Treatment of opioid use disorders

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Treatment of opioid use disorders Gerardo Gonzalez, MD Associate Professor of Psychiatry Director, Division of Addiction Psychiatry

Disclosures I have no financial conflicts to disclose I will review evidence based off-label use of medications

Outline

Outline Epidemiology Neurobiology Preventive efforts Treatment Longitudinal outcomes Conclusions

Epidemiology NSDUH, 2014

Drug overdose deaths involving opioids by type of opioid United States, 2000 2014 CDC, 2016

Prescription Opioids and Heroin use during the Previous Year United States, 2000 2014. Comptom, 2016

Prescription Opioids and Heroin Drug Poisoning United States, 2000 2014. Comptom, 2016

Massachusetts Department of Public Health, 2015

Source Where Pain Killers Were Obtained Age 12 or Older: 2010-2011

Neurobiology

Substance use disorders (DSM-5) Neuroadaptation: Tolerance Withdrawal Cognitive distortion: Importance of substance use Subjective awareness of decrease control Craving or a strong desire or urge to use Behavioral dyscontrol: Obtaining, using and recovering Use despite knowledge of problems Using more and longer than intended

Substance use disorders (DSM-5) Neuroadaptation: Tolerance Withdrawal Cognitive distortion: Importance of substance use Subjective awareness of decrease control Craving or a strong desire or urge to use Behavioral dyscontrol: Obtaining, using and recovering Use despite knowledge of problems Using more and longer than intended

Preventive efforts

Preventive efforts Education of medical and nursing students on universal precautions with controlled substances Prescription guidelines for practicing physicians and dentists on safe pain management Prescription monitoring program (PMP) Safe storage of opioid analgesics (locked box) Appropriate disposal of unused opioid analgesics Naloxone rescue kits available (standing orders)

Treatment

Patients in Treatment, by type of care received: 2006-2010 The proportion of all clients receiving methadone was 22 to 25 percent between 2006 and 2010. The proportion of clients receiving buprenorphine was 1 percent or less from 2006 to 2008, but increased to 2 percent in 2009 and 2010.

Substance Abuse Treatment Services 1. Detoxification / stabilization units 2. Inpatient acute hospitalization 3. Nonhospital residential rehabilitation 4. Partial day hospital / intensive outpatient program (IOP) 5. Outpatient treatment / office-based

Psychosocial treatments 1. Drug Counseling 2. Cognitive Behavioral Therapy 3. Relapse prevention 4. Mindfulness 5. Contingency Management 6. Twelve Steps facilitation 7. Motivational Enhancement Therapy 8. Self-help groups

Let s expand our view.

Use of Medications

Managed withdrawal In-patient stabilization units Reduce opioid withdrawal symptoms Transition off daily opioid use Evaluate and treat comorbid medical and psychiatric problems Usually 4-5 days needs follow-up

Managed withdrawal Methadone Clonidine Buprenorphine

Medication assisted treatment (MAT) Outpatient settings Suppress opioid withdrawal symptoms Suppress craving for opioids Stop opioid use and relapse Adjust daily dose to avoid sedation

Medication assisted treatment (MAT) Naltrexone Methadone Buprenorphine + Naloxone

Naltrexone Indications: Severe opioid use disorder Mechanism: Opiate receptor antagonist Efficacy: Oral is good in high motivated. Implementation: 50-100 mg/per day; LFT s Side effects : nausea, headache, anxiety, OD Compliance: Improved with naltrexone depot (IM) (Comer, 2006; Krupitsky, 2011)

Naltrexone Depot Krupitsky, 2011

Methadone Indications: Severe opiate use disorder Mechanism: Full opiate receptor agonist. Efficacy: 70-80 % retention in OTP. Implementation: Start at 25-30mg and built-up dose until opiate free urines. Side effects : sedation Interactions: benzodiazepine alcohol.

Methadone Age >18 or 2 documented failures of detox. One year history of severe opiate use disorder Exceptions: Pregnancy Release from prison History of previous treatment.

Methadone dose: illicit opioid use Strain, 1999

Buprenorphine Partial opiate receptor agonist Combination tablet /film 4:1 (Bup/naloxone) Sublingual administration High affinity and slow dissociation Office based opiate use treatment Death associated with IV use and with benzodiazepines

Mean % Negative Buprenorphine, Methadone, LAAM: Opioid Urines 100 80 60 All Subjects 49% 40% LAAM Bup Hi Meth 40 20 39% 19% Lo Meth 0 1 3 5 7 9 11 13 15 17 Study Week Johnson, 2000

Treatment of opioid dependent youth Woody, 2008

Buprenorphine with Memantine for young adults Gonzalez, 2015

Buprenorphine and Memantine for young adults Gonzalez, 2015

Long-term outcomes

Long-term outcomes Reduction of mortality compared to untreated controls (Gronbladh, 1990) Decrease IVDU from 81% to 29% vs 82% at 1 year of those who left treatment (Ball and Ross, 1991) HIV seroconversion: methadone 3.5% vs active IVDU 22%

Prevalence of past month heroin use, heroin dependence and other drug use across the 11-year follow-up period Teesson, 2015

Comorbid disorders impact Major Depression * 1.96 (1.50 2.55) Antisocial Personality 1.02 (0.70 1.32) Borderline Personality 1.16 (0.91 1.48) PTSD 0.81 (0.63 1.05) Teesson, 2015

Treatment effect MAT 1.11 (0.90 1.38) Detoxification * 1.52 (1.20 1.92) Residential Rehab * 0.59 (0.46 0.76) Teesson, 2015

Conclusion Current opioid use epidemic is responsibility of all to help reduce. Education and change in prescription practices are key elements in prevention. Reduction of diversion and appropriate disposal is important. Medication - assisted treatments are effective. There is still need to develop effective short-term treatments.