"Prescribing Controlled Substances: Problematic Use of Opioids and Benzodiazepines in - PowerPoint Presentation

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

®Slide22
Slide23

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 ProgramSlide63
Slide64

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. Slide77
Slide78

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