0.7 300 Other ill-defined or 2 2007 74 19 (25.7) 1.1 ± 0.4 300 unspecified cause of 2008 83 35 (42.2) 0.8 ± 0.2 330 death 2009 25 4 (0.16) 1.1 ± 0.1 330 Suicide 3 1 Sudden death 4 Septicemia, infection 1 1 COPD 1 to other MMT clinics, and 2.7% to other treatment facilities. DVT 1 Of the 242 opiate addict registrants who were not admitted Unknown 4 2 to any treatment, 47.9% were lost to contact, 18.2% reported py = person years; HCV/B = hepatitis B virus having undergone self-detoxification, 11.2% were in prison or under arrest, 16.1% refused to comply with the regulations involved in the process of admission, 0.4% were not admitted higher than those who were admitted to any treatment (P = due to their violent behavior, and 0.8% had prolonged QTc on 0.005). Their mean survival was 1.97 years (95% CI, 1.95- their electrocardiograms and were referred to cardiology (the 1.99), longer than those who were not admitted (log-rank chi latter 2 patients did not return) (Table 2). square [df = 1] 6.8, P = 0.009), and shorter than those who were eventually admitted (log-rank chi square [df = 1] 8.5, Two-Year Survival P = 0.004). Cause of deaths after up to 2 years are presented Mortality data were available for 583 (95.9%) of the co- in Table 3. hort: they included 358 (97.8%) of those who were admitted to MMT and 225 (92.3%) who were not admitted to any treat- Long-Term Survival (Up to 9 years) ment. The mortality rate after up to 2 years since registration The mortality rate after up to 9 years of follow-up was of the 225 who were not admitted to any treatment was signifi- higher for those who were not admitted to any treatment than cantly higher, that is, 5.0/100 py (21/418.8 py) than of the 358 for those who were treated (2.53/100 py [25 deaths, 989.9 py] who were eventually admitted, that is, 0.42/100 py (3/707.1 vs 1.68/100 py [29 deaths, 1723 py], respectively), but the py) (Fisher exact test, P < 0.0005). Their mean survival was difference did not reach a level of significance (Fisher exact 1.88 years (95% CI, 1.83-1.94) versus 1.99 years (95% CI, test, P = 0.09). Their mean survival was 7.87 years (95% CI, 1.98-2.0), respectively (log-rank chi square [df = 1] 25.7, P < 7.55-8.20) versus 7.97 years (95% CI, 7.77-8.16), respectively 0.0005) (Fig. 2). (log-rank chi square [df = 1] 2.1, P = 0.1) (Fig. 3). The mortality rate after up to 2 years of the early cohort control group was 2.2/100 py (17/774.7 py), lower than those who were not admitted to any treatment (P = 0.02), and TABLE 4. Cause of Death After up to 9 Years by Registrants who did or did not Receive any Treatment Received No Received Any TABLE 2. Place of Admission and Reason for Nonadmission Cause of Death Treatment Treatment Early Cohort to Any Treatment All causes n = 25 N = 29 N = 62 n % Deaths After 2 y Overdose 3 3 14 Trauma 3 2 7 Registered 608 100 (n) Cancer 2 9 8 Admitted to any treatment 366 100 Heart diseases/CVA 0 1 7 Our MMT 194 53.0 2 HCV/B-related 1 3 9 Other MMT/buprenorphine 162 44.3 1 Other ill-defined or 200 Other treatment 10 2.7 0 unspecified cause of Not admitted for any treatment 242 100 death No response 116 47.9 8 COPD/pulmonary 1 3 7 Self-report of detoxification 44 18.2 0 Suicide 3 1 2 Imprisonment/arrest 27 11.2 0 Sudden death 4 1 0 Refused 39 16.1 0 Septicemia 1 1 0 Violent behavior 1 0.4 0 Amyloidosis 0 1 Prolonged QTc* 1 0.8 0 DVT 0 0 1 Death 13 5.4 13 Unknown 5 4 7 MMT indicates methadone maintenance treatment. COPD indicates chronic obstructive pulmonary disease; CVA indicates cerebral *Referred to cardiology and did not return. vascular accident; HCV/B = hepatitis B virus; py = person years.

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FIGURE 2. Survival analyses at up to 2 years since registration to enter methadone maintenance treatment (MMT) among opiate addicts who received treatment, those who did not, and the early cohort controls who admitted with no delay.

The mortality rate after up to 9 years of the early cohort On the contrary, the earlier cohort group did present control group was 1.92/100 py (62/3221.8 py) and their mean higher mortality rate than those who were admitted after an survival was 8.3 years (95% CI, 8.1-8.5). Both mortality rate average delay of 1 year. These findings add to our preview and mean survival did not differ significantly from those who report that compared the retention rate of the early and late were or were not admitted to any treatment. Cause of deaths cohorts (Peles et al., 2012) and found the late cohort to present after up to 9 years are presented in Table 4. better retention rate. There were no differences between mean time to first This finding emphasizes the need to provide treatment as call, mean time to the latest call, mean number of total calls, soon as patients seek it. Our findings are consistent with other and vital status (data not shown). reports. In a large national study from Norway, of all opiate- dependent individuals who applied for opioid maintenance DISCUSSION treatment (a total of 3789 subjects), the mortality rate was Of the 608 opiate addicts who were seeking treatment higher among those on the waiting list between 1 and 365 and registered for our MMT clinic, 60.2% were eventually days compared to the addicts in treatment (Clausen et al., admitted either to our MMT clinic or to any other treatment 2008). Another Norwegian study on a small sample reported a facility. The remaining 39.8% were not treated anywhere. higher mortality rate for addicts while they were on the waiting Throughout the 2 years since they registered, 21 of the 24 list compared with those in MMT (Blix et al., 1999). Similar opiate addicts who died were among those who did not enter findings were reported in a summary of a few meta-analyses any treatment at all. The mortality rate was more than 10-fold (Amato et al., 2005). higher for the nontreated addicts compared with those who Because of the need to wait for a place to open, we were admitted to MMT. missed treating about 40% of the registered candidates. An- One may argue and think of the possibility that those other report among injection drug abusers who attempted to who died while on the waiting list could have died also while enter treatment reported that 66.7% did not come because they in treatment. We cannot rule out this possibility. Thus, we were placed on a waiting list (Pollini et al., 2006). A national emphasize our finding with the additional comparison group; study that included 28,920 subjects from 40 US metropolitan the earlier cohort group of patients who entered treatment with areas (Gryczynski et al., 2011) compared the characteristics of no delay and also presented lower mortality rate than of those patients who entered immediately with those whose treatment who were not admitted to any treatment. admission was delayed. The latter were characterized as having

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FIGURE 3. Survival analyses at up to 9 years of follow-up since registration to enter methadone maintenance treatment (MMT) among opiate addicts who received treatment, those who did not, and the early cohort controls who admitted with no delay. a racial/ethnic minority status, lower education, criminal jus- other causes, such as overdose, trauma, or suicide (all found tice referral, prior treatment experience, secondary cocaine or to be higher in the nontreated group). A separate study on alcohol use, and co-occurring psychiatric problems. Another the comparative incidence of cancer morbidity between the 2 study (Milloy et al., 2010) on 889 injection drug users who groups would be needed to arrive at any definitive conclusions. were randomly recruited from a supervised injection facility Studies that compared “interim methadone” with “stan- found that being unable to access treatment was independently dard methadone” (Schwartz et al., 2009; Schwartz et al., 2011) associated with recent incarceration, daily use of heroin, and found them both to be beneficial and concluded that either can borrowing used syringes. We could not characterize the indi- serve well as a solution when being on a waiting list to start viduals who did not enter our clinic, but our clinic guidelines MMT is unavoidable. On the basis of our mortality rate among and rules apply equally to all registrants and the only priority the waiting list registrants and the urgent need of immediate in jumping the queue is for pregnant women and HIV-positive expansion of MMT availability, an “interim methadone” could individuals. be considered as a temporary solution worth more investigat- A group of opioid-dependent persons from the streets ing. of Baltimore who underwent an ethnographic interview reported that having to be placed on a waiting list was one of the LIMITATIONS barriers to entering MMT (Peterson et al., 2010). They also Despite our interpretation of the findings, it is still pos- reported about problems with health insurance and having an sible that some of those who died while waiting to be admitted identification card with a photograph. Israel has a policy of were in such a deteriorated physical condition, that they might mandatory health insurance for all citizens and the posses- have died even if accepted without delay. However, the fact sion of such identification, leaving the waiting list as the only remains that these drug addicts wanted to enter treatment (ie, potential barrier to the entrance into MMT. they had registered and were willing to start immediately), but In terms of the cause of death after up to 9 years of they encountered the barrier of a long waiting list and died follow-up, 1/3 of the nonsurviving patients who entered any before their treatment could begin. treatment died of cancer, compared with less than 1/10 of those who did not enter treatment. We had earlier noted that REFERENCES our MMT patients had high mortality rates due to cancer (Peles Addenbrooke WM, Rathod NH. Relationship between waiting time and re- et al., 2010). The relatively “low” rates of cancer among those tention in treatment amongst substance abusers. Drug Alcohol Depend who did not enter any treatment could be due to death from 1990;26:255–264.

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