Download "Prescribing Controlled Substances: Problematic Use of Opioids and

"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, 2017
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
misuse
Definitions
• Misuse
• Diversion
• Dependence
Definitions
• Misuse
• Diversion
• Dependence
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)
Misuse (2)
• Motives for Non-Prescribed Medication Use
– Intoxication
• High dose, intravenous
• Combined with alcohol or other drugs
– Therapeutic use
• Bona 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.
Misuse (3)
• Group differences
– Adolescents
• Sedative/hypnotics, opiates = therapeutic > recreation
• Stimulant medications = recreation
– College students
• Therapeutic benefit > recreation
– Older adults
• Withdrawal, dependence
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-medication
Misuse (5)
• Clinical implications of different forms of
misuse
– Increased risk of overdose
– Mitigation of other substance effects
Definitions
• Misuse
• Diversion
• Dependence
Diversion
• Exchange of prescription medications
• Leads to drug use by unintended persons
• Under conditions associated with
– “Doctor shopping”
– Misrepresentation of medical problems
– Theft
– Trading, selling, loaning, giving away
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 times
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.
Definitions
• Misuse
• Diversion
• Dependence
Dependence
• Physiological and/or psychological
• Compulsive
• Use despite negative consequences
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 men
Risk Factors - Opioids
• Age between 16-45 years
• History of preadolescent sexual abuse
• Psychological/mental health concerns
– ADD, OCD, Bipolar disorder, Schizophrenia
– Depression
Naturally occurring
- Opium
- Morphine
- Codeine
Opium poppy, Papaver somniferum
Opioid Formulations
Morphine
Hydromorphone
Oxycodone
Oxymorphone
Oral immediate-release: MSIR®
Oral extended-release: MS Contin®, Oramorph®,
Avinza®, Kadian®
Others: solution, suppositories, intravenous
Oral immediate-release: Dilaudid®
Others: solution, suppositories, intravenous
Oral immediate-release: Oxy IR®, Roxicodone
Oral extended-release: Oxycontin®
Others: solution
Oral immediate-release: Opana®
Oral extended-release: Opana ER®
Others: intravenous
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®)
Opioid Formulations
• Combination Products
Hydrocodone
Lortab®, Lorcet®, Vicodin®,
Norco®
Oxycodone
Percocet®, Endocet®,
Roxicet®, Combunox®
Codeine
Tylenol #3®, Tylenol #4®
Propoxyphene
Darvocet®
20.8 million Americans (~8%) current users of
illicit substances
2.6 million persons with
Opioid Use Disorder
591,000 persons with
heroin abuse or
dependence
2.0 million persons
with pain reliever
abuse or dependence
ED Visits for Drug Misuse
250,000
200,000
Heroin
150,000
Hydrocodone
Oxycodone
100,000
Methadone
Morphine
50,000
0
2004
2005
2006
2007
2008
2009
http://DAWNinfo.samhsa.gov/data/report.asp?f=Nation/AllMA/Nation_2009_AllMA_E
D_Visits_by_Drug
DAWN (2009)
1.2 million ED visits involving nonmedical use of
pharmaceutical or dietary supplement
Hydrocodone (alone
or in combination)
104,490 ED visits
Oxycodone (alone or
in combination)
175,949 ED visits
Methadone (alone
or in combination)
70,637 ED visits
These 3 medications account for roughly 30% of the ED visits involving nonmedical
use of pharmaceuticals/dietary supplements
http://www.nida.nih.gov/infofacts/hospitalvisits.html
CASE – Steve
• 62y Vietnam Era male veteran presents to PCP
• PMHx
– HTN
– Hypercholesterolemia
– Gout
– Chronic shoulder pain
─ GERD
─ Obesity
─ Chronic back pain
• PSHx
– Right knee arthroscopy x 2
– Left shoulder – rotator cuff repair
CASE – Steve
• PΨHx
– Major Depression ─ Generalized Anxiety
• Medications
– Lisinopril
– HCTZ
– Allopurinol
– Citalopram
– Sildenafil PRN
─ Gemfibrozil
─ Simvastatin
─ Omeprazole
─ Trazodone
─ Hydrocodone 10mg Q4H
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
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, anxiety
Strategic Focus
• Accurate diagnosis
• Appropriate pharmacotherapy
• Referral to specialty services
29
Three Common Scenarios…
1. Patient presents with previous or self-diagnosis
of Opioid Use Disorder (OUD)
2. Suspicion of OUD
a) Self
b) Referring provider
c) Family
3. Incidental finding of OUD
30
DSM-5 Opioid Use Disorder
•
•
•
•
•
•
•
•
Opioid Use Disorder
Opioid Intoxication
Opioid 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 Disorder
• Tolerance
• Hazardous use
• Withdrawal
• Physical/psychological
problems from use
• Attempts to cut down
• Much time spent using
• Social/interpersonal
problems from use
• Use larger amounts
• Activities given up
• Neglecting roles
• Craving
32
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!
OUD Specifiers
• On maintenance therapy
– Methadone
– Buprenorphine
– Naltrexone (oral or depot)
• In a controlled environment
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 psychosis
Opioid Intoxication
• Small, constricted pupils
• Slowed breathing
• Decreased alertness
• Decreased HR, BP
• Reports of fatigue
Opioid Withdrawal
• Dysphoric (sad) mood
• Nausea/vomiting
• Muscle aches
• Diarrhea
• Lacrimation (tearing) or
rhinorrhea (runny nose)
• Yawning
• Pupillary dilation,
piloerection (goose
flesh), or sweating
• Fever
• Insomnia
37
Assessment
Clinical Opiate Withdrawal Scale
•
•
•
•
•
•
Resting heart rate
Sweating
Restlessness
Pupil size (dilation)
Bone/Joint aches
Runny nose or tearing
Score
• GI upset
• Tremor (outstretched
hands)
• Yawning
• Anxiety
• Gooseflesh skin
5-12 = Mild
13-24 = Moderate
25-36 = Moderately Severe
More than 36 = Severe
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)
Adapted from Prescription Drug Use Questionnaire (PDUQ)
39
DSM-5 Opioid Use Disorder
•
•
•
•
•
•
•
•
Opioid Use Disorder
Opioid Intoxication
Opioid 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)
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
41
Assessment
• PMP AWARxE
– Prescription drug monitoring program through
Texas State Board of Pharmacy
– www.pharmacy.texas.gov/PMP
• Urine drug screening
42
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 PRN
CASE – Steve
• Lab WNL
• UDS +opiates; negative MJ, bzdp, coc
• Imaging
– Previous right shoulder procedure
– Mild osseous changes in lower spine
CASE – Steve
• Visit #2
– Reports ↓ hydrocodone  ↑ shoulder/lower back
pain
– Diminished activity, functioning
– ↑ Depression/anxiety
Strategic Focus
• Accurate diagnosis
• Appropriate pharmacotherapy
• Referral to specialty services
46
Patient diagnosed with OUD
Yes
Naloxone
Overdose?
No
Acute intoxication/withdrawal?
Medical complications?
Yes
Inpatient
Admission
Abrupt
Discontinuation
Plus Clonidine
Opioid
Substitution
with Taper
No
Outpatient
Management
Opioid Agonist
(Methadone,
Buprenorphine)
Naltrexone (oral
or sustained
release)
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, 1994
Clonidine
Most effective in suppressing autonomic signs of withdrawal, less
effective for subjective symptoms
Lethargy, restlessness, insomnia, craving are likely to persist
Adjuvant therapy may be needed
• NSAIDs (for myalgia)
• Trazodone (for insomnia)
• Antiemetics (for GI distress)
• Propranolol (for restlessness)
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
50
•Clonidine
Opioid
Withdrawal •Agonist
Long term •Antagonist
Rx of OUD •Agonist
51
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 α2-adrenergic agonist based Rx
• Buprenorphine
– Up to 8mg/day
– ↓ by 2mg every 1-2 days over 7-10 days
52
•Clonidine
Opioid
Withdrawal •Agonist
Long term •Antagonist
Rx of OUD •Agonist
53
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
54
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
55
MMT Drawbacks
• Overdose common in early treatment
• Cannot be prescribed from general practice
• Strict government control and paperwork
• Stigma of daily clinic attendance
56
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
Alcohol Medical Scholars Program
57
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
Alcohol Medical Scholars Program
58
Buprenorphine Pharmacology (2)
• Clinical impact
– Less subjective euphoria than methadone
– Long-lasting clinical action
– Partially blocks intoxication
– Reduced overdose risk
Alcohol Medical Scholars Program
59
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 sublingual or buccal film
Alcohol Medical Scholars Program
60
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
Alcohol Medical Scholars Program
61
Buprenorphine Treatment
• Initiation
– Goal: avoid precipitated withdrawal & OD
– Patient stops opioid misuse 12-36 hrs prior
– Patient demonstrates early withdrawal
• COWS rating > 8
Alcohol Medical Scholars Program
62
CASE – Alfred
• 57y Vietnam Era male veteran presents to PCP
• PMHx
– HTN
─ Migraine HAs
– Chronic pain
─ Gastritis
– Gastric neoplasm (benign)
• PSHx
– Tonsillectomy – childhood
– Multiple EGDs
CASE – Alfred
• PΨHx
– Major Depression
• Medications
– Lisinopril
─ Omeprazole
– ASA
─ Sumatriptan PRN
– Loratadine
─ Alprazolam (Xanax) 2mg TID
– Hydrocodone 5mg Q6H PRN
CASE – Alfred
• Family Hx
– Dad – CVA, DM
– Mom – Depression, HTN, obesity
• Substance Use Hx
– Alcohol – 3-4 12oz. beers/session ~1-2x/week
– Occasional marijuana (<1 joint/use)
– H/o cocaine use in 20s and 30s
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 out
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 irritable
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,
solution
Indications (FDA)
• Alcohol withdrawal
• Muscle relaxant
• Insomnia
• Antiepileptic
• Anxiety disorders
• Anesthesia adjunct
• Panic disorder
Clinical use (non FDA)
• Catatonia
• Agitation
• Abnormal movements
• Tourette’s syndrome
• Delirium
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)
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)
BZD & Mental Health (1)
• 30% of psychiatry pts receive BZD
–Affective disorders
–Long duration of illness
–High utilizers of psychiatric services
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%)
BZD and Suicide
• 2009: 2nd 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.
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 appropriate
Assessment
“Legitimate” Prescription
BZD Use Disorder
• GOAL: Treat underlying
illness
• GOAL: Confirm SUD dx
• FOCUS: Safe discontinuation
• FOCUS: Assess risk of SUD
Clinical Approach (1)
• Identify risk factors
– Co-occurring SUD or psychiatric d/o
– Highest abuse: diazepam, lorazepam, alprazolam
– Prior BZD treatment > 8 wks
Clinical Approach (1)
• Minimize potential harms
– Aggressive short-term treatment
• Use high dose over few weeks while SSRI/SNRI take
effect
– Short-term treatment
• PRN versus continuous schedule
– Drug holiday implementation
• Intermittent use of medication
• Only during high demand situations
Clinical Approach (2)
• Recognize TYPES of BzUD
• Underlying (anxiety) disorder; tolerant
• Recreational user
• Complicated
– High-dose
– Poly-BZD use
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 substances
BZD Discontinuation (1)
• Convert from fast/short acting to slow/long acting BZD
over 2-4 weeks
Drug
Diazepam
Comparative dose
5mg
Alprazolam
0.5mg
Clonazepam
0.25mg
Lorazepam
1mg
Chlordiazepoxide
25mg
Temazepam
10mg
BZD Discontinuation (2)
• Cross taper with alternative agent
– GABAergic
• Buspirone
• Valproate**
• Carbamazepine
• Gabapentin
• Pregabalin
– Serotonergic
• TCA (Imipramine)
**indicates improved
rates of long-term
abstinence
BZD Discontinuation (3)
• Cross taper with medication for anxiety reduction
– Hydroxyzine
– Quetiapine
– Trazodone**
• Inpatient management
– Flumazenil
Patient is
overtaking
benzodiazepine
Wean patient
gradually
No
Does the patient have primary
anxiety disorder?
Yes
SOCIAL
ANXIETY
PANIC
D/O
GAD
PTSD
OCD
Wean patient
gradually
STEP 1
Decrease the
total daily
dose by 25%
in the first
week
STEP 2
Another
25% on
week two
STEP 3
Followed by
10% per
week until
d/c
Use greater than 1
yr?
No
Yes
Decrease by
10% q12wks
When 20% of
the original
dose remains
then decrease
5% reduction
of dose q24wks.
STEP 1
STEP 2
Anxiety d/o
Currently taking an SSRI/SNRI?
No
Yes
Start SSRI/SNRI
+
Switch to long
acting BZD
Continue
AD
+
Wean BZD,
if possible
Yes
Maximize SSRI/SNRI
+
Switch to long acting
BZD & initiate taper
Sx
controlled?
No
Imipramine, buspirone,
gabapentin, VPA, CBZ. Cont to
wean off BDZ if possible
Yes
Continue
AD
+
Wean BZD,
if possible
Take Home Points
• Risk 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)
Take Home Points
• Risk Factors for BZD Use Disorder
– Personal h/o substance use
– Long term BZD use
– High dose BZD use
– Concomitant opioid use (esp. Methadone)
Take Home Points
• Screening 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