Duration of Addiction Treatment

Transcription

1 Comprehensive Addiction Evaluation and Treatment is Necessary Screening Assessment Treatment Plan Bh Behavioral ltherapy and Counseling Substance Use Monitoring (drug screening) Pharmacotherapy Clinical and Case Management Continuing Care ( Aftercare ) Self help/peer Support Groups Duration of Addiction Treatment Depends on specific patient problems/needs Less than 90 days of treatment is of very limited effectiveness in the residential or outpatient setting. Longer treatment is frequently indicated. Matching Patients to Individual Needs No single treatment is appropriate for all individuals. Effective treatment attends to multiple needs of the individual, not just his/her drug use. Treatment must address medical, social, vocational, psychological, as well as legal problems. 1

2 Comprehensive Treatment Strategies The mechanisms of gene expression, prolonged changes in brain function in the areas of cognition, motivation and inhibition, and a myriad of changes in social and family relationships are just some of the many direct and indirect sequelae of opioid dependence that both result from prior opioid use and also promote future use. Comprehensive Treatment Strategies None of the medications discussed here can be considered an effective treatment for opioid dependence by itself all medications are designed for useaspartof more comprehensivetreatmentstrategies strategies that include counseling, social supports, and behavioral change strategies. How is the Efficacy of Pharmacotherapy Determined? 2

3 Measures of Effectiveness 1. Withdrawal Symptom Suppression Reduce or eliminate direct physiological symptoms leading to physiological stabilization and relatively normal behavioral function Withdrawal and craving may be reliably measured by selfreporting instruments and physiological signs Measures of Effectiveness 2. Patient Retention Patients should remain engaged in & actively participating in the therapeutic components of a comprehensive treatment plan Measurable by patient visits actually attended Measures of Effectiveness 3. Reduction of Opioid Use Cardinal measure of the effectiveness for any opioid addiction treatment, measured by urine drug screening as well as by selfreport Medications are expected to produce significant reductions in the frequency and amount of opioid use 3

4 Measures of Effectiveness 4. Reduction of Opioid Related Health and Social Problems Problems associated with addiction itself, such as HIV and hepatitis B and C Problems indirectly related to opioid use such as employment, criminal acts, improved mood and physical health, and improved family and social relationships Medication Assisted Therapy for Opiate Addiction Medications for Opioid Addiction Effects of Medication Agonist Antagonist Maintain physiological dependence and the potential for withdrawal + Potential for tolerance development +/ Euphoric effect or abuseliability ++ Compatible with ongoing illicit opioid use ++ May alter use of other drugs +/ ++ Extinction of heroin reinforced behaviors/ reversal of underlying neurobiology + ++ Favorable long term outcomes + ++ Cultural/ideological barriers to availability Broad professional/public appeal ++ 4

5 Medications for Opioid Addiction Methadone - Agonist Suboxone (buprenorphine) Agonist Naltrexone Antagonist ReVia (oral tablet) Vivitrol (injection) 14 Methadone 5

6 Methadone Orally active, long acting synthetic opioid Useful for chronic pain disorders Recognized in the 1960s as having the potential to treat opioid (primarily heroin) dependence Produces a tolerance to the effects of heroin, hydromorphone, and other opioids Methadone For maintenance or detoxification, must be prescribed through a federally and state licensed facility (e.g., CompDrug, Maryhaven in Columbus) Starting dose usually 30mg May give an additional 10mg first 24 hours Most maintenance doses mg per day Any physician may continue to administer methadone for a patient during a hospitalization Methadone: Therapeutic Range Goal: to achieve a blood drug concentration that lies between the minimum effective level and the level at which side effects appear Craving relief, but also sedation, vomiting, dysphoria, or itching Methadone blood levels Side effects start Craving relief with minimal or no side effects Minimum needed for craving control Cravings Therapeutic range Dose given Time 24 hrs 6

7 Methadone Methadone for the treatment of opioid dependence remains among the most thoroughly researched medications. Several researchers have advocated methadone as the front line treatment for opiate addiction. 1 Over 50 clinical studies comparing different types of maintenance treatment concluded that methadone maintenance treatment was effective at curbing opiate use, retaining patients in treatment, and reducing criminal activity. 1 7

8 Methadone Analysis of clinically controlled trials of methadone maintenance treatment against other non opioid therapies found evidence of superiority of methadone over control in treatment retention as well as reductions in both self reported heroin use and positive hair/urine screens. 7 Analysis of clinically controlled trials also showed methadone maintenance treatment was effective at reducing drug related deaths, unemployment and HIV risk behavior. 6 Methadone Results of quality of life (QOL) studies revealed that methadone maintenance patients, as opposed to other forms of treatment studied, experienced significant improvements in terms of physical health, spare time, vitality, psychosocial QOL, material satisfaction, if i affective QOL, and overall core QOL index, and significant improvements in terms of all QOL domains evaluated (physical, psychological, social relationships, and environmental). 8,9 Methadone For many patients with opioid addiction, maintenance treatment with an opioid agonist is effective as a long term modality. Discontinuation of methadone maintenance carries substantial risk associated with relapse to intravenous drug use. 8

9 Methadone Discontinuation of methadone maintenance should be attempted only when strongly desired by the successfully treated patient, and conducted with adequate supervision and support. Individuals with addiction who have been discontinued from methadone maintenance should be carefully followed in a clinical setting and encouraged to participate in an ongoing program of recovery. In the event of relapse or impending relapse, additional therapeutic measures should be used including, when appropriate, prompt resumption of methadone maintenance treatment. 5 Methadone Treatment should be continued: As long as the patient continues to benefit from treatment and wishes to remain in treatment The patient remains at risk of relapse to opioidoror other substance use The patient suffers no significant adverse effects from continued methadone maintenance treatment As long as continued treatment is indicated in the professional judgment of the prescribing physician. 5,10,13 Methadone and Cognitive Impairment Methadone has not been found to be neurotoxic. Factors increasing the likelihood of significant cognitive impairment include Overdose Concomitant alcohol use disorder Traumatic head dinjury due to exposure to violence Some studies regarding driving ability have raised the issue to whether buprenorphine patients have greater alertness than methadone patients, but results are equivocal. Significant improvement in concentration and executive functions after 8 10 weeks of treatment have been reported in both methadone and buprenorphine maintained patients. 10 9

10 Methadone and Pregnancy Methadone maintenance is an established treatment for pregnant opioid dependent patients and may be initiated at any time during pregnancy. Methadone discontinuationisrarely appropriateduringpregnancy pregnancy. When attempted, methadone discontinuation should be undertaken slowly under close monitoring and only in the second trimester. Methadone and Pregnancy Individual dose determinations are more appropriate than arbitrary low dose policies that often contribute to relapse to heroin use and to misuse of alcohol and other drugs during pregnancy. Provision of prenatal care, including high risk maternal fetal medicine i care when indicated dand available, is important tfor opioid addicted pregnant women. Proper nutrition, ongoing individual, family, and/or group counseling, to include prenatal and parenting classes, should be offered along with methadone maintenance. 5 Buprenorphine 10

11 Buprenorphine is Sublingual Suboxone (buprenorphine + naloxone) Subutex (buprenorphine alone now generic only) 30% bioavailability Peak plasma concentration in minutes Duration of action around 28 hours Mu Opioid Receptor Activation Full agonist eg, morphine Partial agonist mu receptor site eg, buprenorphine Full activation of mu receptor site Antagonist mu receptor site eg, naloxone Partial activation of mu receptor site mu receptor site Prevents or reverses activation of mu receptor site 11

12 Buprenorphine Properties High affinity, partial mu opioid agonist and weak kappa antagonist Agonist effects plateau at higher doses and it begins to behave more like an antagonist Ceiling effect imparts safety ft Less respiratory depression and risk of overdose No significant hepatotoxicity or effect on QTc interval (heart electrical rhythm) Less physical dependence capacity Naloxone added to reduce misuse/abuse liability Suboxone Sublingual film 12

13 Brand Name + Generics Subutex (buprenorphine sublingual tablets) including generic equivalents Suboxone (buprenorphine and naloxone sublingual tablets), including generic equivalents Zubsolv (buprenorphine p and naloxone sublingual tablets) 2 mg buprenorphine 8 mg buprenorphine Medication Content(s) 2 mg buprenorphine/0.5 mg naloxone 8 mg buprenorphine/2 mg naloxone 1.4 mg buprenorphine/0.36 mg naloxone 5.7 mg buprenorphine/1.4 p mg naloxone 8.6 mg buprenorphine/2.1 mg naloxone 11.4 mg buprenorphine/2.9 mg naloxone Suboxone sublingual film (buprenorphine and naloxone sublingual film) 2mg buprenorphine/0.5 mg naloxone 4 mg buprenorphine/1 mg naloxone 8 mg buprenorphine/2 mg naloxone 12 mg buprenorphine/3 mg naloxone Bunavail (buprenorphine hydrochloride and naloxone hydrochloride buccal film) 2.1 mg buprenorphine/0.3 mg naloxone 4.2 mg buprenorphine/0.7 mg naloxone 6.3 mg buprenorphine/1 mg naloxone Corresponding Doses of Buprenorphine Products that Contain Naloxone Suboxone Suboxone Zubsolv Bunavail Suboxone sublingual tablets, including generic equivalents Suboxone sublingual films Zubsolv sublingual tablets Bunavail buccal films 2 mg buprenorphine/ 0.5 mg naloxone 2 mg buprenorphine/ 0.5 mg naloxone 1.4 mg buprenorphine/ 0.36 mg naloxone 4 mg buprenorphine/ 1 mg naloxone 2.1 mg buprenorphine/ 0.3 mg naloxone 8 mg buprenorphine/ 2 mg naloxone 8 mg buprenorphine/ 2 mg naloxone 5.7 mg buprenorphine/ 1.4 mg naloxone 4.2 mg buprenorphine/ 0.7 mg naloxone 12 mg buprenorphine/ 3 mg naloxone 8.6 mg buprenorphine/ 2.1 mg naloxone 6.3 mg buprenorphine/ 1 mg naloxone 11.4 mg buprenorphine/ 2.9 mg naloxone 13

14 Buprenorphine Advantages More favorable safety profile and long duration of action than other opioid medications Newer option, and may engender less fear of stigma than methadone More accessible over a wide geographic area due to its availability in office based primary care May be more appropriate as an early intervention strategy for those with short dependence histories (e.g., adolescents) or those with less physical dependence 10 14

15 Buprenorphine Maintenance Therapy Methadone to Buprenorphine transfer Patients dependent on methadone have a higher risk of precipitated withdrawal transitioning to buprenorphine Daily dose of methadone should ideally be tapered down to 40 mg/day or less before transition Buprenorphine doses of 24 32mg are approximately equivalent to 60 70mg of methadone 14 Buprenorphine: Retention in Treatment at 6 Months Buprenorphine: Decrease in Negative Behaviors 15

16 Buprenorphine: Effects on Patients Employment Patient Ratings of Buprenorphine Buprenorphine: Ideal patient Treatment seeking wants off of illicit opioids Opioid dependent, no other active substance use disorder issues No acute medical conditions (eg: unstable hepatitis) No untreated/unstable major psychiatric disorders 16

17 Buprenorphine: Ideal patient Liver enzymes less than 3X normal levels Willing to enter and persevere with an addiction treatment program and aftercare program Must able and willing to follow instructions Manageable environmental stressors and optimally no other actively using opiate dependent individuals in the patient s living environment Buprenorphine vs. Methadone One study showed that a stepped approach of starting patients on buprenorphine and transferring those who did not stabilize onto methadone had identical outcomes to directly admitting patients to methadone treatment. In this study, 46% of these stepped patients did well on buprenorphine. 19 Buprenorphine: Duration of Treatment For most patients, it may be inappropriate to decide arbitrarily on the length of treatment at initial evaluation. More likely that patients will need to be started in treatment within a flexible time frame that responds to the progress and needsof the patient. The design of long term treatment depends in part on the patient s personal treatment goals and in part on objective signs of treatment success. Maintenance can be relatively short term (e.g., 12 months) or, more likely, a longer term (several years), or a lifetime process. 17

18 Buprenorphine: Duration of Treatment Treatment success depends on the achievement of specific goals that are agreed on by both the patient and the physician. Following successful stabilization, decisions to decrease or discontinue buprenorphine should be based on a patient s desires andcommitment to recovery and to their becomingmedication medication free, and on the physician s confidence that tapering would be successful. Factors to be considered when determining suitability for longterm mediation free status include stable housing and income, adequate psychosocial support, and the absence of legal problems. Buprenorphine: Duration of Treatment For patients who have not achieved these indices of stabilization, a longer period of maintenance, during which they work through any barriers that exist, may be appropriate. Data suggest that longer duration of medication treatment is associated with less illicit drug use and fewer complications. 4 Under ideal conditions, discontinuation of medication should occur when a patient has achieved the maximum benefit from treatment and no longer requires continued treatment to maintain a drugfree lifestyle. Buprenorphine: Duration of Treatment Once this goal is achieved, buprenorphine should be tapered slowly and appropriately while supportive psychosocial services continue to be provided. Patients should be assessed for continued stability in maintaining their drug free lifestyle. Patients should then be followed with medical services, psychosocial services, and/or the reintroduction of medication, if needed, for continued progress and sustained abstinence. 4 18

19 Buprenorphine: Duration of Treatment Certain situations undoubtedly will arise, however, in which a physician (as the prescribing member of the treatment team) may feel that a patient is not progressing satisfactorily (e.g., not in compliance with the treatment plan or with office policies and procedures). Treatment programs should develop practicesfor dealingwith infractions of rules or policies and with non adherence to treatment plans. In the event of involuntary termination of treatment, it is necessary for physicians/treatment programs to make appropriate referrals to methadone maintenance programs, to other physicians willing to prescribe buprenorphine, or to other appropriate treatment facilities. 4 Naltrexone Naltrexone Synthetic drug, chemically similar to oxymorphone (Dilaudid ) with no opioid agonist effect Reversibly blocks the subjective effects ( high ) of opioids Availableas 50mgoraltablets Available as 50mg oral tablets Precipitates withdrawal in subjects who are physically dependent on opioids 50 mg daily will block the effects of 25 mg of IV heroin (or other opioids) for 24 hours 100 mg will block opioids for 48 hours 19

20 Naltrexone Naltrexone is effective in preventing relapse when used as directed; however, because the medication does not ease cravings for illicit opioids and does not produce withdrawal symptoms when discontinued, poor compliance with long term naltrexone therapy has been found for the oral formulation % dropout rates from oral naltrexone therapy have been routinely reported. 20

21 Opioid Drugs Excessively Stimulate the Dopamine Reward System Through this mechanism, opioids can relieve pain as well as produce feelings of pleasure and euphoria. Over time, repeated exposure to escalating doses of opioid drugs diminishes the activity of the opioid receptor, producing tolerance. As tolerance develops, higher quantities of opioids are required to stimulate the release of dopamine in an attempt to achieve the pleasure experienced during the 62 initial opioid use. Naltrexone is an opioid receptor antagonist with highest binding affinity for the mu opioid receptor. Naltrexone does not stimulate the dopamine reward system. 21

22 Opioid Naltrexone The opioid blockade prevents the subjective effects of opioids, such as euphoria and reward. This blockade combined with appropriate psychosocial treatment, contributes to the prevention of relapse to opiate use. Naltrexone is contained in microspheres composed of biodegradable polymers. The microspheres gradually release naltrexone over one month, and are then metabolized and eliminated as carbon dioxide and water. Microspheres release naltrexone in therapeutic concentrations over a one month period. 22

23 Naltrexone High dose (384mg) extended release naltrexone was associated with higher retention rates than placebo or low dose (192mg) extended release naltrexone. Less than 10% of patients reported significantsideside effects, usually short term side effects such as headache, nausea, fatigue, and injection site pain. Results suggest that treatment with extended release naltrexone increases treatment compliance versus oral naltrexone, especially with monitoring of adherence. Naltrexone A recent study showed a longer proportion of weeks of confirmed abstinence of 90% in the extended release group (vs. 35% in placebo group). When this is combined with psychosocial counseling, the treatment group revealed lower opioid use, craving, and better treatment retention. 17 Naltrexone Available studies suggest that it is safe, generally well tolerated and results in immediate and complete blockade of opioid receptors and thus discontinuation of self administered opioids. 4 Despite the comparatively fewer trials of extended release naltrexone, it has been shown to be safe and effective for use for up to 18 months. 23

24 GOOD Candidates for Naltrexone Patients who are not interested or are unable to be on opiate agonist therapy, i.e.: Active 12 step participants with a high degree of motivation for abstinence Healthcare professionals, pilots, etc., who are not allowed to practice/work on opiate agonist therapy Patients successful on opiate agonist therapy but want to try complete abstinence from therapeutic agonist medications GOOD Candidates for Naltrexone Patients who have failed prior treatment with agonist: Continued use of heroin or other opiates Did not improve or dropped dout of treatment Patients who detoxify easily but also relapse easily Patients for whom relapse would be disastrous (e.g., physicians, pharmacists, parolees, etc.) GOOD Candidates for Naltrexone Patients who are abstinent but are at elevated risk for relapse Moving to old neighborhood associated with drug use Increased stressors Co occurring psychiatric disorders Patients with less severe addiction? Short history of addiction Lower level of drug use 24

25 POOR Candidates for Naltrexone Patients with history of overdoses, particularly following detoxifications Patients with serious co occurring occurringpsychiatric disorders Disorganized thinking Homelessness Patients with chronic pain potentially requiring periodic or chronic opioid therapy POOR Candidates for Naltrexone Patients with severe pain disorders (Crohn s disease, ulcerative colitis, sickle cell anemia, etc.) which may exacerbate during periods of abstinence who may then legitimately require opiates for pain relief Patients with advanced liver disease Naltrexone Treatment Issues Candidates require complete detoxification prior to treatment initiation with 7 10 days of complete opiate abstinence. Methadone and buprenorphine have longer half lives and may persist in system longer than other opioids. Precipitated withdrawal may occur if treatment with naltrexone starts too early. Address concerns with patients about overdose while on naltrexone as well as potential treatments for pain. 25

26 Treatment of Pain on Naltrexone First try full doses of NSAIDs [e.g., Toradol (ketorolac) injection], or oral NSAIDs or other non opiate pain control medications/methods (not tramadol). Trial of regional nerve blocks may be helpful. High potency opiates (e.g., fentanyl) can override the opiate blockade, but an anesthesiologist should be involved. Patients should wear medical ID bracelet or wallet card with contact number for information. In Summary: 26

27 Opioid Pharmacotherapy: Treatment Goals Suppress withdrawal symptoms Minimize/eliminate cravings for opioids Block or attenuate euphoric effect of ingested or injected opioids Improve functional status in all spheres of life Opioid Pharmacotherapy Summary: Methadone and buprenorphine are opiate agonist medications approved by the FDA for treatment of opiate dependence. The best clinical evidence so far supports maintenance; staying on maintenance gives better results than premature discontinuation. Opioid Pharmacotherapy: Monthly Cost of Medications Naltrexone (oral) ~ $ Vivitrol ~ $ 750 1,250 Buprenorphine ~ $

28 Opioid Pharmacotherapy Summary: Treatment is continued as long as: The patient benefits The patient is at risk for relapse There are no serious side effects The clinician believes maintenance therapy is still required Opioid Pharmacotherapy Summary: Discontinuation attempts should have maintenance as a back up in case of relapse. When detoxification is chosen (as a prelude to drug free treatment), maintenance should be considered as a backup strategy in case abstinence cannot be established. Questions? 28

29 References 1. Amato, L., Davoli, M., Perucci, C.A., Ferri, M., Faggiano, F., & Mattick, R.P. (2005). An overview of systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research. Journal of Substance Abuse Treatment, 28(4), Kinnock, T. W., Gordon, M. S., Schwartz, R. P., O Grady, K., Fitzgerald, T. T., & Wilson, M. (2007). A randomized clinical trial of methadone maintenance for prisoners: Results at 1 month post release. Drug and Alcohol Dependence, 91(2 3), Kleberg, H. (2007). Pharmacologic treatments for opioid dependence: detoxification and maintenance options. [Review]. Dialogues in Clinical Neuroscience, 9(4), Advancing Access to Addiction Medications: Implications for Opioid Addiction Treatment. American Society of Addiction Medicine publication. (2013). 5. Public Policy Statement on Methadone Treatment of Addiction. American Society of Addiction Medicine. (2006). 6. Booth, R.,Corsi,, K., Mikulich Gilbertson, S. (2004). Factors associated with methadone maintenance treatment retention among street recruited injection drug users. Drug Alcohol Depend 2004 May 10;74(2): Mattick, R.P., Breen, C., Kimber, J., & Davoli,M. (2009). Methadone maintenance therapy versus non opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews, Issue 3. Art. No: CD Karow, A., Reimer, J., Schafer, I., Krausz, M., Haasen, C., Verthein, U. Quality of life under maintenance treatment with heroin versus methadone in patients with opioid dependence. Drug Alcohol Depend Dec 1;112(3): Musa R, Abu Bakar AZ, Ali Khan U. Two year outcomes of methadone maintenance therapy at a clinic in Malaysia. Asia Pac J Public Health Sep;24(5): Principles of Addiction Medicine, Fifth Ed. American Society of Addiction Medicine. Ries, R., Sr. Ed. Wolters Kluwer. (2014). 11. Harris, K Jr., Arnsten, J, Joseph, H, et. Al. A 5 year evaluation of a methadone medical maintenance program. J Subst Abuse Treat 2006:31(4): Kissin W., McLeod, C., Sonnefeld, J. Experiences of a national sample of qualified addiction specialists who have and have not prescribed buprenorphine for opioid dependence. J Addict Dis 2006:25(4): Payte, J, Khuri, E. Treatment duration and patient retention. In: Parrinw, M., ed. State methadone treatment guidelines. Rockville, MD: US Dept. of Health and Human Services, 1993: References 14. Buprenorphine: An alternative to methadone. The Medical Letter. Vol. 45 (W1150A). February 17, Center for Substance Abuse Treatment. Clinical Guidelines for the Use of buprenorphine in the treatment of opioid addiction. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); (Treatment Improvement Protocol (TIP) Series, No. 40). 16. Krupitsky, E., Nunes, E., Ling, W., Illeperuma, A., Gastfriend, D., & Silverman, B. (2011). Injectable extended release naltrexone for opioid dependence: A double blind, placebo controlled, multicentre randomised trial. The Lancet, 377(9776), Krupitsky, E., Nunes, E. V., Ling, W., Gastfriend, D., Memisoglu, A., & Silverman, B., (2013). Injectable extended release naltrexone (XR NTX) for opioid dependence: long term safety and effectiveness. Addiction, 108, Knudsen, H., Abraham, A., Roman, P. Adoption and implementation of medications in addiction treatment programs. Journal of Addiction Medicine. 2011;5: Kakko, J., Gronbladh, L., Svanborg, K., et al. A stepped care strategy using buprenorphine and methadone vs. conventional methadone maintenance in heroin dependence: a randomized controlled trial. Am J Psychiatry y 2007:164(5): Ling, W., Wesson, D. Charuvastra, C., et al. A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence. Arch Gen Psychiatry 1996;53(5): Winstock, A., Lea, T., Sheridan, J. What is diversion of supervised buprenorphine and how common is it? J Addict Dis 2009;28(3): Martin, J., Campbell, A., Killip, T., et al. QT interval screening in methadone maintenance treatment: report of a SAMHSA expert panel. J Addict Dis 2011;30(4): Salsitz, E., Joseph, H., Fran, B., et al. Methadone medical maintenance (MMM): treating chronic opioid dependence in private medical practice a summary report ( ). Mount Sinai J Med 2000;67(5 6): Harris, K. Jr, Arnsten, J., Joseph, H., et al. A 5 year evaluation of a methadone medical maintenance program. J Subst Abuse Treat 2006;31(4): Oliva, E., Gordon, A., Harris, A., et al. Tends in opioid agonist therapy in the Veterans Health Administration: is supply keeping up with demand? Am J Drug Alcohol Abuse 2013;39(2):