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Does Treatment for Substance Abuse Work?

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Presentation on theme: "Does Treatment for Substance Abuse Work?"— Presentation transcript:

0 Medication and Addiction Treatment
Karen Miotto, M.D. UCLA School of Medicine Addiction Studies Program for Journalists December 2005

1 Does Treatment for Substance Abuse Work?

2 Treatment Interventions
Detoxification Narcotic Treatment Programs Pharmacotherapy Residential treatment Therapeutic community Sober living Motivational Enhancement Cognitive behavioral therapy (CBT) Relapse prevention 12-Step oriented support Individual therapy: supportive Brief intervention Group therapy Couple/family therapy Network therapy Vocational Training

3 “Self-Directed Cessation” or “Natural Recovery” Factors
Recognition of health/legal/family hazards Financial considerations Conflict with career goals Social mores and peer pressure Reduced access/availability of drugs Conflict with personal values “Maturation”

4 INTERVENTION Professional Family Consequential No Further Problem
Drug use Successful Continuing Problem Drug Use Continued Problem Drug Use Unsuccessful

5 “Interventions” Professional
Primary care physicians Mental health professionals EAP’s Clergy Law enforcement personnel School counselors

6 “Interventions” Family
Any family member or friend

7 “Intervention” Consequential
Accident Arrest Job loss (last chance agreements) Relationship loss Work place drug test Negative drug experience Sanctions in school Loss of health

8 Factors Affecting Treatment Consideration
Recognition of drug use as a problem Medical/legal/financial problems Employer influence (EAP) Family influence Awareness of treatment Perception of treatment

9 Factors Affecting Treatment Participation
Access issues (time of day, transportation, child care, etc) Treatment environment Treatment context Treatment content External pressure Participant need/treatment service match Family participation

10 Effective Treatment Strategies
Accurate information Contingency management techniques Cognitive-Behavioral approaches Family participation Drug and alcohol testing Self-help support Adequately trained staff Medication/Detoxification

11 Role of Pharmacotherapy
“Cure” of withdrawal or overdose To increase the holding power of outpatient treatment and thus reduce costs To create a “window of opportunity” during which patients can receive psycho-social intervention to decrease the risk of relapse To serve as a long-term maintenance agents for patients who can’t function without them, but can lead productive lives with them

12 Types of Pharmacotherapy
Anti-withdrawal Agonists Antagonists Anti-craving Treatment of co-morbid disorders

13 When Drugs Make You Feel Normal No Drugs = Danger
Alcohol withdrawal – DT’s and seizures GHB – “I go crazy when I stop” Sedatives – “crawling out of my skin” Heroin - kicking with medication or cold turkey Stimulants – sad and fat Marijuana – “wet dog shakes” Nicotine – irritable and fat

14 GHB marketed to bodybuilders in 1980’s
Purported effects of muscle mass increase and fat loss Euphoric and sexual effects led to more widespread use as a “party drug” No data at that time about addictiveness or lethality of GHB GHB abuse is widespread. It’s common in the club and gay scene. Dancers think it makes their performance more sexy. Bodybuilders are deeply involved in this problem, believing it is a great sleep aid that enhances growth hormone production, but it doesn’t work that simply. Anyone taking it daily is at risk of becoming addicted. Rapists are using it. People on drug testing are also using it as a substitute for alcohol or other drugs because it isn’t included in most drug test protocols, but that will be changing. Remember, those giving GHB to others, especially in rape situations, may be liable for their death or injury.

15 Opiate Addiction Pharmacotherapy
Agonists: Methadone Partial Agonists: Buprenorphine Antagonists: Naltrexone Anti-Withdrawal &Anti-Craving: Methadone Buprenorphine Clonidine

16 Locus Coeruleus in Opiate Withdrawal
located in the pontine tegmentum largest group of NE-containing neurons activated by pain, blood loss and cardiovascular collapse LC hyperactivity - neural substrate for opiate withdrawal clonidine or lofexidine (alpha-2 agonist) and opiates inhibit the LC

17 Opiate Detoxification Anesthesia-aided Rapid Opiate Detoxification (AROD)
Shortens withdrawal to 4-6 hours especially useful for “detox phobic” controlled study of risk/benefit ratio withdrawal symptoms can persist for significant period post detoxification expensive large increase in stress hormones

18 Opiate Detoxification: Pros & Cons of Various Techniques
Methadone taper Pro: Simple to use few side effects Con: Requires special license longest withdrawal rebound symptoms associated with relapse

19 Maintenance Opiate Agonist
Reduce medical complications and death Satisfy drug hunger, reduce craving, prevent withdrawal Blocks effects of abused opiates Reduce medical care burden and costs Reduce crime rate Reduce “hassle” of addict lifestyle Social rehabilitation (e.g. tax eater to tax payer)

20 Methadone Maintenance
Best studied & most effective opiate treatment program so far, but also most controversial Treatment provided in licensed clinics Methadone is an orally effective, 24-hour opioid drug used to maintain heroin or other opiate addicts Patients maintained usually several years, but many need maintenance for many years

21 . . . As long as patient desires and benefits from continued treatment
How Long Does OAT Last? Long Enough!! . . . As long as patient desires and benefits from continued treatment 21 Opioid Agonist Treatment of Addiction - Payte

22 Maintenance Opiate Agonist
Reduce medical complications and death fold reduction in death rate Satisfy drug hunger, reduce craving, prevent withdrawal Blocks effects of abused opiates Reduce medical care burden and costs Reduce crime rate Reduce “hassle” of addict lifestyle Social rehabilitation (e.g. tax eater to tax payer)

23 Buprenorphine Detoxification or Maintenance Treatment – Physician Office Based High affinity partial mu agonist & kappa antagonist Reduced opioid agonist effects, with less respiratory depression Withdrawal easier than from methadone or heroin Combo form (buprenorphine/naloxone) may further decrease diversion potential & will be main maintenance form

24 Intrinsic Activity: Full Agonist (Methadone), Partial Agonist (Buprenorphine), Antagonist (Naloxone)
100 90 Full Agonist (Methadone) 80 70 Intrinsic Activity 60 Partial Agonist 50 (Buprenorphine) 40 30 20 10 Antagonist (Naloxone) -10 -9 -8 -7 -6 -5 -4 Log Dose of Opioid

25 Naltrexone Opioid antagonist approved by FDA in 1984
Blocks opioids without agonist effects Need to be off opiates to begin Can be abruptly stopped without withdrawal No tolerance to antagonist effect even after years “Ideal” drug but most addicts uninterested in using it

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27 Ideal ‘Anti-Cocaine’ Medication
In active users it will induce abstinence (or significantly decrease cocaine use) It will decrease withdrawal dysphoria in binge users In abstinent patients it will attenuate the reactivity to drug-related cues In abstinent patients who lapse it will block the progression to the full relapse Safe in combination with cocaine, low abuse potential, no dysphoric effects Now I would like to move on to pharmacotherapy and start with the description of an ideal Anti-Cocaine medication. In active users, such a medication will induce abstinence or significantly decrease cocaine use with improvement in other areas of functioning. It will decrease withdrawal dysphoria in binge users. In abstinent patients it will attenuate the reactivity to drug-related cues. I n abstinent patients who lapse it will block the progression to the full relapse. An “ideal medication” should be safe in combination with cocaine, have a low abuse potential, and have no dysphoric effects and and possibly have mild positive subjective effects that will foster compliance. It is unknown if a single medication will be able to “fulfill” this role, more likely several therapeutics will be used to treat various components of cocaine dependence syndrome.

28 Treatment of Stimulant Addiction: Current Status
There are several effective psychotherapies for stimulant dependence but no effective medication Medication development was predominantly centered on dopamine receptor and models of drug reinforcement Medication that may prevent relapse in abstinent patients may be a more viable option Stimulant Addiction is a behavioral disorder and behavioral interventions must play a major role in any treatment paradigm I am going to start with a summary slide which is also an outline for my talk. The main message I have for you today is that we have several effective psychotherapies for cocaine dependence but no effective medication. A great effort has been put to develop medications that affect dopaminergic neurotransmission by either substituting for or blocking effects of cocaine. This receptor-centered approach was based on the effective treatments for heroin and nicotine dependence and used animal models of cocaine self-administration for testing new medications. Unfortunately, this approach has not been successful. Despite many positive findings in animal models, dopaminergic medications tested so far do not help our patients. Perhaps we have to look beyond dopamine and beyond cocaine reinforcement. Cocaine dependence is different from heroin or nicotine dependence. It is not difficult to stop using cocaine for a few days or even a week. The problem is that most individuals eventually return to drug use. Therefore relapse to cocaine use following periods of abstinence may be more central from treatment perspective than simply the euphoric and reinforcing effects of cocaine. Understanding the neural mechanisms and factors that contribute to relapse should guide the development of new medications. But even if we had medication, we cannot forget that Cocaine Addiction is primarily a behavioral disorder, and therefore behavioral interventions must play a major role in any treatment paradigm.

29 Determinants of Stimulant Use
Euphoria and reinforcement Effect of Cues Exteroceptive (environmental) Interoceptive (stress, emotions, drug euphoria) Availability of alternative reinforcers Presence of psychopathology Withdrawal dysphoria Several factors can change cocaine-taking behavior in humans and understanding them can help us in the development of new treatments. People report taking cocaine for its euphorigenic effects. Euphoria is dependent on the route of administration and the dose. The slower the entry of cocaine to the brain and lower the dose the less reinforcing it s effects. There is a little interest in abusing topical cocaine and low purity samples are not popular. These observations lead to thought that if one can develop medication attenuating the euphoric effects of cocaine, cocaine will become less reinforcing, and patients will eventually stop taking it.However, this turned out to be not that simple. The other major determinants of cocaine use are cues previously associated with exposure to drugs. These are exteroceptive, environmental cues like people, places, and things as well as internal, subjective states like the experience of stress, negative affect, and drug euphoria. Drug euphoria is particularly central to relapse. Small dose of cocaine will invariably increase urge for more cocaine with eventual loss of control. Which is why drug dealers give the first dose for free. Cues are believed to have major impact on the relapse to cocaine taking in abstinent individuals. Medication that will attenuate the effects of cues in combination with therapy that helps to extinguish the effects of cues can be useful in maintaining abstinence, perhaps more useful than medication that block effects of cocaine. Availability of alternative reinforcers is another important determinant of cocaine use. Animal studies reliably show that the presence of alternative reinforcers (like sweetened water) can significantly impair cocaine self-administration. Similarly in humans, presence of reinforces like a decent job or a happy marriage can diminish cocaine taking. This observations were central to the development of a Contingency Management Therapy - a behavioral intervention that promotes alternative reinforcers. Presence of psychiatric pathology, like depression or hypomania is a well known determinant of cocaine use. Luckily, we have effective treatments for those comorbid conditions. Withdrawal is traditionally a factor that greatly determines taking of heroin or sedatives. It appears to be less significant for cocaine and some even question its presence. Treating withdrawal is however an important stage of treatment as it engages patients in the process and facilitates transition to long-term therapy.

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31 Amphetamine-Induced Disorders
Amphetamine Intoxication Amphetamine Withdrawal Amphetamine Intoxication Delirium Amphetamine-Induced Psychotic Disorder, With Delusions Amphetamine-Induced Psychotic Disorder, With Hallucinations Amphetamine-Induced Mood Disorder Amphetamine-Induced Anxiety Disorder

32 Alcohol Pharmacotherapy
Agonists: None yet Antagonists: Disulfiram (Antabuse) Anti-withdrawal: Benzodiazepines Anti-convulsants Anti-craving: Naltrexone (ReVia), Campral Ondansatron, Topamax

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34 Antabuse (disulfiram)
Helpful in maintaining abstinence Inhibits aldehyde dehydrogenase Leads to the accumulation of acetaldehyde if alcohol is consumed Acetaldehyde is toxic and produces nausea and hypotension Daily dose 250 mg, or 3-4 day interval dosing

35 Disulfiram Use for cocaine and methamphetamine dependence
Inhibits Dopamine beta Hydroxylase (catalyzing the synthesis of NE from DA) Indirectly increases the ratio of DA to NE Increasing the dopamine availability , enhances the aversive effects of stimulants.

36 Adjunctive medication for alcohol craving - naltrexone
Opiate antagonist Proposed mechanism of action Dosing and side effects Clinical efficacy

37 Topiramate Inhibition of mesocortical dopamine release via facilitation of GABA activity Inhibition of glutamate function Hypothesis: Decreases mesocorticolimbic dopamine activity after alcohol intake Antagonize chronic changes induced by alcohol in the glutamate system

38 Abstinence-initiation trial N=150
Oral Topiramate for Treatment of Alcohol Dependence Bankole Johnson et al (2003) Abstinence-initiation trial N=150 N=150 Double-blind randomized control trial 12 week Topiramate (up to 300 mg per day) Outcomes 2.9 fewer drinks per day 3.1 fewer drinks per drinking day 27.6% fewer drinking days 26.2% more abstinent days Reduced craving

39 Acamprosate Amino acid derivative - acetyl-homotaurine
similar to homocysteic acid (NMDA receptor) mimics GABA (GABAA receptor) interacts with calcium channel proteins Reduces alcohol craving (conditioned withdrawal) Reduces severity and frequency of relaspe Suppress physical signs of withdrawal in animal models (J Littleton Addiction 1995)

40 Acamprosate Amino acid derivative - acetyl-homotaurine
similar to homocysteic acid (NMDA receptor) mimics GABA (GABAA receptor) interacts with calcium channel proteins Reduces alcohol craving (conditioned withdrawal) Reduces severity and frequency of relaspe Suppress physical signs of withdrawal in animal models (J Littleton Addiction 1995)

41 CAMPRAL NORMAL EQUILIBRIUM-Glutamate and GABA balanced
This figure represents the brain (triangle) in a regular state of equilibrium with regard to excitation and inhibition processes. Excitation Inhibition Alcohol ACUTE ALCOHOL INTAKE-Increased levels of GABA Acute alcohol intake disrupts the equilibrium by exaggerating the inhibitory processes Excitation Inhibition Neuro- Adaptation Alcohol CHRONIC ALCOHOL CONSUMPTION-Increased levels of glutamate Chronic alcohol consumption induces neuroadaptation (increase in glutamate) to counteract the inhibitory action of alcohol. Excitation Inhibition

42 CAMPRAL ACUTE WITHDRAWAL AND POST-ACUTE WITHDRAWAL-Increased glutamate
Acute Withdrawal of alcohol triggers a hyperexcitatory state because of the excess of glutamate present dur to the neuroadaptation. This results in withdrawal symptoms. Post-Acute Withdrawal stage follow. Environmental of learned cues associated with alcohol intake may trigger a hyperexcitatory state similar to acute withdrawal in abstinent patients. This precipitates mini-withdrawal symptoms in the post-acute stage-eg, anxiety tremors, sweating-that may contribute to relapse. Environmental/ Learned Cues No Alcohol Excitation Inhibition Environmental/ Learned Cues CAMPRAL CAMPRAL-Modulation of glutamate restores balance CAMPRAL interacts with the glutamate neurotransmitter system to block the response to environmental and learned cues. CAMPRAL is though to restore the normal balance. The mechanism of action of CAMPRAL is believed to address the biochemical aspect of alcohol dependence, complementing psychosocial therapy that targets the emotional and behavioral components of the disease. Excitation Inhibition

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46 Conclusion Addiction is a complex chronic medical disorder
Opioid - methadone, buprenorphine Stimulants - vaccine Alcohol - campral New developments in medication for addiction


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