Download What is Addiction and How Do We Treat It? Roger D. Weiss, M.D.

What is Addiction
and
How Do We Treat It?
Roger D. Weiss, M.D.
Professor of Psychiatry, Harvard
Medical School
Clinical Director, Alcohol and Drug
Abuse Treatment Program, McLean
Hospital, Belmont, MA
DSM-IV SUBSTANCE
DEPENDENCE CRITERIA
„
A maladaptive pattern of substance use, leading to
clinically significant impairment or distress, as
manifested by 3 or more of the following in the same 12month period.
1. Tolerance, as defined by:
a. A need for markedly increased amounts of the
substance to achieve intoxication or desired effect, or
b. Markedly diminished effect with continued use of
the same amount of the substance.
DSM-IV SUBSTANCE
DEPENDENCE CRITERIA (CONT.)
2. Withdrawal, as manifested by:
a. The characteristic withdrawal syndrome for the
substance, or
b. The same (or a closely related) substance is
taken to relieve or avoid withdrawal sx
3. The substance is often taken in larger amounts or
over a longer period than was intended.
DSM-IV SUBSTANCE
DEPENDENCE CRITERIA (CONT.)
4. A persistent desire or unsuccessful efforts to cut
down or control substance use.
5. A great deal of time spent in activities necessary
to obtain the substance (e.g., visiting multiple
doctors), use the substance, or recover from its
effects.
6. Important social, occupational, or recreational
activities given up or reduced because of
substance use.
DSM-IV SUBSTANCE
DEPENDENCE CRITERIA (CONT.)
7. Continued substance use despite knowledge of
having a persistent or recurrent physical or
psychological problem likely to have been caused
or exacerbated by the substance.
DSM-IV SUBSTANCE
DEPENDENCE
Tolerance and withdrawal are neither necessary
nor sufficient for a diagnosis of substance
dependence
Physical dependence vs. drug dependence
(addiction)
Quantity/frequency, level of consequences not part
of the DSM-IV criteria
Abuse vs. Dependence
„
„
„
„
No tolerance, withdrawal,
compulsive use in abuse
Some people remain abusers, never
become dependent
Not inevitably progressive
Alcohol problems occur along a
continuum of severity
Recovery from Alcohol
Dependence
„
„
Over 50% recovery rate in
community male samples
Drinking rate: 40% after 2 years,
4% after 5 years sobriety
PSYCHOTHERAPY FOR
SUBSTANCE USE DISORDERS
„ Formerly viewed as contraindicated
„ In past 2 decades, renewed interest
„ SUD-specific treatment
„ Rigorous outcome studies
Behavioral Therapy for Substance
Use Disorders
Numerous studies show positive results for
various types of behavioral therapy
„ Non-confrontational approaches, positive
contingencies appear most helpful
„ Self-help groups (e.g., AA) are commonly used
and are associated with positive outcomes,
lower healthcare costs
„
PHARMACOTHERAPY OF
SUBSTANCE USE DISORDERS
Maintenance drugs (e.g., methadone,
buprenorphine)
„ Drugs to block euphoria (eg., naltrexone for
opioids)
„ Drugs to induce aversive consequences
(disulfiram)
„ Drugs to treat co-existing psychiatric disorders
„ Drugs to treat substance-induced disorders,
e.g., acute or protacted withdrawal, craving
(naltrexone, acamprosate for alcohol)
„
Prescribing Medication
vs.
Taking Medication
What Are the Parameters Used
to Determine Treatment Efficacy?
For alcohol
Percent days abstinent
„ Percent days heavy drinking
„ Likelihood of any drinking
(abstinence rate)
„ Likelihood of heavy drinking
„ Drinks per drinking day
„ Time to first drink/relapse
„ Consequences of drinking
„ Biological markers
„
METHADONE MAINTENANCE
Goal is rehabilitation, not abstinence
„ Substitutes a long-acting, oral, legal, qualitycontrolled drug for a short-acting, illegal, poorquality,expensive, injectable drug
„ Dose of >60 mg/day most successful
„ Best results occur with concomitant
psychosocial tx
„
METHADONE MAINTENANCE
ADVANTAGES
„ Decreased illicit opioid use, crime,
unemployment, HIV seroconversion,
healthcare costs
„ Randomized study of MM vs. drug-free tx
showed better results for MM, but neither
did particularly well
METHADONE MAINTENANCE
DISADVANTAGES
„ Patients may be tied to clinic
„ Takehomes may lead to illicit diversion
„ Interactions with other drug users
„ Other substance use disorders: EtOH,
cocaine, BZs, marijuana
„ Difficult to detoxify
Buprenorphine
„
„
„
„
„
A partial agonist; does not fully activate opioid receptors.
Binds tightly and dissociates slowly from opioid receptors
A ceiling effect on opioid activity, including respiratory
depression.
Result = likelihood of death from buprenorphine overdose
markedly diminished.
Advantage over naltrexone: has mild agonist effects;
patient does not have to be detoxified to begin treatment.
Intrinsic Activity: Full Agonist (Methadone), Partial Agonist
(Buprenorphine), Antagonist (Naloxone)
Intrinsic Activity
100
90
80
70
60
50
40
30
20
10
0
Full Agonist
(Methadone)
Partial Agonist
(Buprenorphine)
Antagonist (Naloxone)
-9
-8
-7
-6
Log Dose of Opioid
-5
-4
Buprenorphine Maintenance
Therapy
„
Clinical trials have established the effectiveness of
buprenorphine for treatment of heroin addiction.
„
Direct comparisons to methadone suggest that it as
effective as moderate doses of methadone (e.g., up to
60 mg/day), although it is not clear whether it can be
as effective as higher doses of methadone for
maintenance therapy.
„
Buprenorphine is mildly reinforcing , thus ensuring
better compliance than naltrexone or “drug free”
therapies.
Buprenorphine-Naloxone
(Suboxone)
„Naloxone added to maintenance formulation to deter
parenteral abuse
„Naloxone has low bioavailability when used
sublingually
„Safety and efficacy of buprenorphine/naloxone appear
equivalent to buprenorphine alone
„No special safety or side effect considerations for this
combination
Naltrexone for Opioid Dependence
Naltrexone is long-acting oral analog of
naloxone (Narcan): a pure opiate antagonist
(blocker)
„ Binds to opiate receptors more strongly than
opiates do
„ Taking opiates on naltrexone leads to blockade
of opiate effects
„ Naltrexone has no opiate properties
„ Efficacy limited by limited acceptability,
except by specific populations, usually under
pressure
„
Naltrexone for Alcohol Dependence
Volpicelli et al (1992)
„ 70 VA patients, all men with alcohol dependence
„ 12-wk double-blind, placebo controlled
„ Naltrexone 50mg/day
„ Day treatment (6hrs/d) for 1 month, then twice/week
group therapy for 2 months
„ Major psychiatric illness excluded
„ 23% of NTX Ss vs. 54% placebo Ss relapsed; similar
rate of drinking
Subjective “High” Produced by
Alcohol
0.2
0.1
0
-0.1
-0.2
-0.3
-0.4
-0.5
-0.6
Placebo
Naltrexone
(N=35)
(N=35)
+1 = Increased high
0 = No change in high
-1 = Decreased high
p<0.006; Volpicelli JR et al. Am J Psychiatry. 1995(April);152(4):613-615
Naltrexone forAlcohol
Dependence
„
„
„
„
„
„
May reduce alcohol-induced craving
May reduce craving independent of drinking
Differences in the experience of a slip
Does not make someone a controlled drinker
Helps a pt get back to abstinence faster
Mostly positive studies, but some negative
NTX Outcome Measures
1.2
1.0
0.8
0.6
0.4
0.2
0
1.0
1.0
1.0
1.1
0.7
Cr
av
Ti
m
Ab
st
in
g
0.0
in
en
et
ce
o
1s
tD
rin
#o
k
fD
rin
kin
Da g
Dr
ys
in
ks
/D
rin
kD
ay
Re
lap
se
He
av
yD
rin
kin
g
0.0
„
NTX score measures the strength of evidence favoring naltrexone,
represented by averaging efficacy scores for all RCTs that measured the
particular outcome. Points were assigned as: 0 (NS), 1 (+), and
2 (++). Score of 1 or above represents statistically significant advantage
of NTX over placebo
Leavitt SB. Addiction Treatment Forum. 2002(March):1-8
Long-Acting Injectable Naltrexone
Reduces Heavy Drinking Days
Cumulative heavy drinking days*
70
17%
reduction
Placebo
60
Naltrexone 190 mg
50
Naltrexone 380 mg
40
26%
reduction
30
20
10
0
0
10
20 30
40
50
60 70
80 90 100 110 120 130 140 150 160 170 180 190 200
Naltrexone 380 mg vs placebo, P=.03; naltrexone 190 mg vs placebo, P=.07.
*Heavy drinking defined as ≥5 drinks per day for men and ≥4 drinks per day for women.
Garbutt et al., JAMA 2005;293:1617.
Acamprosate (N-acetylhomotaurine)
„ Mechanism: interacts with glutamate and GABA
neurotransmitters systems
„ In animal models of alcohol dependence,
acamprosate reduced deprivation-induced drinking
„ Does not cause dependence or withdrawal
„ May reduce protracted withdrawal symptoms
Acamprosate in Alcohol
Dependence Treatment (Sass,1996)
Study conducted in Germany/Austria
„ 272 patients receiving routine counseling and
treated with 2 g/day acamprosate or placebo
for 48 weeks
„
Sass H et al. Arch Gen Psychiatry. 1996(Aug);53(8):673-680
% of Abstinent Patients
Acamprosate in Alcohol
Dependence Treatment (Cont.)
Treatment Period*
100
Follow-Up Period†
Acamprosate
calcium (N=136)
Placebo (N=136)
80
60
43%
40
21%
37%
20
17%
0
0
24
48
72
96
Weeks
*p=0.001; †p=0.003; 272 patients were entered into the study over 2 years; Kaplan-Meier survival
analysis (survival function estimate); continuous abstinence for the treatment and follow-up periods;
Sass H et al. Arch Gen Psychiatry. 1996(Aug);53(8):673-680
NIAAA COMBINE Study
„
Studied optimal combinations of medications, behavioral
Tx for alcohol dependence
„
Patients received naltrexone, acamprosate, both, or
neither
„
Half of patients received psychotherapy in addition to
medical management
„
One patient cohort received psychotherapy alone, no pills
COMBINE Study: Results
„
For patients receiving MM, naltrexone or CBI therapy
improved outcomes over placebo plus MM
„
Acamprosate did not add benefit to naltrexone or CBI, and
was no more effective than placebo plus MM
„
Taking pills and seeing a health care professional was more
effective than receiving CBI alone (possible placebo effect)
Disulfiram
„
„
„
„
Inhibits aldehyde dehydrogenase, an
enzyme in the metabolism of alcohol
Leads to acetaldehyde poisoning when
alcohol is ingested
Reaction occurs 10-15 min. after drinking
Reaction can be quite severe, occasionally
fatal; severity is related to dose and
individual characteristics
Percent Remaining Abstinent
Disulfiram and Abstinence Rates
50
40
Disulfiram 250 mg (N=202 men)
Disulfiram 1 mg (N=204 men)
Placebo
30
20
10
0
Noncompliant (80%)
Fuller RK et al. JAMA. 1986(Sept);256(11):1449-1455
Compliant (20%)
Disulfiram
ADVANTAGES:
„ Built-in impulse control because of
prolonged elimination time (up to 2 weeks)
„ May indirectly reduce desire to drink
„ Best used in careful, impulsive, situational
drinkers
„ May be used prn later
„ Importance of adherence strategies
Disulfiram
DISADVANTAGES:
„ Side effects, including liver toxicity
„ Risk of unintentional or intentional
alcohol reaction
„ Possible overreliance on disulfiram,
underreliance on other supports
Topiramate
Johnson et al., 2007
„ 371pts at multiple sites received topiramate 50-300
mg/d (tapered upward) or placebo x 14 wks
„ Patients were drinking heavily at study entry
„ Topiramate pts had better drinking outcomes,
beginning at 100 mg
„ Fewer heavy drinking days
„ Greater likelihood of abstinence
Percentage of Heavy Drinking
Days from Study Week 1
Heavy drinking days (%)
A
P=.0 0 0 6
80
To piram ate
Placebo
60
40
20
0
1
2
3
4
5
6
7
8
9
S tu d y w e e k
10
Courtesy of Professor Bankole Johnson
11
12
13
14
Time to First Day of 28 or More Days of
Continuous Non-Heavy Drinking
heavily continuously
Probability of not drinking
0 .4
T o p ira m a t e
P la c e b o
0 .3
0 .2
P < .0 0 0 1
0 .1
0 .0
0
N u m b e r o f p a r t ic ip a n t s
T o p ir a m a t e
179
P la c e b o
185
20
a t r is k
139
174
40
60
S tu d y d ay
80
103
164
79
139
68
121
Courtesy of Professor Bankole Johnson
100
22
39
120
0
0
Pharmacotherapy of Cocaine
Dependence
No reliably effective medications for cocaine
dependence in general
„ Pharmacotherapy for specific subgroups of
cocaine dependent patients may be effective:
„Antidepressants for pts with major
depressive disorder (Nunes, 1991).
„ Amantadine for patients with severe
withdrawal symptoms (Kampman,2000)
„