Recognizing and Managing Substance Use Disorders Katherine Julian, - - PDF document

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Recognizing and Managing Substance Use Disorders

Katherine Julian, M.D. Professor of Medicine

UCSF Division of General Internal Medicine December 10, 2015

Disclosures

n None

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Quiz…Your Clinic Panel

n In your clinic panel, what percentage of your

current clinic patients would be classified as at- risk drinkers?

• A. <1%
• B. 2-5%
• C. 6-9%
• D. 10%
• E. >20%

Substance Use Issues are Highly Prevalent in Americans (12+years)

At Risk Drinking* 27-29% Alcohol Dependence 3.5% Alcohol Dependence among binge drinkers 10.2%

National Survey on Drug Use and Health, Prev Chronic Disease, 2014

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Alcohol Use Disorders in Older Adults

n 3% met full criteria for an alcohol use disorder n At-risk drinking was reported in:

n 13% of all respondents ages 65+

n Binge drinking was reported in:

n 15% of all respondents ages 65+

NSDUH, 2009 Blazer D, Wu L. Am J Psychiatry, 2009

Outline

§ Substance Use Disorders - Definitions § SBIRT § Screening § Brief Intervention § Referral to Treatment § ETOH Substance Use Pharmacotherapy § Treatment of Non-Cancer Pain: Balance risks/benefits § Opiate Substance Use Pharmacotherapy

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Quiz…

n Which of the following is NOT

considered to be “at risk” drinking?

• A. 45 yo woman who drinks 1-2

glasses of wine each night

• B. 70 yo man who drinks 1-2 beers

each night

• C. 25 yo woman who drinks 4-5

drinks once a week when she goes

• ut with friends
• D. 40 yo man who drinks 1-2 glasses
• f wine each night

Definition – At Risk Drinking

n Men

• >4 drinks/day or
• >14 drinks/week

n Women (and > than 65 yrs)

• >3 drinks/day or
• >7 drinks/week

n Increased risk of alcohol-related

problems

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What is a Drink?

A standard drink is any drink that contains about 14 grams of pure alcohol (about 0.6 fluid

• unces or 1.2 tablespoons)

DSM5 - Substance Use Disorder

n No longer need to differentiate between

substance abuse and substance dependence

n Each substance can be categorized as a disorder n Ex: Alcohol use disorder, stimulant use

disorder, etc

n Grade Severity: Mild, Moderate, Severe

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DSM5 - Substance Use Disorder

n “Maladaptive pattern of substance use leading to

clinically significant impairment or distress, as manifested by 2 (or more) of the following, occurring within a 12-month period:”

n Failure to fulfill role obligations n Recurrent substance use in situations that are physically

hazardous

n Persistent use despite social/interpersonal problems

Criteria for Substance Use Disorder (contd)

n Tolerance n Withdrawal n Using more than originally intended n Persistent desire or unsuccessful efforts to cut-down n Time spent obtaining/using substance or recovering from

side effects

n Reduction of social/occupational activities n Use despite physical/psychological problems n Craving

n Need 2 criteria for SUD n 2-3 criteria =mild n 4-5 = moderate n >6 = severe

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Screening

U.S Preventive Services Task Force recommends screening all adult patients for alcohol misuse AND “provide persons engaged in risky drinking with brief behavioral counseling interventions”

How to Screen?

§ Ask permission: “Would it be ok to spend the next few

minutes talking about alcohol?”

§ Pre-screen: Do you sometimes drink beer, wine, or

• ther alcoholic beverages?

§ Single Alcohol Screen Question:

§ Men: How many times in the past year have you had 5 or

more drinks in one day?

§ Women (or >65 yo): How many times in the past year

have you had 4 or more drinks in one day?

§ Positive Screen=1 or more

Smith PC, et al. J Gen Intern Med 2009;24(7) NIAAA Guidelines 2005

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How to Screen?

§ Single Drug Use Screen Question: §

How many times in the past year have you used an illegal drug or used a prescription medication for nonmedical reasons?

§ Positive Screen=1 or more

Smith PC, et al. J Gen Intern Med 2009;24(7); NIAAA Guidelines 2005

Evidence for the Single Screen

§ Single question screen generally equal to other

screenings (CAGE, AUDIT)

§ 82-88% sensitivity for at-risk drinking § 97-100% sensitivity for drug use disorder

Smith PC, JGIM 2009; Smith PC, Arch Intern Med 2010 Saitz R et al. J Stud Alcohol Drugs, 2014

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A Positive Screen…

n What to do next? Assess…

n Determine how many drinks/day in a week n Ask which drugs the patient has been using n Ask about negative impacts

The follow-up questions assess impact and determine whether he/she has a substance use

disorder diagnosis.

Determining “At Risk” vs. “Substance Use Disorder”

n Pts who meet criteria for “at-risk” should get a brief

intervention

n Patients who meet substance use disorder criteria

abuse should get a

n

Brief intervention AND

n

A referral to specialty care (if they are willing) AND

n

Be considered for pharmacotherapy

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What is a Brief Intervention?

n Short motivational interviews that encourage

patients to create a plan of action that is based

• n their willingness to change their behavior

n Non-judgmental, direct, honest feedback n If not ready to change→harm reduction n Plan for follow-up

Brief Intervention

n “You are drinking more than is medically safe” n “I strongly recommend that you cut down or

quit and I’m willing to help”

n “Are you willing to consider making changes in

your drinking?”

How to Help Patients: A Clinical Approach: NIAAA 2005 Resource for Clinicians

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Motivational Interviewing

n Express empathy, develop

discrepancy, support self-efficacy

n Tools:

n Listen for “change talk” n Readiness to change ruler n Importance/confidence ruler

Pharmacotherapy

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Decision Making

(Counseling) Limbic Drive (Pharmacotherapy) From Pettinati, NIH 2006

Addiction Treatment Model: Treating Limbic Drive and Cortical Thinking Structures

Alcohol Use Disorder Pharmacotherapy

Two Phases of Alcohol Use Disorder Treatment:

n

Acute Alcohol Withdrawal

n

Maintenance medications to reduce use or prevent relapse (FDA approved)

n

Disulfiram

n

Acamprosate

n

Naltrexone (oral and injectable)

http://store.samhsa.gov/shin/content/SMA15-4907/SMA15-4907.pdf

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Alcohol Relapse Prevention Meds: Disulfiram (Antabuse)

n

Blocks alcohol metabolism (prevents acetaldehyde→acetate); increase in blood acetaldehyde levels

n

Antabuse reaction: flushing, weakness, nausea, tachycardia, hypotension

n

VA Cooperative Study of Disulfuram in 605 men

n

High rate of non-compliance: 80%

n

If adherent, more likely to be abstinent

n

Works best if given in monitored fashion

n

Clinical Dose: 250mg daily (range 125-500mg/d)

n

SE: Hepatotoxicity (check LFTs qmo x 3 then q3 mo)

Fuller RK, et al. JAMA, 1986;256

Naltrexone for Alcohol Use Disorder

n Similar structure to naloxone (Narcan) n Potent inhibitor of Mu opioid receptor

binding

n Endogenous opioids involved in the

craving and reinforcing (pleasure) effects of alcohol

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Naltrexone for Alcohol Use Disorder

n Cochrane Review of NTX (based on 50 RCT)

n Reduced risk of heavy drinking to 83% of the risk vs.

placebo (RR 0.83; CI 0.76-0.90)

n Decreased drinking days by 4% n Not significant for return to any drinking (RR 0.96;

CI 0.92-1.00)

n Estimate…helps 1 out of 9…

Srisurapanont & Jarusuraisin (2005) Cochrane Database Syst Rev. 2010 Jan 25;(1):CD001867

Pharmacotherapy of Alcohol Dependence: Naltrexone

n Oral Naltrexone Hydrochloride

n DOSE: 50 mg per day

n Extended-Release Injectable Naltrexone (Vivitrol)

n 380mg IM per month

n Must be opioid-free for 7-10 days before starting n Contraindicated in liver failure or acute hepatitis

Garbutt et al. JAMA, 2005

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Alcohol Relapse Prevention Meds: Acamprosate

§ Acts on GABA and glutamate neurotransmitter systems § Impact is anti-craving, reduced protracted withdrawal § Dose: 2 g daily (6 pills/day= TWO 333 mg pills three

times/d)

§ SE: Diarrhea (up to 16%), nausea, itching (up to 4%) § Contraindications: severe renal disease (creat cl < 30

ml/min); dose adjust if CrCl 30-50

§ Only approved for people who are abstinent

Alcohol Relapse Prevention Meds: Acamprosate

§ Recommended length of treatment: 1 year § Effective in reducing relapse to alcohol use in studies

leading to FDA approval

§ Meta-analysis of European trials: 36% on acamprosate

abstinent at 6 months vs. 23% on placebo

§ Not effective in Project COMBINE: 1383 patients

§ Only naltrexone effective § More severe dependence in European trials (acamprosate

with greater effect in longer h/o dependence)?

§ Fewer abstinence days required to enter COMBINE

Mann K et al. Alcohol Clin Exp Res, 2004 Anton RF et al. JAMA, 2006

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Summary – Alcohol Use Disorder

n If abstinent:

n Consider disulfiram as “insurance” (if monitored) n Consider naltrexone for relapse prevention n Can consider acamprosate

n If still drinking

n Consider naltrexone

n If on opioids

n Consider acamprosate

Quiz…

n Which of the following is the most commonly

misused class of prescription drugs?

• A. Opiates

B.

Stimulants

• C. Benzodiazepines

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Rates of Prescription Medication Abuse – Ages 12+

Ever Use Use in Last Year (2014) Non-Medical Use of Psychotherapeutics 20.5% 5.6% Pain Medications 13.6% 3.9% Sedatives 3% 0.3%

http://www.samhsa.gov/data/sites/default/files/NSDUH- DetTabs2014/NSDUH-DetTabs2014.pdf

Prescription Opioid Abuse

Unintentional US Overdoses 1970-2007

n In 2007, one overdose death

every 19 minutes

n More than heroin and

cocaine combined

National Vital Statistics System. Available at http://www.cdc.gov/nchs/nvss.htm.

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Source Where Pain Relievers Were Obtained for Most Recent Nonmedical Use among Past Year Users Aged 12 or Older: 2006

Bought/Took from Friend/Relative 14.8% Drug Dealer/ Stranger 3.9% Bought on Internet 0.1% Other 1 4.9% Free from Friend/Relative 7.3% Bought/Took from Friend/Relative 4.9% One Doctor 80.7% Drug Dealer/ Stranger 1.6% Other 1 2.2%

Source Where Respondent Obtained Source Where Friend/Relative Obtained

One Doctor 19.1% More than One Doctor 1.6% Free from Friend/Relative 55.7% More than One Doctor 3.3%

Case

n 64 yo woman presenting with c/o chronic osteoarthritis

in both knees. X-rays are c/w OA. She has a h/o ulcer approximately 3 years ago. She says she needs something for pain as she is not interested in knee

• replacement. Do you:

n A) Start her on acetaminophen with codeine n B) Refer her to orthopedics anyway n C) Start an NSAID with clear precautions on GI side

effects

n D) Try other treatment modalities (PT, tramadol)

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Non-Cancer Pain

n Complete hx and PE to evaluate pain n Agree on pain control goal and function goal n Consider non-medication options if appropriate

n Lifestyle changes n Exercise, PT n Therapy, biofeedback n Alternative medicine: mindfulness, massage,

acupuncture, etc

Makris UE, et al. JAMA, 2014

How to Treat Non-Cancer Pain?

n Consider non-opiate meds first

n Tylenol, topical NSAIDS, NSAIDS n Neuropathic pain: gabapentin, TCAs (nortriptyline),

pregabalin, lidocaine patch

n Duloxetine (SNRI) n Muscle relaxants n Tramadol (weak affinity for Mu receptor)

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Opioids for Non-Cancer Pain

n Good evidence opioids help with acute pain in the short-term

(<6 weeks)

n No good evidence long-term opioids help with chronic (>3 mo)

non-cancer pain

n May cause harm (quality of evidence low) n Increased risk overdose, abuse, addiction, MI, fractures n 9940 patients on opioids >3 months n Risk of annual overdose 3.7X for 50-99mg/d morphine

equivalent (0.7% annual overdose rate)

n 8.9X for > 100mg/d (1.8% annual overdose rate)

Chou R, Ann Intern Med, 2015; Dunn KM, Ann Intern Med, 2010

Opioid Dose and Risk for Overdose

Dunn et al. 2010 Annals Daily Opioid dose (MSO4 eq) Hazard Ratio for OD (95% CI) None 0.31 (0.12-0.8) 1 to <20 mg 1 20 to <50 mg 1.44 (0.57-3.62) 50 to <100 mg 3.73 (1.47-9.5) 100+ 8.87 (3.99-19.72) Any dose 5.16 (2.14-12.48)

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What is a High Dose of an Opioid?

n Cut-off is not exact n MSO4 50 mg is about the same as….

n Codeine 60 mg q4h n Hydrocodone/APAP 10/300 5 times a day n Methadone 5 mg tid n Hydromorphone 4 mg tid n Oxycodone/APAP 10 mg/300 tid n Oxymorphone ER 7.5 mg bid n Fentanyl 25 mcg/hr patch

Opioidcalculator.practicalpainmanagement.com

Long vs. Short-Acting Opiates and Risk of Overdose

Duration of Use Event Rates/ 10,000 person years LONG- ACTING Event Rates/ 10,000 person years SHORT- ACTING Hazard Ratio Any 35 15 2.33 <14 days 143 25 5.25 15-60 days 36 16 2.30

Miller M, et al. JAMA Intern Med, 2015

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How To Balance Treating Pain with Risk*

n ID factors for abuse

n Opioid Risk Tool, Current Opioid Misuse Measure

and others

n Pain Agreement to discuss risks of opioids n Toxicology screening before prescribing and get

• ld records

n Get permission to talk to one family/friend who

is NOT on opiates

*For all patients

Building a Patient-Provider Agreement

http://pain.ucsf.edu/docs/UCSF_Patient_Provider_Agreement_on_Opioids.pdf

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The “PEG” tracks benefits of opioids

On a scale of 0-10, over the last week: What has your average pain been? (0-10) How much has your pain interfered with your enjoyment of life? (0-10) How much has your pain interfered with your general activity? (0-10)

Krebs, 2009

Using Opiates for Non-Cancer Pain

n Avoid concomitant benzos/sedative-hypnotics

n Check medication list for interactions (esp methadone)

n Initiate with short-acting low dose

n Don’t increase more frequently than q2 weeks

n Document pain score and function each visit

(PEG)

n Avoid escalating doses above 80-120 mg/d

morphine equivalent doses

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How To Balance Treating Pain with Opioid Risk?

n Compliance monitoring

n Pill counts, Utox, CURES reports

n Watch for aberrant behaviors

n Unsanctioned use, drug seeking behaviors, rx losses,

etc

n Re-assess function and goals at each visit n Check last dosing (for Utox)

Urine Drug Testing

n Test everyone, with frequency standardized

according to risk.

n Morphine equiv 200 mg+ or recent aberrancy:

monthly

n 50-199 mg: quarterly n 20-49 mg: annually

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http://pain.ucsf.edu/docs/UCSF_Patient_Provider_Agreement_on_Opioids.pdf

Drug ¡ Window of Detection3 (Days) ¡ Medications that Cause False Positives (Common Examples) ¡ Confirmatory Testing Available for Screening Test? ¡ Amphetamine ¡ 1-3 days ¡ Bupropion, ciprofloxacin, ephedrine, labetalol, melatonin, metoprolol, phenylephrine, pseudoephedrine, ranitidine, sertraline. ¡ Yes ¡ Benzodiazepines* ¡ 1-7 days (2-30 days for diazepam) ¡ Diphenhydramine, gemfibrozil, hydroxyzine, indomethacin, sertraline, trazodone ¡ Yes ¡ Cocaine ¡ 1-3 days ¡

• ¡

No ¡ Methadone ¡ 3-10 days ¡

• ¡

No ¡ Opiates (only codeine, morphine, heroin) ¡ 1-3 days ¡ Fluoroquinolones, quinine, poppy seeds, rifampin ¡ Yes** ¡ Oxycodone ¡ 1-2 days ¡ Codeine, hydrocodone, hydromorphone, oxymorphone ¡ Yes ¡

Urine Toxicology Results

Adapted from UCSF Outpatient Handbook, 2014

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Urine Toxicology Results

n If concern for tampering, order urine creatinine (should be >20) n ALWAYS cause opiate screen to be positive? n Heroin, morphine, codeine n SOMETIMES cause opiate screen to be positive? n Hydrocodone, hydromorphone, oxycodone, oxymorphone n NEVER cause opiate screen to be positive? n Buprenorphine, fentanyl, meperidine, methadone, tramadol n Check fentanyl immunoassay or methadone screen

Steiger S, Drug Testing FAQ

When to Taper Prescription Opioids (Non-Cancer Pain)?

n When risks > benefits

n Aberrant behaviors

n If multiple agents, convert to morphine equivalents

to calculate total dose

n http://opioidcalculator.practicalpainmanagement.com/ n Reduce long-acting agents first vs. convert to short-

acting and taper

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When to Taper Prescription Opioids (Non-Cancer Pain)?

n Slow Taper: reduce dose by 10%/month n Minimizes withdrawal sx n Rapid Taper n Remove 10-15%/week n Indications: substance abuse, loss of control over pill use n Consider referral for substance abuse counseling/

treatment

n Immediate Cessation n Overdose, suicide attempt, rx forgery, diversion, other

threats

Reducing Risk for All Patients

Which of the following interventions has been demonstrated to reduce rates of overdose in patients prescribed opioids for chronic non-cancer pain?

a) Implementing pill count visits b) Random urine toxicology testing c) Tapering them to lower doses d) Prescription of naloxone

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Reducing risk for all patients

n Reduction in OD among heroin users since late

90’s

n Project Lazarus in NC showed decrease in

• pioid OD from 47 to 29 per 100,000*

n http://prescribetoprevent.org/prescribers/

palliative/

*Albert et al., Pain Med 2011 http://prescribetoprevent.org/wp2015/wp-content/uploads/ CA.Detailing_Provider_final.pdf

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Pharmacotherapies for Opiate Dependence

§

Methadone

§

Buprenorphine

§

Naltrexone

Opioid Dependence Maintenance Therapy: Methadone

§

Can only be prescribed through a registered “narcotic treatment program”

§

Long acting mu agonist (24-36h)

§

30-40 mg will block withdrawal, but not craving

§

80-100 mg is more effective at reducing opioid use than lower doses (e.g.: 40-50 mg/d)

§

Interacts with LOTS of medications

§

QT prolongation (approx 2%)

Strain EC, et al. JAMA, 1999

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Opioid Dependence Maintenance Therapy: Buprenorphine

§ Mu Opioid receptor, high affinity, partial agonist § Binds opioid receptors; slow to dissociate

§

If recent opioids, may withdraw

§

OD can’t be reversed with standard dosing of naloxone

§ Dosing may be daily, every other day or three

times weekly

§ Average dose 8-16 mg daily § Little effect on respiration or cardiovascular

responses at high doses

McNicholas, 2004

Opioid Dependence Maintenance Therapy: Buprenorphine

§

To reduce diversion, combined with naloxone in 4:1 ratio

§

Cheaper price than buprenorphine alone!

§

Occas increase in LFTs

§

SE: N/V (?if due to withdrawal)

§

Equivalent to lower dose of methadone in reducing illicit opioid use (though 80mg methadone better)

§

Buprenorphine DEA certification required to prescribe (8 hrs of training)

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Opioid Dependence Therapy: Antagonist Treatment (Naltrexone)

n

Prevent impulsive use of drug

n

Relapse rates high (90%) following detoxification with no medication treatment

n

Dose (oral): 50 mg daily, 100 mg every 2 days, 150 mg every third day

n

Dose (IM): 380mg IM q month

n Side effects: hepatotoxicity, monitor liver

function tests every 3 months

n Biggest issue is lack of compliance

Take Home Points

§ At-risk and substance use disorders common § Three medications FDA-approved for the

maintenance treatment of alcoholism

n Prescription opioids high abuse/misuse potential n Consider non-opioid treatments for chronic non-

cancer pain

n Ongoing monitoring required for opioid

prescribing

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Thank You!

n Special thanks to Scott Steiger, MD, UCSF

Division of General Internal Medicine

n Resources

n Local mutual help groups

n www.ncadi.samhsa.gov (resources) n www.aa.org

n Substance Abuse Facility Treatment Locator

Website

n http://findtreatment.samhsa.gov/

n http://www.niaaa.nih.gov/Pages/default.aspx

Katherine Julian, MD December 2015

Substance Use Disorders Selected References

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• dependence. JAMA, 2005;293:1617-1625.

Garbutt JC. The state of pharmacotherapy for the treatment of alcohol dependence. Journal of Substance Abuse and Treatment, 2009;36:S15-S23.

Gordon A, et al. Prescribing opioids for chronic noncancer pain in primary care: risk

• assessment. Postgraduate Medicine, September 2014;126(5):159-166.

Hill KP et al. Diagnosing and treating opioid dependence. J Fam Pract. 2012 Oct;61(10):588-97 Makris UE, et al. Management of persistent pain in the older adult. JAMA, 2014;312(8):825- 836. McCance-Katz EF. Office-based buprenorphine treatment for opioid-dependent patients. Harv Rev Psychiatry, 2004;12:321-338. Merrill JO and Duncan MH. Addiction disorders. Med Clin N Am, 2014;98:1097-1122. Miller M, Barber CW, et al. Prescription opioid duration of action and the risk of unintentional

• verdose among patients receiving opioid therapy. JAMA Intern Med, 2015;175:608-615.

National Institute on Alcohol Abuse and Alcoholism. Helping patients who drink too much: a clinician's guide. 2005. http://www.niaaa.nih.gov/Publications/EducationTrainingMaterials/Pages/guide.aspx National Institute on Drug Abuse. http://www.drugabuse.gov/DrugPages/DrugsofAbuse.html (accessed 2/2/2011) Nicholls L, et al. Opioid dependence treatment and guidelines. J Manag Care Pharm, 2010;16(1-b):S14-S21. Rosner RS, et al. Acamprosate for alcohol dependence (review). The Cochrane Collaboration. 2011. Rosner RS, et al. Opioid antagonists for alcohol dependence (review). The Cochrane

• Collaboration. 2010.

Rubak S et al. Motivational interviewing: a systematic review and meta-analysis. British Journal of General Practice, 2005;55:305-312. Saitz R, et al. Screening and brief intervention for drug use in primary care: the aspire randomized clinical trial. JAMA, 2014;312(5):502-513. Saitz R, et al. The ability of single screening questions for unhealthy alcohol and other drug use to identify substance dependence in primary care. J Stud Alcohol Drugs, 2014; 75:153-157. Smith PC et al. A single-question screening test for drug use in primary care. Arch Intern Med, 2010;170(13):1155-1160. Smith PC et al. Primary care validation of a single-question alcohol screening test. J Gen Intern Med, 2009;24(7):783-788.

Vasilaki EI et al. The efficacy of motivational interviewing as a brief intervention for excessive drdinking: a meta-analytic review. Alcohol & Alcoholism, 2006;41(3):328-355. Wu LT and Blazer DG. Illicit and nonmedical drug use among older adults: a review. Journal

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