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Co-occurring Psychiatric and Substance Use Disorders: The Concept of Comorbidity Ricardo Restrepo, MD; MPH The Addiction Institute of NY St. Luke’s-Roosevelt Hospitals VI Simpósio Internacional de Alcoologia e Outras Drogas Vila Serena Bahia Outline Epidemiology Neurobiology Overview of comorbidity Theories Dual diagnosis principles Comorbid treatment: Anxiety Disorders, Affective Disorders, Psychotic Disorders, and Personality Disorders Conclusions 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 ECA Odds Ratios of SUD’s in persons with Mental Illness Mental disorder Odds ratio (Risk for Substance Abuse Increase) 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. Comorbidity: Other biological factors contribute to Addiction Conway KP, Compton W, Stinson FS, Grant BF. J Clin Psychiatry. 2006;67(2):247. Reward Pathway: Comorbid activation from mesolimbic to mesocortical Prefrontal cortex Thalamus Nucleus accumbens Ventral tegmental area Locus Coeruleus 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 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 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 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. 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 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) 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) 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. 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) 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 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 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 cooccurring disorders can be a first step to organizing treatment matching. Dual Diagnosis Principles Both High Severity Mental Illness Low Severity Substance use disorder High Severity MI High Severity SUD Low Severity Both Low Severity 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 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. 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. 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. 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 Pharmacotherapy and Psychotherapy in comorbid psychiatric disorder and substance abuse disorders Double Blind Controlled Trial Data IS ALMOST NON-EXISTENT 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 presentstate assessment; the key is to get the longitudinal course, the natural history of the condition) 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 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 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 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) 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). 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 Results of studies of antidepressant use in patients with comorbid depression and alcohol dependence Outcomes (med vs. placebo) STUDY (N) Medication Average daily dose (no wks) Depression Drinking Mason (28) Desipramine 200 mg (24) Med< plac Med < plac McGrath (69) Imipramine 260 mg (12) Med < plac Med = plac Cornelliuos (51) Fluoxetine 20-40 mg (12) Med < plac Med < plac Roy (36) Sertraline 100 mg (6) Med < plac Med = plac Roy-Byrne (64) Nefazodone 460 mg (12) Med < plac Med = plac Pettinati (29) Sertraline 170 mg (14) Med = plac Med = plac Moak (82) Sertraline 186 mg (12) Med < plac Med = plac Hernandez-Avila Nefazadone (41) 413 mg (10) Med = plac Med < plac Kranzler (345) 50-100 mg (10) Med = plac Med = Plac Sertraline New treatment strategy Study (N) Medication Average daily dose (no.wks) Depression Drinking abstinence Pettinati (170) Sertraline and Naltrexone 200 mg (14) Med combination < Single medication < placebo Med combination < Single medication < placebo 100 mg (14) Single Medication Placebo (Double blind, placebo-controlled trial combining sertraline and naltrexone for treating cooccurring 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 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 Percent with schizophreniform disorder at age 26 Comorbid Psychotic Disorder and Substance Use Disorder COMT genotype Casp A, Moffitt TE, Cannon M, et al., Biol Psychiatry, May 2005 Cannabis and psychosis risk Hypotheses linking cannabis and psychosis Hypothesis Strenght of Evidence for evidence Evidence against Cannabis worsens existing psychotic disorders Strong Cannabidiol and Δ9-THC improve symptoms in some patients with schizophren ia •Cannabis is associated with increased symptoms, relapse, and treatment nonadherence among those with schizophrenia •Patients with schizophrenia are more vulnerable to cannabisinduced psychosis under experimental conditions 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 Cannabis and psychosis risk Hypotheses linking cannabis and psychosis Hypothesis Strenght of Evidence for evidence Evidence against Cannabis increases the risk of chronic psychosis among vulnerable individuals Strong Cannabis use is not always a risk factor for conversion to psychosis in studies of prodromal schizophrenia •For patients with schizophrenia, a history of cannabis use is associated with illness onset 2 to 3 years earlier compared with non-users. •Cannabis use is a risk factor for conversion to psychosis in some studies of prodromal schizophrenia 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 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. 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. 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 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 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) 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) 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) 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) 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 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 (EarlyOnset). 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 Tools TIP 42 Substance Abuse Treatment For Persons With CoOccurring Disorders Inservice Training based on Treatment Improvement Protocol (TIP) 42 Substance Abuse Treatment For Persons With CoOccurringDisorders.http://kap.samhsa.gov/products/trainin gcurriculums/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/ 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 THANKS! Gracias! Obrigado! Questions? Comments?