November 23, 2015 Arthur Robin Williams MD MBE American Academy of Addiction Psychiatry Division on Substance Abuse Department of Psychiatry, Columbia University New York State Psychiatric Institute MAT Overview NCBH Learning Community

Other Psychotherapy - CRA - RPT -TSF Family Therapy Patient Behavioral - CBT - MI/MET - CM Medications (MAT) - AA/NA - Self-help - Smart Recovery SUD Treatment Options Level of Care: - Outpatient - Individual - Program - Residential - Inpatient/ Hospital Level of Care: - Outpatient - Individual - Program - Residential - Inpatient/ Hospital

Other Psychotherapy - CRA - RPT -TSF Family Therapy Patient Behavioral - CBT - MI/MET - CM Medications (MAT) - AA/NA - Self-help - Smart Recovery SUD Treatment Options Level of Care: - Outpatient - Individual - Program - Residential - Inpatient/ Hospital Level of Care: - Outpatient - Individual - Program - Residential - Inpatient/ Hospital - Detoxification - Aversion - Anti-Craving - Substitution

- Excessive amounts used - Excessive time spent using/obtaining - Tolerance - Withdrawal - Hazardous use despite - Health problems - Missed obligations - Interference with activities - Personal problems - Craving or urges to use - Unsuccessful attempts to cut down 11 Symptoms of Addiction

- Excessive amounts used - Excessive time spent using/obtaining - Tolerance - Withdrawal (not all substances) - Hazardous use despite - Health problems - Missed obligations - Interference with activities - Personal problems - Craving or urges to use - Unsuccessful attempts to cut down Targeting Symptoms Medication s (MAT) - Detox taper (Librium or Methadone)

- Excessive amounts used - Excessive time spent using/obtaining - Tolerance - Withdrawal (not all substances) - Hazardous use despite - Health problems - Missed obligations - Interference with activities - Personal problems - Craving or urges to use - Unsuccessful attempts to cut down Targeting Symptoms Medication s (MAT) -Aversion (Antabuse) - Anti-Craving (Naltrexone)

- Excessive amounts used - Excessive time spent using/obtaining - Tolerance - Withdrawal (not all substances) - Hazardous use despite - Health problems - Missed obligations - Interference with activities - Personal problems - Craving or urges to use - Unsuccessful attempts to cut down Targeting Symptoms Medication s (MAT) -Substitution (methadone or buprenorphine)

SUDCOD COD SUD SUDCOD SUDs and Co-Occurring Disorders: Assessing Causality

 Diagnosis may require collateral from multiple sources: i.e. timeline for symptom onset  Worse consequences from SUDs at treatment intake and poorer long-term outcomes  Yet most programs (and clinicians) either focus only on the SUD or the COD ! SUDs and COD

Currently, the FDA has approved medications for adults for the treatment of addiction to: – Opioids – Alcohol – Nicotine MAT

 The FDA approves medications after trials with adults demonstrate efficacy and safety  Typically trials exclude subjects under 18 years, dually diagnosed, pregnant women, hindering generalizability  Efficacy v. Effectiveness  Thus far, none approved for cannabis or stimulants Evidence-Based Addiction Psychopharmacology (MAT)

Background: OUD Neurochemistry  “Opioids” include synthetic pain pills and heroin  “Opiates” are natural opioids like opium or morphine  Opioids activate mu, delta, kappa receptors  In OUD, receptors are unstable when not activated  Unstable receptors lead to:  Withdrawal symptoms  Intense cravings  Great risk, such as overdose death  Injection adds infectious disease (HIV, Hepatitis C) and injuries

Background: MAT for OUDs  Receptors are stabilized with MAT medications  Patients on MAT experience fewer and less intense cravings and use drugs at much lower rates  MAT is the gold standard for OUD treatment:  Reduces drug use  Protects against overdoses  Prevents injection behaviors

 Detoxification  Is not a treatment on its own (risk factor for OD)  Should be a mechanism to get someone on MAT  Maintenance  Agonist (methadone) or partial agonist (buprenorphine)  Antagonist Therapy  Naltrexone pill or xr-naltrexone (Vivitrol) injection MAT: Opioids

 Increased pulse  Sweating  Restlessness  Pupil dilation  Bone/joint pain  Runny nose/tearing  GI upset  Tremor  Yawning  Anxiety/irritability  Gooseflesh  Higher score= worse w/d Clinical Opioid Withdrawal Scale (COWS)

Detoxification Buprenorphine and Methadone better than clonidine Maintenance for 2+ years Use sufficient dose bup >8mg, methadone >100mg Buprenorphine more likely to successfully lead to Naltrexone afterward Pregnant women should continue on maintenance given risks of relapse, withdrawal, and overdose following attempted taper MAT: Opioids

Buprenorphine: Pregnancy Lund, et al. 2013

Antagonist therapy Naltrexone daily pill (low adherence rates) or Vivitrol injection given every 3-4 weeks “Blockers” prevent euphoric/rewarding drug effects Can satisfy cravings Does NOT cause an “aversion reaction” Naloxone (Narcan) reverses overdoses and only lasts minutes MAT: Opioids

XR-Naltrexone: Hard to find Krupitsky, et al  Opioid-free weeks (Krupitsky 2012)

 Neuropathology  Anti-glutaminergic  Potentiates GABA  Dopamine release Alcohol

MAT: Alcohol Detoxification (Youth typically binge drink and rarely require) Use benzodiazepines, phenobarbital Outpatient v. inpatient models Aversion Antabuse 250mg or 500mg daily (FDA 1951) Start after all alcohol has cleared Can dose on site or have observer at home Effects for up to 2-3 weeks for some Consider as an adjunct to psychosocial therapies Monitor liver function every 1-3 months

MAT: Alcohol Anti-Craving Campral 666mg TID (FDA 2004) – Stabilizes neuroexcitability in protracted withdrawal – Dosing is problematic (but no side effects) – Better choice for patients with liver disease Naltrexone 50mg daily (NTX) (FDA 1994) – Reduces number of drinks per drinking day and cravings – Side effects limited (nausea/sedation) – LFTs should be followed intermittently (every 3 months) Vivitrol 380mg IM (XR-NTX) (FDA 2006) – Long acting monthly injection of naltrexone

 MAT includes 3 modalities:  Methadone (schedule II)  Buprenorphine (schedule III)  Naltrexone (not controlled)  MAT should be provided in addition to intensive psychosocial and behavioral therapy  Most patients require MAT for a minimum of 1-2 years of sobriety before attempting to taper Summary: Opioids

 MAT includes  Antabuse (disulfiram) 250mg or 500mg daily  Naltrexone 50mg daily or monthly Vivitrol injection  Acamprosate 666mg PO TID  Dosing should be observed by family or program  Check liver function regularly if on naltrexone or Antabuse Summary: Alcohol

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 Krupitsky, et al. (2012). Randomized Trial of Long-Acting Sustained-Release Naltrexone Implant vs Oral Naltrexone or Placebo for Preventing Relapse to Opioid Dependence. Archives General Psychiatry. Sep; 69(9):  Lund IO et al. (2013). A comparison of buprenorphine + naloxone to buprenorphine and methadone in the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes. Subst Abuse 7:61–74,  Moore, S. K., et al. (2011). "Improvement in psychopathology among opioid-dependent adolescents during behavioral-pharmacological treatment." J Addict Med 5(4):  Niederhofer, H. and W. Staffen (2003). "Acamprosate and its efficacy in treating alcohol dependent adolescents." Eur Child Adolesc Psychiatry 12(3):  Niederhofer, H. and W. Staffen (2003). "Comparison of disulfiram and placebo in treatment of alcohol dependence of adolescents." Drug Alcohol Rev 22(3):  Scherphof, C. S., et al. (2014). "Short-term efficacy of nicotine replacement therapy for smoking cessation in adolescents: a randomized controlled trial." J Subst Abuse Treat 46(2):  Simkin, D. R. and S. Grenoble (2010). "Pharmacotherapies for adolescent substance use disorders." Child Adolesc Psychiatr Clin N Am 19(3): References