Assessment and Management of Co-Occurring Psychiatric Illnesses During Office-Based Opioid Treatment

Transcription

1 Assessment and Management of Co-Occurring Psychiatric Illnesses During Office-Based Opioid Treatment Joji Suzuki, MD Assistant Professor of Psychiatry Harvard Medical School Director, Division of Addiction Psychiatry Brigham and Women s Hospital *Images used for educational purposes only. All copyrights belong to image owners*

2 Outline 1. Independent vs substance-induced psychiatric disorders 2. Treatment of mood disorders comorbid with SUD 3. Treatment of anxiety disorders comorbid with SUD 4. Treatment of ADHD comorbid with SUD 5. Treatment of other SUDs comorbid with OUD

3 Outline 1. Independent vs substance-induced psychiatric disorders 2. Treatment of mood disorders comorbid with SUD 3. Treatment of anxiety disorders comorbid with SUD 4. Treatment of ADHD comorbid with SUD 5. Treatment of other SUDs comorbid with OUD

4 Poor concentration Inattention Insomnia Depressed mood Anhedonia Anxiety Depression, anxiety, ADHD or SUD? Guilt Suicidality

5 Independent Psychiatric Disorder Symptoms develop before substance use Persistence of symptoms during abstinence for more than several weeks Family history of independent disorder Substance-Induced Psychiatric Disorder Symptoms develop after substance use Depression and anxiety remit within several weeks after cessation Symptoms exceed what would be expected from usual toxic or withdrawal effects Adapted from Nunes et al 1994

6 Gender differences in relationship between depression and SUD (ECA study, n=14,480) Odds of Developing.. In Women In Men.MDD at 1-year followup with high levels of alcohol use at baseline.aud at 1-year followup with major depression at baseline Gilman and Abraham, 2001

7 Outline 1. Independent vs substance-induced psychiatric disorders 2. Treatment of mood disorders comorbid with SUD 3. Treatment of anxiety disorders comorbid with SUD 4. Treatment of ADHD comorbid with SUD 5. Treatment of other SUDs comorbid with OUD

8 Depression and Anxiety Measure Scores Depression and anxiety improve after alcohol detoxification Beck Depression Inventory Scores STAI-X2 Trait Anxiety Scores Depression & Anxiety Group Anxiety Group No Comorbidites Depression & Anxiety Group2 0 Baseline 1 week post detox 2 weeks post detox 3 weeks post detox Driessen et al 2001

9 Antidepressants alone exert a modest beneficial effect on depressed substance users Meta-analysis 300 potential citations 14 met inclusion criteria (prospective, parallel group, double-blind, placebo-controlled, random assignment) 827 subjects total Results: Effect on depression scores: Overall effect size 0.38 (CI ) Effect on substance use: Overall effect size 0.25 (CI ) Nunes and Levin 2004

10 Approach to treating SUD patients with depression Substantial reduction in substance use Nunes and Levin 2004 Offer evidencedbased psychosocial treatments first for depressive symptoms (unless patient preference for medications or severe symptoms) If depressive symptoms persist for > 2 weeks, then consider addition of medications

11 Individuals with depression and OUD (current and lifetime) have improved outcomes while on buprenorphine (n=360) Success defined as abstinent from illicit opioid use at week 24 Current depression 41% Lifetime depression 26% 27% 14% Success Failure Dreifuss et al 2013

12 Suicide attempts are more common in depressed patients with SUD Davis et. al 2005

13 Harris and Barraclough 1997; Wilcox 2004 Risk of completed suicide compared to no SUD Risk of completed suicide compared to control 14x 10x 4x Heavy alcohol use Alcohol use disorder Opioid use disorder

14 Suicide attempts in 431 heroin users at 11-year follow-up N=431 Ever attempted suicide in lifetime 42.2% No. of lifetime attempts 1: 23.7% 2: 4.9% 3: 5.6% >4: 8.1% Current ideation 10.4% Current plan 4.2% Darke et al 2010

15 Naltrexone and depression (1) Hypothesis that naltrexone may cause depression or anhedonia has been around for decades Studies do not support the emergence of dysphoria in naltrexone treatment for alcohol and opioid use disorders (Miotto et al 2002; Sayed et al 2013; Dean et al 2006; Lobmaier et al 2011; Krupitsky et al 2016) istockphoto

16 Naltrexone and depression (2) Improvement in depression in subjects with AUD + MDD when treated with naltrexone + sertraline (Pettinati et al 2010) Fear of worsening depression should not preclude the use of naltrexone in SUD patients with comorbid depression

17 Adapting motivational interviewing (MI) for depressed SUD patients (1) MI remains an important approach to dual diagnosis patients regardless of their readiness for treatment MI should be conceptualized as a pretreatment for existing therapies Ambivalence towards psychotherapy or medications is common among depressed patients, and can become the target for MI intervention Arkowitz et. al 2008; burke et. al 2003

18 istockphoto Adapting motivational interviewing (MI) for depressed SUD patients (2) Clinicians may need to be more active with depressed patients than compared with nondepressed patients Arkowitz et. al 2008; burke et. al 2003

19 SUD and depression summary (1) Mood symptoms often improve after cessation of substance use. Reasonable to first offer psychosocial treatment for the depression, and hold off initiating medications unless the depression persists for some time (i.e., >2 weeks) Suicidal ideation and suicide attempts occur more frequently in OUD patients with depression, highlighting the importance of assessing for suicidal ideation in all OUD patients

20 istockphoto SUD and depression summary (2) Naltrexone should not be withheld from patients for fear of worsening the depression Buprenorphine treatment may be particularly effective for OUD patients with depression

21 Bipolar disorder Very high rates of SUD comorbidity o High rates of alcohol (42%), cannabis (20%), illicit drug (17%) (Hunt et al JAD 2016) Treatment options o Mood stabilizers first, not SSRIs o Lithium (Geller et al., JAACAP, 1998) o Valproate (Salloum et al., Arch Gen Psych, 2005) o Lamotrigine o Second generation antipsychotics o Use antidepressants with caution o Group psychotherapy for bipolar disorder and SUD comorbidity (Weiss et al DAD 2009)

22 Outline 1. Independent vs substance-induced psychiatric disorders 2. Treatment of mood disorders comorbid with SUD 3. Treatment of anxiety disorders comorbid with SUD 4. Treatment of ADHD comorbid with SUD 5. Treatment of other SUDs comorbid with OUD

23 Co-morbidity of DSM-IV anxiety disorders with SUD Anxiety Disorder Alcohol Dependence (Odds Ratio) Drug Dependence (Odds Ratio) Specific phobia Social phobia Generalized anxiety disorder (GAD) Panic with agoraphobia Any anxiety disorder Hasin et al 2007

24 Anxiety disorders precede the development of SUD in 75% of the cases, and they both help to maintain each other SUD Anxiety Disorder McHugh HRP 2016; Kushner et al 2008; Merikangas et al 1998

25 Medications for anxiety disorders / PTSD and SUD Very few medication studies to guide medication treatment, most have focused on SSRIs for anxiety and substances other than opioids o o Paroxetine for AUD and social anxiety disorder (Randall et al 2001; Book et al 2008) Sertraline for AUD and post-traumatic stress disorder (PTSD) (Brady et al 2005) o Buspirone for AUD and GAD (Kranzler et al 1994) Benzodiazepines should be used with caution, and primarily used for acute anxiety because they can increase risk of injury (Schuman-Olivier et al 2013) Most opioid-related overdose victims have both opioids and benzodiazepines in their system

26 Integrated approaches for anxiety / PTSD and SUD have promise, but more research is needed (1) Cognitive behavioral therapy (CBT) most studied, and CBT is equal to or superior to medication therapy for anxiety disorders (Barlow et al JAMA 2000; Foa et al AJP 2005; Davidson et al AGP 2004) Concurrent treatments have been studied: o Alcohol treatment ± CBT (and optional SSRI) for AUD and phobia (Schade et al 2005) o Naltrexone vs placebo ± prolonged exposure vs supportive counseling for AUD and PTSD (Foa et al 2013)

27 Integrated approaches for anxiety / PTSD and SUD have promise, but more research is needed (2) Integrated treatments have also been studied o Integrated CBT or exposure therapy for both SUD and anxiety disorders (Kushner et al 2013; McGovern et al 2015; Brady et al 2001) o Most studied is Seeking Safety for SUD and PTSD, however multi-site trials have not demonstrated their efficacy (Najavits et al 1998; Hien et al 2010) o Concurrent treatment of PTSD and SUD using prolonged exposure has shown promise (Mills et al 2012)

28 Among heroin users seeking treatment, trauma exposure and diagnosis of PTSD are very common Trauma exposure (92%) Lifetime PTSD (41%) Women more likely to develop PTSD in their lifetime following exposure (61% vs 37%) PTSD chronic in the vast majority (84%), with average duration of symptoms 9.5 years More extensive polydrug use, poor general physical and mental health, and service utilization Mills et. al 2005

29 Opioid use disorder patients with comorbid PTSD are often more difficult to treat than those without, and are likely to be underdiagnosed Methadone maintenance treatment (MMT) patients with PTSD need higher dose, more psychotherapy sessions, and remain in treatment longer (Trafton et al 2006) Heroin users with PTSD continue to experience PTSD symptoms despite treatment for the OUD and associated with substantial disability up to 2 years following treatment (Mills et al 2007)

30 istockphoto MMT patients have high rates of traumatic event re-exposure, which predicts worse treatment outcomes (Peirce et. al, 2016) In primary care settings, PTSD is prevalent and likely under-diagnosed (Liebschutz et. al, 2007)

31 Treatment of PTSD can lead to improved SUD outcomes, but not the other way around Improving PTSD symptoms can lead to improvement in SUD Improving SUD does not necessarily lead to improvement in PTSD symptoms Hien et. al, 2010

32 istockphoto Treatment of PTSD (1) Patient preference is always an important factor Psychotherapy o Strong evidence for effectiveness of traumafocused psychotherapies (eg., exposure-based therapies and cognitivebased), as well as stress inoculation training The Management of Post-traumatic Stress Working Group, Dept of VA, 2010

33 The Management of Post-traumatic Stress Working Group, Dept of VA, 2010 Treatment of PTSD (2) Medications o o o o o Antidepressants are first-line and superior to placebo in reducing PTSD symptoms in 3 agents, but with modest effect size (Fluoxetine, Paroxetine, Venlafaxine) Prazosin for sleep/nightmares Mirtazapine is second-line antidepressant Second-generation antipsychotics may be adjuncts, but not monotherapy Lack of strong evidence for benzodiazepines, and should not be mono-therapy, and can be extremely dangerous if mixed with opioids

34 SUD and anxiety / PTSD summary Anxiety disorders often predate the SUD, but once they co-occur they help to maintain each other SSRIs remain first-line and most studied for the comorbidity Caution should be exercised in using benzodiazepines in this patient population Trauma and PTSD are common comorbidities, are often underdiagnosed, and the PTSD can worsen treatment outcomes if not addressed Both psychosocial and medication treatments are effective for PTSD, and may have beneficial effect on OUD treatment

35 Outline 1. Independent vs substance-induced psychiatric disorders 2. Treatment of mood disorders comorbid with SUD 3. Treatment of anxiety disorders comorbid with SUD 4. Treatment of ADHD comorbid with SUD 5. Treatment of other SUDs comorbid with OUD

36 Treatment of ADHD: Is it safe to use stimulants or not? Approximately 10 20% of SUD patients will also have ADHD (Levin et al 1998; Clure et al 1999; King et al 1999; Schubiner et al 2000; Daigre et al 2009) Meta-analysis with some conflicting results about impact of stimulant treatment of ADHD: o ADHD treatment with stimulants do not show any impact on later development of SUD (Humphreys et al JAMA Psychiatry 2013) o Stimulant treatment of ADHD was linked with reduced risk of later SUD (Groenman et al BJP 2013)

37 istockphoto Factors leading to overdiagnosis of ADHD in those with SUD (1) Acute and chronic effects of substances can mimic ADHD Relying on screening instruments alone Not ensuring symptoms in multiple domains/significant impairment Desire for nonmedical use of stimulants Levin 2016 AAAP

38 Factors leading to overdiagnosis of ADHD in those with SUD (2) Inability to recall symptoms prior to age 12 due to chaotic home environment Estrangement from family members who can provide collateral information Parents with SUD may not be able to remember Levin 2016 AAAP

39 Treatment of comorbid ADHD and SUD Nonstimulants may be best first-line agents o Best evidence: Atomoxetine o Limited evidence: TCA, clonidine, bupropion Stimulants o In general, methylphenidate is effective for ADHD, but impact on SUD controversial o In research studies, patients do not commonly misuse or divert methylphenidate Psychosocial treatments o CBT o Psychoeducation Wilens TE. Psychiatr Clin North Am. 2004;27(2): Riggs PD et al., J Am Acad Child Adolesc Psychiatry, 1998;37(3): Schubiner H. CNS Drugs. 2005;19(8): Wilson JJ, Levin FR. J Child Adolesc Psychopharmacol. 2005;15: Mariani JJ, Levin FR. Adv Psychiatry, 2006.

40 Outline 1. Independent vs substance-induced psychiatric disorders 2. Treatment of mood disorders comorbid with SUD 3. Treatment of anxiety disorders comorbid with SUD 4. Treatment of ADHD comorbid with SUD 5. Treatment of other SUDs comorbid with OUD

41 Self-report past year use of other substances for those seeking buprenorphine treatment in urban primary care clinic (n=382) 79.6% 47.1% 43.2% Alcohol Cocaine Tobacco Alford et al 2011

42 Use of other substances in the past 7 days among OUD patients seeking buprenorphine treatment in urban primary care clinic (n=103) 82% 18% 23% 30% Heavy alcohol use Benzodiazepine Cocaine Tobacco Lee et al 2008

43 Comorbid SUD in prescription opioid-dependent patients at baseline in those entering buprenorphine treatment (n=653) Past year Rx opioid dependence Lifetime opioid dependence Alcohol Dependence Cannabis Dependence Cocaine Dependence Other stimulant Dependence Sedative Dependence None Weiss et al 2011

44 Alcohol Alcohol use common among OUD patients (Hartzler et al 2010) Alcohol use does not predict worse OUD outcomes (Weinstein et al 2017) Given the synergistic effects of CNS depressants and opioids, patients should be counseled about the dangers of mixing alcohol, sedative/hypnotics, and opioid medications

45 Treatment for alcohol Pharmacologic treatments Acamprosate and disulfiram Naltrexone is contraindicated for those on medication for addiction treatment such as buprenorphine or methadone Psychosocial treatments Motivational enhancement therapy Cognitive behavioral therapy (CBT) Recovery Activities/Resources 12-step facilitation 12-step programs Donovan et al 2008; Jonas et al 2014

46 Marijuana Marijuana use common among OUD patients Studies show that marijuana use does not predict worse OUD outcomes (Hill et al 2013; Budney et al 1998; Church et al 2001; Epstein and Preston 2003; Nierenberg et al 1996; Saxon et al 1993) Some that do show worse outcomes during MMT (Dupont and Saylor 1998; Wasserman et al 1998) Improved outcomes with naltrexone (Church et al 2001; Raby et al 2009) No reason to conclude treatment is not working or that it will derail treatment if there is ongoing marijuana use

47 Treatment for Marijuana (1) Pharmacologic treatments No FDA-approved medications currently available Some promising medications exist but research very limited o Cannabinoid Agonists (THC, dronabinol, nabilone) o Gabapentin o N-Acetylcysteine

48 istockphoto Treatment for Marijuana (2) Psychosocial treatments Motivational enhancement therapy Cognitive behavioral therapy (CBT) Contingency management (CM) Family-based program

49 Cocaine Cocaine use prevalent among OUD patients, and difficult to treat even if patients are motivated Cocaine use could lower buprenorphine levels (McCance-Katz 2010) Studies show mixed results, some showing no difference in outcomes, while others show cocaine users have worse outcomes (Stein et al 2005; Cunningham et al 2008, 2013; Sullivan et al 2010a, 2010b) More consistent results in MMT showing cocaine use associated with worse outcomes (Perez et al 1997; Hartel et al 1995; Magura et al 1998) Cunningham et al 2013

50 Evidence supports treating OUD with buprenorphine in patients with or without cocaine use (1) Cunningham et al 2013

51 Evidence supports treating OUD with buprenorphine in patients with or without cocaine use (2) Cunningham et al 2013

52 Treatment for cocaine Pharmacologic treatments No FDA-approved medications currently available Some promising results but research limited Psychosocial treatments No evidence for any single intervention to be effective But cognitive approaches with contingency management shows promise (Knapp et. al, Cochrane Review 2007)

53 Dual diagnosis patients are disproportionately affected by tobacco Individuals with mental illness or substance use disorders AIDS Obesity Alcohol Motor Homicide Drug Suicide Smoking Vehicle Induced Centers for Disease Control and Prevention, NHIS, 2007; CDC 2014

54 Should tobacco use be treated at the same time as other SUDs, or should it be delayed? Majority of studies support concurrent treatment of tobacco and other substances (Prochaska et al 2004) Treatment with individuals in addictions treatment was associated with a 25% increased abstinence from alcohol and illicit drugs

55 Treatment for tobacco Pharmacologic treatments First-line agents o Nicotine replacement (patch, gums, etc) o Varenicline o Bupropion Psychosocial treatments mpaign/tips/quit-smoking/ Physician advice, individual counseling, telephone counseling, group programs, hypnotherapy, motivational interviewing

56 Lindson-Hawley et al 2015 Motivational interviewing (MI) is effective for reducing tobacco use Cochrane Systematic Review o 28 studies, 16,000 participants o 1 to 6 sessions, 10 to 60 minutes each o Biochemically validated abstinence o Delivered by PCPs, hospital clinicians, nurses or counselors MI vs brief advice: RR 1.26 (95%CI 1.16 to 1.36) PCPs had the greatest impact (RR 3.49) Single sessions of <20 mins were effective!!

57 Unit Resources: The Management of Post-Traumatic Stress Guideline Summary (pdf) Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition) National Health Interview Survey (2014) CDC- Tips from Former Smokers