Behavioral Interventions for Addictions and Co-Occurring Disorders Suzette Glasner-Edwards, Ph.D. UCLA Integrated Substance Abuse Programs February 28 th, 2013

Acknowledgements Collaborators: Patricia Marinelli-Casey, Ph.D., Maureen Hillhouse, Ph.D., Alfonso Ang, Ph.D., Larissa Mooney, M.D., Richard Rawson, Ph.D. Thanks to the treatment and research staff at the participating community-based center sites and the study investigators in each region. Thanks to the treatment and research staff at the participating community-based center sites and the study investigators in each region. The research presented in this talk was supported by grants provided by NIDA (K23DA20085 and R21DA029255), the Center for Substance Abuse Treatment (CSAT), Substance Abuse and Mental Health Services Administration (SAMHSA), US Department of Health and Human Services.

Disclosure Information Continuing Medical Education committee members and those involved in the planning of this CME Event have no financial relationships to disclose. Suzette Glasner-Edwards I have no financial relationships to disclose

Overview Clinical course and outcomes of substance users with comorbid psychiatric disorders Clinical course and outcomes of substance users with comorbid psychiatric disorders Behavioral interventions with promise Behavioral interventions with promise Integrated treatments Integrated treatments CBT/MI CBT/MI Mindfulness Based Relapse Prevention Mindfulness Based Relapse Prevention

Background  Affective Disorders are among the most common Axis I disorders for most drugs of abuse.  26% of adults with SUDs have lifetime history of affective disorder  27% of adults with unipolar depression have lifetime history of SUDs.  Depression-SUD comorbidity is associated with poorer outcomes whether treatment targets the SUD or the depression. (e.g., Stein et al., 2004)  Outcomes for this population appear to be optimized by: (1) Integrating therapy content for both problems (1) Integrating therapy content for both problems (2) Using CBT (3) Improving retention

Course and Outcomes of Methamphetamine Users With Co-Occurring Disorders Participants: a subset (N=526) of adults who were recruited to participate in the Methamphetamine Treatment Project (Rawson et al., 2004) participated in a longitudinal follow- up study. Participants: a subset (N=526) of adults who were recruited to participate in the Methamphetamine Treatment Project (Rawson et al., 2004) participated in a longitudinal follow- up study. Inclusion criteria: Inclusion criteria: Age 18 or over Age 18 or over MA dependence MA dependence Able to understand English and attend treatment Able to understand English and attend treatment Exclusion criteria: Exclusion criteria: Medical impairment compromising safety to participate Medical impairment compromising safety to participate Need for medical detox from alcohol/opioids/other substances Need for medical detox from alcohol/opioids/other substances Psychiatric impairment warranting hospitalization/primary tx Psychiatric impairment warranting hospitalization/primary tx

Study Design (cont’d) Assessments conducted by trained interviewers at Assessments conducted by trained interviewers at Baseline Baseline Tx discharge Tx discharge Post-treatment (M=3.1 years) Post-treatment (M=3.1 years) Inclusion criteria: Inclusion criteria: Age 18 or over Age 18 or over MA dependence with recent use (i.e., past 30 days) MA dependence with recent use (i.e., past 30 days) Able to understand English and attend treatment Able to understand English and attend treatment Exclusion criteria: Exclusion criteria: Medical impairment compromising safety to participate Medical impairment compromising safety to participate Need for medical detox from alcohol/opioids/other substances Need for medical detox from alcohol/opioids/other substances Psychiatric impairment warranting hospitalization/primary tx Psychiatric impairment warranting hospitalization/primary tx Recent participation in another drug treatment program Recent participation in another drug treatment program

Measures Mini-International Neuropsychiatric Interview (MINI) (Sheehan et al., 1998) was given at 3-year follow-up to assess DSM-IV current psychiatric disorders Mini-International Neuropsychiatric Interview (MINI) (Sheehan et al., 1998) was given at 3-year follow-up to assess DSM-IV current psychiatric disorders Life Experiences Timeline was given at follow-up to assess substance use Life Experiences Timeline was given at follow-up to assess substance use Addiction Severity Index (McLellan et al., 1980) was given at all timepoints, providing data regarding: Addiction Severity Index (McLellan et al., 1980) was given at all timepoints, providing data regarding: MA use frequency in the 30 days prior MA use frequency in the 30 days prior Composite severity scores in 7 functional domains Composite severity scores in 7 functional domains Beck Depression Inventory (Beck et al., 1961) was given at each assessment to measure depression severity Beck Depression Inventory (Beck et al., 1961) was given at each assessment to measure depression severity Brief Symptom Inventory (Derogatis and Melisaratos, 1983) was given at each assessment to measure psychological symptom severity across 9 domains. Brief Symptom Inventory (Derogatis and Melisaratos, 1983) was given at each assessment to measure psychological symptom severity across 9 domains. Treatment adherence: continuous variable indicating the number of weeks of scheduled treatment attended Treatment adherence: continuous variable indicating the number of weeks of scheduled treatment attended

Psychiatric Disorders in Methamphetamine Dependent Adults Glasner-Edwards, S., Mooney, L.J., Marinelli-Casey, P., Hillhouse, M., Ang, A., Rawson, R.A. (2010). Psychopathology in methamphetamine dependent adults 3 years after (2010). Psychopathology in methamphetamine dependent adults 3 years after treatment. Drug and Alcohol Review, 29:

Results: Psychiatric Diagnoses (N=526) DiagnosisCurrent (%)Life (%) Any Psychiatric Disorder Affective Disorders Major Depression15.2*** Major Depression, Recurrent***9.1 Mania Hypomania Any Affective Disorder Any Anxiety Disorder23.4*** Psychotic Disorders Antisocial Personality Disorder***25.8

Psychiatric Diagnoses and Outcomes Of those who participated in the Methamphetamine Treatment project, 48% met criteria for a current or past psychiatric disorder. Of those who participated in the Methamphetamine Treatment project, 48% met criteria for a current or past psychiatric disorder. Mood disorders, anxiety disorders, and antisocial personality disorders were the most common diagnoses. Mood disorders, anxiety disorders, and antisocial personality disorders were the most common diagnoses. MA use MA use Those with an Axis I disorder reported greater frequency of MA use during follow-up (M=15.5 months, SD=0.8) compared to those without a diagnosis (M=12.8 months, SD=0.8), t(523)= -2.0, p=0.03. Those with an Axis I disorder reported greater frequency of MA use during follow-up (M=15.5 months, SD=0.8) compared to those without a diagnosis (M=12.8 months, SD=0.8), t(523)= -2.0, p=0.03. Those with Antisocial Personality Disorders reported using less frequently than those without ASPD (M=11.9 vs. M=14.8 months), t(523)=2.0, p=0.03. Those with Antisocial Personality Disorders reported using less frequently than those without ASPD (M=11.9 vs. M=14.8 months), t(523)=2.0, p=0.03. MA use frequency during FU increased as a function of the number of psychiatric diagnoses (β=0.68, SE=0.29, p=0.02). MA use frequency during FU increased as a function of the number of psychiatric diagnoses (β=0.68, SE=0.29, p=0.02). Other psychosocial and functional outcomes Other psychosocial and functional outcomes Those with an Axis I disorder evidenced problems of significantly greater severity from baseline to follow-up on a subset of ASI composites and BSI scales: Those with an Axis I disorder evidenced problems of significantly greater severity from baseline to follow-up on a subset of ASI composites and BSI scales: ASI: Alcohol, drug, psychiatric ASI: Alcohol, drug, psychiatric BSI: anxiety, phobic anxiety BSI: anxiety, phobic anxiety

Major Depressive Disorder in Methamphetamine Dependent Adults Glasner-Edwards, S., Marinelli-Casey, P., Hillhouse, M., Ang, A., Mooney, L.J., Rawson, R.A. (2009). Depression among methamphetamine users: association with outcomes from the Methamphetamine Treatment Project at 3-year follow-up. Journal of Nervous and the Methamphetamine Treatment Project at 3-year follow-up. Journal of Nervous and Mental Disease, 197:

Depressive Symptoms and MA Use Those who remained abstinent from MA showed a greater reduction in depressive symptoms as compared to those who used within 30 days prior to treatment discharge (β=5.1, SE=0.69, p<0.0001).

Results: Major Depressive Disorder

Major Depressive Disorder: cont’d Summary of findings Summary of findings Abstainers shifted from clinically significant depressive symptoms at treatment entry to the normal/minimal symptom range at discharge. Abstainers shifted from clinically significant depressive symptoms at treatment entry to the normal/minimal symptom range at discharge. Those with Major Depressive Disorder at follow-up had poorer methamphetamine use outcomes. Those with Major Depressive Disorder at follow-up had poorer methamphetamine use outcomes. Depression severity at follow-up was greater for those who used methamphetamine intravenously, relative to those who used other routes of administration. Depression severity at follow-up was greater for those who used methamphetamine intravenously, relative to those who used other routes of administration. Those with Major Depression had worsening depressive symptoms, overall psychiatric severity, and psychosocial outcomes from discharge to follow-up. Those with Major Depression had worsening depressive symptoms, overall psychiatric severity, and psychosocial outcomes from discharge to follow-up.

Anxiety Disorders in Methamphetamine Dependent Adults Glasner-Edwards, S., Mooney, L.J., Marinelli-Casey, P., Hillhouse, M., Ang, A., Rawson, R.A. (2010). Anxiety disorders among methamphetamine dependent adults: association with posttreatment outcomes. American Journal on Addictions, 19(5):

Results: Anxiety Disorders 26.2% of the sample was diagnosed with an anxiety disorder (current or past). 26.2% of the sample was diagnosed with an anxiety disorder (current or past). Those with anxiety disorders reported greater MA use frequency during 3-year follow-up compared to those without an anxiety disorder. Those with anxiety disorders reported greater MA use frequency during 3-year follow-up compared to those without an anxiety disorder. Those with anxiety disorders were more likely to have been hospitalized within the year prior to FU than those without a diagnosis (OR=1.8, 95% C.I., ) and to have attempted suicide in their lifetimes (OR=3.1, 95% C.I., ). Those with anxiety disorders were more likely to have been hospitalized within the year prior to FU than those without a diagnosis (OR=1.8, 95% C.I., ) and to have attempted suicide in their lifetimes (OR=3.1, 95% C.I., ). Participants with anxiety disorders had poorer treatment adherence (M=6.2 vs. 7.6 weeks, t=2.3, df=524, p=0.02), were more likely to meet criteria for alcohol- (OR=1.8) or other substance dependence (OR=2.2) at 3-year follow-up, and evidenced declining functional outcomes on the ASI (drug, psychiatric) from baseline to FU. Participants with anxiety disorders had poorer treatment adherence (M=6.2 vs. 7.6 weeks, t=2.3, df=524, p=0.02), were more likely to meet criteria for alcohol- (OR=1.8) or other substance dependence (OR=2.2) at 3-year follow-up, and evidenced declining functional outcomes on the ASI (drug, psychiatric) from baseline to FU.

PTSD Symptoms as Risk Factors for Post- Treatment Methamphetamine Use Glasner-Edwards, S., Mooney, L.J., Ang, A., Hillhouse, M., Rawson, R.A. (in press). PTSD symptoms as risk factors for Drug and Alcohol Review, 29: (in press). PTSD symptoms as risk factors for Drug and Alcohol Review, 29:

Results: PTSD Those with PTSD reported greater MA use frequency during 3-year follow-up compared to those without an anxiety disorder. Those with PTSD reported greater MA use frequency during 3-year follow-up compared to those without an anxiety disorder. MA use frequency was associated with specific PTSD symptom clusters; higher levels of use were predicted by avoidance ( β=1.58, SE=0.58; p<0.01) and arousal (β=1.50, SE=0.62; p<0.05) symptoms. MA use frequency was associated with specific PTSD symptom clusters; higher levels of use were predicted by avoidance ( β=1.58, SE=0.58; p<0.01) and arousal (β=1.50, SE=0.62; p<0.05) symptoms. Participants with PTSD were more likely to have an additional Axis I disorder (particularly, mood psychotic, and eating disorders). Participants with PTSD were more likely to have an additional Axis I disorder (particularly, mood psychotic, and eating disorders).

Psychotic Disorders in Methamphetamine Dependent Adults Glasner-Edwards, S., Mooney, L.J., Marinelli-Casey, P., Hillhouse, M., Ang, A., Rawson, R.A. (2008). Clinical course and outcomes of methamphetamine dependent adults with psychosis. Journal of Substance Abuse Treatment. 35,

Results: Psychotic Disorders 12.9% of the sample was diagnosed with a psychotic disorder (current or past). 12.9% of the sample was diagnosed with a psychotic disorder (current or past). Those with psychotic illness were more likely to have been hospitalized within the year prior to FU than those without a diagnosis (OR=2.4, 95% C.I., ) and reported more episodes (β=0.33, SE=0.11, p<0.01). Those with psychotic illness were more likely to have been hospitalized within the year prior to FU than those without a diagnosis (OR=2.4, 95% C.I., ) and reported more episodes (β=0.33, SE=0.11, p<0.01). Those with psychotic illness evidenced declining functional outcomes on the ASI (medical, employment, legal) and worsening psychological impairment on the BSI from baseline to FU. Those with psychotic illness evidenced declining functional outcomes on the ASI (medical, employment, legal) and worsening psychological impairment on the BSI from baseline to FU. No difference in MA use frequency among those with and without psychotic disorders during FU (M= versus months); no difference in tx adherence. No difference in MA use frequency among those with and without psychotic disorders during FU (M= versus months); no difference in tx adherence.

Summary Rates of psychiatric disorders in MA users are moderate relative to that observed in cocaine users but notably higher than prevalence estimates of such syndromes in the general population. Rates of psychiatric disorders in MA users are moderate relative to that observed in cocaine users but notably higher than prevalence estimates of such syndromes in the general population. Poorer functional outcomes are associated with psychiatric illness in MA users. Poorer functional outcomes are associated with psychiatric illness in MA users. MA use outcomes are poorer among MA users with psychiatric comorbidity. MA use outcomes are poorer among MA users with psychiatric comorbidity. Abstinence promotes psychiatric symptom recovery. Abstinence promotes psychiatric symptom recovery. Concurrently addressing psychiatric symptoms and relapse susceptibility may optimize outcomes in this population. Concurrently addressing psychiatric symptoms and relapse susceptibility may optimize outcomes in this population.

True or False: People who stay abstinent from methamphetamine during treatment show reductions in depression symptoms.

Integrated Interventions (CBT and MI)

Integrated Interventions  Gold standard approach for the treatment of COD; demonstrated efficacy in:  Reducing hospitalizations in substance users with comorbid affective disorders or schizophrenia (e.g., Granholm et al., 2003)  Reducing psychiatric symptoms and substance abuse among those with co-occurring SUD and PTSD (Back et al., 2010)  Improving depressive symptoms and reducing substance use among adults with SUD and major depression (Brown et al., 2006)

Changes in Depression in Twelve-Step Facilitation versus Integrated CBT Source: Brown et al. (2006) PreTx Treatment Posttreatment TSF ICBT

Changes in Substance Use in Twelve-Step Facilitation versus Integrated CBT Source: Brown et al. (2006) TSF ICBT PreTx Treatment Posttreatment

Continuing Care Approaches  Continuing care is critical, particularly within the first 6 months after treatment, given the relapsing nature of addictive disorders  Randomized continuing care trials for substance users to date have mostly excluded those with concomitant psychopathology  12-step self-help programs are the most prevalent aftercare approaches, and outcomes appear to be comparable to CBT and MET (Ouimette et al., 1997, Brown et al., 2002) for those with SUD-only.  But what about those with comorbidity?

Study Overview  Pilot clinical trial of integrated CBT and Motivational Therapy (CBT-MT) for Substance Dependent adults with Major Depressive Disorder (N=68)  CBT-MT addresses both depression and substance dependence with CBT and incorporates motivational exercises in each session targeting engagement and retention in continuing care for both conditions.  CBT-MT is expected to facilitate retention in treatment and to improve depression and substance use outcomes, relative to treatment as usual, a dual recovery anonymous self-help group (DRA).  Study Design: Participants receiving treatment in a day hospital program at UCLA were randomly assigned at discharge to either:  Integrated CBT and Motivational Therapy (CBT-MT)  Treatment As Usual (Dual Recovery Anonymous) (DRA)

Inclusion Criteria  Participants qualified for the study if they:  Were at least 18 years old  Had a diagnosis of current substance dependence (alcohol, cannabis, stimulant, or opioid)  Had a diagnosis of lifetime Major Depressive Disorder (independent of substance use)  Had current depressive symptoms >13 on the BDI Potential participants were excluded for psychosis and bipolar disorder, or suicidality warranting hospitalization.

Study Design  Group CBT-MT, a weekly, 12-week group intervention draws from group CBT and MI manualized treatments:  Integrated CBT for depression and SUDs (Brown et al., 2006)  Group Motivational Interviewing (Santa Ana, 2005)  Participants were assessed for depression and substance use at baseline, weekly during treatment, and 12 and 24 weeks post-treatment. Measures included:  BDI  HAM-D  Addiction Severity Index  Psychiatric Research Interview for Substance and Mental Disorders (PRISM) (Hasin et al., 2006)  We hypothesized that CBT-MT would produce superior treatment retention, depression and substance use outcomes.

Demographics OverallCBTDRA N%N%N% Age Gender Male Female Ethnicity Caucasian Marital Status Married Never Married Baseline BDI scores The sample comprised mostly cannabis (40%) and alcohol (25%) users, followed by prescription drug (19%) and stimulant users.

Percent Attending Sessions Each Week, By Group.

Percentage of Participants With Improvement in Depression, By Attendance to >10 Sessions In the overall sample, a significantly greater % of those who attended more than 10 sessions experienced improvements in depressive symptoms, (100%) chi- square=4.8, p=0.02, relative to those who attended 10 sessions or fewer (67%).

Percentage of Participants Attending >10 Sessions, by Group Compared to those who received DRA, the proportion of those in CBT-MT who completed most or all of the sessions was significantly greater, chi square=4.48, p=.03.

Percentage of Participants With Improvement in Depressive Symptom Severity Over Baseline A significantly greater proportion of those in the CBT-MT condition (67%) showed a reduction from baseline to their last available assessment in total BDI scores, as compared to controls (37%); chi-square=5.9, p=0.01).

Percentage of Participants Who Used Drug of Choice in the Past 30 Days

Conclusions In our pilot study of CBT-MT as a continuing care approach for depressed substance users, preliminary results suggest that : In our pilot study of CBT-MT as a continuing care approach for depressed substance users, preliminary results suggest that : This approach effectively facilitates treatment retention. This approach effectively facilitates treatment retention. Treatment retention is associated with reductions in depressive symptoms. Treatment retention is associated with reductions in depressive symptoms. Preliminary drug use outcomes do not differ between groups. Preliminary drug use outcomes do not differ between groups. Areas we are currently evaluating include: mechanisms of therapeutic change, effects of the intervention on time to relapse, and evaluation of the impact of baseline cognitive functioning on treatment response. Areas we are currently evaluating include: mechanisms of therapeutic change, effects of the intervention on time to relapse, and evaluation of the impact of baseline cognitive functioning on treatment response.

References Brown, S.A., Glasner, S.V., Tate, S.R., McQuaid, J.R., Chalekian, J., & Granholm, E. (2006). Integrated cognitive behavioral therapy versus twelve-step facilitation for substance dependent adults with depressive disorders. Journal of Psychoactive Drugs., 38(4): Brown, T.G., Seraganian, P., Tremblay, J., & Annis, H. (2002). Process and outcome changes with relapse prevention versus 12-step aftercare programs for substance abusers. Addiction, 97: Hasin, D., Samet, S., Nunes, E., Meydan, J., Matseoane, K., & Waxman, R. (2006). Diagnosis of comorbid disorders in substance users: Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV). American Journal of Psychiatry., 163(4), Ouimette, P.D., Finney, J.W., & Moos, R.H. (1997). Twelve-step and cognitive-behavioral treatment for substance abuse: a comparison of treatment effectiveness. Journal of Consulting and Clinical Psychology, 65: Santa Ana, E. (2005). Group Motivational Interviewing Treatment Manual (GMI) for Individuals with Psychiatric and Comorbid Substance Use Problems (pp. 1-25): Yale University School of Medicine and VA CT Healthcare System. Stein, M.D., Herman, D.S., Solomon, D.A., Anthony, J.L., et al. (2004). Adherence to treatment of depression in active injection drug users: the Minerva study. Journal of Substance Abuse Treatment, 26(2):

True or False: Outcomes of integrated treatments for continuing care are no better than those of standard, 12-step self-help based continuing care for those with co- occurring disorders.

Mindfulness Based Relapse Prevention

Study Overview  Pilot RCT of Mindfulness Based Relapse Prevention (MBRP) for Stimulant Users (N=62)  Mindfulness involves cultivating awareness of one’s moment-to- moment experience in a non-judgmental way.  Mindfulness is expected to improve affect regulation as well as stress reactivity, thereby reducing relapse susceptibility  Study Design: All participants receive contingency management for 12 weeks and are concurrently randomly assigned to either  Mindfulness Based Relapse Prevention (MBRP) or  Health Education

Beck Depression Inventory Those in the MBRP condition showed a greater reduction in depressive symptoms through 1 month post-treatment, relative to controls (p<0.03; Effect Size=0.58).

Beck Anxiety Inventory Those in the MBRP condition showed a greater reduction in anxiety symptoms through 1 month post-treatment, relative to controls (p<0.02; Effect Size=0.72).

Addiction Severity Index: Psychiatric Composite Those in the MBRP condition showed a greater reduction in overall psychiatric severity through 1 month post-treatment as compared to controls (p<0.02; Effect Size=0.61).

Short Inventory of Problems Those in the MBRP condition showed a greater reduction from baseline to 1 month post-treatment in problems related to stimulant dependence, as compared to controls (p<0.10; Effect Size=0.06).

Stimulant Use Outcomes Number of stimulant-free UA% UA that were stimulant-free Those in the MBRP condition showed comparable reductions in stimulant use during both the 4-week Contingency Management Lead-In and the subsequent 8- week Mindfulness Intervention Phase, compared to controls.

Stress Reactivity Before and After Treatment With Mindfulness or Health Education Control After treatment ended (right panel), cortisol levels during the hour following exposure to a laboratory stressor were elevated in a substantially larger proportion of control group participants, relative to MBRP participants, for whom post- stressor cortisol levels returned to baseline or lower. Post-TreatmentPre-Treatment

Difficulty in Emotional Regulation Scale

Five Factor Mindfulness Scale

Summary In our pilot study of mindfulness based relapse prevention for stimulant users, preliminary results suggest that : In our pilot study of mindfulness based relapse prevention for stimulant users, preliminary results suggest that : This approach effectively reduces negative affect, stress reactivity, psychiatric impairment, and may reduce stimulant dependence severity. This approach effectively reduces negative affect, stress reactivity, psychiatric impairment, and may reduce stimulant dependence severity. Changes in putative psychological mechanisms underlying the effectiveness of mindfulness (e.g., emotion regulation, adoption of a mindful approach to living) are observed in this population. Changes in putative psychological mechanisms underlying the effectiveness of mindfulness (e.g., emotion regulation, adoption of a mindful approach to living) are observed in this population.

True or False: Mindfulness interventions were originally developed as a means of reducing stress.

Conclusions Clinical course and outcomes of substance users with COD are poorer across multiple domains compared to those with SUD alone. Clinical course and outcomes of substance users with COD are poorer across multiple domains compared to those with SUD alone. Integrated interventions effectively improve outcomes, both as a primary treatment strategy, and for continuing care for those with affective disorders and SUDs. Integrated interventions effectively improve outcomes, both as a primary treatment strategy, and for continuing care for those with affective disorders and SUDs. Mindfulness based interventions are a promising new target for COD, with efficacy in reducing stress reactivity, negative affect, and overall psychiatric severity among substance users. Mindfulness based interventions are a promising new target for COD, with efficacy in reducing stress reactivity, negative affect, and overall psychiatric severity among substance users.

Thank you! Suzette Glasner-Edwards, Ph.D