Medication Assisted Therapy Overview. ATTC Network s Third Thursday itraining Thomas E. Freese, Ph.D., Pacific Southwest ATTC February 17, 2011

Transcription

1 Medication Assisted Therapy Overview ATTC Network s Third Thursday itraining Thomas E. Freese, Ph.D., Pacific Southwest ATTC February 17, 2011

2 Goals of the Training As a result of participating in this training, participants will be able to describe or name: Common perceptions of medication-assisted treatment (MAT) The basics of brain functioning in relation to MAT How medications to treat alcoholism and drug abuse work in the brain The types of agencies where MAT is offered Additional resources available to you.

3 What Is the Perception of MAT in the Substance Use Disorders Treatment Community?

4 What the big book says But this does not mean that we disregard human health measures. God has abundantly supplied this world with fine doctors, psychologists, and practitioners of various kinds. Do not hesitate to take your health problems to such persons. Most of them give freely of themselves, that their fellows may enjoy sound minds and bodies. Try to remember that though God has wrought miracles among us, we should never belittle a good doctor or psychiatrist. Their services are often indispensable in treating a newcomer and in following his case afterward. [Chapter 9, p. 133 (emphasis added)]

5 MAT FOR ALCOHOL

6 Neurotransmitters neurotransmitter effects when alcohol is consumed. dopamine makes you happy endogenous opioids make you euphoric and feel no pain glutamate the main excitatory neurotransmitter it speeds you up GABA the main inhibitory neurotransmitter it slows you down

7 Alcohol Neuronal Activity 1. Alcohol is ingested 2. The brain s natural endogenous opioids are first released. 3. This activates the areas the pleasure centers of the brain.

8 Alcohol Neuronal Activity 3. This caused dopamine to released. 4. Since dopamine is a main reward neurotransmitter, increases in the nucleus accumbens makes the drinker feel good. 5. The brain remembers those good feelings caused by the dopamine and alcohol. 6. The brain desires to repeat the behavior again to get the same good feelings.

9 Another Neuronal Activity (at the same time ) 1. Alcohol is ingested. 2. GABA, a major inhibitory neurotransmitter, is increased and creates an imbalance in the brain. 3. The brain is constantly trying to maintain a balance of inhibitory and excitatory signals so homeostasis can be achieved, and this increase in GABA caused by alcohol creates an imbalance. 4. The excitatory signals of glutamate are overridden by the increase in GABA, and the body generally slows down.

10 Another Neuronal Activity 5. Since the glutamate excitatory signals are overridden by the GABA inhibitory signals, glutamate is not able to activate the NMDA (glutamate) receptors as it usually does. 6. So, the brain increases the amount of NMDA receptors available for glutamate, in hopes that more opportunities for activation will yield more activity. This process is called upregulation.

11 Another Neuronal Activity 7. As the brain desired, this method of upregulation works and the imbalance is corrected. 8. However, more alcohol is required to feel the same level of intoxication (tolerance).

12 Another Neuronal Activity Normal Intoxicated Tolerance Glutamate Gaba Glutamate Gaba So now the brain has fully adapted to constant presence of alcohol. What do you think will happen once alcohol is taken away?

13 Another Neuronal Activity What do you think will happen once alcohol is taken away? WITHDRAWAL Gaba Glutamate

14 MEDICATIONS FOR ALCOHOLISM Acamprosate Naltrexone Disulfram Extended-Release Naltrexone

15 Acamprosate Campral

16 Acamprosate General Facts Generic Name: acamprosate calcium Marketed As: Campral Purpose: Encourages sobriety by reducing post-acute withdrawal symptoms from alcohol dependence Indication: For the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. Year of FDA-Approval: 2004

17 Additional Information Addictive Properties: Has not been found to be addictive and no reports of misuse Cost: $ per month, which is around $4.53 a day. 46 Third-Party Payer Acceptance: Patient Assistance Program through Forest Laboratories, Inc. Covered by most major insurance carriers, Covered by Medicare, Medicaid, and the VA (if naltrexone is contraindicated).

18 How Does Acamprosate Work? Mechanism of Action: glutamate receptor modulator Remember that repetitive consumption of alcohol causes: the brain to suppress glutamate activity, which causes an increase in NMDA receptors, counteracting alcohol s depressive effects. NOTE: The mechanism of action of acamprosate is not completely understood.

19 How Does Acamprosate Work? reduces glutamate activity by monitoring the amount of glutamate that can react at the NMDA receptors limits the amount of glutamate released by the neuron Pre-Synaptic Neuron Post-Synaptic Neuron = Glutamate NMDA Receptors = acamprosate

20 How Does Acamprosate Work? Withdrawal Post Acute Withdrawal Normal A Gaba Glutamate Gaba Glutamate Gaba Glutamate

21 Research about Acamprosate When compared to placebo, participants treated with acamprosate: Were able to maintain complete abstinence more frequently Had a greater reduction in the number of drinking days Were able to regain complete abstinence after one relapse more frequently than those treated with placebo. (Paille, et al., 1994; Pelc, et. al, 1997; Sass, et al., 1996)

22 Naltrexone Revia or Depade

23 Naltrexone General Facts Generic Name: naltrexone hydrochloride Marketed As: ReVia and Depade Purpose: To discourage drinking by decreasing the pleasurable effects experienced by consuming alcohol. Indication: In the treatment of alcohol dependence and for the blockade of the effects of exogenous administered opioids. Year of FDA-Approval: 1994

24 Additional Information Addictive Properties: Has not been found to be addictive or produce withdrawal symptoms when the medication is ceased. Administering naltrexone will invoke opioid withdrawal symptoms in patients who are physically dependent on opioids. Cost: $ per month, which is around $3.69 a day. 69 Third-Party Payer Acceptance: Covered by most major insurance carriers, Medicare, Medicaid, and the VA. 68

25 How Does Naltrexone Work? Remember: 1. Endogenous opioids are first released from the arcuate nucleus, which activates the areas of the brain known as the ventral tegmental area and the nucleus accumbens. 2. In response to this increased endogenous opioid activity, dopamine is released. 3. Since dopamine is a main reward neurotransmitter, increases in the nucleus accumbens makes the drinker feel good. 4. The brain remembers those good feelings caused by the dopamine and alcohol. 5. The brain desires to repeat the behavior again to get the same good feelings.

26 How Does Naltrexone Work? Naltrexone is an opioid receptor antagonist and blocks opioid receptors. By blocking opioid receptors, the reward and acute reinforcing effects from dopamine are diminished, and alcohol consumption is reduced. N N N N N N N N Opioid Receptor N = naltrexone = opioids Post-Synaptic Neuron

27 Research for Naltrexone When compared to placebo, those receivine naltrexone Were NOT able to maintain complete abstinence more frequently Had a greater reduction in relapse during the entire study (Paille, et al., 1994; Pelc, et. al, 1997; Sass, et al., 1996)

28 Naltrexone for Extended-Release Injectable Suspension Vivitrol

29 Extended-Release Naltrexone Administration Amount: one 380mg injection Method: deep muscle in the buttock Frequency: every 4 weeks Must be administered by a healthcare professional and should alternate buttocks each month.

30 How Does Extended-release Naltrexone Work? Extended-release naltrexone works in the brain exactly like oral naltrexone. Blocks opioid receptors for one entire month compared to approximately 28 doses of oral naltrexone to receive the same longevity. Since it is an intramuscular injection and not an implanted device, it is not possible to remove it from the body once extendedrelease naltrexone has been injected.

31 Additional Information for Extended-Release Naltrexone Addictive Properties: Not addictive, no high abuse liability, does not build tolerance, nor produce withdrawal symptoms when the medication is ceased. There were no reports of misuse, such as injection, smoking or prescription deviation during the clinical trials. However, administering naltrexone will invoke opioid withdrawal symptoms in patients who are physically dependent on opioids. Cost: According to Alkermes, private insurance pays ~$1,100. There is special pricing for FHQHs where they can get it for $483. Third-Party Payer Acceptance: Approximately 90% of patients thus far have received insurance coverage with no restrictions. In addition, extended-release naltrexone now has a J code for payors.

32 Scientific Research about Extended-Release Naltrexone (cont.) When compared to placebo, those treated with extended-release naltrexone Did NOT maintain complete abstinence more frequently Had a greater reduction in the number of heavy drinking days during the entire study Those who had a seven-day abstinence period prior to treatment initiation had a greater reduction in the number of heavy drinking days during the entire study

33 Disulfiram Antabuse

34 Disulfiram General Facts Generic Name: disulfiram Marketed As: Antabuse Purpose: Discourages drinking by making the patient physically sick when alcohol is consumed. Indication: An aid in the management of selected chronic alcohol patients who want to remain in a state of enforced sobriety so that supportive and psychotherapeutic treatment may be applied to best advantage. Year of FDA-Approval: 1951

35 Additional Disulfiram Information Addictive Properties: Has not been found to be addictive, have a high abuse liability, or produce withdrawal symptoms when the medication is ceased. There were no reports of misuse, such as injection, smoking or prescription deviation during the clinical trials. 61 Cost: $57.59 per month, which is around $1.92 a day. 62 Third-Party Payer Acceptance: Covered by most major insurance carriers, Medicare, Medicaid, and the VA. 61

36 How Does Disulfiram Work? Disulfiram works by blocking the oxidation of alcohol during the acetaldehyde stage. When alcohol is ingested: 1. alcohol is broken down in the liver by the enzyme alcohol dehydrogenase to acetaldehyde; 2. then, acetaldehyde is converted by the enzyme acetaldehyde dehydrogenase to acetic acid. Disulfiram works by blocking the enzyme acetaldehyde dehydrogenase. This causes acetaldehyde to accumulate in the blood at 5 to 10 times higher than what would normally occur with alcohol alone.

37 How Does Disulfiram Work? Since acetaldehyde is poisonous, a buildup of it produces a highly unpleasant series of symptoms, which is commonly referred to as the disulfiram-alcohol reaction. throbbing in head/neck brief loss of consciousness throbbing headache lowered blood pressure difficulty breathing marked uneasiness copious vomiting nausea flushing sweating thirst weakness chest pain dizziness palpitation hyperventilation rapid heartbeat blurred vision confusion respiratory depression cardiovascular collapse myocardial infarction congestive heart failure unconsciousness convulsions death

38 Side Effects of Disulfiram Common side-effects: skin rash acneform eruption headache mild drowsiness mild fatigue impotence metallic or garlic-like aftertaste Consult a physician: extreme fatigue weakness loss of appetite nausea vomiting general sense of uneasiness yellowness of the skin or eyes (liver disease) dark urine (liver disease) Serious side effects = eye pain, peripheral neuritis, polyneuritis, peripheral neuropathy, hepatitis, hepatic failure

39 Scientific Research about Disulfiram (cont.) When compared with placebo, those receiving disulfiram: Did NOT maintain complete abstinence more frequently Had a greater reduction in the number of drinking days during the entire study (Fuller, et al., 1986)

40 MAT FOR OPIOID ADDICTION

41 How does Buprenorphine Work? Partial vs. Full Opioid Agonist death Opiate Effect Full Agonist (e.g., methadone) Partial Agonist (e.g. buprenorphine) Dose of Opiate Antagonist (e.g. Naloxone)

42 Medications for Opioid Addiction Naltrexone Methadone Buprenorphine Buprenorphine/Naloxone

43 Naltrexone Revia or Depade

44 Research About Naltrexone for Opioids Meta analysis of 7 studies. Naltrexone lowered the risk of drug abuse better than placebo, with or without psychological support This effect can be seen to fall off over time and may be of limited clinical significance. Risk of reimprisonment seemed to decreased while on naltrexone therapy, but the number of participants was small. Patient compliance is an issue that must be addressed (Adi, et al., 2007)

45 Naltrexone for Extended-Release Injectable Suspension Vivitrol

46 Research About Extended-Release Naltrexone When compared to placebo, those recivining extended release naltrexone: Had fewer opioid positive urines Stayed in treatment longer Had less craving Showed greater improvement in the mental component of quality of life and overall heatlh status Krupitsky, et al., 2010

47 Methadone Dolophine Methadose

48 Methadone General Facts Generic Name: methadone hydrochloride (information from medication package insert) Marketed As: Methadose and Dolophine (among others) Purpose: To discourage illicit opioid use due to cravings or the desire to alleviate opioid withdrawal symptoms. Indication: For the treatment of moderate to severe pain not responsive to non-narcotic analgesics; for detoxification treatment of opioid addiction; for maintenance treatment of opioid addiction, in conjunction with appropriate social and medical services.

49 Methadone Additional Information (information from medication package insert) Pregnancy: Methadone is the preferred method of treatment for medication-assisted treatment for opioid dependence in pregnant women. An expert review of published data on experiences with methadone use during pregnancy concludes that it is unlikely to pose a substantial risk. But, there is insufficient data to state that there is no risk. Methadone has not been adequately tested on pregnant women. Therefore, methadone has a Pregnancy Category C designation, meaning that it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution should be exercised when using methadone with this population.

50 Methadone Additional Information Pregnancy: (information from medication package insert) Detoxification is relatively contraindicated unless done in hospital with monitoring. Babies born to mothers who have been taking opioids regularly prior to delivery may be physically dependent and may experience opioid withdrawal symptoms. It is known that methadone is excreted through breast milk, and a decision should be made whether to discontinue nursing or to discontinue the medication, taking into account the importance of the medication to the mother and continued illicit opioid use.

51 How does methadone work? Methadone binds to the same receptor sites as other opioids. Orally effective Slow onset of action Long duration of action Slow offset of action

52 Treatment Outcome Data: Methadone 8-10 fold reduction in death rate Reduction of drug use Reduction of criminal activity Engagement in socially productive roles; improved family and social function Increased employment Improved physical and mental health Reduced spread of HIV Excellent retention

53 Crime among 491 patients before and during MMT at 6 programs 300 Crime Days Per Year Before TX During TX 50 0 A B C D E F

54 Relapse to IV drug use after MMT 105 male patients who left treatment 100 Percent IV Users Treatment Months Since Stopping Treatment IN 1 to 3 4 to 6 7 to 9 10 to 12

55 Buprenorphine Buprenorphine/ Naloxone Subutex Suboxone

56 How Does Buprenorphine Work? Partial Opioid Agonist Produces a ceiling effect at higher doses Has effects of typical opioid agonists these effects are dose dependent up to a limit Binds strongly to opiate receptor and is longacting

57 Research about Buprenorphine Buprenorphine is marketed for opioid treatment under the trade names of Subutex (buprenorphine) and Suboxone (buprenorphine/naloxone) Over 25 years of research Over 5,000 patients exposed during clinical trials Proven safe and effective for the treatment of opioid addiction

58 Research about Buprenorphine Clinical trials have established the effectiveness of buprenorphine for the treatment of heroin addiction. Effectiveness of buprenorphine has been compared to: Placebo (Johnson et al. 1995; Ling et al. 1998; Kakko et al. 2003) Methadone (Johnson et al. 1992; Strain et al. 1994a, 1994b; Ling et al. 1996; Schottenfield et al. 1997; Fischer et al. 1999) Methadone and LAAM (Johnson et al. 2000)

59 Advantages of Buprenorphine/Naloxone Combination tablet is being marketed for U.S. use Discourages IV use Diminishes diversion Allows for take-home dosing

60 How Does Buprenorphine/Naloxone Work? Buprenorphine and naloxone have different sublingual(sl)-to-injection potency profiles that are optimal for use in a combination product. SL Bioavailability Injection to Sublingual Potency Buprenorphine 40-60% Buprenorphine 2:1 Naloxone 10% or less Naloxone 15:1

61 How Does Buprenorphine/Naloxone Work? Basic pharmacology, pharmacokinetics, and efficacy is the same as buprenorphine alone. Partial opioid agonist; ceiling effect at higher doses Blocks effects of other agonists Binds strongly to opioid receptor, long acting

62 You might be wondering -WHO is a good candidate to refer? Consider: History of substance abuse Willingness to consider MAT -WHERE is MAT typically offered? Which local agencies? What happens after you make a referral?

63 Final Note: Behavioral Treatments The FDA labeling on these medications is clear: The medications should be used in combination with behavior treatments for addiction Good treatment is holistic, integrated and multifaceted, taking into account the physical, behavioral and spiritual wellbeing of the individual. Medications can help us take care of the physical we need to do the rest

64 Resources Buprenorphine Reckitt Benckiser Naltrexone for Extended-Research Injectable Suspension Alkermes VIVITROL ( )

65 For more information, contact: Thomas E. Freese, PhD Beth Rutkowski, MPH