Daryl Shorter MD Staff Psychiatrist Michael E DeBakey VA Medical Center March 2 2017 Objectives By the completion of the presentation learners will be able to 1 List risk factors for misuse diversion andor dependence upon opioid medications and benzodiazepines ID: 633672
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Slide1
"Prescribing Controlled Substances: Problematic Use of Opioids and Benzodiazepines in Clinical Care"
Daryl Shorter, MD
Staff Psychiatrist
Michael E.
DeBakey
VA Medical Center
March 2, 2017Slide2
Objectives - By the completion of the presentation, learners will be able to:
(1) List risk factors for misuse, diversion, and/or dependence upon opioid medications and benzodiazepines
(2) Identify clinical scenarios in which there is problematic use/prescribing of opioid medications and benzodiazepines
(3) Employ treatment algorithms to successfully taper opioid medications and benzodiazepines
(4) Discuss strategies for patient monitoring and mitigating risk factors for opioid and benzodiazepine misuseSlide3
Definitions
Misuse
Diversion
DependenceSlide4
Definitions
Misuse
Diversion
DependenceSlide5
Misuse (1)
Any medication use that occurs without prescription (therapeutic benefit v intoxication?)
Legitimately prescribed medication used for intoxication/euphoria
Medication use in context of dependence (methadone,
buprenorphine
)Slide6
Misuse (2)
Motives for Non-Prescribed Medication Use
Intoxication
High dose, intravenous
Combined with alcohol or other drugs
Therapeutic use
B
ona fide condition/appropriate indication
Correct dosing pattern
Barrett SP et al. What constitutes prescription drug misuse? Problems and current conceptualizations.
Curr
Drug Abuse Reviews. 2008;1:255-62.Slide7
Misuse (3)
Group differences
Adolescents
Sedative/hypnotics, opiates = therapeutic > recreation
Stimulant medications = recreation
College students
Therapeutic benefit > recreation
Older adults
Withdrawal, dependenceSlide8
Misuse (4)
Quasi-legitimate Reasons?
Immediate/acute need
Unable to seek formal medical consultation
Barriers to access
Socioeconomic
Geographic
Temporal
Provider reluctance to prescribe
Under-medicationSlide9
Misuse (5)
Clinical implications of different forms of misuse
Increased risk of overdose
Mitigation of other substance effectsSlide10
Definitions
Misuse
Diversion
DependenceSlide11
Diversion
Exchange of prescription
medications
Leads
to
drug
use
by unintended persons
U
nder conditions associated with“Doctor shopping”Misrepresentation of medical problemsTheft
Trading, selling, loaning, giving awaySlide12
Diversion (2)
Gender differences in diversion patterns
20% of girls, 13% of boys borrow and/or share medications
Of the girls
16% borrowed
15% shared
7% shared meds more than 3 timesSlide13
Diversion (3)
Motivations for sharing drugs & gender
Receiving person ran out of drug: 40% of girls, 27% of boys
Received from family: 33% of girls, 27% of boys
Daniel KL et al. Sharing prescription medication among teenage girls: potential danger to unplanned/undiagnosed pregnancies. Pediatrics 2003;111:1167-70.Slide14
Definitions
Misuse
Diversion
DependenceSlide15
Dependence
Physiological
and/or psychological
Compulsive
Use
despite negative consequencesSlide16
Risk Factors - Opioids
Personal
Hx
of Substance Abuse
Rx drugs > Illegal drugs > Alcohol
Family
Hx
of Substance Abuse
Rx drugs > Illegal drugs > Alcohol
Equivalent danger of illegal drugs and
EtOH in menSlide17
Risk Factors - Opioids
Age between 16-45 years
History of preadolescent sexual abuse
Psychological/mental health concerns
ADD, OCD, Bipolar disorder, Schizophrenia
DepressionSlide18
Opium poppy,
Papaver
somniferum
Naturally occurring
- Opium
-
Morphine
-
CodeineSlide19
Opioid Formulations
Morphine
Oral immediate-release
: MSIR
®
Oral extended-release
: MS
Contin
®
,
Oramorph
®
,
Avinza
®
,
Kadian
®
Others
: solution, suppositories, intravenous
Hydromorphone
Oral immediate-release
:
Dilaudid
®
Others
: solution, suppositories, intravenous
Oxycodone
Oral immediate-release
: Oxy IR
®
, Roxicodone
Oral extended-release
:
Oxycontin
®
Others
: solution
Oxymorphone
Oral immediate-release
:
Opana
®
Oral extended-release
:
Opana
ER
®
Others
: intravenousSlide20
Opioid Formulations
Fentanyl
Transdermal patch
:
Duragesic
®
Oral lozenge
:
Actiq
®
Others
: intravenous
Methadone
Oral immediate-release
:
Methadose
®
,
Dolophine
®
Others
: solution, intravenous
Meperidine
Oral immediate-release
: Demerol
®
,
Mepergan
®
Others
: solution, intravenous
Mixed agonists/ antagonists
Butorphanol
(
Stadol
®
),
Nalbuphine
(
Nubain
®
)
Pentazocine
(
Talwin
®
)
Partial agonists
Buprenorphine (
Subutex
®
,
Suboxone
®
)Slide21
Opioid Formulations
Combination Products
Hydrocodone
Lortab
®
,
Lorcet
®
,
Vicodin
®
, Norco
®
Oxycodone
Percocet
®
,
Endocet
®
,
Roxicet
®
,
Combunox
®
Codeine
Tylenol #3
®
, Tylenol #4
®
Propoxyphene
Darvocet
®Slide22Slide23
ED Visits for Drug Misuse
http://
DAWNinfo.samhsa.gov
/data/
report.asp?f
=Nation/
AllMA
/Nation_2009_AllMA_ED_Visits_by_DrugSlide24
DAWN (
2009)
These 3 medications account for roughly 30% of the ED visits involving nonmedical
u
se of pharmaceuticals/dietary supplements
http://
www.nida.nih.gov
/
infofacts
/
hospitalvisits.htmlSlide25
CASE – Steve
62y Vietnam Era male veteran presents to PCP
PMHx
HTN ─ GERD
Hypercholesterolemia ─ Obesity
Gout ─ Chronic back pain
Chronic shoulder pain
PSHx
Right knee arthroscopy x 2
Left shoulder – rotator cuff repairSlide26
CASE – Steve
P
Ψ
Hx
Major Depression ─ Generalized Anxiety
Medications
Lisinopril ─ Gemfibrozil
HCTZ ─ Simvastatin
Allopurinol ─ Omeprazole
Citalopram ─ Trazodone
Sildenafil PRN ─ Hydrocodone 10mg Q4HSlide27
CASE – Steve
Family
Hx
Dad – CAD, MI, Alcohol Use Disorder
Mom – HTN, DM, Dementia
Brother – CAD, Obesity, Alcohol Use Disorder
Substance Use
Hx
“Social” alcohol – two 6pks of beers on weekends
Denies tobacco or illicit substance use Slide28
CASE – Steve
Exam (pertinent findings)
Appearance: Older than stated age, but NAD
Gastrointestinal: protuberant abdomen, no TTP, HSM
Musculoskeletal: TTP R shoulder (subscapular region);
↓
(?) ROM with lateral arm raise; no ROM deficits for trunk/lower back; gait WNL
Mental Status: Mild dysphoric mood, anxietySlide29
Strategic Focus
Accurate diagnosis
Appropriate pharmacotherapy
Referral to specialty services
29Slide30
Three Common Scenarios…
Patient presents with previous or self-diagnosis of Opioid Use Disorder (OUD)
Suspicion of OUD
Self
Referring
provider
Family
Incidental finding of OUD
30Slide31
Opioid Use DisorderOpioid IntoxicationOpioid Withdrawal
Opioid Delirium (Intoxication/Withdrawal)
Opioid Depressive Disorder (I/W)
Opioid Panic and Anxiety Disorder (W)
Opioid Induced Sexual Dysfunction (I/W)
Opioid Sleep Disorder (I/W)
DSM-5 Opioid Use DisorderSlide32
DSM-5 Opioid Use Disorder
Tolerance
Withdrawal
Attempts to cut down
Much time spent using
Use larger amounts
Neglecting roles
H
azardous use
Physical/psychological problems from use
Social/interpersonal problems from use
Activities given up
Craving
32Slide33
OUD Specifiers
In early remission – none of the criteria met for at least 3 months, but less than 12 months
In sustained remission – none of the criteria met for 12 months or longer
Note: Craving may be present!Slide34
OUD Specifiers
On maintenance therapy
Methadone
Buprenorphine
Naltrexone (oral or depot)
In a controlled environmentSlide35
OUD Caveats
Symptoms of tolerance and withdrawal occurring during appropriate medical treatment are
not
counted when diagnosing SUD
Opiates are not listed in DSM-5 as causative agent for substance-induced psychosisSlide36
Opioid Intoxication
Small, constricted pupils
Slowed breathing
Decreased alertness
Decreased HR, BP
Reports of fatigueSlide37
Opioid Withdrawal
Dysphoric
(sad) mood
Muscle
aches
Lacrimation
(tearing) or rhinorrhea (runny nose)
Pupillary
dilation, piloerection (goose flesh), or sweating
Nausea/vomiting
Diarrhea
Yawning
Fever
Insomnia
37Slide38
Assessment
Resting heart rate
Sweating
Restlessness
Pupil size (dilation)
Bone/Joint aches
Runny nose or tearing
GI upset
Tremor (outstretched hands)
Yawning
Anxiety
Gooseflesh skin
Clinical Opiate Withdrawal Scale
Score 5-12 = Mild
13-24 = Moderate
25-36 = Moderately Severe
More than 36 = SevereSlide39
Assessment
“Has a family member ever expressed concern about your Rx opioid use?”
“Has a physician ever expressed concern about your Rx opioid use?”
“Have you ever used your Rx opioid to treat other symptoms (e.g., sleep, irritability, sadness)
39
Adapted from Prescription Drug Use Questionnaire (PDUQ)Slide40
Opioid Use DisorderOpioid IntoxicationOpioid Withdrawal
Opioid Delirium (Intoxication/Withdrawal)
Opioid Depressive Disorder (I/W)
Opioid Panic and Anxiety Disorder (W)
Opioid Induced Sexual Dysfunction (I/W)
Opioid Sleep Disorder (I/W)
DSM-5 Opioid Use DisorderSlide41
Assessment
Aberrant drug related behaviors
Multiple prescribers
Early prescription refills
Dose/frequency escalation
ER visits for analgesics
Use of alcohol/psychoactive drugs
Taking a family member’s medication
Personal history of opioid detox
41Slide42
Assessment
PMP
AWARxE
Prescription drug monitoring program through Texas State Board of
Pharmacy
www.pharmacy.texas.gov/PMP
Urine drug
screening
42Slide43
CASE – Steve
You are concerned that Steve may have OUD, but decide a short-term prescription for opioids is appropriate while laboratory studies and imaging are obtained
You decrease from Hydrocodone 10mg Q4H PRN to Hydrocodone 10mg Q6H PRNSlide44
CASE – Steve
Lab WNL
UDS +opiates; negative MJ,
bzdp
,
coc
Imaging
Previous right shoulder procedure
M
ild osseous changes in lower spineSlide45
CASE – Steve
Visit #2
Reports
↓
hydrocodone
↑
shoulder/lower back pain
Diminished activity, functioning
↑
D
epression/anxietySlide46
Strategic Focus
Accurate diagnosis
Appropriate pharmacotherapy
Referral to specialty services
46Slide47
Patient diagnosed with OUD
No
Yes
Inpatient Admission
Outpatient Management
Overdose?
Naloxone
Acute intoxication/withdrawal?
Medical complications?
Yes
No
Naltrexone (oral or sustained release)
Opioid Agonist (Methadone, Buprenorphine)
Abrupt Discontinuation
Plus Clonidine
Opioid Substitution
with TaperSlide48
Clonidine Detoxification
Day
From
short-acting opioid (heroin, oxycodone)
From methadone
(25mg or less)
1
0.3-0.6
mg/day (includes 0.1-mg test dose)
0.3-0.6 mg/day (includes 0.1-mg test dose)
2
0.4-0.8 mg/day
0.4-0.6 mg/day
3-6
0.6-1.2mg/day, then
reduce daily dose by 50% each subsequent day; daily reductions not to exceed 0.4mg
0.5-0.8 mg/day
6-10
0.6-1.2mg/day, then
reduce daily dose by 50% each subsequent day; daily reductions not to exceed 0.4mg
Adapted from
Kosten
&
Kleber
, 1994Slide49
Clonidine
Most effective in suppressing autonomic signs of withdrawal, less effective for subjective symptoms
Adjuvant therapy may be needed
NSAIDs (for myalgia)
Trazodone
(for insomnia)
Antiemetics
(for GI distress)
Propranolol (for restlessness)
Lethargy, restlessness, insomnia, craving are likely to persistSlide50
Withdrawal Management (1)
Symptom-triggered
clonidine Rx
For
COWS > 8, give 0.1-0.2mg
clonidine
On day 1, target dose of 0.3-0.6mg
May to 0.6-1.2mg/day, as necessary
Once stabilized, reduce daily dose by 50% per day
50Slide51
51Slide52
Withdrawal Management
(2)
Use opioid agonist to
symptoms
Methadone
Up to 30mg/day
10-20% every 1-2 days over 2-3 weeks
Better than
α
2-adrenergic agonist based Rx
Buprenorphine
Up to 8mg/day
↓ by 2mg every 1-2 days over 7-10 days
52Slide53
53Slide54
Long-term Rx of OUD
Opioid Antagonist Therapy
Intramuscular naltrexone (
Vivitrol
)
Administer every 30 days
Prevents opioid high
Low compliance
No other FDA-approved medications
54Slide55
Long-term Rx of OUD (2)
Methadone maintenance treatment (MMT)
Taken daily by mouth
Obtained through federally-regulated program
Optimal dose varies (target = 80mg/day)
-- Must ↑ dose slowly to avoid OD
55Slide56
MMT Drawbacks
Overdose common in early treatment
Cannot be prescribed from general practice
Strict government control and paperwork
Stigma of daily clinic attendance
56Slide57
Office-Based Buprenorphine
Taken daily, sublingually
Rx in offices of physicians with special training
Individual dose varies (target = 16-24mg/day)
Daily visits not necessary
57
Alcohol Medical Scholars ProgramSlide58
Buprenorphine Pharmacology
Partial agonist at
μ
-opioid receptor
Slow dissociation from receptor
Half-life = 24-36 hrs
Metabolizes quickly, if give orally
So Rx is sublingual or
buccal
58
Alcohol Medical Scholars ProgramSlide59
Buprenorphine Pharmacology
(2)
Clinical impact
Less subjective euphoria than methadone
Long-lasting clinical action
Partially blocks intoxication
Reduced overdose risk
59
Alcohol Medical Scholars ProgramSlide60
Formulations
Buprenorphine alone (
Subutex
)
Buprenorphine + naloxone (
Suboxone
)
Naloxone = antagonist
risk of diversion and IV misuse
Combined in 4 mg bup:1 mg
naloxone
Combo in
s
ublingual or buccal film
60
Alcohol Medical Scholars ProgramSlide61
More Buprenorphine Info
Side effects
Neuro: Sedation, dizziness, headache
GI: Constipation, nausea/vomiting
Respiratory depression
Availability and cost
Prescribed by MDs with special training
Reimbursed by Medicaid, health insurances
─ But
costs more than methadone
61
Alcohol Medical Scholars ProgramSlide62
Buprenorphine Treatment
Initiation
Goal: avoid precipitated withdrawal & OD
Patient stops opioid misuse 12-36
hrs
prior
Patient demonstrates early withdrawal
COWS rating > 8
62
Alcohol Medical Scholars ProgramSlide63Slide64
CASE – Alfred
57y Vietnam Era male veteran presents to PCP
PMHx
HTN ─ Migraine HAs
Chronic pain ─ Gastritis
Gastric neoplasm (benign)
PSHx
Tonsillectomy – childhood
Multiple EGDsSlide65
CASE – Alfred
P
Ψ
Hx
Major Depression
Medications
Lisinopril ─ Omeprazole
ASA ─
Sumatriptan
PRN
Loratadine ─ Alprazolam (Xanax) 2mg TIDHydrocodone 5mg Q6H PRNSlide66
CASE – Alfred
Family
Hx
Dad – CVA, DM
Mom – Depression, HTN, obesity
Substance Use
Hx
A
lcohol – 3-4 12oz.
b
eers/session ~1-2x/weekOccasional marijuana (<1 joint/use)
H
/o cocaine use in 20s and 30sSlide67
CASE – Alfred
Vague report
“Do I have to answer that?”
6-year history of Alprazolam use
Obtained from both providers and illicit sources
Anxious between dosages
Insomnia if he runs outSlide68
CASE – Alfred
Exam (pertinent findings)
Appearance: Older than stated age, fidgety
Gastrointestinal: protuberant abdomen
mild TTP, no HSM
Mental Status: Mildly dysphoric, anxious appearing and irritableSlide69
BZD Formulations
Diazepam
Oral immediate-release
:
Valium
®
,
Diastat
®
Others
:
intramuscular, intravenous, suppository
Alprazolam
Oral immediate-release
:
Xanax
®
Oral extended-release
: Xanax-XR
®
Others
: solution
Clonazepam
Oral
:
Klonopin
®
,
Klonopin
wafer
®
Others
:
orally disintegrating tablet
Lorazepam
Oral immediate-release
:
Ativan
®
Others
:
intramuscular, intravenous, sublingual, solutionSlide70
Indications (FDA)
Alcohol withdrawal
Insomnia
Anxiety disorders
Panic
disorder
Muscle relaxant
Antiepileptic
Anesthesia adjunctSlide71
Clinical use (non FDA)
Catatonia
Agitation
Abnormal
movements
Tourette’s syndrome
DeliriumSlide72
Epidemiology (1)
2011: Alprazolam, Lorazepam, Diazepam were the most common prescribed
2011: 47.8 million Alprazolam prescriptions written
(137 million Hydrocodone Rx)
2.3% of adults in US report nonmedical use of sedatives
10% of those meet criteria for abuse or dependence
From SAMHSA NSDUH (2012), DAWN (2010) Slide73
Epidemiology (2)
2011: 345,528 ER visits related non illicit drugs
25% related with non medical
use
of BZD
10% Alprazolam
5% Clonazepam
3.5% Lorazepam
2% Diazepam
41,257 (3.3%) ER visits related non medical
use of SSRIs
From SAMHSA NSDUH (2012), DAWN (2011) Slide74
BZD &
Mental
Health (1)
30
% of psychiatry pts receive BZD
Affective disorders
Long duration of illness
High utilizers of psychiatric servicesSlide75
BZD &
Mental Health (2)
High
risk patients
Personal AUD history
(15-20
%
misuse
BZD)
Family h/o of alcohol use disorder
Personal
h/o of opioid use
disorder
Methadone maintenance (47%) Slide76
BZD and Suicide
2009: 2
nd
most common class of drug used in suicide attempt
Alprazolam most commonly used BZD in SA (12%)
Clonazepam second most common (8%)
Zolpidem third most common (6%)
From SAMHA 2011. Slide77Slide78
CASE – Alfred
You are concerned about Alfred’s combined use of BZD and opiates as well as his patterns of BZD use.
You decide a taper off the BZD is appropriateSlide79
Assessment
“Legitimate” Prescription
GOAL
: Treat
underlying illness
FOCUS: Assess risk of SUD
BZD Use Disorder
GOAL
: Confirm SUD dx
FOCUS: Safe discontinuationSlide80
Clinical Approach (1)
Identify risk factors
Co-occurring SUD or psychiatric d/o
Highest abuse: diazepam, lorazepam, alprazolam
Prior BZD treatment > 8
wks
Slide81
Clinical Approach (1)
Minimize potential harms
Aggressive short-term treatment
Use
high
dose
over
few
weeks while SSRI/SNRI take effect
Short-term
treatmentPRN versus continuous scheduleDrug holiday implementationIntermittent use of medication
Only
during high demand situationsSlide82
Clinical Approach (2)
Recognize
TYPES
of
BzUD
Underlying (anxiety) disorder
;
tolerant
Recreational user
Complicated
High-dose
Poly-BZD useSlide83
Clinical Approach (2)
DSM
V
Criteria for SUD
Aberrant drug related behaviors
Early refills, ER visits
Multiple providers
Taking the medication as prescribed
UDS + for
illicit substancesSlide84
BZD Discontinuation (1)
Convert from fast/short acting to slow/long acting BZD over 2-4 weeks
Drug
Comparative dose
Diazepam
5mg
Alprazolam
0.5mg
Clonazepam
0.25mg
Lorazepam
1mg
Chlordiazepoxide
25mg
Temazepam
10mgSlide85
BZD Discontinuation (2)
Cross taper with alternative agent
GABAergic
Buspirone
Valproate**
Carbamazepine
Gabapentin
Pregabalin
Serotonergic
TCA (Imipramine)
**indicates improved rates of long-term abstinenceSlide86
BZD Discontinuation (3)
Cross taper with medication for anxiety reduction
Hydroxyzine
Quetiapine
Trazodone**
Inpatient management
FlumazenilSlide87
Patient is overtaking benzodiazepine
Does the patient have primary anxiety disorder?
Yes
GAD
PTSD
OCD
PANIC D/O
SOCIAL
ANXIETY
No
Wean patient gradually Slide88
Use greater than 1 yr?
Decrease by 10% q1-2wks
STEP 1
When 20% of the original dose remains then decrease 5% reduction of dose q2-4wks
.
STEP 2
Yes
No
Decrease the total daily dose by 25% in the first week
STEP 1
Another 25% on week two
STEP 2
Followed by 10% per week until
d/c
STEP 3
Wean patient gradually Slide89
Anxiety d/o
Currently taking an SSRI/SNRI?
Start SSRI/SNRI
+
Switch to long acting BZD
Yes
No
Imipramine,
buspirone
, gabapentin, VPA,
CBZ.
Cont
to wean off BDZ if possible
No
Yes
Continue AD
+
Wean BZD, if possible
Continue AD
+
Wean BZD, if possible
Yes
Sx
controlled?
Maximize SSRI/SNRI
+
Switch to long acting BZD & initiate taper Slide90
Take Home PointsRisk Factors for Opioid Misuse
Personal or family h/o substance use
Age (16-45y)
Psychiatric conditions (such as MDD, OCD, SCZ)
Preadolescent sexual abuse (women)Slide91
Take Home PointsRisk Factors for BZD Use Disorder
Personal h/o substance use
Long term BZD use
High dose BZD use
Concomitant opioid use (esp. Methadone)Slide92
Take Home PointsScreening and assessment should include urine drug screening
Initiation of taper should take into consideration length of time patient has been on medication and may require patience