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Medication Assisted Therapy Advances
Dr. Dawn-Elise Snipes

CEUs available at: allceus.com/member/cart/index/product/id/16/c/

Objectives
– Review the purpose and efficacy of MAT in general
– Review current research on MAT for
– Nicotine
– Alcohol
– Opioid
– Methamhetamine
General
– Approximately 1 million people aged 12 or older (about 0.4 percent of the population) had a methamphetamine use disorder in 2017 which is almost 30% higher in 2016.
РAlcohol the third leading preventable cause of death in the United States.  The first is tobacco, and the second is poor diet and physical inactivity.
– According to the 2018 NSDUH, 14.4 million adults (~6%) ages 18 and older and ~2% of adolescents had Alcohol Use Disorder.
General
– Patients who use MAT
– Remain in therapy longer
– Are less likely to commit suicide
– Are less likely to overdose
– Have improve health outcomes including reductions in transmission of infectious diseases and improved overall health
– Have reduced involvement in the criminal justice system
– Have improved birth outcomes
– Improves child permanency outcomes
– Are less likely to discharge against medical advice compared with those receiving counseling and supportive care only (30.0% vs 59.6%).
– Are less likely to relapse on any drugs Readmissions rates were lower within 90 days for patients who were discharged with any form of ongoing medication-assisted therapy 27.3% vs 42.7%
NonPharmacological
– FDA (2017) permitted marketing of the first mobile medical application to help treat substance use disorders (SUD) except opioid dependence.
– The Reset device is an app containing a patient application and clinician dashboard which delivers CBT to teach the user skills that are intended to increase abstinence and retention in outpatient therapy programs.
– Data showed a statistically significant increases in abstinence for the patients with alcohol, cocaine, marijuana and stimulant SUD (but not opioids) in those who used Reset, 40.3 percent, vs. 17.6 percent.
– They have recently released Reset-O for opioid dependence
Advances in Opioid MAT
– FDA approves the first non-opioid treatment for management of opioid withdrawal symptoms in adults (Lucemyra (lofexidine hydrochloride))
– FDA approves first once-monthly buprenorphine injection, a medication-assisted treatment option for opioid use disorder
– FDA approves first buprenorphine implant for treatment of opioid dependence
Opioid MAT and Pregnancy
РFluctuating levels of opioids in the mother may expose the fetus to repeated periods of withdrawal, which can harm placenta function leading to prematurity, stunted growth and alterations in neurodevelopment.
РOne-third of pregnant women with opioid use disorder were required to go through withdrawal, contrary to medical guidelines.
– Most sites stopped medication for opioid use disorder postpartum, signaling prioritization of the fetus, not the mother.
РEvidence does not support detoxification as a recommended treatment intervention as a result of low detoxification completion rates, high rates of relapse.
РMedication assisted treatment favors buprenorphine use when compared to methadone with an increased birthweight, reduced need for newborn treatment, and a shorter newborn length of stay in term infants.
Opioid MAT and Pregnancy
– As a result of conflicting findings, a 2019 article in the American Journal of Obstetrics and Gynecology indicated a reassessment of current recommendations.
– Opioids adversely affect the human brain, primarily the developing oligodendrocyte and the processes of myelinization (white matter microstructure), connectivity between parts of the brain, and the size of multiple brain regions, including the basal ganglia, thalamus, and cerebellar white matter.
– The long-term impact of these changes in the fetal brain is unclear, but there it the possibility of lasting injury
– In light of the recent data on medically supervised withdrawal and the emerging evidence suggesting adverse effects of opioids on the developing fetal brain, a new paradigm of care is needed that includes the preferred option of medication-assisted treatment but also the option of medically supervised opioid withdrawal for a select group of women
OTP in Pregnancy
РNaltrexone and buprenorphine were not associated with the high rates of neonatal mortality or congenital anomalies seen in methadone-exposed neonates
РNaltrexone crosses the placenta.  Opioid signaling is believed to play a role in neurodevelopment, it is important to know what the effects of blocking that signaling may be.
РNeurodevelopmental effects of naltrexone in animal studies include alterations in brain size, opioid receptor expression and function, and altered neuronal development.  However in 2020, a study of 230 pregnant women found no differences in outcomes between women on buprenorphine vs naltrexone.
– For newborn outcomes, the rate of neonatal abstinence syndrome in neonates >34 weeks gestation was significantly lower in the naltrexone medication-assisted treatment group
Alcohol Neuroactivity
– Alcohol increases GABA, Glycine, Adenosine when initially consumed
– Alcohol initially reduces glutamate via NMDA activation
– Alcohol reduces 5HT2 and prompts increased development of 5HT2 receptors
– Alcohol increases serotonin levels, esp. 5HT3 (stimulating)
– Body responds by trying to rebalance the system producing more glutamate
MAT for Alcohol
– FDA Approved
– Acamprosate (Campral) stabilizes chemical signaling in the brain in NMDA receptors (glutamate/GABA) that would otherwise become overactive during alcohol withdrawal causing symptoms such as agitation, hypertension and seizures.
– Disulfram (Antabuse)
– Naltrexone (Pill or monthly injection)
MAT for Alcohol
– Off Label
– Zofran (5HT3 antagonist) reduces anxiety, antiemetic
– Anticonvulsants:
– Gabapentin (GABA analog for neuropathic pain, seizures)
– Topiramate (migraines, seizures) is associated with reductions in relapse as well as anxiety and depression (increases 5HT2, dopamine via 5HT2)
– Varenicline (Chantix) (nicotinic & dopamine receptors not serotonin)
MAT for Methamphetamine
– Five medications were subject to multiple RCTs and demonstrated limited evidence of benefit for reducing amphetamine use:
– Methylphenidate, Dexamphetamine (controlled stimulation via SNDRI)
– Buprenorphine (blunts opioid receptor associated euphoria)
– Modafinil (SDRI)
– Naltrexone (blocks opioid receptor associated euphoria)
– SSRIs and antipsychotics are also being studied

MAT for Nicotine
– Nicotine/smoking stimulates
– Norepinephrine (focus) and the HPA-Axis
РGABA (also blocks GABA’s ability to block dopamine)
– Release of dopamine (concentration, perseveration, energy) and endogenous opioids (pleasure, pain management)
– MAO which reduces the rate of dopamine breakdown
MAT for Nicotine
– Varenicline (increases dopamine (ceiling effect), GABA)
– Buproprion (NDRI)
– Nicotine Replacement patch, spray, lozenge
Summary
– Some progress has been made for the treatment of SUDs with medications
– Medications help
– Replace self medication behaviors
– Transition off the drug gradually to maintain neurotransmitter balance while allowing the brain to recover
– Medications either provide controlled activation, block activation or make use unpleasant (Antabuse)