MEDICATION ASSISTEDTREATMENT FOR ADDICTION: … · 2017. 6. 19. · ©university of utah health, 2017 medication assistedtreatment for addiction: available &emerging options elizabeth

© U N I V E R S I T Y O F U T A H H E A L T H , 2 0 1 7

MEDICATION ASSISTED TREATMENT FOR ADDICTION: AVAILABLE & EMERGING OPTIONS

ELIZABETH F. HOWELL, MD, DLFAPA, DFASAMASSOCIATE PROFESSOR OF PSYCHIATRY

TRAINING DIRECTOR, ADDICTION PSYCHIATRY FELLOWSHIPTRAINING DIRECTOR, ADDICTION MEDICINE FELLOWSHIP

ADDICTIONS UPDATE CONFERENCEJUNE 1-2, 2017


ABCDE’S OF ADDICTION

Addiction is characterized by:• Inability to consistently Abstain;• Impairment in Behavioral control;• Craving; or increased “hunger” for drugs

or rewarding experiences;• Diminished recognition of significant

problems with one’s behaviors and interpersonal relationships; and

• A dysfunctional Emotional response.

https://www.asam.org/quality-practice/definition-of-addiction


CHRONIC EFFECTS OF DRUG USE INCLUDE:NEURONAL ADAPTATION, TOLERANCE, DEPENDENCE AND WITHDRAWAL IF DRUG IS REMOVED

E.J.Nestler andG.K.Aghajanian,1997,Science,278,p.59.

Drug Use Drug Abstinence


NEURAL REWARD CIRCUITS IMPORTANT IN THE REINFORCING EFFECTS OF DRUGS OF ABUSE

Cami J, Farre M: NEJM 349:975-986, 2003; Neuropsychopharmacology (2014) 39, 254-262

Neuroplasticity in Brain Circuits Associated with the Development of Addiction


WHY TREAT ADDICTION WITH MEDICATIONS?

• Treat overdose• Facilitate abstinence

– Medically supervised withdrawal– Restore balance to brain systems– Treat co-occurring conditions

• Prevent relapse– Stress reduction– Cues/craving– Block action of drugs– Cognitive enhancement/decision-making


GOALS AND RATIONALE FOR SPECIFICPHARMACOTHERAPY FOR AN ADDICTION

1.Prevent withdrawal symptoms2.Reduce drug craving3.Normalize any physiological functions

disrupted by drug use4.Target treatment agent to specific site of

action, receptor, or physiological system affected or deranged by drug of abuse

MJ Kreek


IDEAL PHARMACOTHERAPY FOR TREATMENT OF ADDICTION

• Orally effective

• Onset of action

– Slow onset for maintenance therapy

– Rapid onset for withdrawal treatment

• Long duration of action

• Slow offset of action

• [Not psychoactive?]

Route of Cocaine Administration

Onset of Effects

Peak Effect (min)

Duration of Euphoria (min)

Plasma Half-life (min)

Inhalation 7 sec 1-5 20 40-60

Intravenous 15 sec 3-5 20-30 40-60

Nasal 3 min 15 45-90 60-90

Oral 10 min 60 60 60-90

http://emedicine.medscape.com/article/813959-overview#a4 andKreek MJ

Cocaine: Onset of Effects, Peak Effects, Duration of Euphoria, and Plasma Half-Life by Routes of Administration• Rates of rise of blood (and presumably brain) levels of drugs of

abuse are related positively to their reinforcing effects• Rates of fall of blood (and presumably brain) levels of drugs of

abuse are related positively to the onset of withdrawal symptoms and/or acute “craving”


HOW MIGHT MEDICATION ASSISTED TREATMENTS WORK?

• Occupy same brain receptors as drugs– Methadone, Buprenorphine

• Decrease craving– Naltrexone, Acamprosate, Bupropion, Buprenorphine, etc.– Topiramate and others?

• Block effects of drugs– Naltrexone, Naloxone, Buprenorphine

• Cause aversive reactions– Antabuse (Disulfiram)

• Reverse drug effects – Amethystic agents [Holy Grail of addiction treatment?]:

mythical treatment capable of counteracting the acute effects of alcohol on the CNS, hastening sobriety

• Help the brain heal?


U.S. FDA-APPROVED MEDICATIONS FOR ADDICTION TREATMENT (LAST NEW ONE 2004)

Medication Indication(s)

Disulfiram (Antabuse®) Alcohol dependence

Nicotine replacement therapies Nicotine dependenceBupropion (Wellbutrin®, Zyban®) Nicotine dependence

Varenicline (Chantix®) Nicotine dependence

Naltrexone (ReVia®, Vivitrol®) Alcohol dependenceOpioid dependence

Acamprosate (Campral®) Alcohol dependence

Methadone Opioid dependence/withdrawal

Buprenorphine (Subutex®, others) Opioid dependence/withdrawal

Buprenorphine-naloxone (Suboxone®, others)

Opioid dependence/withdrawal


ALCOHOL


ALCOHOL INTERACTS WITH MULTIPLE CNS NEUROTRANSMITTER SYSTEMS

• Glutamate• GABA• Dopamine• Serotonin • Endogenous opioids


ALCOHOL: GABA AND GLUTAMATE• Alcohol use temporarily disrupts the balance between neuronal

excitation and inhibition• GABA system:

– Primary CNS inhibitory neurotransmitter– Alcohol and other sedatives activate GABA-A and acutely

decrease cell excitability • Glutamate system:

– Primary excitatory system in CNS– NMDA (N-methyl-D-aspartate) receptors bind glutamate– Chronic alcohol exposure leads to: Upregulation/increasing

number of NMDA receptors --> Contributes to development of tolerance

• Upon stopping alcohol use:– Excessive glutamate-induced excitation– Hyperexcitatory state (hallucinations, hyperactivity, seizures)– Increases risk of excitotoxic cell death– Leads to cognitive deficits?


ALCOHOL: ENDOGENOUS OPIOID SYSTEM

• Alcohol intake is associated with increasedrelease of endogenous opioids (Beta-endorphins)– Mediates euphoric effect of alcohol

• Endogenous opioids stimulate increased release of dopamine in the Nucleus Accumbens


MEDICATIONS FOR ALCOHOL USE DISORDERS, MECHANISMS OF ACTION• FDA-Approved

– Disulfiram (Antabuse®)= aversive contingency, not neuromodulatory for alcohol craving

– Acamprosate (Campral®)=glutamate system– Naltrexone (ReVia®, Vivitrol®)=endogenous

opioid system, indirectly dopamine


DISULFIRAM• Dose125-500 mg per day (usually 250 mg)• Effects can last up to 2 weeks after last dose• Not a neuromodulator, only aversive contingency• Effects depend on compliance; observed dosing best• Disulfiram-alcohol reaction:

– Flushing, throbbing in head and neck, throbbing headache– Respiratory difficulty – Nausea, copious vomiting, sweating, thirst– Chest pain, palpitation– Dyspnea, hyperventilation– Tachycardia, hypotension, syncope– Marked uneasiness, weakness, vertigo, blurred vision– Confusion – In severe reactions, there may be respiratory depression, cardiovascular

collapse, arrhythmias, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death.


NaltrexoneTargets positive reinforcement

Targets negative reinforcement

POTENTIAL TARGETS OF (NON-AVERSIVE) ANTI-RELAPSE MEDICATIONS

Littleton JM, J Addiction Medicine 1(3)September 2007: 115-125


NALTREXONE• Mu Opioid antagonist• Not scheduled, not addicting• Available formulations:

– Oral 50 mg tablets (ReVia®, Depade®, others): take 50 mg qday, or 100 mg q48 hours, or 150 mg q72 hours

– 380 mg depot injectable formulation (Vivitrol®) every 28-30 days

• Same technology as Risperidone Consta• Expensive (cash price $1700 per injection)

• FDA-Approved for treatment of:– Opioid dependence (tablets 1984, depot form 2006):

Long-term opioid blockade in recovering persons– Alcohol Dependence (tablets 1994, depot form 2010):

Treatment of alcohol craving, prevention of relapse


HOW MIGHT NALTREXONE/OPIOID ANTAGONISTS WORK FOR ALCOHOL USE DISORDERS?

• Block pleasurable reinforcing effects of alcohol– Opioid Antagonists block alcohol-induced

Dopamine (DA) release in Nucleus Accumbens• Alleviate craving for alcohol• Increase aversive effects of alcohol

– Nausea, vomiting (not as severe as disulfiram)• Alter neuroendocrine responses to alcohol

– Alcohol activates HPA axis– Alcohol triggers release of ACTH, Beta-endorphins,

glucocorticoids (mediates some of positive effects)


NALTREXONE• Alcohol Use Disorders

– Decreases alcohol craving, rate of relapse, positive reinforcement and length of drinking episodes

– All studies combined medication with psychosocial supports

• Opioid Use Disorders– Long-term opioid blockade in recovering persons– Naltrexone binds tightly to opioid receptor– No drug effect if opioids used while on naltrexone

therapy– Depot naltrexone decreases opioid craving


ACAMPROSATE• (Calcium acetylhomotaurinate)• Chemical structure similar to that of

homotaurine and GABA (naturally occurring amino acid mediators)

• Has neuroprotective and abstinence-promoting effects – Attenuates glutamate release in alcohol withdrawal– Blocks excitotoxicity produced by alcohol– Modulates cue-elicited drinking behaviors

• Reduces alcohol relapse, increases treatment retention, promotes abstinence from alcohol, reduces protracted abstinence

• Available in France since 1989, US since 2005

adaption: subclinicalwithdrawal-like symptoms

Opioid antagonistic

compound

NMDA antagonistic compound

opio

ider

gic

/ dop

amin

ergi

c m

echa

nism

sG

ABAergic / glutamatergic m

echanisms

alcohol intake

CRAVING

relief

conditionedstimuli

conditionedstimuli

reward

Kiefer & Wiedemann, Alcohol Alcohol 2004

attributes incentive salienceto the stimulus


COMBINATIONS OF MEDICATIONS

• Naltrexone + Acamprosate• Naltrexone + Disulfiram• Acamprosate + Disulfiram• Acamprosate + Disulfiram + Naltrexone• FDA-approved medications with emerging

treatments


COMPARING AND COMBINING NALTREXONE 50 MG/DAY AND ACAMPROSATE 1998 MG/DAY IN RELAPSE PREVENTION OF ALCOHOLISM (N=160): NTX+ACAMP>NTX>ACAMP>PBO

Kiefer F et al: Arch Gen Psychiatry. 2003 Jan;60(1):92-9.


NICOTINE


NICOTINE ACTIONS• Binds to nicotinic

acetylcholine receptors

• Mimics acetylcholine (agonist)

• Opens ligand-gated ion channel and depolarizes

• Activates reward pathway– Dopamine release


MEDICATIONS FOR NICOTINE USE DISORDERS, MECHANISMS OF ACTION

• FDA-Approved treatments:– Nicotine replacement therapies

• Gum, patch, lozenges, nasal spray• Replace drug used with safer form

– Bupropion• NE and DA reuptake inhibitor

– Varenicline• Alpha-4-beta-2 nicotinic acetylcholine

receptor partial agonist


BUPROPION• Wellbutrin® or Zyban®

– NDRI: NE and DA reuptake inhibitor– Pregnancy Category C – Approved for use in smoking cessation– Decreases nicotine craving– Increases likelihood of successful quit attempts

• Caution or contraindication with: – Seizure disorder, active eating disorders, impaired liver or

renal function, hypertension• Dosing:

– Set a target quit date– Begin bupropion at least 8 days before quit date– Start with 150 mg Qday x 3 days, then increase to 150 mg BID – Continue for 7-12 weeks or longer


VARENICLINE• Chantix® approved 2006 for smoking cessation

– Not approved in pregnancy, in persons younger than 18, or in combination with other smoking cessation treatments (but recent study in combination with NRTs

• Specific alpha-4-beta-2 nicotinic acetylcholine receptor partial agonist– Stimulates dopamine and simultaneously blocks

nicotine receptors– Nicotine abstinence reduces dopamine release,

associated with withdrawal symptoms and craving for nicotine

• Side effects: – nausea, headache, vomiting, flatulence, insomnia,

abnormal dreams, and dysgeusia (change in taste perception)


VARENICLINE• Varenicline (Chantix®) approved 2006 for smoking

cessation– Not approved in pregnancy, in persons younger than

18, or in combination with other smoking cessation treatments (but recent study in combination with NRTs

• Specific alpha-4-beta-2 nicotinic acetylcholine receptor partial agonist– Stimulates dopamine and simultaneously blocks

nicotine receptors– Nicotine abstinence reduces dopamine release,

associated with withdrawal symptoms and craving for nicotine

• Side effects: – nausea, headache, vomiting, flatulence, insomnia,

abnormal dreams, and dysgeusia (change in taste perception)


VARENICLINE (CHANTIX®)• Set a date to stop smoking. • Varenicline dosing should start one week before

the quit smoking date.• Take after eating and with a full glass of water. • Varenicline dosing:

– 0.5 mg Qday x 3 days– 0.5 mg BID x 4 days– 1 mg BID x 11 weeks

• Use lower maintenance dose (1.0-1.5 mg/day) if SE’s not tolerated at 2 mg/day

• Treat for 12 weeks minimum, preferably 24 weeks or longer to further increase the likelihood of long-term abstinence.


OUTCOMES WITH VARENICLINE

0

5

10

15

20

25

30

35

40

45

12 Weeks 1 year

Varenicline

Bupropion

Placebo

JAMA 2006;295:614.

% A

bst

inen

t


OPIOIDS


MEDICATIONS FOR OPIOID USE DISORDERS, MECHANISMS OF ACTION

• Naltrexone– Oral tablets, Depot injectable– Mu opioid receptor blockade

• Buprenorphine– Sublingual tablets, film; buccal film– Long-acting implantable rods– Mu opioid receptor partial agonist

• Methadone– Tablets, liquid– Mu opioid receptor full agonist

OPIOIDS

• Endogenousopioidpeptidesareproducednaturallyinthebody– Endorphins– Enkephalins– Dynorphins– Endomorphins

LaForge, Yuferov and Kreek, 2000


METHADONE• Actions of methadone:

– Prevents withdrawal symptoms and “drug hunger”– Blocks euphoric effects of short-acting narcotics– Allows normalization of disrupted physiology

• Mechanism of action: – Long-acting narcotic – Provides steady levels of opioid at specific mu

receptor sites – Full mu opioid receptor agonist – Internalizes like endorphins – Modest NMDA receptor complex antagonism

Kreek, 1972; 1973; 2001; 2002; Inturrisi et al; Evans et al


METHADONE• Long-acting synthetic Mu opioid receptor agonist

– Half-life of ~24 hours (varies between 8 to 59+ hours)• Approved by FDA in 1972 for treatment of opioid

addiction• Schedule II, inexpensive

– Available as tablets and liquid • Dosage for maintenance:

– 60-120 mg/day for maximal effectiveness• Benefit for OUD outweighs risk in pregnancy• Metabolized in the liver by N-demethylation• Affects CYP2B6, 3A4, 2C19

– Multiple drug interactions– http://atforum.com/rx-methadone-safety/

FDA Approved


METHADONE DANGERS

• Overdose Risk – Black Box Warning and FDA Health Advisory, 2006

• “Methadone’s peak respiratory depression effects typically occur later, and persist longer, than its peak analgesic effects…” “Patients tolerant to other opioids may be incompletely tolerant to methadone….”

• Pain relief from methadone lasts 4 to 8 hours.• Methadone elimination half-life variable, 8 to 59 hours

• Cardiac Toxicity– Potent inhibitor of hERG potassium channels,

involved in cardiac repolarization– Bradycardia– May cause prolonged QTcàTorsades de Pointes


METHADONE OVERDOSE RISK• Steady-state methadone

concentration reached in about 5 days (5xT1/2) – [range 45 hrs to 12+ days]

• Danger of overdose: – Initial dose too high or– Dose escalation too rapid or– Concomitant use of CYP 450

inhibitors• MMT initial doses capped at 30

mg/day and dose escalation gradual

• Pain treatment and street use comprise most methadone OD’s

Adapted from Payte 2002


METHADONE U.S. FEDERAL REGULATIONS• Methadone cannot be prescribed to opioid

addicted persons for detoxification or addiction treatment in an office-based or hospital setting, except in a Federally-recognized Opioid Treatment Program (“methadone maintenance program”)

• Can be prescribed by any physician or prescriber (with appropriate DEA registration) for the treatment of pain

FDA Approved


BUPRENORPHINE

• Semi-synthetic opioid derived from thebaine(naturally occurring alkaloid of opium poppy)

• 25-40 times more potent than morphine– 1 mg buprenorphine==25-40 mg morphine

• Extensive first-pass metabolism• Very low oral bioavailability

– Minimally absorbed if swallowed (except in kids)– Sublingual bioavailability adequate

• Tmax (Mean time to maximum plasma concentration)==40 minutes to 3.5 hours

• Elimination half-life=37 hours (3-44 hours)


BUPRENORPHINE PHARMACOLOGY• Partial Mu opioid receptor agonist

– Ceiling effect for respiratory depression-clinically– Safer in overdose– High affinity for Mu opioid receptor

• Non-selective Kappa opioid receptor antagonist/partial agonist– ?Antidepressant effects?– ?Antianxiety effects?

• ORL-1 receptor partial agonist– Less hyperalgesia?

• Metabolite norbuprenorphine– N-dealkylated metabolite– Does not contribute to respiratory depression


PARTIAL AND FULL OPIOID AGONIST ACTIVITY

no drug high dose

DRUG DOSElow dose

% Mu ReceptorIntrinsic Activity

0

10

20

30

40

50

60

70

80

90

100

Full Agonist (e.g. heroin)

Partial Agonist (e.g. buprenorphine)

Like full agonists, partial agonist drugs produce increasing mu opioid receptor specific activity at lower doses

At higher doses, even when partial agonist drug completely binds all mu receptors, maximum opioid agonist effect is never achieved


SUBOXONE® BRAND NAMEIS NO LONGER AVAILABLEIN A PILL FORM


BUPRENORPHINE FORMULATIONSFOR ADDICTION TREATMENT

• Buprenorphine with Naloxone (combo product)– Generic sublingual tablets (Formerly Suboxone®)– Zubsolv® tablets, different dosing– Bunavail® buccal film– Sublingual film (Suboxone® and others in

development)• Buprenorphine mono product

– formerly Subutex®

• Implantable formulation (Probuphine®)• Depot injection formulations in development


BUPRENORPHINE FORMULATIONSFOR PAIN TREATMENT, NOT ADDICTION

• Injectable Buprenorphine (Buprenex®)– Schedule III (was Schedule V until 2002)– NOT FDA-approved for treatment of opioid

addiction or detoxification• Transdermal patch (Butrans®)

– For pain only– Expensive– NOT FDA-approved for treatment of opioid

addiction or detoxification


PRESCRIBING OF BUPRENORPHINE IN U.S.• Drug Abuse Treatment Act (DATA 2000):

– Opioid detoxification and primary addiction treatment in the office-based setting allowed with Schedules III, IV or V agents approved for addiction treatment

– Physicians must qualify and register for a special DEA number if using buprenorphine-naloxone or buprenorphine for addiction treatment (XA#######)

– ONLY physicians can prescribe for addiction treatment; 30 patient limit per physician for one year after waiver, then can apply to increase patient limit to 100-275 depending on qualifications

• Approval of sublingual buprenorphine for the treatment of opioid addiction is significant– First time (since a U.S. Supreme Court ruling in 1918) that

physicians have been allowed to manage opioid addiction in the office-based setting

– Shift to medical management model

https://www.samhsa.gov/medication-assisted-treatment/buprenorphine-waiver-management; http://pcssmat.org/; http://pcss-o.org/


1-YEAR RETENTION AND SOCIAL FUNCTION AFTER BUPRENORPHINE-ASSISTED RELAPSE PREVENTION TREATMENT FOR HEROIN DEPENDENCE IN SWEDEN: A RANDOMISED, PLACEBO-CONTROLLED TRIAL

• Subjects were heroin-dependent patients who agreed to the study, and did not fulfill the criteria for methadone treatment

• Double-blind, random assignment to:– 16 mg/day SL

buprenorphine tablets, or

– 6 day buprenorphine withdrawal followed by placebo tablets

• 20 patients per group

Kakko Jetal.Lancet.2003Feb22;361(9358):662-8

Placebo Bupre-norphineCox

regression

Dead 4/20 (20%) 0/20 (0%) c2=5.9;

p=0.015


EMERGING TREATMENTS


POTENTIAL TARGETS FOR ADDICTION TREATMENT

• Drug effects• Withdrawal• Stress• Cues• Priming• Inhibitory deficits• Reinstatement/relapse• Craving• Underlying mechanisms of

addiction• Co-occurring disorder

treatment

• Neurotransmitters, receptors, transporters

• Neurotransmitter systems– Dopamine– Endogenous opioid– Serotonin (5-HT)– GABA/Glutamate– Acetylcholine– Neuropeptide Y– CRF– Endocannabinoid system

• Ligand-gated ion channels• G-protein coupled receptors• Second messenger systems• Transcription factors• Genetic “switches”• Neurotrophic factors• Glial attenuation


Neuropsychopharmacology Reviews (2012) 37, 290–292; doi:10.1038/npp.2011.84


POTENTIAL OFF-LABEL USES OF FDA-APPROVED MEDICATIONSMedication Potential uses (Animal/human studies proposed, in progress, or published)

Ondansetron Alcohol use, cocaine self-administration, opioid withdrawal

Topiramate Alcohol craving and use, methamphetamine reinforcement, nicotine craving, cocaine craving

Varenicline Alcohol consumption

Baclofen Alcohol craving and withdrawal, nicotine self-administration

Gabapentin Alcohol relapse, benzodiazepine dependence, cannabis craving

Memantine Alcohol craving, morphine-conditioned reward, nicotine use

Cabergoline Alcohol intake and relapse, alcohol-seeking

Naltrexone (NTX) Methamphetamine dependence

NTX + Buprenorphine Cocaine dependence

Buspirone Cocaine relapse

N-acetyl cysteine Cannabis relapse

Tizanidine, clonidine Opioid-induced hyperalgesia

Doxazosin Cocaine dependence

Minocycline Opioid addiction

Ceftriaxone Cocaine relapse


EMERGING TREATMENTS FOR ADDICTION• Nutraceuticals

– Citicholine– N-Acetyl Cysteine (NAC)

• Neuromodulation– TMS

Date of download: 1/7/2014 Copyright © 2012 American Medical Association. All rights reserved.

Gabapentin Treatment for Alcohol Dependence: A Randomized Clinical TrialJAMA Intern Med. 2014;174(1):70-77. doi:10.1001/jamainternmed.2013.11950

Gabapentin Effects on Number of Drinks per Week and Number of Heavy Drinking Days per Week During the 12-Week Study in the Intention-to-Treat Population A, Number of drinks per week; B, number of heavy drinking days per week. Error bars indicate SEM (N = 150).

Figure Legend:

Number of Drinks per Week Number of Heavy Drinking Days per Week



Gabapentin Effects on Standardized Measures of Craving, Sleep, and Mood During the 12-Week Study in the Intention-to-Treat Population A, Alcohol Craving Questionnaire; B, Pittsburgh Sleep Quality Index; C, Beck Depression Inventory II. Error bars indicate SEM (N = 150).

Figure Legend:

Alcohol Craving Questionnaire

Pittsburgh Sleep Quality Index

Beck Depression Inventory II



Gabapentin Effects on Rates of No Heavy Drinking and Complete Abstinence During the 12-Week Study in the Intention-to-Treat Population A, No heavy drinking; B, complete abstinence. Error bars indicate 95% confidence intervals (N = 150).

Figure Legend:

No heavy drinking Complete abstinence


GABAPENTIN FOR CANNABIS USE, WITHDRAWAL, EXECUTIVE FUNCTION

• Pre-clinical findings:– gabapentin normalizes the CRF-induced GABA activation in the

amygdala. Calcium-channel-GABAergic mechanism of action has relevance for restoring homeostasis in brain stress (CRF) systems

– cannabis withdrawal produces anxiogenic-like state and increased extrahypothalamic CRF release in the central nucleus of the amygdala in rodents.

– GABA–CRF interactions and their role in the motivational aspects of cannabis relapse provide pre-clinical rationale in healthy volunteers.

• Clinical studies:– gabapentin reduces craving and disturbances in sleep and mood

• the most persistent symptoms of protracted cannabis withdrawal• a key reason patients resume smoking marijuana.

– Gabapentin showed subtle cognitive-enhancing effects in the domains of attention, concentration, visual–motor functioning, inhibition, and set shifting in healthy volunteers.

MasonBJetal:Neuropsychopharmacology (2012)37,1689-1698.

Mason BJ et al: A Proof-of-Concept Randomized Controlled Study of Gabapentin: Effects on Cannabis

Use, Withdrawal and Executive Function Deficits in Cannabis-Dependent Adults

Neuropsychopharmacology (2012) 37, 1689-1698;doi:10.1038/npp.2012.14

Figure 2

From: A Double-Blind Randomized Controlled Trial of N-Acetylcysteine in Cannabis-Dependent Adolescents

American Journal of Psychiatry Volume 169, Issue 8, August 2012, 805-812

PROPORTION OF NEGATIVE URINE CANNABINOID TESTS OVER TIME AMONG CANNABIS-DEPENDENT ADOLESCENTS IN A RANDOMIZED CONTROLLED TRIAL OF N-ACETYLCYSTEINE (NAC) 1200 MG BID

a In this intent-to-treat analysis, all randomized participants (N=116) were included, and urine cannabinoid tests were assumed to be positive for all missed visits. With adjustment for years of cannabis use, baseline urine cannabinoid test results, and major depressive disorder, odds ratio=2.4, 95% CI=1.1–5.2; χ2=4.72, p=0.029.

Copyright © American Psychiatric Association. All rights reserved.

Date of download:06/01/2017


Lyon J. More Treatments on Deck for Alcohol Use Disorder. JAMA. Published online May 24, 2017. doi:10.1001/jama.2017.4760


USE APPROPRIATE MEDICATIONSWhat substances are safe to use

in recovery, and why?


CROSS-ADDICTION: GENERAL PRINCIPLES

• AVOID the use of any psychoactive substances in persons with a history of alcohol/drug use disorders

• Use of any psychoactive substance may lead to:– Addiction to or craving for

that substance– Craving for or relapse

back to the “drug of choice”

• “Dear Doctor” letter

http://bit.ly/2rhWGoR

v. 06-2013 http://efhmd.blogspot.com11 ©"and"developed"by"Elizabeth"F"Howell"MD.""Available"through"https://addictionmedicine.wikispaces.com""May"be"altered"for"your"clinical"use,"but"only"to"add"the"current"date,"your"phone"number"and"your"name.1

To1Whom1It1May1Concern:11 1 1 1 1 1 DATE:11

1 Your1patient1has1been1under1my1care1for1the1treatment1of1addiction.11Because1of1the1risk1of1relapse1and1crossCaddiction,1I1recommend1that1this1patient1should1not1use1any1alcohol,1street1drugs,1or1potentially1addicting1prescribed1medications.11Any1use1of1alcohol,1street1drugs,1or1the1following1medications1can1precipitate1or1increase1the1likelihood1of1relapse1to1addiction.11A"person"who"has"ever"been"addicted"to"alcohol"or"any"other"drugs"has"a"lifetime"risk"of"becoming"addicted"to"other"potentially"addicting"drugs"or"medicationsCCeven"medications"used"for"legitimate"medical"and/or"psychiatric"indications."11 Therefore,"I"recommend"that"you"safeguard"your"patient’s"recovery"and"safety"by"NOT"prescribing"the"following"categories"of"medications"on"an"outpatient"basis:11.11Any1AlcoholCContaining1Liquid1Medications1or1OTC1preparations1(e.g.,1Nyquil1and1many1others)12.11SedativeCHypnotic1Medications11 Benzodiazepines:1 Ativan,1Klonopin,1Librium,1Xanax,1Halcion,1Valium,1and1all1others1in1this1class11 Hypnotics:111 Sonata,1Ambien,1Lunesta,1and1others11 Carisoprodol:1 Soma11 Barbiturates:1 Fiorinal,1Fioricet,1Phenobarbital,1Seconal,1and1all1others1in1this1class11 Other1sedatives:1 Equanil,1Miltown,1Noludar,1Chloral1hydrate,1etc.13.11Opioid1Medications11 Morphine11 MSCContin1and1others11 Propoxyphene11 Darvon,1Darvocet,1and1others1(no1longer1available)11 Codeine,1Dihydrocodeine1 Tylenol1#31and1others11 Hydrocodone11 Lortab,1Vicodin,1Hycodan,1and1others11 Oxycodone11 Percodan,1Percocet,1Oxycontin,1Tylox,1Roxicodone,1and1others11 Hydromorphone11 Dilaudid1and1others11 Meperidine11 Demerol1and1others11 Pentazocine11 Talwin1NX11 Fentanyl11 Duragesic,1Actiq,1and1others11 Methadone1 11 Tramadol11 Ultram1and1others11 Buprenorphine1injectable,1

butorphanol,1nalbuphine1Buprenex,1Stadol,1Nubain,1and1others1(Suboxone1and1Subutex1may1be1appropriate1treatments1for1some1pts)1

4.11Stimulant1Medications11 Methylphenidate11 Ritalin,1Concerta,1and1others11 Amphetamines11 Adderall,1Vyvanse,1and1others15.11Cannabinoids11 Dronabinol,1Nabilone11 Marinol,1Cesamet1

Further1information1on1addicting1medications1is1available1through1The1Medication1Guide1for1a1Safe1Recovery:1https://gaphp.org/download/pamphlets#

1Prescribing"or"administering"any"of"these"medications"to"a"person"with"a"history"of"addiction"or"

substance"abuse"is"a"highBrisk"procedure,"can"precipitate"a"potentially"fatal"relapse"to"addiction,"and"should"be"undertaken"with"extreme"caution"and"only"after"consultation"with"an"addiction"specialist."If1you1believe1there1is1a1compelling1medical1reason1to1prescribe1one1of1these1medications1to1this1patient,1please1consult1an1addiction1medicine1specialist1or1an1addiction1psychiatrist1before1you1do1so.1

1If1you1need1to1consult1an1addiction1specialist,1the1American1Society1of1Addiction1Medicine1

(www.asam.org1or1301C656C3920)1and1the1American1Academy1of1Addiction1Psychiatry1(www.aaap.org1or1401C524C3076)1can1assist1you1with1finding1a1specialist1in1your1area.111If1you1have1questions,1please1do1not1hesitate1to1call1me1at:11Your1Phone1Number1Here.1

1Sincerely,1Your"Name"Here1


CROSS-ADDICTION: GENERAL PRINCIPLES • Physicians and other prescribers are woefully

ignorant about, or choose to ignore, the risks for cross-addiction and iatrogenic relapse

• Relapse can result even when there is a legitimate medical or psychiatric rationale for medication use

• Examples • Exceptions?

– Methadone, Suboxone, or Subutex for opioid dependence in some patients

– Stimulants (preferably extended release) for ADHD in some patients


http://bit.ly/2svoCmV


RESOURCESFrom Department of Psychiatry

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RESOURCES

Web Sites with handouts, Links to Resources:

http://addictionmedicine.wikispaces.com

http://utahaddictionrotation.wikispaces.com

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Thank you!

Documents

MEDICATION ASSISTEDTREATMENT FOR ADDICTION: … · 2017. 6. 19. · ©university of utah health, 2017 medication assistedtreatment for addiction: available &emerging options elizabeth