Transcript What is the role of meds in Impulse Control Disorders?

Pharmacotherapy of Addictions
Timothy Fong MD
Addiction Medicine Clinic
310.825.1479
[email protected]
Overview
1. Pharmacotherapy of Addictions
A. Substance Use Disorders
Alcohol
Opiates
Stimulants
Nicotine
Marijuana
Sedative-Hypnotics
Overview (II)
1. Pharmacotherapy of addictions
B. Impulse Control Disorders
i.
Pathological Gambling
ii.
Compulsive Shopping
iii. Compulsive Sexual Behaviors
Drug Use Patterns
Marijuana – 12 million
Cocaine – 2 Million
Hallucinogens – 1.3 million
Heroin – 800,000
1,200 people died in LA in Emergency Rooms
related to drugs in 2000 (officially)
Outcomes of Drug Abuse
2 million people die each year in the US
-430,000 due to tobacco
-100,000 due to alcohol
-16,000 for illicit drugs
Cost of Drug Abuse
Economic costs of Alcohol and Drug Abuse
( NIDA 1992)
$245 Billion Dollars
- Treatment (30%)
- Productivity losses (20%)
- Crime (40%)
- Deaths (10%)
Costs of Drugs
1988 – 1995
$57 Billion dollars spent on drugs (does not
include alcohol or nicotine)
$20 billion spent on cigarettes / year
Goals of Medication
Tx in Addictions
1. Abstinence (or Reduction)
2. Treat or prevent withdrawal symptoms
3. Reduces urges/cravings
4. Diminish “the high” / make it less worthwhile
5. Minimize relapses time and intensity
6. Treat comorbid disorders
Medication Strategies
1. Agonist
Substitute effects of drug
2. Antagonist
Block the effects of drug
3. Deterrent Medications (aversive)
4. Reduce Drug Intake
Target cravings, reinforcement
Alcohol Dependence
1.
2.
3.
4.
Disulfiram (Antabuse)
Naltrexone (Revia)
Topiramate (Topamax)
Acamprosate (Campral)
Antabuse
FDA Approved 1951
MOA: Inhibits aldehyde dehydrogenase,
increasing acetaldehyde.
Evidence: So-so
Most likely to benefit:
highly motivated patients, directly observed
patients,
Antabuse
Dosing:
250 mg – 500 mg qd
Side effects:
Nausea, metallic taste,dysphoria, fatigue,
hepatitis, psychosis (dopamine)
Effects can last 72 hours after last dose
Naltrexone (Revia)
FDA Approved 1994
MOA: Opiate Antagonist
decrease positive, reinforcing effects
increase negative aspects
decrease craving from first dose (prime)
decrease craving from cues
Naltrexone
Starting: (50 mg or 100 mg)
25 mg and increase by 25 mg week until SE
or target dose of 200 mg
SE: dysphoria, nausea, increased LFTs
Costly
Modest effect, at best
Depot formulation coming . . .
Topiramate
MOA: blocks NA channels, augments GABA,
inhibits glutamate
Early phase of investigation
may reduce drinking days
reduce cravings
improve quality of life measures
Topiramate (Topamax)
Dosing Strategy:
25 mg and then increase
by 25 mg every week
(target dose = 200 mg
or higher)
Side Effects: cognitive
dulling, weight loss,
fatigue, somnolence
Acamprosate (Campral)
MOA: Made from taurine ; NMDA receptors in the
glutamate system – generally inhibitory
Not much action on GABA
Dose: 333mg bid – 333mg tid (1,998 mg)
Notes:
European data – 4500 patients,
FDA approved Sept 2004
Relapse Prevention,
targets “negative reinforcement”
SE: Diarrhea, rash.
Opiate Dependence
• 800,000 meet criteria for dependence but
180,00 in treatment
Opiate Dependence
1.
2.
3.
4.
Methadone
Buprenorphine
LAAM
Naltrexone
Methadone
Methadone
FDA Approved 1973 (detox and maintenance)
MOA: Long-acting opiate, full agonist at mu
receptor
Notes:
179,000 actively in treatment
No notable tolerance
Methadone
Methadone Clinics
Starting dose – 20 mg – 40 mg
and up to no more WD sxs
Maintenance Dose: 80-120 mg
Side effects: prolonged QT with increasing
dose
LAAM
Levo-alpha-acetylmethadol
“Long-acting methadone”
No longer made
Prolonged QT
Naltrexone (for Opiates)
Purported to reduce pleasure from opiates
Only 15% stay in treatment
Doesn’t seem to reduce cravings in opiate
dependents
Best for highly motivated patients or
pregnancy
Overdose risk increased after d/c
Buprenorphine
(Suboxone, Subutex)
FDA Approved 2003
MOA: Partial Agonist; tight binding
Ceiling Effects
Schedule III
Need special DEA number/waiver
Buprenorphine
Formulations: Sublingual
Subutex (Buprenorphine)
2mg, 8mg
Suboxone (Bup + Naloxone 4:1)
2mg, 8mg
Buprenorphine
Starting (Detox)
Wait until opiate wd starts then give first
dose (30-60 min until effect)
starting doses 8mg –16 mg until wd sx are
gone
maintenance: 16-24 mg qd
maximum: 32mg qd
Buprenorphine
Notes:
Office based but needs support
Indicated for detox and maintenance
Good for about a year
30 patient limit
Some effectiveness for depression and
cocaine dependence
Stimulant Dependence
1. Cocaine
2. Amphetamines
Classes of medications tried
Dopamine agonists (amphetamines)
Dopamine partial agonists (aripiprazole)
Dopamine Reuptake Inhibitors (amantadine)
Dopamine Metabolism Inhibitors (disulfiram)
Dopamine Antagonists
GABA
Beta Blockers
Opioids
Antidepressants (SSRIs, TCAs)
Cortisol Blockers
Stimulant Dependence
Many strategies tried, none successful,yet
consider:
Baclofen (20 mg – 60 mg) heavy, binge users
Bupropion (300 mg) – reduces craving?
Selegiline (200 mg)– available as patch
Buprenorphine – comorbid opiate dependence
Amantadine 100 mg bid – bad withdrawal sx
Stimulant Dependence
Abilify
ACE-Inhibitors (dopamine)
Antabuse (inhibits dopamine hydroxylase)
Namenda
Novel Approaches
Vaccinations
Acupuncture
Efficacy debatable
Nicotine Dependence
1. Gums (2mg or 4mg)
2. Lozenge (1mg)
3. Inhalers (4 mg) 6-12 per day
4. Nasal Spray (0.5 mg), max 40/day
5. Patch (7,14,21 mg) (passive)
6. Bupropion (300 mg) (primary effect)
Cigarettes = 0.8 – 3 mg each
Nicotine Dependence
Nicotine Replacement Therapies
Increase quit rates 1.5 – 2x
Meds + therapy = 15-30% quit rate
Can combine passive and active NRT
Duration of therapy – 8-12 weeks
Effects of meds wane over time
Marijuana Dependence
No RCT trials
Anecdotes with fluoxetine, nefazadone.
bupropion worsened wd sxs
CB1 Antagonists
CBT, MET and CM have the best evidence
Sedative-Hypnotics
• http://www.benzo.org.uk
• Fastest rising class of drugs of abuse
• Practical pointers:
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No refills
2-4 months, max
Involve families
Printouts from pharamcies
Med logs
Sedative Hypnotics
Principles for detox and maintenance:
Substitute longer acting for shorter acting
Prolonged taper to minimize withdrawal (months,
if needed)
Other Medications:
Baclofen?
Tegretol?
Gabapentin?
Topamax
Depakote?
Sedative Hypnotics
Notes:
Prolonged Withdrawal states – mimic
somatization, derealization, intense anxiety
Not many studies to guide treatments
Some patients remain on BZDs long-term but
most should not . . .
Impulse Control Disorders
1. Pathological Gambling
2. Compulsive Shopping
3. Compulsive Sexual Behaviors (Sexual
Addiction)
What is the role of meds in
Impulse Control Disorders?
• What are the goals of medications?
– To treat comorbid disorders like depression or
anxiety disorders
– Can help with sleep, appetite and concentration
– May reduce urges and cravings
– Lays the groundwork for psychosocial
treatments
– NO MAGIC PILLS
“The Gambler”
MGM 1974
Starring James
Caan
Medications Strategies for
Pathological Gamblers
Usually start with:
SSRIs, (Paxil or Celexa)
To reduce impulsive behaviors?
Topiramate 25mg – 300 mg
To reduce cravings/urges, block the high
Naltrexone (50—200 mg)
Other Meds
Gamblers who are hyperthymic or with
cyclical gambling patterns:
Mood Stabilizers
To treat comorbid disorders / presenting
symptoms use:
SSRIs, ANL
Compulsive Shopping/Buying
• Pathological Shopping
– Characterized by excessive, and uncontrolled
preoccupations regarding shopping and
spending.
– Tension before, relief after
– Causes marked distress
– 2-8% of population, almost 80% female
– Average debt is $23,000
Pharmacotherapy of
Compulsive Shopping
Open Label:
Black (1997)
9/10 improved on Luvox
Koran (2002)
n= 24, Celexa (20-60),
17/21 responded on CGI and YBOCS- SV
Pharmacotherapy of Compulsive
Shopping
• Double Blind
• Black (2000) -- Iowa
– N= 24, 9 wk, PBO washout, Luvox (300 mg),
no therapy
– Outcomes: Scales -- CGI, SDS, YBOCS- SV
– Result
– Luvox = PBO, both improved significantly
(54% vs. 64%)
Pharmacotherapy of Compulsive
Shopping
Philip (2000) -- Emory
N=37, 1 wk PBO washout, 12 weeks of Luvox
(300mg) vs. PBO.
No statistical differences but both groups improved
(9/20 vs 8/17)
Compulsive Sexual Behaviors
• Characterized by excessive or uncontrolled
sexual acting out
• Non-paraphilic vs. paraphilic
• Key is subjective distress and continued
behavior despite negative consequences
• Rise in tension before, pleasure after
CSB Pharmacotherapy
• Case Reports:
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Lithium (3)
TCAs 1)
SSRIs (>15)
Buspar (2)
Serzone (1)
Atypicals (1)
Naltrexone (1)
CSB Pharmacotherapy
• Other Agents:
– Antiandrogens: Progesterone (lower
testosterone)
– GNRH Agonists (IM)
Future Medications
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Cannabinoid Antagonists
CRH Antagonists
Predictors of response / subtyping
Nalmefene (opiate antagonist)
Combinations
Clinical Pearls
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Urine testing is a must
No refills on meds
Utilize scales to quantify efficacy
Know your goals . . Harm reduction or
abstinence?
• Know your psychosocial treatments
High-Yield Websites
http://www.drugabuse.gov
http://www.erowid.org/
http://www.uclaisap.org/addclinic/