Outline

1. Co-occurring Psychiatric and Substance Use Disorders:The Concept of Comorbidity Ricardo Restrepo, MD; MPH The Addiction Institute of NY St. Luke’s-Roosevelt HospitalsVI Simpósio Internacional de Alcoologia e Outras DrogasVila Serena Bahia

2. Outline • Epidemiology • Neurobiology • Overview of comorbidity • Theories • Dual diagnosis principles • Comorbid treatment: Anxiety Disorders, Affective Disorders, Psychotic Disorders, and Personality Disorders • Conclusions

3. Which came first?Psychiatric Symptoms or Substance Abuse In the ECA study an estimated 45 % of individuals with alcohol use disorders and 72% of individuals with drug use disorders had at least one co-occurring psychiatric disorder

4. ECA Odds Ratios of SUD’s in persons with Mental Illness • Bipolar Disorder 6.6 • Schizophrenia 4.6 • Panic Disorder 2.9 • Major Depression 1.9 • Anxiety Disorder 1.7 Epidemiologic Catchment Area (ECA) Study (Regier 1990) Regier, D. A., Farmer, M. E., Rae, D. S., Locke, B. Z., Keith, S. J., Judd, L. L., & Goodwin, F. K. (1990). Comorbidity of mental disorders with alcohol and other drug abuse: Results from the Epidemiologic Catchment Area (ECA) study. Journal of the American Medical Association, 264, 2511–2518.

5. Comorbidity: Other biological factors contribute to Addiction Conway KP, Compton W, Stinson FS, Grant BF. J Clin Psychiatry. 2006;67(2):247.

6. Reward Pathway: Comorbid activation from mesolimbic to mesocortical Prefrontal cortex Thalamus Ventral tegmental area Nucleus accumbens Locus Coeruleus

7. Role of Dopamine: Comorbidity • Psychoactive substances may 1) increase DA release, 2)inhibit reuptake, 3) act as DA agonist • Acute increases in DA in both mesolimbic and mesocortical pathways are thought to be essential to the initial liking and reinforcement of drug taking (The Reward Pathway) • Chronic use Global decrease in DA

8. Role of Dopamine: Comorbidity • Corticotropin Releasing Factor (CRF) and the hypothalamic-pituitary-adrenal (HPA) axis (stress response) • In response to drug use and more precisely, activation of the mesolimbic DA system, CRF and the HPA axis are upregulated • In acute withdrawal this leads to physiological and psychological withdrawal • However, increases in cortisol, CRF, NE in addition to neuropeptide Y, nociceptin, vasopressin are thought to persist weeks/months into sobriety leading to anxiety dysphoria that is called protracted withdrawal

9. Why Do Drug Abuse and Mental Disorders Commonly Co-occur? • Overlapping genetic vulnerabilities • Overlapping environmental triggers • Involvement of similar brain regions • Drug abuse and mental illness are developmental disorders

10. How Can Comorbidity Be Diagnosed and Treated? • The health care systems in place to treat substance abuse and mental illness are typically disconnected, hence inefficient. Physicians tend to treat patients with mental illnesses, whereas a mix of clinicians with varying backgrounds deliver drug abuse treatment. • Some substance abuse treatment centers are biased against using any medications, including those necessary to treat patients with severe mental disorders. • Clinicians and researchers generally agree that broad-spectrum diagnosis and concurrent therapy (pharmacological and behavioral) will lead to better outcomes for patients with comorbid disorders.

11. Psychosocial treatment for comorbid disorders and substance use disorders • Single: treating the primary d/o resolved the other one • Sequential: treating the primary d/o initially, followed by treating the other disorder • Parallel: treating both disorders at the same time but in different settings • Integrated: simultaneously treating both disorders

12. What is Comorbidity and What Are Its Causes? • When two or more disorders or illnesses occur simultaneously in the same person, they are called comorbid. Surveys show that drug abuse and other mental illnesses are often comorbid. They can occur at the same time or one after the other • Three scenarios that we should consider: • Drug abuse can cause a mental illness (Causal Effect) • Mental illness can lead to drug abuse (Self-medication) • Drug abuse and mental disorders are both caused by other common risk factors (Common or correlated causes)

13. Hypothesis 1: Alcohol and drug abuse can cause mental illness (Causal Effect) • Galanter et al. (1988): Drug & ETOH abuse: 1/3 of patients receiving acute psychiatric services • Kosten and Kleber (1988): Specific drugs/alcohol may result in tendency for the development of mental d/o’s • National Institute of Drug Abuse –NIDA- (1991): Prolonged abuse of specific drug combinations : direct causal role/ hasten development of psychiatric d/o’s • Miller and Gold (1991): acute & chronic actions of alcohol & drugs can produce symptoms similar to psychiatric disorders (ie. depression, anxiety, personality disorders & psychosis)

14. Hypothesis 1: Alcohol and drug abuse can cause mental illness (Causal Effect) • Stimulants & cocaine: dose dependent agitation, anxiety, panic & psychosis during acute intoxication; depression post-withdrawal • Hallucinogens & cannabis: psychotic symptoms • Adverse psychiatric reactions to marijuana/THC: panic attacks, anxiety reactions, severe MDD, psychosis • Chronic opiate administration: high rates of major & minor depressions • Lysergic acid diethylamide (LSD): severe panic & anxiety reactions, bipolar manic disorders, schizoaffective disorders & MDD • Irritability & anger attacks, depressed mood, and decreased social interaction may be seen in patients taking BZ or drinking alcohol.

15. Hypothesis 2: Mental illness can cause alcohol and drug abuse (Self-medication) - Drug of choice: interaction between psychopharmacologic actions of the drug & dominant painful feelings - Opioid abuse: powerful muting action of opioids on the disorganizing & threatening affects of rage & aggression - cocaine: relieves distress from depression, hypomania & hyperactivity - psychopathology can alter course of any addictive disorder - most support based on clinical experience McLellan and Druley (1977)

16. Case Presentation….what to do? (Common or correlated causes) • ID: Ms. B; 32 y/o, single, female student from Salvador. • CC: I am depressed and hopeless after terminating my relationship and since I’ve not been able to find a job. “sometimes I cut my self to relieve the pain when I am high” • HPI: Depressed, reports use of alcohol and other drugs including cocaine and heroin to relieve the depressed mood. Patient describes self cutting behavior since age 15 during stressful times. Past Psych Hx: 2 hospitalizations for depression and suicidal attempts Past SA Hx: ETOH use since age 13, THC use since age 15, cocaine and heroin use since age 20

17. Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry We Need to Treat the Person Pharmacological Treatment Behavioral Therapies (Medications) Medical Services Social Services

18. Dual Diagnosis Principles • Dual Diagnosis is an expectation, not an exception • Successful treatment is based on empathic, hopeful, integrated and continuing relationships. • Treatment must be individualized utilizing a structured approach to determine the best treatment. The consensus “four quadrant” model for categorizing individuals with co-occurring disorders can be a first step to organizing treatment matching.

19. Dual Diagnosis Principles

20. Determining Level of Care • Level I: Outpatient treatment • Level II: Intensive outpatient treatment, including partial hospitalization • Level III: Residential/medically monitored intensive inpatient treatment • Level IV: Medically managed intensive inpatient treatment

21. Dual Diagnosis Principles • Case management and clinical care (in which we provide for individuals that which they cannot provide for themselves) must be properly balanced with empathic detachment, opportunities for empowerment and choice, contracting, and contingent learning. • When mental illness and substance use disorder co-exist, each disorder is “primary”, requiring integrated, properly matched, diagnosis specific treatment of adequate intensity.

22. Dual Diagnosis Principles • Both serious mental illness and substance dependence disorders are primary biopsychosocial disorders that can be treated in the context of a “disease and recovery” model. Treatment must be matched to the phase of recovery (acute stabilization, engagement/motivational enhancement, active treatment/prolonged stabilization, rehabilitation/recovery) and stage of change or stage of treatment for each disorder.

23. Dual Diagnosis Principles • There is no one correct approach (including psychopharmacologic approach) to individuals with co-occurring disorders. For each individual, clinical intervention must be matched according to the need for engagement in an integrated relationship, level of impairment or severity, specific diagnoses, phase of recovery and stage of change.

24. Case Presentation part 2 • Patient and clinicians agree with an Integrated treating program where simultaneously both disorders (Comorbid treatment program) are treated: • Pharmacotherapy • Psychotherapy (Intensive outpatient treatment) including • DBT, Dual dx group among others

25. Pharmacotherapy and Psychotherapy in comorbid psychiatric disorder and substance abuse disorders • Double Blind Controlled Trial Data IS ALMOST NON-EXISTENT

26. How do I determine if my addiction patient has a co-morbid psychiatric disorder? • History of symptoms (current history may not be as important as past history) • Family history • No blood tests, physical exam, imaging studies are diagnostic • Must conduct a clinical interview (remember that a ‘mental status examination’ is a present-state assessment; the key is to get the longitudinal course, the natural history of the condition)

27. Comorbid Psychiatric Disorder and Substance Use Disorder • The following scenarios suggest an independent psychiatric disorder: - Psychiatric disturbance precedes substance use - Psychiatric disturbance persists following prolonged abstinence - Psychiatric disturbance occur in excess of those typically seen considering the quantity and frequency of substance consumption

28. Comorbid Anxiety and Substance Use Disorder • Patients with an anxiety disorder • 36% alcohol or illicit drug abuse • 26% of substance dependent pt’s: PTSD * • Exposure to Traumatic Events Puts People at Higher Risk of Substance Use Disorders. Recent epidemiological studies suggest that as many as half of all veterans diagnosed with PTSD also have a co-occurring substance use disorder (SUD) • Primary vs. secondary * substance use → anxiety * substance withdrawal → anxiety * anxiety→ symptom relief w/ substance use • Merikangas KR, Whitaker A, et al. Comorbidity and boundaries of affective disorders with anxiety disorders and substance misuse; results of an international task force. Br J Psychiatry 1996; 168 (Suppl 30): 58-67

29. 12-Month prevalence rates of drug and alcohol dependence in patients with anxiety disorder compared with the general population NESARC: National Epidemiological Survey on Alcohol and Related Conditions 2004

30. Treatment of Anxiety & Substance abuse disorders • SSRIs are the first-line therapy for anxiety disorders with Psychotherapy (CBT) • Use of nonaddictive medications, with the exception of treating withdrawal symptoms • Other antianxiety medications to consider in patients being treated for comorbid SUD: hydroxyzine, gabapentin, quetiapine • Cravings or preoccupation w/ ETOH: naltrexone, acamprosate and disulfiram *Benzodiazepines - popular “mainstay” of treatment, but… - highest abuse potential (40% of substance abusers seeking treatment) - concern for prescribers (abuse risk vs. trigger for relapse vs. disinhibition) Resource : Harvard Psychopharmacology Algorithm Project www.mhc.com Osser DN, Renner JA & Bayog (1999)

31. Comorbid Mood Disorders and Substance Use Disorder • Patients with an affective disorder • 32% alcohol or illicit drug abuse • Prevalence rate of 20.5% of major depressive disorder in patients with alcohol dependence • Among all Axis I conditions, bipolar disorder has the highest prevalence of comorbid substance use. Prevalence rates of alcohol or drug abuse in patients with bipolar disorder have been estimated to range from 21% to 58% (Brady and Lydiard 1992).

32. Treatment of Mood disorders and Substance abuse disorder • SRI (Serotonin Reuptake Inhibitors) are the pharmacotherapeutic intervention of alcohol dependence and major depression • Several studies have identified substance abuse as a predictor of poor response to lithium • Bipolar patients with concomitant substance use disorders appear to have more mixed and/or rapid cycling bipolar disorder than patients with bipolar disorder who do not abuse substances. Therefore, substance-abusing bipolar patients may respond better to anticonvulsant medications (for example, valproate) than to lithium therapy. • The optimal management of patients with comorbid schizophrenia and SA involves both psychopharmacology and psychotherapy Principles of Addiction Medicine, 3rd Edition

33. Results of studies of antidepressant use in patients with comorbid depression and alcohol dependenceOutcomes (med vs. placebo)

34. New treatment strategy(Double blind, placebo-controlled trial combining sertraline and naltrexone for treating co-occurring depression and alcohol dependence)Implication: Combining a medication to treat alcohol dependence (eg, naltrexone) with an antidepressant (eg, sertraline) with some basic psychosocial support and advice for both disorders can provide an aggressive approach to treating patients with co-occuring depression and alcohol dependence

35. Comorbid Psychotic Disorder and Substance Use Disorder • Patients seeking treatment for schizophrenia • 50% alcohol or illicit drug abuse • 70-90% are nicotine dependent • Symptomatic relief • Combat hallucinations/paranoia • Decrease negative symptoms • Ameliorate adverse effects of medication • The optimal management of patients with comorbid schizophrenia and SA involves both psychopharmacology and psychotherapy

36. Comorbid Psychotic Disorder and Substance Use Disorder Percent with schizophreniform disorder at age 26 COMT genotype Casp A, Moffitt TE, Cannon M, et al., Biol Psychiatry, May 2005

37. Cannabis and psychosis risk Hypotheses linking cannabis and psychosis Zammit S, Moore TH, Lingford-Hughes A, et al. Effects of cannabis use on outcomes of psychotic disorders: systematic review. Br J Psychiatry. 2008;193(5):357–363.

38. Cannabis and psychosis risk Hypotheses linking cannabis and psychosis Large M, Sharma S, Compton MT, et al. Cannabis use and earlier onset of psychosis: a systematic meta-analysis. Arch Gen Psychiatry. 2011;68(6):555–561

39. Treatment: Comorbid Psychotic Disorder and Substance Use Disorder • There are few controlled trials on the use of specific antipsychotics on people with psychoses and SUD, although it appears that clozapine (Buckley, Thompson,Way, & Meltzer, 1994) and olanzapine (Conley, Kelly, & Gale, 1998) have approximately equal effectiveness in treatment-resistant patients with and without substance abuse. • Since people taking standard antipsychotic medication have an increased risk of tardive dyskinesia if they misuse alcohol, cannabis (Olivera, Kiefer, & Manley, 1990; Salyers & Mueser, 2001; Zaretsky et al., 1993) and perhaps nicotine (Yassa, Lal, Korpassy, & Ally, 1987), it may be especially important for these patients to be given medications with a lower risk of this side-effect.

40. Comorbid Personality disorder and Substance Use Disorder • About 40% to 50% of individuals with a substance use disorder meet the criteria for antisocial personality disorder (ASPD) and approximately 90% of individuals diagnosed with ASPD also have a co‐occurring substance use disorder (Messina, Wish, & Nemes, 1999). • People with comorbid personality disorder and substance use: • Have more problematic symptoms of substance use than those without a personality disorder. • Are more likely to participate in risky substance-injecting practices that predispose them to blood borne viruses. • Are more likely to engage in risky sexual practices and other disinhibited behaviours • May have difficulty staying in treatment programs and complying with treatment plans.

41. Treatment: Comorbid Personality disorder and Substance Use Disorder • Treatment for substance use in people with personality disorders is associated with a reduction in substance use. • Treatment for substance use is also associated with a reduction in the likelihood of being arrested, suggesting a reduction in criminal activity. • Psychotherapy is the treatment of choice for personality disorders but be aware of pharmacological agents available to help with comorbidity

42. Evidence-Based Practices • Motivational Enhancement Therapy (MET)- Initiate and maintain changes • Cognitive Behavioral Therapy (CBT)- make and identify the cause and consequences of changes • Dialectic Behavioral Therapy (DBT) (Borderline Personality d/o) • Exposure Therapy (anxiety d/o-Phobia and PTSD) • Integrated Group Therapy (IGT) (Bipolar d/o and SA) • Twelve Step Facilitation (TSF)- help to sustain changes • Other considerations: • Managing Medications • Involving the Family • Encouraging participation in group/individual therapy

43. Avoid These group of Medications for Treatment of Substance Abuse disorders Choosing a pharmacological agent include paying particular attention to potential toxic interaction of the medication with drugs and alcohol • MAOI • Opiates • Barbiturates • Stimulants • Short Acting BZDs • Tricyclics (metabolism, cardiac conduction)

44. When to consider Pharmacotherapy Consider Precipitant To Treatment And Severity of Associated Medical/Psychiatric/Psychosocial Problems • Family • Employment • Financial • Medical • Legal • Psychiatric comorbidity (including risk for harm to self or others) • Relapse Potential • The higher the acuity or severity; greater need for use of medication treatment (if there is an appropriate medication intervention available)

45. When to consider Pharmacotherapy Indications: To treat psychiatric disorders and minimize potential relapse to substance use. • Any Primary/Endogenous Psychiatric Disorder • Any Psychosis or mood disorder irrespective of whether drug-induced or primary (e.g., antipsychotics, mood stabilizers, antidepressants) • Secondary anxiety or mood disorders - If there has been clear, lasting, and severe past episodes that led to impaired function. • Psychiatric Disorders that last more than 4 weeks after drug/alcohol use *May need detoxification to ascertain psychiatric diagnosis • Can use psychopharmacotherapy with other medications used to promote/maintain abstinence (e.g., methadone, acamprosate)

46. Pharmacology Treatment (Medications) • Pharmacotherapies that benefit multiple problems: • Bupropion -----depression and nicotine dependence, might also help reduce craving and use of the drug methamphetamine • Pharmacotherapies for Nicotine Dependence: • Nicotine Substitution (Agonist Therapy): Nicotine polacrilex gum, Transdermal nicotine patch, Nicotine nasal spray • Bupropion • Varenicline (nicotine partial agonist)

47. Pharmacology Treatment (Medications) • Pharmacotherapies for Alcohol dependence (Relapse Prevention): • Naltrexone (oral and injectable) • Disulfiram • Acamprosate • Pharmacotherapies for Opiate Addiction • Methadone (Can’t use outside of a registered narcotic treatment program) • Buprenorphine • Naltrexone

48. Pharmacology Treatment (Medications)Alcohol Typologies • Abstinence rates during a 14-week treatment trial with sertraline 200 mg QD. • Sertraline helped Type A (Late-Onset) alcoholics stay abstinent (P=0.004), but not Type B (Early-Onset). Adapted from: Pettinati HM, Volpicelli JR, Kranzler HR, Luck G, Rukstalis MR, Cnaan, A: Sertraline treatment for alcohol dependence: Interactive effects of medication alcoholic subtype. Alcohol Clin Exp Res 24:1041-1049, 2000

49. Tools • TIP 42 Substance Abuse Treatment For Persons With Co-Occurring Disorders Inservice Training based on Treatment Improvement Protocol (TIP) 42 Substance Abuse Treatment For Persons With Co-OccurringDisorders.http://kap.samhsa.gov/products/trainingcurriculums/tip42.htm • NIDA (National Institute of Drug Abuse)http://drugabuse.gov/researchreports/comorbidity/ • SAMHSA (Substance Abuse & Mental Health Services Administration) http://www.samhsa.gov/co-occurring/

50. Conclusions • Identify the need of your patients to get treatment • Addiction and psychiatric disorders are treatable brain diseases • Research is edifying the biological mechanisms involved • Increased understanding of neurobiology is allowing for the development of effective, targeted pharmacotherapies and psychotherapy • Comorbidity disorders are multifactorial, be ready for relapses • Pharmacotherapy and psychotherapy modalities are effective and scientifically based approaches • Prevention is based on screening and early Intervention