The World Journal of Biological Psychiatry, 2014; 15: 629–635
ORIGINAL INVESTIGATION
Impact of lifetime psychiatric diagnosis on long-term retention and survival of former opiate addicts in methadone maintenance treatment
EINAT PELES1,2*, SHAUL SCHREIBER1,2*, YOAV DOMANY1,2 & MIRIAM ADELSON1 1Dr.
Miriam & Sheldon G. Adelson Clinic for Drug Abuse, Treatment & Research, Tel Aviv, Israel, and 2Department of Psychiatry, Tel-Aviv Sourasky Medical Center, and Sackler Faculty of Medicine Tel Aviv University, Tel Aviv, Israel
Abstract Objectives. To characterize lifetime psychiatric diagnosis groups among methadone maintenance treatment (MMT) patients and associations of diagnosis to long-term (up to 20 years) retention and survival either during treatment or post discontinuation. Methods. A total of 758 patients with available psychiatric diagnosis (98% of those ever admitted between June 1993 and June 2012) were followed-up until June 2013. Lifetime psychiatric diagnosis was assessed according to DSMIV-TR (Axis I, II, I & II, or none). Observed urine samples at 1 and 13 months were positive for drugs if at least one was positive. Survival data were based on the Israel National Population Registry. Survival and retention in MMT were compared (Kaplan Meier) between groups. Results. The Axis II (personality disorders) group had the worst mean long-term retention (5.8 years, 95% Confidence Interval (CI) 5.0–6.5) compared with the Axis I, Axis I & II or no psychiatric diagnosis groups (9.6 years, 95% CI 8.8–10.4) (P ⬍ 0.0005). Mean survival since admission (16.4 years, 95% CI 15.9–16.9) was similar for all groups. Axis II patients included more males, more drug injectors, were younger at initial opiate use and more likely left treatment before 1 year. Conclusions. Personality and coping mechanisms (Axis II) could be significant obstacles to the success of MMT, warranting special interventions to overcome them. Key words: opioids, methadone maintenance treatment, survival, retention, personality disorders
Introduction Many of the former opiate addicts in MMT are affected by additional psychiatric disorders. The reported rate of comorbidities ranged between 50 and 70% (Callaly et al. 2001; Ross et al. 2005; Wedekind et al. 2010). In contrast to other medical settings where comorbid psychiatric disorders consistently portended a worse outcome (i.e., depression (Newton-Howes et al. 2014), complex post-traumatic stress disorder (Van Der Kolk et al. 2007), the outcome of individuals with a psychiatric comorbidity among MMT patients has been reported to be comparable (Maremmani et al. 2000; Cacciola et al. 2001; Gerra et al. 2004; Pani et al. 2011), worse (Salamina et al. 2010) or better (Gelkopf et al. 2006; Maremmani et al. 2008, 2013) than the MMT patients without psychiatric comorbidities.
The inconsistent finding could be related to methodology differences such as differences in duration of follow-up; from 3 months of follow-up by Gerra et al. (2004), 6 months by Salamina et al. (2010), 7 months by Cacciola et al. (2001), 1 year (Pani et al. 2011), 2.5 years (Maremmani et al. 2000), 3 years (Gelkopf et al. 2006; Maremmani et al. 2013), and up to 6 years (Maremmani et al. 2008). Studies also differ by sample size (from hundreds of patients in most studies, to a multi-centre study that included more than ten thousand patients (Salamina et al. 2010). It may also be related to study population; some investigators studied any Axis I DSM diagnoses (Maremmani et al. 2008), while others studied specific diagnosis (i.e., treatment-resistant patients with the psychiatric comorbidity of bipolar I disorder only (Maremmani et al. 2013).
*Equal contribution. Correspondence: Einat Peles, PhD, Adelson Clinic for Drug Abuse, Treatment & Research, Tel-Aviv Sourasky Medical Center, 1 Henrietta Szold Street, Tel Aviv 64924, Israel. Tel: ⫹ 972-3-6973226. Fax: ⫹ 972-3-6973822. E-mail:
[email protected] (Received 26 February 2014 ; accepted 2 July 2014 ) ISSN 1562-2975 print/ISSN 1814-1412 online © 2014 Informa Healthcare DOI: 10.3109/15622975.2014.942359
630 E. Peles et al. In the present longitudinal study covering 20 years, we evaluated the characteristics and outcomes (cumulative retention in treatment and survival during treatment or following its discontinuation) of MMT patients with and without psychiatric comorbidities. After comparing four specific groups, i.e., DSM-IV-TR Axis I, DSM-IV-TR Axis II, DSMIV-TR Axis I & II, and no psychiatric diagnosis, it emerged that the Axis II group differed from the other three. We therefore compared the characteristics and outcomes of the Axis II group with those of the other three groups combined in order to determine the reasons for these differences.
others (e.g., women’s issues, violence control, and 12 Steps) (Potik et al. 2011). Only violent aggressive behaviour or selling drugs within the clinic may result in immediate discontinuation of treatment. Urine toxicology
The study was approved by the local IRB of the Tel-Aviv Sourasky Medical Center (TASMC) (No. 05-217).
A randomized observed urine sample (range 1–8 per month, average two samples per month) was provided by each patient throughout his/her entire course of treatment. All urine samples were analysed for opiates, methadone, cocaine metabolite (benzoylecgonine), benzodiazepines (BDZ), cannabis (THC), methadone metabolite and amphetamines using enzyme immunoassay systems (DRI® for the first six and CEDIA® for the last two) (Hawks 1986). Observed urine samples at 1 and 13 months were taken for analyses and defined positive if at least one was of the sample was positive.
Study population
Statistical analyses
All 772 patients ever admitted to our MMT clinic between its establishment in June 1993 until June 2012 were followed-up until June 2013. Psychiatric diagnosis was available for 758 of them, and information on survival was available for 753. Lifetime psychiatric diagnosis (DSM -IV Axis I, II, I & II, and none) was determined by the clinic’s psychiatrists using the “Overview” part of the Hebrew validated version of the SCID (Shalev et al. 1996) and a battery of standard questionnaires (i.e., Hamilton rating scale for depression (HAM-D) (Hamilton 1960); Brief Psychiatric Rating Scale BPRS (Overall and Gorham 1988), etc.). Survival as of June 2013 was based on the Israel National Population Registry that records all deaths in the country. Demographic data were collected from the patients’ charts that routinely include a modified Addiction Severity Index questionnaire (McLellan et al. 1984).
Analysis of variance was used for differences between continuous variables and the chi-squared test was applied for categories variables. Bonferroni correction for multiple comparisons was used when needed. Retention in treatment and survival were calculated from the first MMT admission until the patient left treatment, or died (either during treatment or post discontinuation), respectively, or until the end of follow-up using Kaplan–Meier survival analyses (the results are given as mean and 95% confidence interval [95% CI]). The logistic regression conditional forward model was used to characterize the Axis II group, and it included all variables that were found significant in the univariate analyses.
Methods
Clinic The clinic characteristics have already been described in detail (Peles et al. 2008). In brief, each patient drinks the individual methadone dosage every day in the clinic and is encouraged to earn the privilege to receive “take home” dosages of medication (for up to 2 weeks) if they stop illicit drug use and present acceptable behaviour. Patients attend regular personal psychosocial therapy appointments with specialized counsellors (Potik et al. 2007, 2014; Abramsohn et al. 2009). Patients also participate in several therapy groups (i.e., a mandatory seminar for newly admitted patients) and may participate in
Results Comparisons between characteristics of the psychiatric diagnoses groups (Table I) The groups differed in age of onset of opiate use (the youngest were in the Axis II group) and in the duration of opiate use. Groups did not differ in the proportion of those who ever used THC, but its onset differed by the groups. The age at onset of BDZ use was similar, but the proportion of ever BDZ use differed between the groups. Drug injection was most prevalent among the Axis II patients and least among the no psychiatric diagnosis patients: this was also in accordance with the hepatitis C virus sera-positive rate. There was a trend towards significance for more immigrants being in the no psychiatric diagnosis group, which also had the highest rate of cocaine
Retention and survival of methadone maintained patients
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Table I. Differences in characteristics between the psychiatric groups. Variable Number Admission age, years Opiate onset age, years Duration of usage, years THC ever useda n (%) THC onset age, years BDZ ever usedb n (%) BDZ onset age, years Female, n (%) Education, years Drug injectors, n (%) HCV antibody, n (%) HIV antibodyc, n (%) Immigrant, n (%) Living alone, n (%) BDZ, n (%) THC, n (%) Cocaine, n (%) Retention after 1 year, n (%) Drug after 1 year Opiates, n (%) BDZ, n (%) THC, n (%) Cocaine, n (%)
None
I & II
Axis I
Axis II
P(F)
101 40.4 ⫾ 10.8 23.1 ⫾ 6.9 16.8 ⫾ 9.4 91 (94.8) 18.6 ⫾ 6.2 82 (90.1) 27.1 ⫾ 9.3 27 (26.7) 10.0 ⫾ 2.8 56 (55.4) 46 (45.5) 8 (7.9) 48 (47.5) 69 (68.3) 56 (56) 9 (9.0) 33 (33.0) 80 (79.2)
194 37.9 ⫾ 8.5 23.4 ⫾ 7.4 14.3 ⫾ 8.8 156 (97.5) 16.4 ⫾ 4.0 166 (98.8) 27.4 ⫾ 10.1 60 (30.9) 9.7 ⫾ 2.5 127 (65.5) 100 (51.5) 15 (7.7) 70 (36.1) 129 (66.5) 114 (58.8) 27 (13.9) 34 (17.5) 167 (86.1)
88 38.6 ⫾ 9.4 23.0 ⫾ 7.9 15.4 ⫾ 8.4 74 (92.5) 18.3 ⫾ 6.7 78 (92.9) 29.2 ⫾ 9.9 26 (29.5) 10.0 ⫾ 2.9 63 (71.6) 51 (58.0) 8 (9.1) 27 (30.7) 67 (76.1) 50 (57.5) 13 (14.6) 16 (18.4) 74 (84.1)
375 38.4 ⫾ 9.5 21.7 ⫾ 6.3 16.7 ⫾ 9.2 293 (97.3) 17.0 ⫾ 5.7 299 (98.4) 28.2 ⫾ 9.8 85 (22.7) 9.5 ⫾ 2.9 274 (73.3) 220 (58.7) 28 (7.5) 131 (34.9) 261 (69.8) 222 (59.2) 41 (10.9) 92 (24.5) 264 (70.4)
0.1 0.02* (3.2) 0.02* (3.4) 0.2 0.006* (4.2) 0.001 0.7 0.2 0.2 0.005 0.03 0.9 0.08 0.4 0.9 0.4 0.02 ⬍ 0.0005
22 34 5 18
(27.5) (42.5) (6.2) (22.5)
57 90 33 24
(34.1) (53.9) (19.8) (14.4)
27 42 12 15
(36.5) (56.8) (16.2) (20.3)
80 113 38 45
(30.3) (42.8) (14.4) (17.0)
0.5 0.04 0.03 0.4
THC, cannabis; BDZ, benzodiazepine; HCV, hepatitis C. a16% unknown; b14.6% unknown; c10.2% unknown; d4.1 unknown; e4.6% unknown. *After Bonferroni correction for multiple comparisons Axis I & II group differed Axis II group in opiate onset age (P ⫽ 0.02) and in duration of opiate usage (P ⫽ 0.02), and Axis I & II group differed Non Axis group in THC onset age (P ⫽ 0.02).
abuse on admission. There were no group differences in other drugs at the time of admission. Retention The one-year retention rate was 86.1% for the 194 Axis I & II patients, 84.1% for the 88 Axis I patients, 79.2% for the 101 patients with no psychiatric diagnosis, and 70.4% for the 375 Axis II patients (chisquared ⫽ 22, P ⬍ 0.0005). The mean long-term retention (up to 20 years) for the Axis I & II group was 10.1 years (95% CI 9.0–11.2), 9.4 years (95% CI 7.5–11.2) for the no psychiatric diagnosis group, 8.3 years (95% CI 6.8–9.9) for the Axis I group and 5.7 years (95% CI 5.0–6.5, log rank chi-squared ⫽ 52.0, P ⬍ 0.0005) for the Axis II group. After having left treatment, readmission rate did not differ between the groups (24.6% of the 214 Axis II patients who left, 25.5% of the 51 Axis I, 29.3% of the 123 Axis I & II who left and 13% of the 46 with no psychiatric diagnosis, P ⫽ 0.2). Survival The mean cumulative survival since admission to MMT and up to 20 years did not differ according to
psychiatric diagnoses, and it was 16.4 years (95% CI 15.9–16.9) for all patients. Specifically, the mean cumulative survival for the Axis I & II patients was 17.1 years (95% CI 16.4–17.9), 16.2 years (95% CI 15.5–16.9) for the Axis II patients, 15.5 years (95% CI 13.8–17.2) for the patients with no psychiatric diagnosis, and 15.5 years (95% CI 13.9–17.1) for the Axis I patients (log rank chi-squared ⫽ 3.4, P ⫽ 0.3).
Comparison between the Axis II patients and the other patients (Table II) The Axis II group differed from the other three groups by having fewer females (22.7 vs. 29.5%, respectively, P ⫽ 0.04), a younger mean age at opiate use onset (21.7 ⫾ 6.3 years vs. 23.3 ⫾ 7.4 years, P ⫽ 0.001), longer mean opiate use pre-MMT (16.7 ⫾ 9.2 years vs. 15.1 ⫾ 9.0 years, P ⫽ 0.02), a higher rate of ever drug injectors (73.3 vs. 64.2%, P ⫽ 0.008), and a high rate of hepatitis sera-positive patients (58.7 vs. 51.4%, P ⫽ 0.03). The 1-year retention rate was 70.4% among the Axis II group, which was significantly lower than the rest in combination (83.8%, P ⬍ 0.0005). Logistic regression found that the Axis II group was characterized by more males, more drug injectors, younger age at opiate use onset and more MMT dropouts before
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E. Peles et al. Table II. Differences in characteristics between Axis II and other psychiatric groups. Variable Number Admission age, years Opiate onset age, years Opiate usage, years Female, n (%) THC ever usea, n (%) THC onset age, years BDZ everb, n (%) BDZ onset age, years Education, years Drug injectors, n (%) HCV antibody, n (%) HIV antibodyc, n (%) Immigrant, n (%) Living alone, n (%) BDZ, n (%) THC, n (%) Amphetaminesd, n (%) Cocaine, n (%) Retention after 1 year, n (%) Drug after 1 year Opiates, n (%) BDZ, n (%) THC, n (%) Amphetaminese, n (%) Cocaine, n (%)
Axis II
Others
P(F)
375 38.4 ⫾ 9.5 21.7 ⫾ 6.3 16.7 ⫾ 9.2 85 (22.7) 293 (97.3) 16.9 ⫾ 5.7 299 (98.4) 28.2 ⫾ 9.8 9.5 ⫾ 2.9 274 (73.3) 220 (58.7) 28 (8.8) 131 (34.9) 261 (69.8) 222 (59.2) 41 (10.9) 34 (9.2) 92 (24.5) 264 (70.4)
383 38.6 ⫾ 9.5 23.3 ⫾ 7.4 15.1 ⫾ 9.0 113 (29.5) 321 (95.5) 17.5 ⫾ 5.5 326 (95.0) 27.9 ⫾ 9.9 9.8 ⫾ 2.7 246 (64.2) 197 (51.4) 31 (8.6) 145 (37.9) 265 (69.2) 220 (57.7) 49 (12.9) 21 (5.8) 83 (21.8) 321 (83.8)
0.7 0.001 (10.3) 0.02 (5.1) 0.04 0.3 0.2 0.03 0.7 0.09 0.008 0.03 1 0.4 0.4 0.7 0.4 0.9 0.4 ⬍ 0.0005
80 113 38 11 45
106 166 50 25 57
(30.3) (42.8) (14.4) (4.4) (17.0)
(33.0) (51.7) (15.6) (8.1) (17.8)
0.5 0.04 0.7 0.08 0.9
a19.7%
unknown among Axis II and 12.3% among others; b18.9 and 10.4%, respectively; c15 and 5.7%, respectively; d4.2 and 3.9%, respectively; e5.5 and 4%, respectively. THC, cannabis; BDZ, benzodiazepine; HCV, hepatitis C.
1 year in treatment (Table III). The mean long-term retention (up to 20 years) for the Axis II patients was 5.8 years (95% CI 5.0–6.5) compared to 9.6 years (95% CI 8.8–10.4) for the other three groups in combination (log rank chi-squared 50.9, P ⬍ 0.0005) (Figure 1). The Cox model found none of the variables that differed between the groups (i.e., gender, drug injection and age at opiate onset) to be significantly related to long-term retention (data not shown). Discussion The Axis II group had a worse cumulative and 1-year retention rates compared with the Axis I, Axis I & II and no psychiatric diagnosis groups. We had conTable III. Logistic regression for Axis II psychiatric diagnosis.
B Male Drug injector Opiate onset Left before year Constant
SE
Wald
P Value
.4 .4 .0 .6
.2 .2 .0 .2
4.1 4.7 9.6 7.3
0.04 0.03 0.002 0.007
⫺1.5
.3
20.0
Exp (B)
95% CI
1.5 1.5 1.0 1.8
1.01–2.2 1.04–2.1 1.01–1.1 1.2–2.8
⬍ 0.0005 0.2
ducted a study on retention in MMT that included the first 151 consecutive patients admitted and followed-up for 1 year during the first 3 years of operation of the MMT clinic (Gelkopf et al. 2006). We had found that patients diagnosed with lifetime (at the time DSM-III-R) Axis I disorders remained in treatment longer than non-Axis I patients. We suggested that patients with any Axis II diagnosis (personality disorder) are probably less adherent with therapy and that this may manifest in poor retention in the MMT since they are not receiving any medications for the personality disorder. They also tend to drop out of the program before having the chance to benefit from it. On the other hand, if the Axis II patients also had Axis I psychiatric diagnosis symptoms that were ameliorated with medications, their perceived improvement of their overall condition might increase their adherence with the MMT program. The current study extended that earlier one, and now included 758 patients with a follow-up of up to 20 years. Maremmani et al. (2013) also found that patients with an Axis I psychiatric diagnosis had a better outcome in MMT. A group of treatmentresistant patients with the psychiatric comorbidity of bipolar I disorder showed a better long-term outcome than treatment-resistant patients without
Retention and survival of methadone maintained patients
Figure 1. Long-term retention up to 20 years for Axis II psychiatric diagnosis and other diagnoses.
any psychiatric comorbidity. Cacciola et al. (2001) found no differences based on psychiatric comorbidity after 7 months of follow-up in MMT. Consistent with our findings, they reported a trend indicating poorer treatment adherence for participants with personality disorders. The transition from the way of life in the streets of the heroin-abusing patients to a boundariesdemanding MMT clinic with its regulations and rigid schedules is far beyond the capabilities of some of the most severe DSM-IV-TR Axis II patients (e.g., cluster B antisocial or borderline personality disorder). Non-adherence to a therapeutic program among patients with an Axis II psychiatric diagnosis is not confined to MMT: it has been also reported with respect to other kinds of treatments, such as in liver transplant (Calia et al. 2011), HIV medications (significant nonadherence among individuals with borderline personality disorder) (Palmer et al. 2003), and those for various medical conditions (Dean et al. 2013). We have already reported (Peles et al. 2010), that one of the independent predictors for longer retention up to 15 years in MMT is just not being affected by an Axis II-only diagnosis. In the current study, we specifically compared characteristics and outcomes of the four psychiatric diagnoses and the differences we found were between the one (Axis II) compared to the other three in combination (Axis I, Axis I & II, and no psychiatric diagnosis).
633
The Axis II group had the youngest age at opiate onset as well as THC onset and both substances being used at a young age may be highly likely related to the possibility of self-medication due to their psychiatric condition. The Axis II patients who also had an Axis I diagnosis were younger at the onset of THC use, and this might also similarly reflect self-medication. In contrast to the situation during MMT, of medication advantage among the Axis I and II diagnosis group on the group of Axis II only with no medication, at the young age of starting THC, the Axis I and II had no advantage as most likely they were not under any medication or treatment. Duration of opiate usage before admission to MMT was longer among the Axis II patients: given that all four groups were admitted to MMT at a similar age, this finding indicated that patients with personality disorders might have waited longer to seek treatment. Interestingly, once they had been admitted to MMT, the Axis II group did not differ from the other groups with respect to the tested drugs in urine (cocaine, BDZ, THC and amphetamines). This is in contrast to Brooner et al.’s (1997) findings on 716 MMT patients in whom a psychiatric comorbidity was also associated with a more severe substance use disorder. Our results showed that the personality disorders group consisted mainly of males, a finding that is supported by two previous reports (Samuels 2002, 2011) but not all (Grella et al. 2009). Those studies also characterized the Axis II patients as being less educated and mostly alone (single or divorced), two factors that did not characterize our group. However, the disparity is most likely related to the fact that all of our patients are former opiate addicts, hence most of them characteristically have such problems. Of all the patients in MMT, the personality disorders group had higher rates of drug injectors and, accordingly, more of them were hepatitis C sera-positive on entry to MMT. Despite there not having been differences in drugs found in admission urine tests, fewer patients with personality disorders stayed in treatment for 1 year than the other studied groups. Of those Axis II patients who did stay in treatment, however, fewer were positive to BDZ than those in the other groups who stayed in treatment. This unexpected finding may have been the result of the severe cases having dropped out, leaving a selective, better group, and therefore having less abuse. In contrast to the significant group differences in retention, the survival measured from the time of admission to MMT up to study closure (independent whether patients left treatment) did not differ among the study groups. We would have expected to find those who dropped out of treatment earlier to be at a higher risk to die on the streets: the group size and the person-year
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follow-up may not have been sufficient for any conclusions to reach a level of significance. There are no survival studies specific to Axis II patients, however one that evaluated cancer deaths among a psychiatric population (Perini et al. 2013) found personality disorders as being one of the independent risk factors to higher mortality in specific anatomic sites (standardized mortality ratios ⫽ 28 for the central nervous system) together with alcoholism (5.9 for the larynx) and affective disorders (20 for lymphomas). The cumulative retention seems different following 15 years of follow-up. Thus, analyzing the subgroup of those who stayed at least 15 years we found even the opposite direction. Specifically, of the 14 Axis II only patients who stayed 15 years as compared to the 40 others, the cumulative retention up to 20 years was significantly longer (P ⫽ 0.05). Despite the very small numbers we may cautiously conclude that if an Axis II patient succeeded in staying 15 years, for the next years, no difference exists. We recognize that different psychiatrists may disagree about a patient’s fulfilment of some DSM criteria. One limitation of our study is that different psychiatrists diagnosed the study patients upon admission during the long study period of 20 years. At the same time, our large cohort and long follow-up are also strengths of this study. Moreover, the fact that our current 20 years follow-up study findings were consistent with our earlier smaller and shorter duration analyses reports emphasizes that this is a real finding. In summary, individuals with personality disorders are characterized as having had more risky behaviour prior to admission to MMT, and those maladaptive coping mechanisms (Axis II psychiatric diagnosis) may pose significant obstacles to the long-term success of MMT. The current challenge is to design specific interventions that may help overcome this obstacle. When a personality disorder is accompany with an Axis I mental condition (usually treatable with medications), the outcome in the MMT is comparable to individuals with Axis I only and those with no psychiatric diagnosis at all.
Acknowledgments The study was funded by “The Adelson Family Foundation”. We thank Esther Eshkol for English language editing.
Statement of interest None to declare.
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