URBAN OFFICE-BASED BUPRENORPHINE/NALOXONE OPIOID MAINTENANCE THERAPY: OUTCOMES AT 18 MONTH FOLLOW-UPMedical Student Researcher: Mace AGa

Principle Investigators: Adelman CAa,b, Parran TVa,d

Co-Investigators: Pagano MEa,c, Merkin BJa,b, Defranco Ra,b, Ionescu RAa

a Case Western Reserve University School of Medicine, Cleveland, OH

b St. Vincent Charity Hospital, Rosary Hall, University Hospitals Health System, Cleveland, OH

c Division of Child Psychiatry, Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, OH

d Department of Psychiatry, St. Vincent Charity Hospital, Cleveland, OH

Opioid Dependence A Significant Burden on the Patient

Increased: Mortality, Disability, Hepatitis, HIV, Healthcare costs, Unemployment, Incarceration

Major Public Health Problem $21.8 Billion in medical, legal, and social

costs attributable to heroin addiction alone (1996 est.)

Opioid dependence is a growing problem Incidence: 2006 NSDUH

~2.1 million new initiates to non-medical use of prescription pain relievers Surpassed marijuana Highest of any illicit drug

91,000 new initiates to heroin Prevalence: 2006 NSDUH

5% population reports to non-medical use of prescription pain relievers in 2006

2 per 1000 report heroin use (0.2% population)

( Baral et. al., 2007; Blanchard et. al., 2003,; Dekker, 2007; Donaher & Welsh, 2006; Hser et. al., 2001; Mark et. al.; 2001; McLellan et. al., 2000; White et. al., 2005)

* Formerly NHSDA

Interventions

The Question: How do we help opioid dependent patients achieve abstinence and return to more healthy productive lives? Traditionally a difficult & lengthy road to recovery High rate of relapse Several Approaches:

Abstinence based treatment programs 12-step support programs Pharmacotherapy:

Opioid Maintenance Therapy (Methadone, LAAM, Buprenorphine/Naloxone)

Opioid antagonists (Naltrexone) Palliative therapy for withdrawal sx. (Clonidine,

Loperamide, Trazodone, Dicyclomine, etc.) Multifaceted approach is most effective

Opioid Maintenance Therapy What is it?

Long-term opioid agonist therapy prescribed for / provided to opioid dependent patients as an alternative to illicit opioid use and an adjunct to more intensive treatment programs

Use orally administered agonists with extended half lives or partial agonists daily or alternate day dosing reduced euphoric effect facilitates psychosocial functioning vs. shorter-acting, stronger

opioids Why do it?

Useful adjunct therapy in treatment-refractory patients Significantly increased rates of abstinence from illicit opioid

use Improved functioning within the family and job Decreased legal problems Oral agents eliminate needle sharing and consequent

infectious disease risk

(Schuckit, M.A.,  Segal, D.S, 2005. Chapter 373. Opioid Drug Abuse and Dependence. The McGraw-Hill Companies, Inc.)

Opioid Maintenance Therapy Since the 1960’s: Methadone

Low Cost, but: Few clinics, Stringent criteria, Long waitlists, Social stigma

Only 14% of patients dependent on opioids are treated in methadone clinics

Drug Addiction Treatment Act of 2000 Physicians can provide office-based

treatment to opioid addicted patients Buprenorphine is approved by the

FDA in 2002 for office-based use as opioid maintenance therapy These moves by the FDA paved the

way for major changes in the way addiction is treated in the United States, potentially making opioid maintenance therapy available to a much larger population of patients Above: Methadone

Below: A Methadone Clinic

Buprenorphine Unique Pharmacologic Profile

Partial agonist at mu-opioid receptor, antagonist at the kappa-opioid receptor

Combined with Naloxone in a 4:1 ratio in the Buprenorphine/Naloxone combination tablet (Suboxone®)

Benefits (vs. Methodone/LAAM) Convenience of traditional pharmacy

prescription (rather than daily dose pickup at a methadone clinic)

Decreased potential for harm in the event of medication diversion

Decreased potential for harm in the event of medication overdose

Ease of dosage titration Ease and brevity of eventual tapering

off the medication Probably a decreased impact on the

patient’s cognitive function(Carrieri et al., 2006; Fiellin et al., 2004; Fiellin and O'Connor, 2002a; Fudala et al., 2003; Harris et al., 2000; Jasinski et al., 1978; Johnson et al., 2000; Johnson et al., 1992; Ling et al., 1998; Ling et al., 1996; Mattick et al., 2003; Mendelson and Jones, 2003; Simoens et al., 2005; Strain et al., 1994; Walsh and Eissenberg, 2003).

www.naabt.org

Study Goals

There are a few areas in which research on buprenorphine OMT is lacking, which we address with the present study: Long term outcome data on the use of Bup/Nx

office-based OMT in the United States Effectiveness of Bup/Nx office-based OMT in

disadvantaged populations The impact of patient characteristics on

retention in and outcomes of office-based Bup/Nx therapy

Answers to these questions have the potential to guide clinical decision-making as well as the allocation of, often scarce, resources for substance abuse rehabilitation(Fiellin et al., 2004; Simoens et al., 2005; Alford et al., 2007; Auriacombe et al., 1994; Fhima et al., 2001; Giacomuzzi et al., 2005; Kakko et al., 2003; Kornor et al., 2007; McLellan et al., 2000)

Parameters

Patient characteristics – Chart Review Demographics

Able to pay Drug use characteristics (DOC, ROA, etc.) Medical Comorbidities Legal Comorbidities

Treatment Characteristics – Short Survey Adverse Effects

Outcomes – Telephone Interview at 18 months Substance Use (Primary) 12-Step Affiliation Employment Psychosocial

Hypotheses

Hypothesis A: Individual patient characteristics may increase or

decrease retention in buprenorphine/naloxone office based therapy at 18 months.

Hypothesis B: Retention in buprenorphine/naloxone office-based

opioid maintenance therapy (Hereafter OBT) will decrease substance use, increase 12-step affiliation, and improve occupational and psychosocial function at 18 months.

Hypothesis C: Treatment characteristics may increase or

decrease retention in buprenorphine/naloxone OBT at 18 months.

Patient Population

176 opioid dependant adults Aged between 19 and 65 years Met the criteria for admission into

the treatment program Multiple failed attempts at abstinence Lack of uncontrolled major mental illness

or psychosis Stable living situation

Patient Population

Two Socioeconomic Status levels Possessed the financial means for treatment

(Private insurance, Medicare, or Medicaid). Alternatively, patients with limited financial

means who met all other criteria were accepted and their care was publically funded by a grant from ADASBCC (Alcohol and Drug Addiction Services Board of Cuyahoga County)

Created two distinct populations for study Financially solvent patients traditionally well

studied Indigent patients thus far poorly studied

Definitions

Solvent: “Assets exceed liabilities” Able to meet cost of medical care

Indigent i.e. “Medically indigent adult” “Persons who do not have health insurance and

who are not eligible for other health care coverage, such as Medicaid, Medicare, and cannot otherwise afford treatment”

In our study, the patient population was separated based on this characteristic, which was assessed using insurance status in our research methodology Really a proxy for complex sets of differences in

patient characteristics and living situations

Protocol & Methods

Induction (60 Hours) Preadmission assessment of addictive disorder Admitted to the SVCH – Rosary Hall detoxification unit for buprenorphine

induction therapy When clinical stability was ascertained, discharged to home or a residential

program with a written prescription for a 2 week supply of Bup/Nx sublingual combination tablet (Suboxone®).

Stabilization (6 wks) Intensive outpatient treatment (Residential facility for grant funded

patients) Random urine toxicology screening Participation in aftercare group psychotherapy Regular 12-step meeting (e.g. AA or NA) Pattern of noncompliance resulted in administrative discharge

Follow-Up (2-4 week intervals) Follow up appointments at Rosary Hall were scheduled on a strictly regular

basis A questionnaire comprised of severity ratings on 7 symptom parameters

was completed by the patient at each follow up visit. If continued participation in the program was deemed appropriate by the

physician, a new prescription for Suboxone was written and given to the patient.

Protocol & Methods

Chart Review Basic demographic information Medical history Drug abuse history Information from the patient’s

stabilization phase of treatment

Protocol & Methods

Telephone Interview Confidential interview conducted at

18mo post-induction Questions

Opioid use history Current Bup/Nx medication Current illicit drug use Presence of both long and short term

opioid complications Fifteen questions measuring social role

and occupational function

Results

176 subjects were initially enrolled in our study

110 (63%) completed the follow-up telephone interview at 18 months No significant differences in the baseline

characteristic variables between subjects who completed the telephone interview and those who did not

Exception: Subjects who could not be scheduled for a telephone interview were more likely to have an arrest history than those available for follow-up (44% vs. 26% respectively, χ2

[1]=4.96, p=0.03).

Results Subgroup Analysis: Buprenorphine/Naloxone Status

At follow-up, the majority of subjects reported that they had remained on Bup/Nx-OBT (77%)

Those still using Bup/Nx were: ~24% Less likely to be using any substance (χ2

=6.26, p=0.0123) 21% Less likely to be using heroin (χ2=8.1, p=0.0044)

~29% More likely to be AA Affiliated (χ2=5.49, p=0.0191) 31% More likely to have a sponsor (χ2=4.72, p=0.0298)

8% More likely to have been employed at baseline (χ2=4.92, p=0.0266). 30% More likely to be employed at follow-up (χ2=4.89,

p=0.0271)Preexisting medical and legal comorbidity were important covariates in our analysis and all subgroup analyses have been controlled for baseline medical and legal comorbidity.

Results Subgroup Analysis: Buprenorphine/Naloxone Status

Interesting trends that didn’t quite meet the significance level Those remaining on Bup/Nx at follow-up were:

Less likely to be using alcohol (4% vs. 16.5%, χ2=3.8, p=0.0513)

More likely to have a home group (85% vs. 49%, χ2=3.40, p=0.0654)

More likely to have reported prescription opioid use at baseline (13% vs. 7.5%, χ2=3.13, p=0.0768)

More likely to be newly employed at follow-up (65% vs. 35.5%, χ2=2.84, p=0.0918)

May be directions for future research

ResultsSubgroup Analysis: Solvent vs. Indigent Patients

Sixty two of the 110 patients completing the follow-up telephone interview were indigent (56%).

No significant difference between indigent and solvent patients was noted in: Bup/nx use at follow-up (80% vs. 73% p=0.33)  Employment status across the study period

One Exception – insured were more likely to be employed at baseline (37% vs. 10%, χ2=4.84, p=0.028)*

Indigent patients were 8% More likely to report substance use at follow-up (18%

vs. 10%, χ2=4.09, p=0.0432 ) 9% More Alcohol use (11% vs. 2%, χ2=4.95, p=0.026) 12% More Heroin use (18%vs/ 6%, χ2=7.97, p=0.0047) No significant differences were observed for cocaine use.

Less likely to be from a minority background (16% vs. 35%, χ2=6.82 p=0.009)

Less likely to have a significant other (36.5% vs. 81.5%, χ2 =12.36 p=0.0004)

Results Psychosocial Outcome Measures

Those remaining on Bup/Nx use at follow-up were Less likely to have reported Damaging a close relationship (26% vs. 52%, χ2=6.07, p=0.014) Doing regretful or impulsive things (28% vs. 52%, χ2=4.89, p=0.027) Hurting family (28% vs. 60%, χ2=8.52, p=0.004) Experiencing negative personality changes (26% vs. 48%, χ2=4.43,

0.035) Failing to do things expected of them (24% vs. 56%, χ2=9.54, p=0.002) Taking foolish risks (21% vs. 56%, χ2=11.36, p=0.0008) Being unhappy (27% vs. 60%, χ2=9.27, p=0.002) Having spent too much/lost money (27% vs. 52%, χ2=5.46, p=0.0195) Were significantly less likely to report having money problems

generally (29% vs. 56%, χ2=5.97, p=0.015). Unfortunately, our study design did not allow these results to

be controlled for illicit opioid abstinence. Therefore, the improved psychosocial outcomes we observed

in subjects who remained on Bup/Nx are just as likely due to the markedly decreased rate of substance use observed in that population (8.5% vs. 32% respectively, χ2=6.26, p=0.0123).

Results Adverse Effects

No differences in opioid use complications were found between patients who were and were no longer taking Bup/Nx with two exceptions:

Patients still taking Bup/Nx reported: more constipation (p=.04) lower craving (p=.0001)

However, those data may be confounded by interviewees’ conception of the questions being posed at follow-up

Discussion

110 patients (63%) completed the telephone interview, we believe this study to be the largest US case-series to date to report outcomes of Bup/Nx OBT at long term follow-up.

This study examines outcomes in a different population than other studies conducted to date. Most researchers have studied insured, financially solvent patients One group has studied the homeless Our indigent patients lie somewhere in between.

Most of the patients involved in our study were housed, however, the majority of our indigent patients were also: unemployed (89%) unmarried (86%) injection drug users (82%) As well as unable to afford the costs of treatment (by definition)

In this understudied population, it is possible that unique risk factors and the decreased level of stability associated with their life situation may make office-based Bup/Nx therapy a less effective option.

Our data show this to be untrue by demonstrating no significant differences in OBT retention between our solvent and indigent patients.

Discussion

One overarching goal of this study: determine the proportion of subjects retained in the Bup/Nx OBT protocol at follow-up and thus characterize the effectiveness of our outpatient Bup/Nx treatment program, which was, in part, publically funded. Grant funding from ADABSCC allowed us to provide Bup/Nx

OBT to our indigent participants, but also necessitated that we prove the effectiveness of the therapeutic approach in that population.

To that end, our data show that, at 18 months post-induction, 85 of 110 (77%) subjects remained on Bup/Nx, and within that group: Substance use was ~24% decreased 12-step program affiliation was ~29% increased Employment was ~24% increased

This result definitively demonstrates Bup/Nx-OBT to be an effective adjunct to more intensive treatment programs and may improve abstinence, as well as psychosocial and occupational functioning, in opioid dependent patients, regardless of their socioeconomic status.

Discussion

Another goal of this study was to examine what effect, if any, patient characteristics had on treatment retention and outcomes, and whether these characteristics differed significantly between our two distinct patient populations. To that end: We did not find any patient characteristics to be

reliably associated with retention in the Bup/Nx OBT protocol, with exception of being employed at entry into the study. This finding may indicate that patients with a more stable occupational environment at entry into treatment are more likely to maintain their Bup/Nx-OBT over the long term.

Interestingly, our data also show that at follow-up, our indigent subjects were 8% more likely to report substance use. That result may indicate different environmental and other risk factors for relapse in this population, independent of continued Bup/Nx-OBT.

Discussion

Limitations Convenient Sample: our data are derived from a clinical cohort

stabilized on Bup/Nx as part of a private insurance and publically funded substance abuse treatment program.

An important weakness was the necessity of different treatment of our solvent and indigent populations: Because treatment of uninsured subjects was publicly funded,

these individuals were required to undergo 4-8 weeks of residential treatment that was not required of the insured subjects in our population.

This created a treatment bias and a selection bias Treatment bias: Indigent patients received longer and more intensive

substance abuse treatment Selection bias: Only the indigent subjects who were willing to undergo

and/or were able to complete residential therapy were included in follow-up.

We plan to address these biases in an ongoing version of the present study in which constraints of public funding no longer require residential treatment for all subsidized individuals.

Conclusions

One hope is that the results of this study and others like it may justify increased funding to cover the costs of combined treatment programs for indigent opioid dependent patients

The benefits reaped from improved biopsychosocial functioning and return to gainful employment of these individuals will likely far out weigh the cost of subsidizing such programs

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