|
DIAGNOSIS AND TREATMENT OF SUBSTANCE USE DISORDERS |
Background (AFP 2013;88:113; Ann Int Med 2016;164:ITC49)
Goals: (1) Identify SUD for treatment (2) ↑ trust in primary care, (3) prevent overdose and medical complications, (4) ↓ drug–drug interactions, (5) identify comorbid conditions, (6) ↓ stigma Standard of care: Expert consensus to screen for substance use disorders in primary care clinic based on high prevalence, high
morbidity/mortality, and availability of effective interventions; SUDs are underdiagnosed and undertreated chronic illnesses
| Diagnostic Criteria for Substance Use Disorders (DSM-5) | |
| A problematic pattern of substance use leading to clinically significant impairment/distress, as evidenced by ≥2 of the following over a 12-mo period: | |
| • Failure to fulfill roles
• Use in risky situations • Persistent desire or unsuccessful efforts to cut down • Use despite known ⊖ impact on med/psych dx • Tolerance |
• Cravings
• ↑ doses or longer period of use than intended • ↑ time finding, using, recovering • Evidence of withdrawal • Abandonment of other pleasurable activities • Use despite adverse effects on relationships |
| Severity grading: Mild 2–3, Mod 4–5, Sev ≥6 | |
Evaluation
Screening questionnaires: Many options → consider feasibility based on length, complexity of administration, appropriateness based on substances (EtOH vs. all substances); most do not include tobacco
(https://www.drugabuse.gov/sites/default/files/resource_guide.pdf)
Introduction to screening: Normalize with “I’m going to ask you a few questions that I ask all my patients” and explain purpose, “this will help me give you better medical care; the questions relate to your experience with alcohol, drugs, and nicotine.”
Quick screen (from National Institute on Drug Abuse): 1st pass, designed to precede in-depth screen, e.g., NIDA-modified ASSIST: How many times in the past year have you used an illegal drug or used a prescription medication for nonmedical reasons or had ≥5 (♂) or ≥4 (♀) drinks/day? Score ≥ 1 ⊕ 100% sensitive, 73.5% specific (Arch Intern Med 2010;170:1155). If pts screen positive, use a more in-depth screen (box).
Screen for other comorbidities: Intimate partner violence (IPV) → 50% of pts w/ SUD are victims of IPV (Subst Use Misuse 2009;44:1298); screen for concomitant mental health disorders: anxiety, depression, bipolar, PTSD, personality disorders
Workup: With pt permission: Urine or serum toxicology; screen for hepatitis A/B/C, HIV, STDs, TB
Management
Harm reduction: Goal is to ↓ ⊖ consequences of drug use using a patient-centered, nonjudgmental approach.
Vaccinations: Hepatitis A, B; Meningococcus, tetanus; see “Vaccines”
Infection prevention: Counsel on safe injection techniques: Clean needles/hands/injection site, no needle sharing, use a different site each time, safe needle disposal; Provide information on needle exchange programs Accident reduction: Counsel on driving, firearms
Overdose prevention: Counsel to use small amount of new batch as “test shot” before shooting full amount; Avoid injecting alone; Highest risk of O/D is after a period of no use; Provide naloxone (see “Opioid Use Disorder”); Review prescribed medications for possible interactions; judiciously prescribe opioids/benzodiazepines Ensure access to contraception
Recovery coaches
Detoxification Programs: Manage acute withdrawal, appropriate for pts w/ risk severe withdrawal; wide variability in completion of programs
(J Subst Abuse Treat 2015;52:31); LOS: D–wk, typically 4–6 d
Adjunctive treatment: Counseling should be an adjunct to pharmacotherapy of SUD; Levels of care include inpatient, residential, intensive outpatient, and outpatient counseling. Insufficient evidence to recommend for or against specific psychosocial intervention; Setting should be determined based on patient preference, provider competence, risk of relapse, need for supervision, anticipation of detoxification; Referrals at: findtreatment.samhsa.gov/
Brief Intervention: High efficacy for EtOH abuse, unclear efficacy in other SUD (JAMA 2014;312:502) (sbirttraining.com/about) Motivational Interviewing: Patient-centered, empathetic and nonjudgmental approach; Aims to enhance intrinsic motivation by eliciting discrepancies btw future goals & current behavior and pros & cons of substance use Elicit-provide-elicit method: Elicit knowledge and opinions regarding aspect of SUD, “What do you know about how alcohol affects your health?” Provide salient information and advice. Elicit response to your comments and pt opinion, “How does this information strike you?”
Cognitive behavioral therapy: Development of coping skills; May have efficacy in cannabis use disorder; may be effective as adjunct to nicotine replacement therapy (Cognit Ther Res 2012;36:427) Contingency management (CM): Incentives for target behaviors, often monetary for participation in therapy sessions or abstinence; Vouchers w/ monetary value provided for ⊖ tox screens most effective w/ opioids & cocaine (Addiction 2006;101:1546); Risk of relapse after CM ends may be high; environmental and neurocognitive factors that make CM more successful yet to be identified (J Subst Abuse Treat 2017;72:10) Intensive outpatient program (IOP): Counseling-based outpatient program, typically group setting; May offer adjunctive pharmacotherapy, individual counseling, and/or psychiatry; LOS: Typically 3 half days/wk; Less disruption of work/family/social life Clinical stabilization service (CSS) and transitional support service (TSS): Inpatient programs serve as transition from detox → long-term residential treatment; include education and counseling but services vary; LOS: (CSS) 10–14 d; (TSS) 30 d Residential treatment: Highly structured, sober, and stable living environment; May be private (typically $$$, insurance
not accepted) or publicly funded (may accept insurance); Halfway houses/recovery homes offer stable, sober, supportive place to live with group meetings; typically require mutual help meetings; LOS: Wk–mo, up to 6–12 mo Mutual help meetings: Peer support groups; adjunct to treatment. ↓ risk of relapse largely through facilitating sober contacts and sponsorship; increased engagement with mutual help is associated with increased treatment success Narcotics Anonymous (NA, na.org), Alcoholics Anonymous (AA, aa.org): voluntary attendance, usually 12-step meetings, optional mentor known as sponsor, abstinence not required, free, widely available at different times and locations; closed meetings for those with addiction only vs. open meetings Self-Management and Recovery Training (SMART, smartrecovery.org): Nonreligious, designed for all types of addiction; offers “4-Point Program” (1) building and maintaining motivation, (2) coping w/ urges, (3) managing thoughts, feelings & behaviors, (4) living balanced life; daily online meetings, online message board, chat room, face-to-face meetings 12-Step Facilitation Therapy (National Institute on Alcoholism and Alcohol Abuse 1995 Twelve-Step Facilitation Therapy Manual): Individual, adapted to group format, outpt; typically 12–15 sessions Technologic innovations: Interactive websites, mobile apps, videoconferencing
| National Institute on Drug Abuse Modified ASSIST |
| In your lifetime, which of the following substances have you ever used? (i.e., cannabis, cocaine, prescription stimulants, inhalants, sedatives, sleeping pills, hallucinogens, street/prescription opioids, other) |
| For each drug ask: In the past 3 mo how often have you because of substance use (points): Used the substances mentioned? Never (0), 1–2× (2), Monthly (3), Weekly (4), Daily/Almost
daily (6) Had a strong desire/urge to use? Never (0), 1–2× (3), Monthly (4), Weekly (5), Daily/Almost daily (6) Had health, social, legal or financial problems? Never (0), 1–2× (4), Monthly (5), Weekly (6), Daily/Almost daily (7) Failed to do what was normal expected of you? Never (0), 1–2× (5), Monthly (6), Weekly (7), Daily/Almost daily (8) Had a friend, relative, or anyone else express concern about your use? Never (0), Yes, but not in past 3 mo (3), Yes, in past 3 mo (6) |
| Tried & failed to control, ↓, or stop using? Never (0), Yes, but not in past 3 mo (3), Yes, in past 3 mo (6) Final question: Have you ever used any drug by injection? If answer is “Yes” consider screening for blood-borne disease. If “Yes in the past 3 mo” also counsel harm reduction of IVDU (below) |
| Severity grading: For each substance, calculate Substance Involvement Score: 0–3 lower risk, 4–26 mod, ≥27 high. ASSIST sensitivity 90%, specificity 78% (Drug Alcohol Rev 2005;24:217) |
| Other screening tools:
Drug abuse screening test (DAST-10): Considered as reliable as original DAST-28 or modified DAST-20 (J Subst Abuse Treat 2007; 32:189) Tobacco, EtOH, Prescription Drugs & other Substance Use (TAPS) Tool (Ann Intern Med 2016;165:690) CAGE-AID: Adapts CAGE to include drug use (i.e., cut down on drinking or drug use). “Yes” 1 pt, “No” 0 pt. Score 0–1 ⊖ screen; 2–4 ⊕; 12–78% PPV, 78–99% NPV; sensitivity 79–91%, specificity 48–77% (Wis Med J 1995;94:135). CRAFFT: Only screen validated for adolescents (Arch Pediatr Adolesc Med 2002;156:607) |
TOXICOLOGY TESTING (AFP 2010;81:635; Mayo Clin Proc 2008;83:851)
Background: <50% of pts abusing drugs present with aberrant behavior (Anesth Analg 2003;97:1097)
Sample sources: Testing typically done using immunoassays with gas chromatography/mass spec confirmation. 2nd-hand marijuana exposure unlikely to give a positive result
Urine: Most common modality; Assesses 24–72 h use; only modality approved for federally mandated testing. Standard 9-panel test includes amphetamines, cocaine, marijuana, opiates (codeine, morphine), PCP, barbiturates, benzodiazepines, methadone, propoxyphene; Specific pain panel may be needed to detect oxycodone and other narcotics Subversion: False-negative results may be caused by excess water ingestion, masking agents (niacin), adulterants (ammonia, bleach, eye drops, hydrogen peroxide, nitrates, papain, soap, zinc sulfate), substitution of drug- free urine Serum: May be limited by half-life of illicit substances (i.e., heroin has a serum half-life of 6–15 min); typically performed by liquid chromatography/mass spec Hair: Provides 90-d history of drug use; detects amphetamines, cocaine, marijuana, PCP, opiates Saliva: Allows direct observation of sample collection; common tests include amphetamines, cocaine, marijuana, methamphetamines, opiates, and PCP
| Timeframe When an Ingestion is Likely to Produce a Positive Screen Result | |
| Amphetamines: 1–3 d | Ketamine: 3–7 d |
| Benzodiazepines: 1–7 d (except for
diazepam, which may be weeks) Cocaine: 1–3 d |
Marijuana: Months
Opiates: 1–3 d (except methadone which is 3–10 d) PCP: 1–7 d |
| Substances That May Cause False Positives | |
| Amphetamines: Amantadine, atenolol, bupropion, carbidopa, ephedrine, labetalol, levodopa, phenylephrine, promethazine, pseudoephedrine, trazodone Benzodiazepines: Oxaprozin, sertraline
Marijuana: Hemp food products, marinol, NSAIDs, pantoprazole Opioids: Dextromethorphan, diphenhydramine, fluoroquinolones, poppy seeds, quinine, rifampin, verapamil PCP: Dextromethorphan, diphenhydramine, doxylamine, ibuprofen, imipramine, tramadol, venlafaxine |
|
| ALCOHOL USE DISORDER |
Background (JAMA 2015;314:2123; NEJM 2013;368:365; Niaa, nih.gov)
Epidemiology: 70% of US adults consumed EtOH in last year; 7% of all adults annually have AUD; 88,000 deaths (1 in 10 working age adults) and $250 billion cost in US, 6% of all deaths globally; 15% of pts w/ AUD have another substance use disorder
Special populations: Adolescents: Consume 90% of EtOH by binge drinking; College: ↑ risk of sexual assault; ↓ availability ↓ consumption; Seniors: Medication interactions; ♀: ↑ risk of side effects given lower weight and body water content; Minorities: Variation in cultural norms around abstinence and openness to treatment; 12% of Native American deaths involve EtOH; HIV: ↑ risky behaviors, ↓ adherence to ART
| 1 Drink is 12–14 g EtOH (i.e., 12-oz beer, 5-oz wine, 1.5-oz spirits) |
| “Low-Risk” Drinking: ♂/♀: ≤4/3 drinks/d and ≤14/7 drinks/wk. For pts >65 criteria are the same as for ♀; Light Drinking and the “J-Curve”; some observational studies have shown a “J-curve” suggesting light drinking associated with ↓ risk of CAD but these data are controversial and given risks, encouraging light drinking is not recommended (Arch Int Med 2006;166:2437; BMJ 2014;349:4164; JAMA 2010;303:2065) |
| Binge Drinking: ≥5 drinks/occasion in the last mo |
| Heavy Drinking: ≥5 drinks/occasion on ≥5 days in the last mo |
| Alcohol use disorder (DSM-5): A maladaptive pattern of EtOH use leading to clinically significant impairment or distress as manifested by 2 (or more) of the following, occurring w/in a 12-mo period (≥6 considered severe AUD): (1) Failure to fulfill roles, (2) Use in risky |
| situations, (3) Persistent desire/unsuccessful efforts to cut down, (4) Use despite known ⊖
impact on med/psych problems, (5) E/o tolerance, (6) Cravings, (7) ↑ doses or ↑ period than intended, (8) ↑ time finding, using, recovering, (9) E/o withdrawal, (10) Abandonment of other pleasurable activities, (11) Use despite adverse effects on social/interpersonal fxn |
| Medical and Social Consequences |
| Cardiac: HTN, nonischemic dilated cardiomyopathy, afib. EtOH ↑ HDL short-term; 1 to 2 drink/d associated with 30% ↓ risk of CAD and ~18% ↓ mortality in observational studies (Arch Int Med 2006;166:2437). Moderate drinking not recommended as a CAD preventative strategy given risks/harm of EtOH and absence of randomized trials (JAMA 2010;303:2065). |
| Hematology/oncology: ↓ HCT, ↓ PLT due to B12/folate deficiency, marrow suppression.
Macrocytosis. ↑ breast CA risk even at levels as low as 3 drinks/week (JAMA 2011;306:1884). ↑ risk of oral, GI, & liver CA (Lancet Oncol 2009;10:1033). No safe threshold for EtOH and cancer risk (Am J Public Health 2013;103:641). |
| Neurologic: Korsakoff syndrome (memory deficits), Wernicke’s encephalopathy (encephalopathy, gait ataxia, oculomotor dysfunction), peripheral neuropathy, seizures. |
| Pregnancy: Abstinence recommended. ↑ risk of stillbirth, low birth weight, fetal alcohol syndrome (growth problems, facial dysmorphia, CNS/cognitive problems). Naltrexone and acamprosate are both Category C |
| GI: Cirrhosis, gastritis, hepatitis, pancreatitis. 2× ↑ progression to cirrhosis in pts w/ Hep C (Am J Gastroenterol 2002;97:1807). |
| Social: ↑ domestic violence, sexual assault, use of firearms (in particular suicide), drunk driving (1 US death every 53 minutes), legal consequences (custody of children, employment termination, loss of housing, and incarceration), and ↓ work productivity. |
Evaluation
Screening: Single Item Screening Question: “How many times in the past year have you had (5 for men, 4 for women) or more drinks in a day?” >1 episode is ⊕ for unhealthy EtOH use; 82% sensitive, 79% specific for risky drinking (JGIM 2009;24:783)
AUDIT-C: (1) How often drink containing alcohol? (2) How many drinks on a typical day? (3) How often >6 drinks at once?
History: Quantify drinking, reasons for drinking, screen for comorbid psych conditions (e.g., depression, trauma hx); sleep disturbances & erectile dysfunction assoc w/ EtOH use; review meds that interact assoc w/ EtOH (sedatives, APAP); assess safety (minors/elders dependent on pt, risk of driving, work hazards); assess readiness to change (“On a scale of 0–10, w/ 10 being completely committed to change, how ready are you to stop drinking? Why did you pick 7?”)
(NEJM 2013;368:365)
Family history: ~50% of susceptibility to alcohol use disorder thought to be genetic, prevalence higher w/ affected 1st-degree relative (Curr Psych Rep 2009;11:364) AUD history: Prior tx, other substance use, attempts to quit, duration of episodes of sobriety, environment where drinking occurs, relapse triggers, consequences Evaluation of other substance use and comorbid psych disease
Physical: Hepatomegaly, neuropathy, asterixis, stigmata of chronic liver disease (spider angiomas, caput medusa, splenomegaly, palmar erythema, ascites, jaundice)
Withdrawal Sx’s: Diaphoresis, tachycardia, tremors, nausea, hallucinations, seizures, psychoses, anxiety; sx present <6 h after EtOH cessation; delirium tremens develops 48–96 h after cessation; withdrawal unlikely >5 d after cessation
Labs: AST: ALT >2 typically, CBC w/ macrocytosis; EtOH level, tox screen
Management (Ann Int Med 2016;164;NEJM 2005;352:596)
| Psychosocial Interventions |
| Brief interventions: Counseling (~10–15 min) w/ motivational interview (see “Patient Counseling”) ↓ risky drinking; consider involving family members; arrange f/u; if pt unwilling to stop, consider harm reduction (e.g., to cut back or not to drink & drive) Show concern, give specific feedback: “You are drinking more than is medically safe & most adults drink less than you; my advice is to quit or drink w/in healthy limits; EtOH likely causes your GERD/HTN/fatigue”
Engage: “What do you think about your drinking? How do you feel about cutting back?” Empathy: “Quitting EtOH is difficult for many people” Options: “A number of tx are available including medications and counseling” Anticipate: “What situations prompt you to drink? How can you avoid them?” Follow-up: “Let’s schedule a f/u visit to track your progress” Counselling: (findtreatment.samhsa.gov) Cognitive behavioral tx: Skills to avoid situations that cause heavy drinking Motivational enhancement tx: Resolve ambivalence, elicit pt goals Peer support/mutual help: Not formal treatment but can be very effective. Correlation btwn participation and abstinence; No evidence for mandating. Alcoholics Anonymous (12- step). SMART Recovery (nonreligious alt to AA) |
| Pharmacotherapy (AFP 2016;93:457;2016; 94:155; JAMA 2014;311:1889; NEJM 2005;352:596) |
| General principles: Safe, easy to prescribe & underutilized; naltrexone and acamprosate equal in efficacy with different side-effect profile; typical course 3–12 mo; medication combinations do not ↑ efficacy (JAMA 2006;295:2003); medication + brief counseling by PCP as effective as added behavioral specialist tx (JAMA 2006;295:2003); standard of care includes ongoing
counseling Acamprosate: ~50% ↑ in abstinence vs. placebo (Addiction 2004;99:811); |
| recommended for maintenance of abstinence, ideally abstinent at tx initiation; halve dosage in renal insufficiency (CrCl 30–50 mL/min) Naltrexone: May ↓ craving for EtOH, ↓ frequency & intensity of drinking; useful for controlled consumption; ? effect on abstinence. Daily PO or
monthly naltrexone IM. IM (380 mg) ↓ event rate of heavy drinking in pts w/ AUD by 25% compared to placebo (JAMA 2005;293:1617); contraindicated in pts using or who may take opioids. Use w/ caution if LFTs >5× normal; pts should be opioid-free for >7 d & carry wallet card alerting med personnel; GI s/e early in tx, limited risk of hepatotoxicity at standard dose (NEJM 2008;359:715) Disulfiram: (RCTs do not support efficacy unless dosing is observed, 3rd- line AHRQ); aldehyde dehydrogenase inhibitor leads to ↑ acetaldehyde → vomiting w/ EtOH consumption; efficacious/best suited for supervised administration; s/e include risk of fulminant hepatitis, neuropathy, psychosis; contraindicated in CAD, metronidazole use, or rubber allergy Topiramate: Gradually uptitrated over several weeks from 25 mg BID up to max dose 150 mg BID; should be tapered off to avoid rebound during discontinuation Supportive treatment: Thiamine 100 mg PO QD, folic acid 1 mg PO QD, MVI |
Outpatient detoxification: Requires close supervision by provider, may be safe & effective even in heavy drinkers (AFP 2013;88:589; Alcohol 2000;35:66)
Inpatient detoxification: H/o seizure, detoxes, psych disease, BAL
>150 mg/dL, acute illness, unstable Y sx, med comorbidities, >60 y of age, use of other illicits, no sober/responsible adult to care for pt, lack of a safe home environment
Harm reduction: Counseling about driving, firearms, mixing meds w/ EtOH
Treat comorbid psychiatric conditions: Many affective sx abate w/ abstinence; however, may use SSRI to treat associated depression
(JAMA 2004;291:1887)
Referral: Consider addiction medicine physician/psychiatrist, esp if complex hx
Patient information: Rethinking Drinking: rethinkingdrinking.niaaa.nih.gov; NIAAA AUD Treatment: pubs.niaaa.nih.gov/publications/Treatment/treatment.htm
| OPIOID USE DISORDER |
Background (samhsa.gov/atod/opioids; NEJM 2015;372:241; 2016;374:154; 1253)
Epidemiology: Approximately 4 mil people in US use prescription (Rx) opioids for non–medical use each month; >80% new heroin users start w/ Rx opioids (Drug Alcohol Deped 2013;132:95); overdose deaths are the #1
cause of accidental death in US (3× ↑ since 1999) (MMWR Morb Mortal Weekl Rep 2016;65:1445)
Opioid use disorder (DSM-5): Primary, chronic, treatable, brain
disease arising from genetic risk + environmental exposures; defined by DSM-5 as pattern of opioid use leading to impairment/distress manifested by ≥2 in 12-mo period: (1) Failure to fulfill roles, (2) Use in risky situations, (3) Persistent desire/unsuccessful efforts to cut down,
(4) Use despite known ⊖ impact on med/psych problems, (5) E/o tolerance, (6) Cravings, (7) ↑ doses or ↑ period than intended, (8) ↑ time finding, using, recovering, (9) E/o withdrawal, (10) Abandonment of other pleasurable activities, (11) Use despite adverse effects on social/interpersonal fxn
Chronic disease model: Tx adherence & relapse rates similar to other chronic dz (JAMA 2000;284:1689); Stigma significant barrier to tx. Language counts: In RCT, “abuse” vs “SUD” assoc w/ judgments of culpability & that pts deserve punishment (Int J Drug Policy 2010;21:202)
Consequences: Medical: Respiratory depression, rhabdomyolysis, compartment syndrome, ↑ risk of HIV, hepatitis, osteomyelitis, endocarditis, septic arthritis, skin/soft tissue infections; Social: Incarceration, economic insecurity, homelessness, high-risk sexual behavior, trauma, family instability; loss of child custody (J Food Drug Anal 2013;21:S73)
Evaluation (J Addict Med 2015;9:358; NEJM 2016;375:357)
Screening: No USPSTF-recommended screen. Quick Screen: “How many times in the past year have you used an illegal drug or prescription medication for nonmedical reasons?” ≥1 100% sens, 73.5% spec (Arch Intern Med 2010;170:1155)
History: Concurrent SUDs, esp other CNS depressants inc EtOH, benzos, sedatives; Amount used daily/weekly, route of use, last use, h/o medical complications, OD hx, tx hx (specific medications, dosages, setting of care), prior periods of sobriety, consequences of use, patient’s perception of +/− aspects of use
Exam: S/Sx of intoxication (slurred speech, sedation, miosis, injection sites, recent trauma) withdrawal (rhinorrhea, lacrimation, yawning, muscle twitching, hyperactive BS, piloerection, myadriasis), e/o IDU
(track marks at peripheral venous and subQ sites inc. b/t fingers, legs, neck, under nails, axillae, breast, penis)
Labs: CBC, BMP, LFTs, HIV, syphilis, HepA/B/C serologies, TB skin test, pregnancy if appropriate, UTox (absence of opioid metabolites NOT contraindication to tx)
Meds: Review Prescription Monitoring Program
Management (J Addict Med 2015;9:358; JAMA 2016;316:338; 2017;317:967; NEJM
2005;352:596; 2016;375:357; pcssmat.org)
Counseling: (findtreatment.samhsa.gov)
Cognitive behavioral tx: Skills to avoid situations that cause use Motivational enhancement: Resolve ambivalence, elicit pt goals Peer support/mutual help: Not formal treatment but can be very effective; Correlation btwn participation and abstinence; Alcoholics Anonymous (12-step). SMART Recovery (nonreligious alt to AA)
Withdrawal management: “Detoxification” alone is not treatment (relapse risk >80% with high mortality due to loss of tolerance) (Arch Gen Psych 2011;68:1238; BMJ 2003;326:959); If pt insists on detoxification alone, (1) Counsel re: risk of death, (2) Rx naloxone, and (3) Est firm f/u plan; Methadone, buprenorphine superior to symptomatic treatment with a2- adrenergic agonists (Cochrane Database Syst Rev 2016;3:CD002024)
Opioid agonists: Buprenorphine & methadone ↓ mortality ~50%, ↑ treatment retention, ↓ HIV, HCV, and criminality (Am J Public Health 2013;103:917); buprenorphine and methadone similar in efficacy when adequately dosed; methadone may ↑ pt retention (Cochrane Database Syst Rev 2014;6: CD002207; 2016;9:CD011117); Treatment goals: ↓ withdrawal sx, ↓ cravings, ↓ illicit opioid effects, and ↑ QOL; maintenance tx, not taper is goal; longer duration of tx assoc w/ better outcomes
General principles: Primary care med mgmt noninferior to med mgmt + counseling; frequent visits early on to maintain relationship, facilitate psychosocial support, monitor for relapse, ensure adherence, detect potential diversion; if pt struggling w/ cravings, illicit use, intensify treatment (NOT discontinuation) w/ ↑ visit frequency, medication titration, consider referrals; toxicology offers objective data on treatment response, false positive and false negative can occur; requires pt consent Methadone: Full opioid agonist; only available at Opioid Treatment Programs
(OTPs), highly structured programs w/ daily dosing; initial dose 30 mg/d, uptitration takes wk–mo w/ ↑ risk of OD in first 2 wk; more effective at high doses (60–100 mg) (Cochrane Database Syst Rev 2003;3:CD002208); ↑ QTc, esp at high doses → baseline ECG before initiation, repeat w/ dose ↑ or additional QT prolonging meds; d/c or ↓ dose at >500 ms, consider change to buprenorphine at 450– 500 ms (J Pain 2014;15:321); multiple CYP450 interactions, especially ARVs Buprenorphine: Partial opioid agonist ∴ ceiling effect on respiratory depression ↓ OD risk; strong receptor affinity ∴ displaces most full opioid agonists, can precipitate withdrawal; Eligible prescribers: Licensed MD w/ 8 h “waiver training” or PA/NP w/ 24-h training (www.samhsa.gov) and DEA registration; office-based treatment = more patient flexibility vs. methadone; initiation in acute setting leads to successful remission (JAMA 2015;313:1636); buprenorphine + naloxone formulation prevents IV abuse because naloxone is poorly absorbed orally with proper use Induction: 4-mg initial dose → wait 1–4 h → eval for withdrawal s/s, if + addn’l 4 mg → wait 3–6 h → addn’l 4 mg PRN; daily dose generally 8–24 mg, recent studies show continued benefit at doses up to 32 mg (Addiction 2014;109:79); must induce while pt in moderate withdrawal to avoid precipitating withdrawal; no short- acting opioids ×12 h prior. If on methadone, taper to 20–30 mg daily ×1 wk → initial buprenorphine dose 36–72 h after last dose (J Gen Intern Med 2009;24:226) Antagonist therapy w/ extended-release naltrexone: No head-to-head trials vs. agonist treatment; oral naltrexone not effective for OUD (Cochrane Database Syst Rev 2011;16:CD001333); consider in pts w/ occupational restrictions against agonist therapy, pending incarceration, younger w/ new dx, or in remission on agonist therapy desiring antagonist therapy; improves treatment retention, opioid abstinence vs. placebo (Arch Gen Psychiatry 2012;69:973; Lancet 2011;377:1506); ↓ relapse in recently incarcerated patients (NEJM 2016;374:1232); ↑ risk of death at treatment cessation (Drug Alcohol Rev 2007;26:405); before initiation, pt must be 7–10 d opioid-free w/o s/sx withdrawal.
OD death prevention: Naloxone: Potent, short-acting (duration 30–90 min) antagonist. Lay/community administration assoc w/ ↑ chances of revival (Inj Epidemiol 2015;2:10); available in 4-mg intranasal, 0.4-mg IM, and
0.4-mg Evzio IM/SubQ auto-injector formulations; not a controlled substance; can be Rx’d by any prescriber, and in many states obtained w/o Rx; should be Rx to all pts w/ OUD; counsel patients & family to:
(1) Assess for OD: respiratory depression, cyanosis, unresponsiveness; (2) Call 911; (3) Give rescue breaths; (4) Administer naloxone; (5) Repeat; may need >1 dose; give q2–3 min and stay w/ patient until care escalation; discourage other revival efforts, i.e., salt water injections, milk, cold water baths
Psychosocial support: Individual or group counseling emphasizing relapse prevention, recovery support, self-care, and coping skills required for most OTP programs and encouraged w/ buprenorphine, however no e/o better outcomes than tx alone (J Addict Med 2016;10:283) (see “Psychosocial Support”)
Patient information: samhsa.gov/medication-assisted- treatment/physician-program-data/treatment-physician-locator; JAMA 2013;309:2055
| OTHER DRUG USE DISORDERS |
CANNABIS
Epidemiology: 13.5% past-year use in US; ↑ prevalence in young adults; ♂ > ♀ (2:1)
Cannabis use disorder: 1.5% US prev; ~9% of users (NEJM 2014;370:2219); defined as persistent use leading to clinically significant impairment or distress as manifest by 2 (or more) of the following w/in a 12-mo period (DSM-5): (1) ↑ doses or ↑ period than intended, (2) persistent desire/unsuccessful efforts to cut down, (3) ↑ time finding, using, recovering, (4) Cravings, (5) Failure to fulfill work/school/home roles, (6) Cravings, (7) ↓ social/work/recreational activities d/t cannabis use, (8) recurrent use when physically hazardous, (9) Use despite known ⊖ impact on physical/psych problems, (10) Tolerance (↑ cannabis for desired effect; ↓ effect w/ same amt of cannabis), (11) Withdrawal
Routes of use & pharmacology: Inhalation most common route;
hashish is a resin cake that can be ingested/smoked; tinctures and oils widely used; 50% of THC in cannabis is inhaled, THC absorbed thru lungs & reaches brain through bloodstream in min; rapid onset (s–min) & ↓ duration (2–4 h); bioavailability = 25–30% of smoked amt due to 1st-pass metabolism in liver; onset delayed (0.5–2 h) & ↑ duration (4– 12 h) w/ ingestion (Brit J Clin Psychol 2001;178:101)
Intoxication: Impaired motor coordination, time perception, judgement; anxiety, conjunctival injection, ↑ appetite, dry mouth, ↑ HR, ↑ RR, HTN, orthostatic HoTN, nystagmus, ataxia, slurred speech (Addiction
1996;91:1585; Brit J Clin Psychol 2001;178:101)
Withdrawal syndrome: ≥ daily dose of 180 mg of THC (1–2 joints) × 11–21 d to produce W/D sx restlessness, insomnia, anxiety, increased aggression, anorexia, muscle tremor, and autonomic effects Complications: Include periodontal disease, memory impairment, ↑ psychosis risk
Hyperemesis syndrome: Severe emesis in chronic cannabis users 2/2 downregulation of CNS cannabinoid receptors & upregulation of gut cannabinoid receptors; typically relieved by hot showers; supportive mgmt w/ IVF, antiemetics (ondansetron, metoclopramide), benzos, & cannabis cessation (Hosp Pharm 2013;48:650)
Management: No effective pharmacotherapy; CBT and motivational enhancement therapy effective (Drug Alcohol Depend 2014;132:185; Cochrane Database Syst Rev 2016;5:CD005336)
Toxicology: THC detected in urine × h–12 d (occasional user) & up to 1 mo (chronic user) (J Anal Toxicol 1999;23:323)
| Patient Evaluation for Medical Marijuana (Adapted from JAMA 2015;313:2474) |
| General principles: Laws vary by state. Physicians should counsel patients on risks & benefits and document patient was advised not to drive/engage in dangerous activities. |
| (1) Medical condition: Patient should have Dx that RCT suggest may respond to marijuana Moderate quality evidence in support of marijuana use: Chronic pain, spasticity. Low-quality evidence: N/V from chemotherapy, cachexia from cancer/AIDS, sleep disorders, Tourette syndrome (JAMA 2015;313:2456; NEJM 2013;368:866). |
| (2) Symptoms refractory to pharmacotherapy: Patients sx unrelieved by conventional treatments or a trial of FDA-approved cannabinoid (dronabinol or nabilone) |
| (3) No SUD or psychiatric comorbidity |
SYNTHETIC CANNABINOIDS (K2, SPICE, KRONIC, ETC.)
Epidemiology: ↑ avail in US/Europe since 2000s, rising popularity as not detected in standard tox screens; ↑ toxicity cases reported annually to US poison control centers (thousands), mainly ♂ 20–30s y/o (J Pediatr 2013;163:213)
Routes of use & pharmacology: Hundreds of different compounds; mainly inhaled, but can be ingested or insufflated (i.e., snorted). Binds CB1/CB2 cannabinoid receptors similar to but more tightly than THC; onset of effect usually within minutes, lasts hours, length depending on
compound (NEJM 2015;373:103; Toxicology 2013; 44:360)
Intoxication: Tachycardia, conjunctival injection, N/V, HTN, ↑ appetite, nystagmus, ataxia, slurred speech, hallucinations, delirium, psychosis, agitation, seizure (Am J Med 2016;129:240; Curr Psychiatry Rep 2016;18:52) Withdrawal: Can occur as soon as 15 min after smoking in daily users; presents as headache, anxiety, insomnia, N/V, ↓ appetite, diaphoresis; severe w/d present with seizures, CV/respiratory risks (tachycardia, CP, palp, SOB) (Curr Psychiatry Rep 2016;18:52)
Complications: Cardiac: STEMI w/ clean coronary arteries, mechanism unclear, ? ↑ O2 supply-demand mismatch, vasoconstrictive effect (Pediatrics 2011;128:e1622). Renal: AKI, ATN, rhabdo (Am J Emerg Med 2016;34:121.e1; Clin J Am Soc Nephrol 2013; 8:523)
Management: Supportive w/ benzos & neuroleptics (esp quetiapine)
for agitation/anxiety/psychosis from intox or w/d (Curr Psychiatry Rep
2016;18:52)
Toxicology: Liquid chromatography & mass spec available for some compounds in reference laboratories, but not routinely used given time required for test & constant changes in chemical structures (Am J Med 2016;129:240)
HALLUCINOGENS
Epidemiology: ~4 mil people/y in US use hallucinogens; most common in adolescents/young adults; LSD most common w/ 23 mil US
lifetime users
Complications: Agitation can cause trauma, rhabdo → AKI Management: Mostly supportive, place in calm & quiet environment while intoxicated. Benzos = 1st-line for agitation, antipsychotics as adjunct (e.g., IV haloperidol), may need restraints if violent Toxicology: PCP detected in urine × 2–4 d, up to 1 wk in chronic users; LSD detected in urine × 2–5 d; otherwise, most standard tox screens do not detect hallucinogens
| Common Hallucinogens (Biol Psychiatry 2012; 72:871; Psychopharmacology 2012;223:1) | ||
| Drug (route) | Pharmacology | Intoxication |
| Dextromethorphan
Capsule, pill, liquid |
NMDA antagonist. Onset
~0.5–1 h, lasts up to 6 h |
Out-of-body sensation, ↑ HR, HTN, lethargy, mydriasis, agitation, vomiting. |
| LSD
Capsule, pill, liquid (added to blotter paper) |
Binds 5-HT2A receptors. Effect lasts 6–12 h. | Distortion of time, visual illusions, euphoria, depersonalization, synesthesia, tachycardia, HTN, mydriasis, piloerection, diaphoresis. |
| Mescaline
Prepared as tea |
Binds 5-HT2A & 5-HT2C
receptors. Onset ~ 45–60 min, lasts 4–8 h. |
Similar to LSD. Visual distortion, N/V, sympathomimetic sx. Legal use allowed by Native American Church members |
| PCP
Snorted, smoked, ingested, or injected. Most deaths due to trauma. |
NMDA antagonist. Effect lasts 4–6 h, or longer at higher doses. | Bizarre/violent behavior, nystagmus, amnesia, analgesia. Lower doses: Dissociation, sound/vision distortion. High doses: Severe agitation, violence, auditory hallucinations, catatonic stupor. |
| Psilocybin
Ingested fresh/dried |
Binds 5-HT2A. Effects last up to 6 h. | Similar to LSD. Nausea, vomiting, diarrhea. Serotonin syndrome. |
| Salvia
Leaves chewed (fresh)/smoked (dry) |
κ opioid agonist. Effect lasts 1–2 h if ingested, less when smoked. | Sensory distortion, synesthesia, sedation, euphoria, mild sympathomimetic sx. No deaths/severe toxicity reported |
COCAINE
Epidemiology: Used by 1.4% of US population aged 18–25; 6% of users meet criteria for cocaine use disorder; most common illicit drug assoc w/ ER visits
Pharmacology: 2 forms of same compound–base (smoked/injected) and salt (inhaled/injected); blocks reuptake of dopamine, norepinephrine, and serotonin in the central and peripheral nervous system; onset of effect usually in seconds if smoked, 30 min if delivered via mucous membrane (Biochem Pharmacol 2008;75:196)
Intoxication: Tachycardia, diaphoresis, nausea, mydriasis; alertness, euphoria → dysphoria, paranoia, psychotic syndromes with increasing doses or duration of use
Withdrawal: Depression, anxiety, fatigue, anhedonia; often initially intense “crash” with improvement in 1–2 wk
Complications:
CNS: ↑ risk hemorrhagic and ischemic stroke. No good evidence that cocaine causes seizures. (Drug Alcohol Depend 2013;133:795; Stroke 2016;47:918) HEENT: Snorting → nasal septum perforation, ulcers, chronic rhinitis (NEJM 2016;374:969) Cardiac: ↑ HR, BP, SVR via adrenergic activation, vasospasm → MI, ventricular arrhythmia.
Chronic use → LVH, cardiomyopathy/fibrosis (NEJM 2001;345:351) Pulmonary: Sx in up to 50% of users, e.g., cough, SOB, hemoptysis, asthma exacerbation; Direct lung injury (e.g., PTX, hemorrhage) often 2/2 additives such as levamisole; “Crack lung” is poorly understood acute pulmonary syndrome with fever, hypoxemia, respiratory failure, and diffuse, eosinophil-rich infiltrates (Clin Rev Allergy Immunol 2014;46:82) GI: Gastric ulcers, ischemic colitis
Renal: Rhabdomyolysis, renal infarction
Management, acute intoxication: Supportive care; benzodiazepines; Phentolamine for refractory HTN; Avoid β blockers acutely; nitroglycerin, ASA if c/f ACS; Na bicarb if QRS widened (rare) (NEJM 2001;345:351)
Treatment: Individual/group counseling, intensive outpatient/inpt
setting; best evidence for topiramate (✓ LFTs, Cr; hold in hepatic injury, dose reduce for poor renal fxn); start 25 mg QD, uptitrate weekly, max dose 150 mg BID for remission maintenance; disulfiram 250 mg daily + CBT shown to reduce use; some evidence for stimulant treatment, e.g., dextroamphetamine 30 mg QD (Arch Gen Psychiatry 2004;61:272; J Clin Psychopharmacol 2001;21:522; JAMA Psychiatry 2013;70:1338)
Toxicology: Detected in urine 2–15 d after use
BENZODIAZEPINES
Epidemiology: Commonly abused with EtOH, narcotics (AFP 2000;61:2121)
Pharmacology: ↑ binding of GABA to receptors, making GABA
signaling more efficacious
Intoxication sx: Memory impairment, disinhibition, psychomotor retardation, depression; effect may be amplified with other sedatives/EtOH and may be more pronounced in elderly Withdrawal sx: Anxiety, autonomic instability, insomnia, hypersensitivity; timeline to development of withdrawal symptoms related to half-life of benzodiazepine being abused
Management: To prevent withdrawal, taper daily dose by 10–25% every 2 wk; severe withdrawal should be managed as an inpatient; unclear whether switching short-acting to long-acting benzodiazepines improves success of treating withdrawal; no medication approved for treating benzodiazepine use disorders; psychotherapy and motivational interviewing may help (NEJM 2017;376:1147)
Toxicology: Not detected in standard drugs of abuse screen; benzodiazepine-specific urine screen may not detect clonazepam, lorazepam, midazolam, or alprazolam
| TOBACCO USE |
Background
Consequences: Tobacco use is the leading preventable cause of death in US; 50% of smokers will die due to their tobacco use, losing
10 y of life expectancy (BMJ 2004;328:1519; JAMA 2004;291:1238); smoking accounts for 49% of cancer-related deaths in US (JAMA Int Med 2014;175:1574); smoking is considered a chronic disease requiring longitudinal, coordinated care w/ behavioral & medical tx Epidemiology: 15% of US adults currently use tobacco (MMWR 2012;61:889); ♂ > ♀, Native American >Caucasian, African-American
>Hispanic, Asian; prevalence in pts w/ mental illness & SUD; tobacco contributes to health disparities w/ use & exposure among people w/ ↓ incomes & education (cdc.gov/tobacco; JAMA 2000;284:2606)
Quit attempts: 69% of US smokers want to quit, 52% attempt, only 6% succeed (MMWR 2011;60:1513); only 32% of pts who attempt to quit use any medications to help them do so
Good prognosis: Highly motivated, ready to quit, good self-efficacy, social support Poor prognosis: High nicotine dependence (≥20 cig/d, 1st cig <30 min after waking), Ψ comorbidity, substance use, high stress, living w/ other smokers
Benefits of quitting: Exist for pts of all ages/comorbidities (Public Health Service 2008)
Age <35: Quitting now → survival comparable to nonsmokers Age
<65: Quitting now → avg of 4 y of life gained
Prior MI: Quitting → 36% ↓ relative mortality, comparable to other 2° prevention Head & neck CA: Quitting → 40% ↓ relative mortality (NEJM 1993;328:159) 1 y after quitting → 50% ↓ in risk of CAD; 5 y after quitting → stroke risk normalized to risk of nonsmokers; 10 y after quitting → lung cancer risk normalized to nonsmoker
Evaluation (Ann Int Med 2016;164:ITC33)
70% of smokers see a provider each year; only 51% of these recall being advised to quit despite evidence that medical advice to quit ↑ chances of success (Prev Chronic Dis 2012;9:E130; Addiction 2012;107:1066)
Brief interventions can be delivered by provider in 3 min, based on 5As model
| 5As Model for Treating Tobacco Use and Dependence | |
| Ask | Identify & document use of tobacco (e.g., cigarettes, cigarillos, chewing tobacco, loose tobacco, pipe tobacco, hookah) routinely for every pt |
| Advise | Strongly advise every user to quit; individualize using pt’s current
health concerns, costs, or impact on their household & children “As your provider, I strongly recommend that you quit smoking” “Quitting smoking is the most important thing you can do to protect your health now & in the future” |
| Assess | “Are you ready to quit smoking in the next 30 d? I can help with this” |
| Assist | For those ready to quit, offer medication & counseling
For those not ready to quit, provide a motivational intervention |
| Arrange | F/u w/in 1 wk after quit attempt & at each visit for active smokers |
(US Public Health Service, AHRQ, ahrq.gov)
For those not ready to quit: Motivational interviewing, a specialized counseling technique that future quit attempts (see “Counseling Patients”)
Treatment (Am J Prev Med 2008;35:158; Public Health Service 2008; JAMA 2012;308:1573; 2014;311:193)
General approach: For pts ready to quit, combination of counseling & meds most effective tx (2.1 × more likely than brief intervention; 1.7
× more likely than counseling alone, 1.3 × more likely than meds alone (Cochrane Database Syst Rev 2012;5:CD001837); success rate for unassisted attempts is ~5%; abrupt smoking cessation more likely to result in long- term abstinence compared to taper (Ann Int Med 2016;165:742)
Counseling: Range of options; generally ↑ intensity, time, or number of sessions → ↑ likelihood of quitting; odds of quitting 2.3 × ↑ if counseling
>10 min (Public Health Service 2008); group, individual, & telephone counseling all effective, some evidence effective via text message (JAMA 2012;308:1573; Lancet 2011;378:49; Addiction 2009;103:478); quitlines (smoker offered a series of scheduled telephone calls by trained counselor to guide through quitting process) available nationwide
Behavioral: Smoking “bans” in home & car assoc w/ ↑ quit attempts & abstinence, as well as ↓ 2nd-hand smoke exposure (Nicotine Tob Res
2009;11:1131)
Pharmacotherapy: All smokers trying to quit should be offered medication, except when contraindicated (n.b. evidence insufficient in light smokers, smokeless tobacco users, pregnant smokers)
Nicotine replacement therapy (NRT): Multiple forms available (below); contraindications include caution in immediate post-MI period
(<2 wk), pts w/ serious arrhythmia or UA; however, NRT is safe in pts w/ stable CAD; unclear whether combination of short-acting (i.e., gum) with long-acting (i.e., patch) ↑ success rates; efficacy of nicotine patch beyond 6 m unclear (JAMA Int Med 2015;175:504)
| Nicotine Replacement Therapy (JAMA 2012;308:1573) | ||
| Form | Sample Rx | Notes |
| Patch | Dosing: 21 mg/24 h × 4 wk, then 14 mg/24 h × 2 wk, then 7 mg/24 h × 2–6 wk Duration: 8–12 wk | Slow onset, steady levels for 16 or 24 h
Available OTC. S/e: Skin irritation, insomnia, vivid dreams Efficacy: RR vs. placebo: 1.66 |
| Gum | Dosing: ≥25 cig/d → 4 mg/piece; >25 cig/d = 2 mg/piece, use q1–2 h × 6 wk, max 24 pieces/d Duration: 12 wk | Rapid onset: 20–30 min Available OTC
S/e: Mouth soreness, dyspepsia, hiccups, jaw ache Efficacy: RR vs. placebo: 1.43 |
| Inhaler | Dosing: 6–16 cartridges (4 mg ea)/d
Duration: Up to 6 mo |
Rapid onset: 20–30 min
S/e: Local irritation in mouth, throat Efficacy: RR vs. placebo: 1.90 |
| Lozenge | Dosing: 1st cig after waking:
>30 min → 4 mg/piece <30 min → 2 mg/piece 9–20 pieces/d Duration: 12 wk |
Rapid onset: 20–30 min Available OTC
S/e: Nausea, hiccups, heartburn, HA, coughing Efficacy: RR vs. placebo: 2.00 |
| Nasal Spray | Dosing: 1–2 sprays (0.5 mg) ea;
nostril/h, min 8 doses/d, max 40 doses/d Duration: 3–6 mo |
Most rapid onset: 5–10 min
S/e: Nasal irritation, congestion, highest dependence potential of NRT Efficacy: RR vs. placebo: 2.02 |
Bupropion SR: Works by ↑ DA levels; independent of antidepressant effect; delays wt gain assoc w/ quitting; 1.69 RR of quitting success vs. placebo
Dosing: Start 1–2 wk before quit date; 150 mg QAM × 3 d, then 150 mg BID
Duration: 7 wk–6 mo; safely used for years to treat depression
S/e: Insomnia, dry mouth, ↓ seizure threshold (0.1% sz risk); avoid in pts w/ epilepsy, eating d/o, using another bupropion form or recent (<2 wk) MAOI use; monitor pts w/ psych hx for exacerbations or ↑
SI
Varenicline: Selective partial α4β2 nicotinic receptor agonist, relieves withdrawal & blocks smoking reinforcement; varenicline + NRT ↑ abstinence at 24 wk compared to varenicline alone (49% vs. 33%) (JAMA 2014;312:155); varenicline monotherapy as effective as nicotine patch (JAMA 2016;315:371); combination of varenicline and bupropion did not increase cessation rates (JAMA 2014;311:155)
Dosing: Start 1 wk before quit date; 0.5 mg QD × 3 d, then 0.5 mg BID × 4 d, then 1 mg BID; Duration: 3–6 mo; safety established for up to 1 y S/e: Nausea (take w/ food), insomnia/vivid dreams; use cautiously in pts w/ > stage 3 CKD; varenicline did not ↑ risk of depression, suicidal ideation, or suicide compared to placebo (BMJ 2015;350:h1109)
Combined pharmacotherapy: ↑ effective than monotherapy; approved combos:
- Nicotine patch & PRN (gum, nasal spray, or inhaler); RR patch alone 1.3–1.9
- Patch + bupropion SR (RR vs. patch alone: 3)
2nd-line agents: (not FDA-approved for smoking cessation); Nortriptyline: 75–100 mg QD, start 10–28 d before quit, 6 wk–6 mo, RR vs. placebo 2.03; s/e: Dry mouth, sedation, lightheadedness; avoid if hx arrhythmia, MAOI use; Clonidine: Initial 0.10 mg PO BID or 0.10 mg/d patch, start 1–2 d before/on quit date; s/e: Dry mouth, sedation, ↓ BP Electronic cigarettes: Aerosolize a solvent containing nicotine + flavoring; few randomized trials to assess efficacy in smoking cessation; contain carcinogens such as formaldehyde; meta-analysis shows use of e-cigarettes as a smoking cessation was less successful compared to other forms of nicotine replacement or no cessation aid
(NEJM 2016;374:2172; 2016;375:1372)
Complications of quitting
Wt gain: Most smokers experience modest (≤10 lb) wt ↑ after quitting; bupropion & NRT may delay wt gain; counsel re: diet/exercise (Am J Prev Med 2008;35:158) Drug interaction: Tobacco smoke (but not NRT) induces cytochrome P450, quitting can → supratherapeutic drug levels (e.g., theophylline, fluvoxamine, olanzapine, or clozapine)
Relapse counseling: For those recently quit: relapse is common; best strategy is encouraging use of evidence-based tx w/ each quit attempt Patient resources: Smokefree.gov, 1-800-QUIT-NOW