Methamphetamine Senior Residents Lecture Your name Title Institution
Feb 22, 2016
MethamphetamineSenior Residents Lecture
Your name
Title
Institution
NIDA COE for Physician Education
2
Objective1. Prevalence data2. Diagnostic criteria3. Review of methods of abuse4. Review of methods of action5. Review of effects of use6. Review of symptoms of intoxication7. Review of symptoms of withdrawal8. Review of treatment principles9. Review of pharmacological treatments10. Review of non-pharmacological treatments11. Practical pearls12. Discussion of clinical vignettes13. Treatment outcomes data14. Co-morbidity
NIDA COE for Physician Education
3
Prevalence:The number of people that have a condition at any given time.
Lifetime Prevalence:The number of people that will have the condition at some point in their life.
NIDA COE for Physician Education
4
Prevalence
• Lifetime prevalence of approximately 5.8%• 14 million Americans age >12 have used
methamphetamine
(http://www.drugabuse.gov/infofacts/methamphetamine.html)
NIDA COE for Physician Education
5
Methamphetamine: Epidemiology
Age Group Lifetime Annual Last 30 days
12–17 1.3% 0.7% 0.3%18–25 6.4% 1.7% 0.2%26–34 8.5% 1.3% 0.4%> 35 5.7% 0.5% 0.2%> 12 (Total) 5.8% 0.8% 0.3%
Percentage of Individuals Reporting Methamphetamine Use by Age Group, 2006
Substance Abuse and Mental Health Services Administration survey data
NIDA COE for Physician Education
6
Past Year Methamphetamine Use among Persons Aged 12+, by Age:
2002-2006 Percent Using in Past Year
Age in Years
0.7
2.0
0.50.7 0.7
1.9
0.50.8 0.7
1.9
0.6
1.8
0.5
1.7
0.6
1.0+
0.70.7 0.70.8
0
1
2
3
12 or Older 12 to 17 18 to 25 26 or Older
20022003200420052006
+ Difference between this estimate and the 2006 estimate is statistically significant at the .05 level.Note: Estimates are based on new 2006 questions. 2002-2005 estimates are adjusted for comparability.
NIDA COE for Physician Education
7
Methamphetamine: Epidemiology
High School Students Reporting Methamphetamine Use, 2006
Grade Lifetime Annual Last 30 days
8th 1.8% 1.1% 0.6%
10th 2.8% 1.6% 0.4%
12th 3.0% 1.7% 0.6%National Institute on Drug Abuse and University of Michigan, Monitoring the Future Data from In-School Surveys of 8th-, 10th-, and 12th- Grade Students, 2007.
NIDA COE for Physician Education 8
0.0
1.0
2.0
3.0
4.0
5.0
99 00 01 02 03 04 05 06
8th Grade 10th Grade 12th Grade
P < .05
Percent of Students Reporting Use of Methamphetamine in Past Year, by Grade
*
According to the Monitoring the Future Study Methamphetamine is not Increasing
NIDA COE for Physician Education
9
Past Year Methamphetamine Use among Persons Aged 12+, by Region:
2002 and 2006Percent Using in Past Year
0.1
0.6 0.6
1.6
0.3
0.5
0.7
1.6
0.0
0.5
1.0
1.5
2.0
Northeast Midwest South West
20022006
+ Difference between this estimate and the 2006 estimate is statistically significant at the .05 level.Note: Estimates are based on new 2006 questions. 2002 estimates are adjusted for comparability.
NIDA COE for Physician Education
10
Primary Methamphetamine/amphetamine admission rates (per 100,000 population aged 12 and over)
NIDA COE for Physician Education
11
Methamphetamine Treatment Admissions
0
20000
40000
60000
80000
100000
120000
140000
160000
Num
ber
of A
dmis
sion
s
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
2005 SAMHSA Treatment Episode Data Set
NIDA COE for Physician Education
12
Diagnostic CriteriaBased on the Diagnostic and Statistical
Manual of Psychiatric Diseases IVth Edition (DSMIV)
• Abuse• Dependence
NIDA COE for Physician Education
13
Diagnostic CriteriaMethamphetamine Abuse
• A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one (or more) of the following, occurring within a 12-month period:
– recurrent substance use resulting in a failure to fulfill major role obligations at work, school, home (e.g., repeated absences or poor work performance related to substance use; substance-related absences, suspensions, or expulsions from school; neglect of children or household)
– recurrent substance use in situations in which it is physically hazardous (e.g., driving an automobile or operating a machine when impaired by substance use)
– recurrent substance-related legal problems (e.g., arrests for substance-related disorderly conduct)
– continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (e.g., arguments with spouse about consequences of intoxication, physical fights)
• The symptoms have never met the criteria for Substance Dependence for this class of substances.
[DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, ed. 4. Washington DC: American Psychiatric Association (AMA). 1994.]
NIDA COE for Physician Education
14
Diagnostic CriteriaMethamphetamine Dependence
• A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12-month period:
• tolerance, as defined by either of the following: – a need for markedly increased amounts of the substance to achieve intoxication or desired
effect – markedly diminished effect with continued use of the same amount of substance
• withdrawal, as manifested by either of the following: – the characteristic withdrawal syndrome for the substance – the same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms
• the substance is often taken in larger amounts or over a longer period than was intended • there is a persistent desire or unsuccessful efforts to cut down or control substance use • a great deal of time is spent in activities to obtain the substance, use the substance, or recover from
its effects • important social, occupational or recreational activities are given up or reduced because of
substance use • the substance use is continued despite knowledge of having a persistent or recurrent physical or
psychological problem that is likely to have been caused or exacerbated by the substance (e.g., continued drinking despite recognition that an ulcer was made worse by alcohol consumption)
[DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, ed. 4. Washington DC: American Psychiatric Association (AMA). 1994.]
NIDA COE for Physician Education
15
Video clip
• Diagnostic interview
NIDA COE for Physician Education
16
Methods of abusing Methamphetamine
• Ingesting• Snorting• Smoking• Injecting• Skin popping
NIDA COE for Physician Education
17
Mechanism of Action
• Increased release of Serotonin• Increased release of nor-epinephrine• Increased release of dopamine levels• (primary mechanism of feeling high)
Vmat
transporterActionpotential
DA/5HT
/serotonin
0
50
100
150
200
0 60 120 180Time (min)
% o
f Bas
al D
A O
utpu
t
NAc shell
EmptyBox Feeding
FOOD
100
150
200
DA
Con
cent
ratio
n (%
Bas
elin
e)
MountsIntromissionsEjaculations
15
0
5
10
Copulation Frequency
SampleNumber
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
ScrScrBasFemale 1 Present
ScrFemale 2 Present
Scr
SEX
Natural Rewards Elevate Dopamine Levels
Source: Di Chiara et al.; Fiorino and Phillips
• Release DA from vesicles and reverse transporter
Methamphetamine
Vmat
transporter
/serotonin
DA/5HT
100
150
200
250
0 1 2 3 4hrTime After Ethanol
% o
f Bas
al R
elea
se0.250.512.5
Accumbens
0
Dose (g/kg ip)
ETHANOL
0
100
150
200
250
0 1 2 3 hrTime After Nicotine
% o
f Bas
al R
elea
se
AccumbensCaudate
NICOTINE
Time After Methamphetamine
% o
f Bas
al R
elea
seMETHAMPHETAMINE
0 1 2 3hr 0
100
200
300
400
Time After Cocaine
% o
f Bas
al R
elea
se
DADOPACHVA
Accumbens COCAINE
0 1 2 3 4 5 hr
Source: Shoblock and Sullivan; Di Chiara and Imperato
Effects of Drugs on Dopamine Release1500
1000
500
0
We Know That DespiteTheir Many Differences, most
Abused Substances Enhance theDopamine and Serotonin Pathways
How do drugs work in the brain?
Dopamine Pathways
Functions•reward (motivation)•pleasure, euphoria•motor function (fine tuning)•compulsion•perseveration
Serotonin Pathways
Functions•mood•memory processing•sleep•cognition
nucleusaccumbens
hippocampus
striatum
frontalcortex
substantianigra/VTA
raphe
Prolonged Drug Use Changesthe Brain In Fundamentaland Long-Lasting Ways
Science Has Generated A Lot ofEvidence Showing That…
We Have Evidence That These Changes Can Be Both
Structural and Functional
AND…
Amph
NAC
Saline
Source: Robinson & Kolb, Journal of Neuroscience, 1997
Structurally…
DA
D2
Rec
epto
r A
vaila
bilit
y
Control Addicted
Cocaine
Alcohol
DA
DADA DA DA
DA
Reward Circuits
DA DA DA DA
DA
Reward Circuits
DA
DA
DA
DA DA
DA
Drug Abuser
Non-Drug Abuser
Heroin
Meth
Dopamine D2 Receptors are Lower in Addiction
DA
Functionally…
NIDA COE for Physician Education
28
Effect of Methamphetamines
Courtesy of Jane Koropsak, Brookhaven National Lab.
Dopamine Transporters in Methamphetamine AbusersDopamine Transporters in Methamphetamine Abusers
Normal Control
Methamphetamine Abuser
Motor TaskLoss of dopamine transporters in the meth abusers may result in slowing of motor reactions.
Memory taskLoss of dopamine transporters in the meth abusers may result in memory impairment.
7 8 9 10 11 12 131.01.21.41.61.82.0
Time Gait(seconds)
468101214161.01.21.41.61.82.0
Delayed Recall(words remembered)
Dop
amin
e Tr
ansp
orte
rB
max
/Kd
Source: Volkow et al., Am. J. Psychiatry, 2001.
Partial Recovery of Brain Dopamine Transporters in Methamphetamine
(METH)Abuser After Protracted Abstinence
Normal Control METH Abuser(1 month abstinent)
METH Abuser(24 months abstinent)
0
3
ml/gm
Source: Volkow, ND et al., Journal of Neuroscience, 2001.
NIDA COE for Physician Education
31
Short-Term Effects• Increased attention and decreased fatigue • Increased activity and wakefulness • Decreased appetite • Euphoria and rush • Increased respiration • Rapid/irregular heartbeat • Hyperthermia • A distorted sense of well-being• Effects that can last 8 to 24 hours
http://www.drugabuse.gov/ResearchReports/methamph/methamph3.html#short
NIDA COE for Physician Education
32
Long Term effectsBehavior Changes Medical • Addiction • Psychosis, including: • Paranoia and delusions• hallucinations • repetitive motor activity • Changes in brain structure and
function • Memory Loss • Aggressive or violent behavior • Anxiety and Mood disturbances • Severe dental problems • Weight loss • Fatigue
• High blood pressure• Tachycardia• Tachypnea• Myocardial infarctions• Skin lesions• Stroke• Dehydration • Weight loss• Death
http://www.drugabuse.gov/ResearchReports/methamph/methamph3.html#short
NIDA COE for Physician Education
33
Video clip
• Effects of Methamphetamine use
QuickTime™ and aDV/DVCPRO - NTSC decompressor
are needed to see this picture.
Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic
In Several Ways
Disease Transmission
• IV Drug Use• Drug User Disinhibition Leading to
High Risk Sexual Behaviors
Progression of Disease
NIDA COE for Physician Education
35
Fetal Effects of Methamphetamine
•Lower arousal•Poorer self-regulation•Poorer quality of movement•Increased central nervous system stress•Small for gestational age•Long-term consequences???
Preliminary evidence suggests that prenatal methamphetamine exposure is associated with subtle physical and neurobehavioral effects including:
NIDA COE for Physician Education
36
Clinical PresentationIntoxication
• Rush (5-30 min) – – Adrenal gland release of epinephrine – Explosive release of dopamine– Intensely euphoric– Tacchycardia, BP spike, heart rhythm
abnormalities
NIDA COE for Physician Education
37
Clinical PresentationIntoxication
• High (4-16 hrs) – Continuation of the physical and mental
hyperactivity• Binge (3-15 days)
– Continuation of the high – Larger doses required to achieve same intensity – Little or no rush or high felt– Physical and mental hyperactivity
NIDA COE for Physician Education
38
Clinical PresentationWithdrawals
• “Crash” – Follows a binge – Feelings of emptiness and dysphoria– Often repeat use of this drug or alcohol/other
drugs used to self-medicate withdrawal symptoms
NIDA COE for Physician Education
39
Clinical PresentationWithdrawals
• “Crash” (1-3 days) – Tired, lifeless and sleepy
• Withdrawal (30-90 days) – Slow progression to depression, lethargy,
cravings, suicidal thoughts
NIDA COE for Physician Education
40
Treatment options
NIDA COE for Physician Education
41
Basic Principles of Treatment1. No single treatment is appropriate for all individuals. 2. Treatment needs to be readily available. 3. Effective treatment attends to multiple needs of the individual, not just his or her drug
use. 4. An individual's treatment and services plan must be assessed continually and modified
as necessary to ensure that the plan meets the person's changing needs. 5. Remaining in treatment for an adequate period of time is critical for treatment
effectiveness. 6. Counseling (individual and/or group) and other behavioral therapies are critical
components of effective treatment for addiction. 7. Medications are an important element of treatment for many patients, especially when
combined with counseling and other behavioral therapies. 8. Addicted or drug-abusing individuals with coexisting mental disorders should have both
disorders treated in an integrated way. 9. Medical detoxification is only the first stage of addiction treatment and by itself does
little to change long-term drug use.10. Treatment does not need to be voluntary to be effective. 11. Possible drug use during treatment must be monitored continuously. 12. Treatment programs should provide assessment for HIV/AIDS, hepatitis B and C,
tuberculosis and other infectious diseases, and counseling to help patients modify or change behaviors that place themselves or others at risk of infection.
13. Recovery from drug addiction can be a long-term process and frequently requires multiple episodes of treatment.
(National Institute on Drug Abuse, Principles of Drug Addiction Treatment: A Research-Based Guide )
Source: Adapted from Volkow et al., Neuropharmacology, 2004.
DriveSaliency
Memory
Control
Non-Addicted Brain
NO GO
Addicted Brain
Drive
Memory
Control
GOSaliency
Why Can’t Addicts Just Quit?
Because Addiction Changes Brain CircuitsBecause Addiction Changes Brain Circuits
CONTROL
REWARD DRIVE
CONTROL
DRIVE
MEMORY
CONTROL
DRIVE
MEMORY
CONTROL
Strengthen frontal control
MEMORY
Weaken learnedpositiveassociationswith drugsand drugcues
REWARD
Decreasethe rewardingvalue ofdrugs REWARD
Increase the rewarding valueof non-drugreinforcers
Treating the ADDICTED Brain
DRIVE
MEMORY
REWARD
NIDA COE for Physician Education
44
Pharmacological treatments
• No approved medications• Off label use / treatment of co-morbid
conditions– Antidepressants– Mood stabilizers– Antipsychotic medications
• Supportive treatment(http://www.drugabuse.gov/about/Legislation/MethReport/Introduction.html)
NIDA COE for Physician Education
45
Non-pharmacological Treatments
• Motivation Enhancement Therapy• Cognitive Behavioral Therapy• Contingency Management• MATRIX Model• Family Education• Group therapy• Self-Help Groups (12 step program)
http://www.drugabuse.gov/pdf/news/Meth1106.pdf
NIDA COE for Physician Education
46
Video clip 3 & 4
• Traditional / Interventional model– Video Clip 3
NIDA COE for Physician Education
47
Video clip 3 & 4
• Motivational Enhancement Therapy (MET)– Video Clip 4
NIDA COE for Physician Education
48
Role of SpiritualitySpecific information on role of religion for
methamphetamine limitedData on general drug use suggests principles of:• Honesty• Open mindedness• Willingness
Spirituality:• promotes treatment adherence• promotes mental health• promotes decreased use
http://www.drugabuse.gov/TXManuals/IDCA/IDCA3.html
NIDA COE for Physician Education
49
Pearls
• Methamphetamine users like stimulants and often abuse caffeine.
• Methamphetamine users often get depressed and suicidal when coming off of methamphetamines
• Methamphetamine may seek stimulants for ADHD.
NIDA COE for Physician Education
50
Clinical Vignette # 1A 22 year old white male is admitted to the ER with paranoia, olfactory, tactile, auditory and visual hallucinations, agitation and behavior disturbances. This is atypical behavior for him. Acute management should include:
• Medical assessment, including CT of head, EEG• Urine Drug Screen• Pharmacotherapy with tranquilizers
(Benzodiazepines and antipsychotics) , IV fluids and general supportive treatment
NIDA COE for Physician Education
51
Clinical Vignette # 2A 62 year old white male is admitted to the ER with history of alcohol and IV drug use history. He is very depressed, tired and suicidal with some paranoia. His ADL are poor. Acute management should include:
• Medical assessment, blood workup and CT of head• Urine Drug Screen• Pharmacotherapy with tranquilizers
(Benzodiazepines and antipsychotics), IV fluids and general supportive treatment
NIDA COE for Physician Education
52
Clinical Vignette # 3A 32 year old, 30 weeks pregnant white female, with a previous history of Bipolar Disorder presents to the Obstetric Clinic for a routine well check. She has facial sores, that she says are acne related to her pregnancy. She is also presenting with symptoms of hypomania. She is denying any alcohol or drug use. Her grooming and hygiene are poor.
• Medical/Obstetric assessment, blood workup• Urine Drug Screen• IV fluids and general supportive treatment• Benzodiazepine treatment to control agitation• Social work consult
NIDA COE for Physician Education
53
Comparison to Other Chronic Diseases
NIDA COE for Physician Education
54
Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses
Source: McLellan, A.T. et al., JAMA, Vol 284(13), October 4, 2000.
Drug Addiction Type I
Diabetes
0102030405060708090
100
Hypertension Asthma
40 to
60%
30 to
50%
50 to
70%
50 to
70%
Perc
ent o
f Pat
ient
s W
ho R
elap
se
NIDA COE for Physician Education
55
Co-morbidity:Co-morbidity is Common in SUD
• 2 / 3 of the individuals have a co-morbid diagnosis
• Most common is another substance use disorder(Kaplan and Sadock, Text Book of psychiatry)
• Most are Conduct disorder/Anti Social Personality Disorder and/or another substance use disorder
• Others might be medical and/or psychiatric
NIDA COE for Physician Education
56
Suggested reading
• NIDA InfoFacts: Methamphetamine. Summary of research findings on methamphetamine for a general audience.
• NIDA Research Report: Methamphetamine: Abuse and Addiction. More detailed look at the latest research findings. For a general audience.
• http://www.drugabuse.gov/TXManuals/IDCA/IDCA1.html
NIDA COE for Physician Education
57
Suggested reading
• Meredith CW, Jaffe C, Ang-Lee K, Saxon AJ. Implications of chronic methamphetamine use: a literature review. Harv Rev Psychiatry. 2005 May-Jun;13(3):141-54.
• Barr AM, Panenka WJ, MacEwan GW, Thornton AE, Lang DJ, Honer WG, Lecomte T. The need for speed: an update on methamphetamine addiction. J Psychiatry Neurosci. 2006 Sep;31(5):301-13.
NIDA COE for Physician Education
58
Assessment Questions:
1. For a diagnosis of methamphetamine abuse, a maladaptive pattern of abuse needs to be present over a period of:
1. One month2. One year3. One week4. One decade
NIDA COE for Physician Education
59
Assessment Questions:
2. Diagnosis of Methamphetamine dependence requires the presence of the following number of criteria out of the possible seven:
1. Three2. Four3. Five4. Six5. Seven
NIDA COE for Physician Education
60
Assessment Questions:
3. Methamphetamine works primarily by:1. Increasing dopamine breakdown2. Increasing serotonin release3. Increasing acetylcholine blockade4. Increasing nor epinephrine synthesis
NIDA COE for Physician Education
61
Assessment Questions:
4. Methamphetamine can cause death by:1. Respiratory depression2. Hyperthermia3. Metabolic acidosis4. Metabolic Alkalosis
NIDA COE for Physician Education
62
Assessment Questions:
5. The fastest way to get a high form methamphetamine use is:
1. Skin popping2. Ingesting3. Snorting4. Smoking
NIDA COE for Physician Education
63
Assessment Questions:
6. Approximately the following percentage of people can be expected to have used methamphetamine in the United Sates:
1. 10%2. 4%3. 2%4. 1%
NIDA COE for Physician Education
64
Assessment Questions:
7. The effects of methamphetamine can generally last for:
1. 60 seconds or less2. 1 hours3. 2 hours4. Methamphetamine’s effects can last for a long
time, perhaps up to 24 hours
NIDA COE for Physician Education
65
Assessment Questions:
8. Methamphetamine dependence can be successfully treated with:
1. Naltrexone2. Disulfiram3. Antidepressant medications4. Behavioral therapies
NIDA COE for Physician Education
66
Assessment Questions:
9. Cues that produce cravings can:1. Stimulate the amygdala2. Stimulate the frontal cortex3. Stimulate the nigrostriatal pathway4. Can inhibit the nucleus accumbens5. Can stimulate the temporal lobe
NIDA COE for Physician Education
67
Assessment Questions:
10. The treatment of substance use disorders is:
1. Less effective than treatment of other chornic diseases.
2. More effective than the treatment of other chronic diseases.
3. Has similar efficacy to the treatment of other chronic diseases.
NIDA COE for Physician Education
68
Assessment Questions:
11. Methamphetamine use most commonly presents with another co-morbid condition that is:
1. Bipolar disorder2. Hypertension3. Suicidal disorder4. Another substance use disorder
NIDA COE for Physician Education
69
Assessment Questions:
12. In the treatment of methamphetamine use disorders:
1. A high stimulus environment is required to ensure that the patient stays awake
2. Hydralazine treatment is often required3. Haloperidol treatment is contraindicated as it
can lower the seizure threshold. 4. Antidepressant are prescribed to decrease
their depression.