Substance Use Disorders: What Can We Do to Help Break the Cycle of Addiction

Transcription

1 Handout for the Neuroscience Education Institute (NEI) online activity: Substance Use Disorders: What Can We Do to Help Break the Cycle of Addiction

2 Learning Objectives Identify patients who are dependent on or at risk of becoming dependent on substances of abuse using evidence-based screening tools Provide preventive counseling and brief interventions for patients who are at risk of becoming addicted/dependent Implement evidence-based management strategies for individuals with substance use disorders Monitor improvement and address treatment adherence for patients with substance use disorders

3 Pretest Question 1 A 73-year-old man is asked some basic screening questions about alcohol use. The patient states that he drinks 1 mixed drink (containing a single 1-ounce shot) each night. How would you categorize this patient's drinking behavior? A. Low-risk drinking B. At-risk drinking C. Alcohol use disorder

4 Pretest Question 2 A 38-year-old man who developed opioid dependence after back surgery is encouraged by his practitioner to attempt to stop the opioid. They decide that naltrexone along with appropriate non-pharmacological services is the best option. Which of the following is true? A. The patient should initiate naltrexone before stopping his current opioid B. The patient should initiate naltrexone while down-titrating his current opioid C. The patient should be abstinent from his current opioid before beginning naltrexone treatment

5 Risk Factors for Addiction Experimentation Abuse Addiction Regular drug use Dependence Early exposure, social deprivation, stress Drug characteristics Genetics, mental illness, prenatal exposure psychosocial neurobiological Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press; Volkow ND et al. PNAS 2011;108(37):

6 Site Neurotransmitter Reward and Reinforcement: Many Neurotransmitters, but Dopamine is Key Stimulant Opioid Alcohol Nicotine THC DA X X X X X GABA X X X Opioid X X X X CB X X X ACh X NA X X X X X AMYG X X X VTA X X X X Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press.

7 % of Peak Dopamine: Not Just How Much, But How Fast DA uptake (IV cocaine) Self-reported high Time Volkow ND et al. PNAS 2011;108(37):

8 The Reactive Reward System

9 The Reflective Reward System

10 Progression to Compulsive Drug Use: Dysregulation of Reward Circuits

11 Why is Relapse so Common? Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press.

12 Treating the Real-World Patient: Comorbid Psychiatric Disorders Comorbidity is the norm Increased risk of suicide and impulsive aggression How do you treat? Ideal: integrated treatment Depending on severity, sequential treatment may be necessary Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press.

13 Treating the Real-World Patient: Comorbid Psychiatric Disorders SUD first Adherence to psychiatric medication is generally better Psychiatric disorder first May be necessary if symptoms are severe Can differentiate between substanceinduced and other symptoms Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press.

14 Treating the Real-World Patient: Comorbid Psychiatric Disorders When does an SUD affect medication selection? Avoid benzodiazepines in patients abusing alcohol Avoid QTc-prolonging agents in patients abusing stimulants Avoid TCAs (risk of seizure) Be aware of drug metabolism (i.e., via CYP450 1A2) in patients who smoke Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press.

15 Alcohol Use Disorder Screening and Management

16 Patterns of Addiction by Drug: Alcohol profound craving anticipation/ preoccupation compulsivity abstinence profound dysphoria and physical and emotional pain binge/ intoxication tolerance to intoxication Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press; Koob GF, Le Moal M. Annu Rev Psychol 2008;59:29-53.

17 Recommended Drinking Limits (NIAAA) Men<65 Men>65 and Women Daily Weekly

18 Standard Drink A standard drink contains approximately 14 grams (0.6 fluid ounces, 1.2 tablespoons) of pure alcohol That is: 5 oz. of table wine 12 oz. of beer 1.5 oz. of hard alcohol

19 Categorizing Drinking Behavior Abstinent or low-risk Drinks less than NIAAA limits At-risk Harmful Dependent Chronic dependent Drinks more than NIAAA limits 12 or more times per year Drinks more than NIAAA limits monthly to daily No disability No disability Limited disability Drinks 6 10 drinks/day every or nearly every day Mild to moderate disability Drinks 10 or more drinks/day every or nearly every day Moderate to severe disability Willenbring et al. Am Fam Physician 2009;80(1):44-50.

20 Screening Methods Written self-report prior to interview AUDIT (10 questions) CAGE (4 questions) During clinical interview, just ask: "Do you sometimes drink wine, beer, or other alcoholic beverages?" If yes: "How many days in the past year have you had X or more drinks?"* (5 for men, 4 for women) *It may help to show your patients what a standard drink is.

21 Management for Patients With Alcohol Use Problems Cleary state your conclusion and recommendation: At-Risk Drinking "You are drinking more than is medically safe. I strongly recommend that you cut down (or quit)." If No: Restate concern about health Ask about major barriers to change Reaffirm your willingness to help when patient is ready Alcohol Use Disorder "I believe that you have an alcohol use disorder. I strongly recommend that you quit drinking, and I'm willing to help." "Are you willing to consider making changes in your drinking?" Willenbring et al. Am Fam Physician 2009;80(1):44-50;

22 Management for Patients With Alcohol Use Problems If the patient is ready to make a change: At-Risk Drinking Help set a goal and a plan: What steps the patient will take How drinking will be tracked How the patient will manage high-risk situations Who might be willing to help Alcohol Use Disorder Help set a goal (abstinence) Assess need for inpatient treatment Recommend mutual help group Prescribe pharmacological treatment Engage significant others Willenbring et al. Am Fam Physician 2009;80(1):44-50;

23 Follow-up: At Each Visit, Assess if the Patient was Able to Meet and Sustain Goals If No Acknowledge that change is difficult Support any positive change and address barriers to reaching the goal Renegotiate the goal and plan; consider a trial of abstinence Consider engaging significant others Reassess the diagnosis if the patient is unable to either cut down or abstain If Yes Reinforce and support continued adherence to recommendations Renegotiate drinking goals as indicated (e.g., if the medical condition changes or if an abstaining patient wishes to resume drinking) Encourage patient to return if unable to maintain adherence Rescreen at least annually

24 Psychosocial Treatment for Alcohol Use Disorder CBT MET Behavioral therapy IPT Family therapy Selfhelp/ 12-Step Alcohol X X X X X Opioid X X X X Nicotine X X X Stimulant X X X Marijuana X X CBT: cognitive behavioral therapy. MET: motivational enhancement therapy. Behavioral therapy: contingency management, community reinforcement, cue exposure and relaxation, aversion therapy. IPT: interpersonal therapy. Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press.

25 Pharmacological Treatment for Alcohol Use Disorder TCA? SNRI? topiramate comorbid depression naltrexone acamprosate disulfiram second line first line Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press.

26 Acamprosate Increases GABA, decreases glutamate For patients who have achieved abstinence Dosing: 1998 mg/day in 3 doses (>60 kg); 1332 mg/day in 2 doses (<60 kg) No known interactions with psychotropic medications Most common side effect: diarrhea No sedation or weight gain; generally well tolerated Contraindicated in cases of severe kidney impairment Dosing schedule may affect adherence Patients should continue treatment even if relapse occurs but should disclose any new drinking Stahl SM. Stahl's Essential Psychopharmacology: The Prescriber's Guide. 4th ed

27 Naltrexone Mu opioid receptor antagonist For patients who have achieved abstinence, are trying to achieve abstinence, or are trying to reduce heavy drinking Dosing: 50 mg/day (oral); 380 mg/4 weeks (injection) Can block effects of opioid-containing medications Side effects: nausea, vomiting, site reactions (injection) Hepatocellular injury may occur at excessive doses Contraindicated in acute hepatitis or liver failure and in patients currently dependent on or taking any opioid or in acute opiate withdrawal Individuals who abstain for several days prior to initiating treatment may have better outcomes May be preferred treatment if goal is reduced-risk drinking Adherence is greatly increased with the injectable formulation Stahl SM. Stahl's Essential Psychopharmacology: The Prescriber's Guide. 4th ed

28 Disulfiram Irreversible inhibitor of aldehyde dehydrogenase Interaction with alcohol leads to hypotension, flushing, nausea, vomiting; can be toxic For patients who have achieved abstinence Dosing: mg/day, 1-year duration Common side effects: metallic taste, dermatitis, sedation Patient adherence is necessary for benefits Needs monitoring (spouse, relative) Reaction may occur for up to 2 weeks after disulfiram is stopped Kenna GA. Am J Health-Syst Pharm 2004; Castro LA et al. Rev Bras Psiquiatr 2004.

29 Topiramate Inhibits glutamate release and potentiates GABA activity; also a carbonic anhydrase inhibitor May be useful for patients who have achieved abstinence, are trying to achieve abstinence, or are trying to reduce heavy drinking Dosing: up to 300 mg/day; requires slow up-titration to reduce side effects Side effects include sedation, nausea, weight loss Can cause metabolic acidosis or kidney stones Might be useful as an adjunctive agent Johnson et al. JAMA 2007;298(14): ; Johnson et al. Lancet 2003;361(9370):

30 Alcohol Withdrawal Mild to Moderate Tremor Elevated pulse rate and blood pressure Sweating Agitation, nervousness Sleeplessness Anxiety Depression Severe Hallucinations Psychotic symptoms Delirium tremens Seizures Extremely high alcohol intake Outpatient Supportive care Repletion of nutrients Benzodiazepines (abuse liability) Other: carbamazepine, valproate, topiramate Inpatient Soyka et al. World J Biol Psychiatry 2008;9(1):6-23.

31 Reduced-Risk Drinking May be best for patients with less severe drinking problem Set clear drinking parameters and ask patient to keep a drinking diary Consider adjunct medication Contraindications Condition exacerbated by alcohol Use of agents contraindicated with alcohol (disulfiram) History of failed attempts with reduced-risk drinking Plan of becoming pregnant; breastfeeding History of severe alcohol withdrawal symptoms Ambrogne. J Subst Abuse Treatment 2002;22(1):45-53.

32 Opioid Use Disorder Screening and Management

33 Patterns of Addiction by Drug: Opioids profound craving anticipation/ preoccupation compulsivity abstinence profound dysphoria and physical and emotional pain binge/ intoxication tolerance to intoxication Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press; Koob GF, Le Moal M. Annu Rev Psychol 2008;59:29-53.

34 Screening for Opioid Abuse Warning Signs Vague history Poor rapport Lost/stolen meds Early renewal request Urgent calls Doctor shopping No relief with opioids Other drug/alcohol abuse Intoxication Constricted pupils Slurred speech Itching Euphoria Agitation Dry mouth Drowsiness Poor judgment Self-report: Current Opioid Misuse Measure, Opioid Risk Tool Comprehensive: Drug Abuse Screening Test, CAGE-AID, UNCOPE Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press. Copyright 2011 Neuroscience Education Institute. All rights reserved. Withdrawal Dysphoric mood Irritability, anxiety Nausea, vomiting Muscle aches, weakness Runny nose, sneezing Dilated pupils Goose bumps, chills Sweating Diarrhea Yawning Fever Insomnia

35 Psychosocial Treatment for Opioid Use Disorder CBT MET Behavioral therapy IPT Family therapy Selfhelp/ 12-Step Alcohol X X X X X Opioid X X X X Nicotine X X X Stimulant X X X Marijuana X X CBT: cognitive behavioral therapy. MET: motivational enhancement therapy. Behavioral therapy: contingency management, community reinforcement, cue exposure and relaxation, aversion therapy. IPT: interpersonal therapy. Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press; Veilleux JC et al. Clin Psychol Rev 2010;30:

36 Pharmacological Treatments for Opioid Use Disorder sedative hypnotic diphenhydramine sedating antidepressants hydroxyzine withdrawal second line methadone clonidine naltrexone buprenorphine methadone buprenorphine naltrexone withdrawal first line first line Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press.

37 Treatment Settings Inpatient Outpatient clinic/office Outpatient opioid treatment program Drug-free program Overdose X Withdrawal methadone, buprenorphine, naltrexone, clonidine buprenorphine,* naltrexone, clonidine methadone, buprenorphine -- Maintenance -- X X X Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press; Veilleux JC et al. Clin Psychol Rev 2010;30: *requires DEA Data 2000 waiver

38 Methadone Mu opioid receptor agonist Blocks rewarding effects of opioids and suppresses withdrawal symptoms Regulated programs Most effective for suppressing use in the most highly dependent patients Common side effects: constipation, sweating, sexual dysfunction Dodrill CL et al. Am J Psychiatry 2011;168(5):

39 Partial opioid agonist Buprenorphine "Take-home" medication: flexible dosing, ease of discontinuation, low abuse potential Less stigma, better adherence than methadone Best for patients with mild to moderate physical withdrawal Patient must experience at least mild withdrawal symptoms before beginning treatment Common side effects: oral hypoesthesia, glossodynia, headache, constipation Requires special training (DEA DATA 2000 waiver) to prescribe Dodrill CL et al. Am J Psychiatry 2011;168(5):

40 Maintenance (based on patient's needs) Stabilization (up to 2 months) Initiation (7 days) Buprenorphine/Naloxone Treatment Stages Stage Typical Dosage Visits Goal After achieving mild withdrawal state: Day 1: 8 mg B/2 mg N Day 2: add'l 4 mg/1 mg up to 16 mg/4 mg Days 3 7: increase in units of 4 mg/1 mg until withdrawal symptoms cease; maximum 32 mg/8 mg Generally ranges from 8 mg/2 mg to 24 mg/6 mg Dose as determined during stabilization At least 2 hours of observation with initial dose, then 1 2 visits in first week 1/week Biweekly or monthly Dodrill CL et al. Am J Psychiatry 2011;168(5): Achieve lowest dose that eliminates withdrawal symptoms and illicit opioid use Eliminate withdrawal symptoms, side effects, and illicit drug use Address lifestyle changes and social and psychological needs; if desired, plan for medically supervised withdrawal

41 Buprenorphine for Opioid Withdrawal Inpatient: 8 mg/day; outpatient: 8 32 mg/day Relieves physiological and psychological symptoms May be better accepted and more effective than clonidine Once stabilization dose is achieved, can be tapered in 2-mg increments over several days (longer in outpatient settings) Minimal withdrawal symptoms during taper Buprenorphine/naloxone combination is preferred in outpatient settings Dodrill CL et al. Am J Psychiatry 2011;168(5):

42 Naltrexone Opioid antagonist; blocks pleasurable effects of opioids No abuse potential Patients must be completely withdrawn and abstinent for 5 days (short-acting opioid) to 7 days (long-acting opioid) Requires 0.8-mg IM test dose to ensure that patient is no longer dependent on opioids before starting treatment Usual dose is 50 mg/day or 100 mg Mon/Wed and 150 mg Fri Common side effects: dysphoria, anxiety, GI distress, site reaction (injection) After discontinuing naltrexone: increased sensitivity to opioid effects; risk that overdose will lead to respiratory depression APA. Am J Psychiatry 2007;164(4):1-124.

43 Clonidine for Opioid Withdrawal 0.1 mg 3 times daily (can be higher in inpatient setting) Used when an opioid is stopped abruptly Relieves noradrenergic symptoms (vomiting, diarrhea, cramps, sweating) Does not reduce insomnia, distress, or drug cravings Detox can be achieved in 4 6 days for short-acting opioids Does not produce opioid-like tolerance or dependence Next dose should be withheld if blood pressure falls below 90/60 mm Hg Outpatients should not be given more than a 3-day supply Contraindicated in patients with cardiac disorders, renal or metabolic disease, or moderate to severe hypotension APA. Am J Psychiatry 2007;164(4):1-124.

44 Stimulant Use Disorder Screening and Management

45 Patterns of Addiction by Drug: Stimulants profound craving anticipation/ preoccupation compulsivity abstinence dysphoria binge/ intoxication profound tolerance to intoxication Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press; Koob GF, Le Moal M. Annu Rev Psychol 2008;59:29-53.

46 Screening and Management for Stimulant Intoxication Common Euphoria, pleasure Energy Mental acuity Tremor Emotional lability Restlessness Irritability Panic Stereotyped behavior Supportive High Doses Intense anxiety Paranoia Hallucinations Hypertension Tachycardia Ventricular irritability Hyperthermia Respiratory depression CV: beta blocker, DA antagonist Agitation: benzodiazepine Hallucinations: antipsychotic Overdose Seizures Acute heart failure Stroke APA. Am J Psychiatry 2007;164(4):1-124.

47 Interaction Between Cocaine and Alcohol: Cocaethylene cocaine cocaethylene Cocaine-like effects More toxic Longer half-life McCance EF et al. J Pharmacol Exp Ther 1995;274(1):215-23; McCance-Katz EF et al. Biol Psychiatry 1998;44(4):250-9; Wiener SE et al. Am J Emerg Med 2010;28(9):

48 Pharmacological Treatments for Stimulant Use Disorder TCA? modafinil? carbamazepine? vaccine? cocaine esterase? DA agonist? dependence Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press.

49 Screening and Management for Stimulant Withdrawal psychosocial treatment APA. Am J Psychiatry 2007;164(4):1-124.

50 Psychosocial Treatment for Stimulant Use Disorder CBT MET Behavioral therapy IPT Family therapy Selfhelp/ 12-Step Alcohol X X X X X Opioid X X X X Nicotine X X X Stimulant X X X Marijuana X X CBT: cognitive behavioral therapy. MET: motivational enhancement therapy. Behavioral therapy: contingency management, community reinforcement, cue exposure and relaxation, aversion therapy. IPT: interpersonal therapy. Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press.

51 Marijuana Use Disorder Screening and Management

52 Patterns of Addiction by Drug: Marijuana anticipation/ preoccupation compulsivity abstinence dysphoria binge/ intoxication initially intense; transitions to regular titrated intake Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press; Koob GF, Le Moal M. Annu Rev Psychol 2008;59:29-53.

53 Screening and Management for Marijuana Use Intoxication Well-being Relaxation Friendliness Special insight Temporally unaware Slow thought processes Impaired memory High Doses Panic Toxic delirium Psychosis (rare) Long-Term Heavy Use Amotivation Poor attention span Poor judgment Distractibility Poor communication Introversion Poor interpersonal skills Loss of insight Depersonalization APA. Am J Psychiatry 2007;164(4):1-124.

54 Screening and Management for Marijuana Withdrawal Psychological anger anxiety depressed mood irritability sleep difficulty Physiological weight loss appetite loss psychosocial treatment APA. Am J Psychiatry 2007;164(4):1-124.

55 Pharmacological Treatments for Marijuana Use Disorder?? Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press.

56 Psychosocial Treatment for Marijuana Use Disorder CBT MET Behavioral therapy IPT Family therapy Selfhelp/ 12-Step Alcohol X X X X X Opioid X X X X Nicotine X X X Stimulant X X X Marijuana X X CBT: cognitive behavioral therapy. MET: motivational enhancement therapy. Behavioral therapy: contingency management, community reinforcement, cue exposure and relaxation, aversion therapy. IPT: interpersonal therapy. Stahl SM, Grady MM. Stahl's Illustrated Substance Use and Impulsive Disorders; in press.

57 Summary A substance use disorder can be conceptualized as a progression from an impulsive to a compulsive disorder This progression is linked to alterations in not only dopamine and the reward circuit, but also other neurotransmitters and circuits involved in memory, motivation, executive function, and stress The management of SUDs can differ by substance, but it generally involves both psychosocial and pharmacological treatment The substances with evidence-based pharmacological treatments are alcohol, opioids, and nicotine (not covered)