Addiction Medicine - Substances of Abuse

Bradley J. Miller, DO

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Practical Approaches to Managing Substance Abuse and

Nicotine Addiction

ACOFP Intensive Update and Board Review in Osteopathic Family Medicine

Bradley J. Miller, DO, FAAFPWilliamsport Family Medicine Residency

Objectives• Review current statistics and disease burden of

substance abuse in the United States.

• Describe importance of screening for, provide brief intervention for, and recognize when to refer to treatment for substance abuse disorders in the primary care setting.

• Review specific substances of abuse (alcohol, nicotine, MJ, opiates) and accepted pharmacologic treatments

Question # 1

In patients who die from an opioid overdose, a second substance is often present that contributes to the patient’s death. Which one of the following additional substances is most likely to be found in conjunction with a fatal opioid overdose?

A) THC (Marijuana) B) AntidepressantsC) CocaineD) BenzodiazepinesE) Alcohol

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Current Statistics and Disease Burden

2012 National Survey on Drug Use and Health

• 23.9 million people over 12 years are current illicitdrug users

• 52.1% of individuals over 12 years report being current drinkers

• Of all individuals over 12 years who drink

– 23% binged in the last month

– 6.5% participate in heavy drinking

Current Statistics and Disease Burden

• 2.1 M ED visits associated with drug misuse or abuse in

• 53% of all ED visits involved pharmaceuticals– Pain relievers- most common

• Other pharmaceuticals included BZDs – alprazolam most reported

Substance Abuse and Mental Health Services Administration, Drug Abuse Warning Network, 2009: National Estimates of Drug-Related Emergency Department Visits. HHS Publication No. (SMA) 11-4659, DAWN Series D-35. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2011.

SAMHSA National Survey

Past Month Use of Selected Illicit Drugs among Youths Aged 12 to 17: 2002-2012

Substance Abuse and Mental Health Services Administration, Results from the 2012 National Survey on Drug Use and Health: Summary of

National Findings, NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD: Substance Abuse and Mental Health Services

Administration, 2013

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SAMHSA National Survey Past Month Nonmedical Use of Types of Psychotherapeutic Drugs among Persons Aged 12 or Older:

2002-2012

Substance Abuse and Mental Health Services Administration, Results from the 2012 National Survey on Drug Use and Health: Summary of

National Findings, NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD: Substance Abuse and Mental Health Services

Administration, 2013

Mokdad et al., 2004

SAMHSA National Survey Source Where Pain Relievers Were Obtained for Most Recent Nonmedical Use among Past Year Users

Aged 12 or Older: 2011-2012

Substance Abuse and Mental Health Services Administration, Results from the 2012 National Survey on Drug Use and Health: Summary of

National Findings, NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD: Substance Abuse and Mental Health Services

Administration, 2013

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Top Medications Prescribed 2011

Enough opiate pain medications were prescribed in 2010 to medicate every American adult with 5 mg of hydrocodonetaken every 4 hours…

for an entire MONTH

Warner M, Chen LH, Makuc DM. Increase in fatal poisonings involving opioid analgesics in the United States, 1999-2006. NCHS data

brief, no 22. Hyattsville, MD: National Center for Health Statistics. 2009

Vital Signs: Overdoses of Prescription Opioid Pain Relievers – United States, 1999-2008.

MMWR Volume 60, No. 43. pp. 1487-1492. November 4, 2011

Death Rates* for Three Selected Causes of Injury†— National Vital Statistics

System, United States, 1979–2012

Center for Disease Control, Morbidity and Mortality Weekly, November 21, 2014

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The Neurochemistry of Addiction

– Dopamine: Amphetamines, cocaine, alcohol

– Serotonin: LSD, alcohol

– Endorphins: Opioids (heroin and narcotics), alcohol

– GABA: Benzodiazepines, alcohol

– Glutamate: Alcohol

– Acetylcholine: Nicotine, alcohol

– Endocannabinoids: Marijuana, alcohol

SCREENING

Alcohol• What is Low-Risk Drinking?:

• Females

< 7 drinks per week

< 3 drinks per occasion

• Males

< 14 drinks per week

< 4 drinks per occasion

• Adults over 65 years of age

< 7 drinks per week

< 3 drinks per occasion

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Alcohol

What constitutes “1 drink”?*

• Beer – 12 ounces

• Shot – 1.5 ounces

• Wine – 5 ounces

* The definition of a standard drink varies from country to country and study to study; the above is the WHO definition, and is used by the SBIRT initiative

One 12oz. Can/Bottle of Beer

A single shot (1.5 oz.) of distilled spirits (gin, vodka, rum, etc…)

A glass of wine (5 oz.) or a small glass of sherry

What is a standard drink?

DSM-IV SUD

Substance Abuse

1 or more of the following at the sametime in a 12-month period:

• Recurrent use resulting in failure to fulfill major role obligations

• Recurrent use in situations that are physically hazardous

• Recurrent legal problems resulting from use

• Continued use despite having persistent social or interpersonal problems caused or exacerbated by the substance

• Does not meet criteria for Dependence

Substance Dependence

3 or more of the following at the sametime in a 12-month period:

• Tolerance

• Withdrawal

• Taken in larger amounts or over longer period than intended

• Persistent desire or unsuccessful efforts to cut down

• Great deal of time spent in obtaining, using, and recovering from substance

• Important activities are given up as a result of substance use

• Use continues despite knowledge of physical or psychological problem that is caused or exacerbated by the substance

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DSM-V Substance Related Disorders

–A major overhaul of the DSM-IV criteria for substance use includes the following:

•Substance Use Disorder (SUD) is a single disorder, measured on a continuum from mild to severe, that combines the DSM-IV abuse and dependence criteria with the following two exceptions:

–DSM-IV recurrent legal problems has been removed

–New criterion for craving or a strong desire or urge to use has been added

•Each specific substance is addressed as a separate use disorder (e.g. alcohol use disorder, opiate use disorder)

•Cannabis and Caffeine withdrawal are new for DSM-V

•Gambling disorder has been added

DSM-V Substance Use Disorder

•SUD is accompanied by criteria for intoxication, withdrawal, substance/medication-induced disorders and unspecified substance-induced disorders.

•The severity of SUD in DSM-V is based on criteria endorsed:

–2-3 – mild disorder

–4-5 – moderate disorder

–6 or more – severe disorder

•Helps define SUD as a continuum and removes confusion regarding dependence with “addiction” when in fact dependence can be a normal body response to a substance

•Additional modifiers and specifies exist as well.

•Substance INTOXICATION & WITHDRAWAL are different codes and are dependent on the severity of the SUD

National Institute on Alcohol

Abuse and Alcoholism

www.niaaa.nih.govNIH Publication No. 13–7999

November 2013

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Question # 2

A 67 year old male with was brought to the emergency department after his friend found him confused at home. The patient typically drinks up to 12 cans of beer daily but has increased over the past 2 months. He has had some falls while intoxicated over the past year and has tried to cut down but hasn’t been able to do so. His family has been encouraging him to cut down and he has been unsuccessful. He decided to stop drinking and his last drink was about 20 hours ago. When found, the patient referred to his friend as his wife who has been deceased for 2 years. Which of the following is most accurate?

(A) The patient meets diagnostic criteria for moderate alcohol use disorder and is beginning to have delirium tremens

(B) The patient meets diagnostic criteria severe alcohol use disorder and is beginning to have delirium tremens

(C)The patient meets diagnostic criteria for moderate to severe alcohol use disorder and is beginning to have alcohol hallucinations

(D) Naltrexone, thiamine and folate should be given to the patient prior to treatment with lorazepam

(E) None of the above

Alcohol

Alcohol Withdrawal Syndromes

• Pathophysiology of ETOH withdrawal– Abrupt withdrawal unmasks compensatory over-activity of

the nervous system.

– Alters levels of GABA, Norepinephrine and Serotonin

• Minor Withdrawal Symptoms– Due to CNS and sympathetic hyperactivity

– Usually present within 6 hrs of drinking cessation

– Insomnia, tremulousness, anxiety, GI upset, HA, diphoresis, palpitations, or anorexia

– Resolve within 24-48 hours

– consistent from one episode to the next

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Alcohol Withdrawal Syndromes

• Withdrawal Seizures

– Usually tonic-clinic convulsions within 48 hours of last drink

– 3% of chronic alcoholics have withdrawal seizures of which 3% develop status epilepticus

– Usually a singe episode. Recurrent or prolonged seizures require investigation of another source

Alcohol Withdrawal Syndromes

• Alcoholic Hallucinations

– Often mistaken for delirium tremens (DTs)

– Hallucinations that develop 12-24 hrs from abstinence and resolve within 24-48 hrs (which is when DTs typically begin)

– Usually visual but can be auditory and tactile

– Usually associated with specific hallucinations and not global clouding of the sensorium (as with DTs)

Alcohol Withdrawal Syndromes

• Delirium Tremens

– Occurs in 5% of pts experiencing withdrawal

– Hallucinations, disorientation, tachycardia, HTN, low grade fever, agitation, and diaphoresis.

– Typically begin between 48 & 72 hrs and last one to five days

– Mortality rate of 5%

• death usually from arrhythmias or complicating illnesses such as pneumonia

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Treatment

• Inpatient vs outpatient

• For all patients:

1. Thiamine 100mg oral/IV daily (before glucose containing fluids to avoid Wernickeencephalopathy)

2. Folate 1 mg oral for 3 days

Outpatient Pharmacotherapy

for ETOH Dependence

• Three agents approved by FDA for adjunctive therapy for the treatment of alcohol dependence (other agents exist)– Naltrexone

• Pure opioid receptor antagonist

• Blunts pleasurable effects of alcohol and reduces cravings

• Reduces relapse and number of drinking days

• CAUTION: Will cause opiate withdrawal !

• BLACK BOX WARNING-acute hepatic toxicity

NaltrexonePO (ReVia®) / IM Depot (Vivitrol®)

• Typical starting and maintenance oral dose is 50mg daily

• High risk patients should start at 12.5mg or 25mg and titrate up

OR

• 380mg IM q 4 weeks

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Outpatient Pharmacotherapyfor ETOH dependence

– Acamprosate (Campral)

• Structural analog of GABA

• Decreases excitatory glutameric neurotransmission during withdrawal

• 666 mg TID. May need to adjust if pt has diarrhea

– Disulfiram (Antabuse)

• Deterrent- causes flushing, nausea, vomiting, tachycardia, dyspnea, HA, blurred vision, vertigo and anxiety 15-30 minutes after ingestion of ETOH

Indications for inpatient alcohol detoxification

Indications for inpatient alcohol detoxification

- History of severe withdrawal symptoms

- History of alcohol withdrawal seizures or DTs

- Multiple past detoxifications

- Other medical or psychiatric illness

- Recent high levels of alcohol consumption

- Lack of reliable support network

- Pregnancy

Myrick,H. Treatment of alcohol withdrawal. Alcohol Health and Research World, 1998, Vol.22 Issue 1, 38-46.

Treatment

• Gradual Tapering Regimen

- predetermined dosing schedule for several days as the medication is gradually discontinued (mostly used outpatient)

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Treatment

One of the following:

1. Chlordiazepoxide (Librium®) 50-100mg every 6 hours for 4 doses then 25-50 mg every 6 hours for 8 doses

2. Diazepam (Valium®) 10-20mg every 6 hours for 4 doses then 5-10mg every 6 hours for 8 doses

3. Lorazepam (Ativan®) 2-4 mg every 6 hours for 4 doses then 1-2 mg every 8 hours for 8 doses (medication of choice with hepatic dysfunction)

4. Carbamazepine (Tegretol®)200 mg QID x 1 day 200 mg TID x 1 day200 mg BID x 1 day200 mg BID x 1 day200 mg daily x 2 days

Asplund.C. Three regimens for alcohol withdrawal and detoxification. The Journal of Family Practice. July 2004. Vol. 53.

Treatment

• Fixed Schedule Regimen

1. Diazepam (Valium®)– Dose: 10-25 mg PO q1h prn while awake – Endpoint: until adequate Sedation

2. Lorazepam (Ativan®)– Dose: 1-2 mg IV q1h prn while awake for 3-5 days – Endpoint: until adequate Sedation

3. Chlordiazepoxide (Librium®)– Dose: 50 to 100 mg PO/IM/IV q4h (max: 300 mg/day) – Endpoint: until adequate Sedation

Associated with overmedication

Moses,S. Alcohol Withdrawal. www.fpnotebook.com

Treatment

• Symptom-Triggered Regimen

- Pt withdrawal score is determined hourly or bihourly and the medication is administered only when the score is elevated >8 on clinical withdrawal scale

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Treatment

Clinical Institute Withdrawal Assessment Revised Scale (CIW-Ar)

<10: Very mild withdrawal

10-15: Mild withdrawal

16-20: Modest withdrawal

>20: Severe withdrawal

Smith,M. Management of alcohol intoxication and withdrawal. Principles of Addiction Medicine. 4th edition. 559-572.

Additional Interventions

• Phenobarbital or propofol for refractory DTs – May require mechanical ventilation and ICU admission

• Phenothiazines and butyrophenones (including Haldol) –AVOID- lower seizure threshold

• Anticonvulsants- controversial if effective. – Most seizures are self limited and do not require

medication

– Consider phenytoin

Question # 3

The “five A’s Model” for treating tobacco abuse and dependence include all of the following except

A – Ask about tobacco use on every patient

B – Advise to quit

C – Assess willingness to made a quit attempt

D – Assist in the quit attempt

E – Arrange for nicotine support group

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Nicotine

Nicotine

• Tobacco is the chief avoidable cause of illness and death in our society

• Accounts for more than 435,000 deaths/yr

• 45 million smokers in the United States

– 70% of them want to quit

– 20 million attempt to quit each year, unaided

– only 4-7% are successful

Dependence

among users

nicotine>heroin>cocaine>alcohol>caffeine

Difficulty achieving

abstinence

(alcohol=cocaine=heroin=nicotine)>caffeine

Tolerance (alcohol=heroin=nicotine)>cocaine>caffeine

Physical

withdrawal severity

alcohol>heroin>nicotine>cocaine>caffeine

Deaths nicotine>alcohol>(cocaine=heroin)>caffeine

Importance in

user's daily life

(alcohol=cocaine=heroin=nicotine)>caffeine

Prevalence caffeine>nicotine>alcohol>(cocaine=heroin)

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The “5 A's” Model for Treating Tobacco Use and Dependence

• Ask about tobacco on every patient

• Advise to quit.

• Assess willingness to make a quit attempt.

• Assist in quit attempt

• Arrange follow up

• Nicotine Replacement Therapy (NRT)-Patch (OTC)

-Gum (OTC)

-Lozenge (OTC)

-Oral Inhaler (Rx)

-Nasal Spray (Rx)

• Non-Nicotine Medications-Varenicline (Chantix, Rx)

-Bupropion Hydrochloride (Rx)

First-Line Medications

NRT Medications

• Use high enough dose

• Scheduled dosing better than PRN

• Can be combined with Bupropion

• Don’t combine with Varenicline

• Can be combined with each other

• Have very few contraindications

• Have no drug-drug interactions

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Nicotine PatchDosing:

< 10 cigs/day: 14 mg patch

≥ 10 cigs/day: 21 mg patch

Length of Treatment:

-Up to 12 weeks

Pros:-Easy, good compliance-Continuous nicotine delivery-OTC

Cons:-Slow onset of action -Skin reaction-Insomnia

Nicotine GumDosing:

2mg < 25 cigarettes/day4mg > 25 cigarettes/day

Length of Treatment: 8-10 weeks

Use:- Chew and park (Slow, buccal absorption)- Acidic foods ↓ absorption

Pros:-Flexible dosing (every 1-2 hours, up to 24

pieces/day)-Keeps mouth busy-OTC

Cons: -Need to use correctly (chew and park)-Nausea, Heartburn Mouth and throat burning

Nicotine LozengeDosing:

Based on Time To First Cigarette (TTFC)

4 mg ≤ if 30 mins TTFC 2mg > if 30 mins TTFC

Length of Treatment:12 weeks

Use:-Allow to dissolve (Don’t Chew but Suck like a hard candy.)Pros:-Flexible dosing (Up to 20 lozenges/ day) More discreet than gum-Keep mouth busy-OTCCons: Need to use correctly (don’t chew, suck)May cause insomnia, some nausea, hiccups, heartburn, coughing

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Nicotine Nasal SprayDosing:

1-2 doses per hour

1 does = 2 spays (1 spray/nostril)

Use enough to control withdrawal symptoms

Length of Treatment:

3-6 months weeks (PDR)

Use:

-Spray (don’t sniff, swallow, or inhale)

-PRN or fixed-schedule (1-2 doses/hour)

Pros:

-Rapid delivery though nasal mucosa

-Flexible dosing (up to 40 doses)

Cons:

-Nasal irritation, rhinitis, coughing, & watering eyes.

-Rx needed

Non-Nicotine Pharmacotherapy

• First-line non-NRT medications

• FDA approved

-Bupropion (Zyban/Wellbutrin)

-Varenicline (Chantix)

• Others (nortriptyline, clonidine)

Bupropion Hydrochloride

• Dopamine and norepinephrine(noradrenaline) effects

• Reduces cravings, withdrawal

• Improved abstinence rates in trials

• Less weight gain while using

• Start 7-10 days prior to quit date

• Continue 7-12 weeks or longer

( > 6 months)

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Bupropion Precautions• Contraindicated: seizure disorder, eating

disorders, electrolyte abnormalities, MAO use– OK with SSRIs

• NOT dangerous to smoke while taking• Monitor blood pressure• Side effects:– Insomnia (40%)– Dry mouth– Headaches– Rash

Varenicline (Chantix)

• Action at 42 nicotine receptor

• Partial agonist/antagonist

• Releases lower amounts of dopamine into brain than smoke– Reduces withdrawal

– Not as addictive as smoke

• Blocks nicotine from binding to receptor– Prevents reward of smoking

Varenicline (Chantix)

• In 2008 FDA added a warning regarding the use of varenicline noting that depressed mood, agitation, changes in behavior, suicidal ideation, & suicide have been reported in patients attempting to quit smoking while using varenicline .

• FDA recommends that:1. Patients tell their healthcare provider about any history of

psychiatric illness prior to starting this medication

2. Clinicians monitor patients for changes in mood and behavior when prescribing this medication

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Electronic Cigarettes

• Introduced into US in 2007

• Use has tripled among teens from 2013-14

• No FDA regulations (yet)– Can be purchased online

– No age restrictions

• Solvents used to dissolve nicotine are irritants and may be carcinogenic

• Companies don’t disclose all ingredients of their electronic cigarette

Electronic Cigarettes

• E-cigs vs. placebo – helped with abstinence from smoking traditional cigs 30 days or less but not long term

• Surpasses all other forms of tobacco in youth population

• Flavors that might appeal to younger age group (chocolate, bubble gum…)

Question # 4

Which of the following is the most commonly abused illicit drug in the US?

A – lorazepam

B – cannabinoids (marijuana)

C – opiates (heroin and pain medication)

D – alcohol

E – cocaine

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Marijuana

Marijuana

• Marijuana is the most commonly abused illicit drug in the United States

• Long-term marijuana abuse can lead to addiction; – compulsive drug seeking and abuse despite its known

harmful effects upon social functioning– Long-term marijuana abusers trying to quit report

irritability, sleeplessness, decreased appetite, anxiety, and drug craving, all of which make it difficult to quit

• Effect on Mental Health:– Causes increased rates of anxiety, depress, SI, and

schizophrenia.

National Institute on Drug Abuse (NIDA) Website; http://www.nida.nih.gov/infofacts/costs.html

Question # 5

An intoxicated patient is brought to the emergency department. Ocular examination reveals mydriasis. This patient was most likely using which of thefollowing substances?

(A) alcohol(B) cocaine(C) opioids(D) PCP(E) sedatives

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Opiates

• Opiate Agonists– Methadone

• Partial Agonist, Partial agonist/antagonist– buprenorphine

– buprenorphine/naloxone

• Antagonist– Naltrexone (Vivtrol®)

Opiate Addiction Pharmacologic Interventions

Why are opioid medications used to treat opioid addictions?

• Common myth is that all medications used to treat addictions are simply “substituting one addiction for another”

• Research has found that addiction to opioids results in significant changes in brain chemistry and function.

• Some of these changes may be permanent, meaning some individuals may require an opiate to bind to their changed receptors in order to function normally.

• Medication therapy significantly helps individuals stay in treatment more consistently, stay healthier, stay out of legal trouble, and generally function well in society.

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Naltrexone (Vivitrol®)• Naltrexone is a opiate antagonist• Tightly blocks mu opioid receptors

• FDA approved for treating alcohol dependence and opiate dependence– Decreases cravings in patients who abuse alcohol

• Comes in oral and IM depot formulations– oral used to trial naltrexone prior to committing to IM

– IM- (Vivitrol®) – depot formulation that is given monthly. If patients use opiates while on, no high.

• CAUTION: Will cause opiate withdrawal • BLACK BOX WARNING-acute hepatic

toxicity

What is buprenorphine?

• Buprenorphine is a partial agonist of the mu opioid receptor

– Binds to and activates the receptor

– Partial agonists have a “ceiling effect:”

• larger doses do not produce greater highs-- has a very low risk of abuse and overdose.

How does being a partial agonist safeguard against abuse?

• Features of Suboxone include: – buprenorphine mixed with the antagonist naloxone (not in pregnancy)

– It must be taken correctly (dissolved under the tongue) to work correctly.

– If injected, the naloxone will bind to the receptors and put the person into rapid withdrawal.

– If it is swallowed without dissolving, there is no effect.

– When taken correctly, will act as an agonist and reduce craving and withdrawal symptoms. Once “ceiling effect” is achieved, other opioidssuch as heroin, are not able to bind to the receptors and therefore will produce no effects.

– If administered while using other opiates, it may act as an antagonist and put the person into immediate withdrawal.

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References• “Creating Opportunities for Reducing Alcohol Related Harm in the Veteran Community; Session 6: Brief Intervention.”

Version 2.3. Department of Veterans’ Affairs, Australia. December 2002 <http://www.dva.gov.au/health/younger/mhealth/alcohol/training/session6.htm

• Thomas Babor, John Higgins-Biddle. Brief Intervention for Hazardous and Harmful Drinking-A Manual for Use in Primary Care. World Health Organization, Department of Mental Health and Substance Dependence. 2001

• Gentilello et al. “Alcohol Interventions in a Trauma Center as a Means of Reducing Risk of Injury Recurrence”. Annals Surgery1999;230:473-483

• 2012 National Survey on Drug Use and Health (NSDUH) sponsored by the U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration (SAMHSA), Office of Applied Studies (OAS). http://www.oas.samhsa.gov/nsduh/2k6nsduh/2k6Results.cfm#Ch1

• National Institute on Drug Abuse (NIDA) Website; http://www.nida.nih.gov/infofacts/costs.html

• Gold, MS and Aronson, MD. Treatment of Alcohol Use and Dependence. In: UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, 2008.

• Weinhouse, GL. Alcohol Withdrawal Syndromes. In: UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, 2008.

• Motivational Interviewing: Resources for clinicians, researchers and trainers. Interaction Techniques.http://www.motivationalinterview.otg/clinical/interaction.html

• Fiore MC, Jaén CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. May 2008.

• American Academy of Family Physicians. Studies Suggest E-Cigarettes Don't Aid Long-term Smoking Cessation: American Family Physician. http://www.aafp.org/news/health-of-the-public/20150605e-cigstudies.html , June 2015