# Presentation: 108339

## Objectives

- The importance of identifying and treating bipolar disorder among patients with SUD’s as early as possible
- Ways to address and treat bipolar patients' SUDs – through psychosocial interventions, integrated care, or other treatment models
- Psychopharmacologic treatment of patients with bipolar disorder & SUD’s

## Early Identification of Bipolar Disorderin Substance Use Disorder (BD-SUD)

- 7- to10-year lag diagnosing BD in the general population
- Clinical Barriers:
- Substances as triggers  more episodes
- Episodes as triggers  substance use
- Diagnostic dilemmas and dismissals:
- “It’s all due to...substances.”
- “It’s all due to...bipolar disorder.”

## Early Identification in BD-SUD

- System Barriers
- Financing
- Healthcare Organization
- Training and Culture
- SAMHSA’s No Wrong Door Policy
- VHA Advantage: There is no wrong door...
- 		...theoretically...

## Principles of BD-SUD Treatment

- Parallel (not serial) treatment
- Goals of Parallel Treatment
- Get substances “off the table” for dealing with illness and life
- Stabilize symptoms to allow participation in substance treatment

## Principles of BD-SUD Treatment

- Look for and seek out complications
- Depression
- Mania
- Subtle Psychosis
- Anxiety
- Perseverance:
- “Sometimes the 17th time’s a charm...”
- Collaboration beats confrontation

**Notes:**
Bauer MS, Altshuler L, Evans DR, et al. VA Cooperative Study #430 Team. Prevalence and distinct correlates of anxiety, substance, and combined comorbidity in a multi-site public sector sample with bipolar disorder. J Affective Disorders 2005;85:301-15. 

## Paternalistic Medicine

**Paternalistic Medicine**

**Maternalistic Medicine**

- “Load ‘em on.”

- “Thus I say...”

- “Yes I shall!”

- “Fix me up!”

## Collaborative Practice

**Collaborative Practice**

- Technical
- Expert
- “Coach”

- Values
- Expert
- “Athlete”

## Examples of Collaborative Interventions for BD-SUD

- Motivational Interviewing
- Miller & Rollnick and others
- Integrated Group Therapy
- Weiss
- Life Goals Program & Collaborative Chronic Care
- VA Cooperative Study #430

**Notes:**
Bauer MS, Williford WO, Dawson EE. Principles of effectiveness trials and their Implementation in VA Cooperative Study #439: “Reducing the efficacy-effectiveness Gap in Bipolar Disorder.” J Affect Disorder 2001; 67: 61-78.
Miller WR, Yahne CE, Moyers TB, Martinez J, Pirritano M A randomized trial of methods to help clinicians learn motivational interviewing. J of consulting and clinical psychology. 2004; 72:1050-62.
Miller WR, Yahne CE, Tonigan JS Motivational interviewing in drug abuse services: a randomized trial. Journal of consulting and clinical psychology. 2003; 71:754-63. 
Miller W, Rollnick S. Motivational interviewing: preparing people to change. New York: Guilford Press, 2002. 
Salloum IM and Thase, ME. Impact of substance abuse on the course and treatment of bipolar disorder. Bipolar Disorders 2000; 2:269-280.
Weiss RD, Najavitis LM. Overview of treatment modalities for dual diagnosis patients: pharmacotherapy, psychotherapy and 12-step programs. In: Kranzler H, Rounsaville H, Bruce J, eds. Dual Diagnosis and Treatment: Substance Abuse and Comorbid Medical and Psychiatric Disorders, viii ed. New York: Marcel Dekker, 1998;107-137.
Weiss RD, Greenfield SF, Najavitis LM, et al. Medication compliance among patients with bipolar disorder and substance use disorders. J Clin Psychiatr 1998; 59: 172-74.
Weiss RD, Najavitis LM, Greenfeld SF, A relapse prevention group for patients with bipolar and substance use disorders. J Subst Abuse Treat. 1999; 16: 47-54.

## Purposes of Psychosocial Interventions 

- Supplement (not replace) pharmacologic treatment
- Enhance illness management skills
- Address independent determinants of disease outcome (stressors, comorbidities)
- Enhance social role function and quality of life
- Reduce depression

## Types of PsychosocialInterventions 

- Psychotherapies: Add-on
- Integrated Treatment Models: Multimodal Packages

## Types of Individual Psychotherapy 

- Psychodynamic (Past life events)
- Supportive (Current life events)
- Interpersonal (Social relationships)
- Cognitive Behavioral (Thought habits)
- Social Rhythm (Stabilizing social rhythms)
- Psychoeducation (Knowledge and coping strategies)

## Group Psychotherapy  

- Mutual support
- Shared experiences
- Work on personal goals
- Stigma reduction

## Other Psychotherapy 

- Family Therapy
- Challenges in relationships between family members-conflict resolution
- Increase supportive family relationships
- Self-help Groups

## Integrated Treatment Models

- Intensive Case Management
- Recovery-Oriented Programs
- Collaborative Chronic Care Models

## Intensive Case Management

- Involves mobile community outreach, rehabilitative services via provider teams
- Examples: ACT, MHICM
- Effective for SMI and co-occurring SUD
- High start-up costs impede dissemination into routine care

**Notes:**
ACT=Assertive Community Treatment
MHICM=Mental Health Intensive Case Management
SMI= Serious Mental Illness

## Recovery-Oriented Programs

- “Mental health recovery is a journey of healing and transformation enabling a person with a mental health problem to live a meaningful life in a community of his or her choice while striving to achieve his or her full potential.” SAMHSA 2005
- Include peer support, vocational training, family involvement, and other services

## Collaborative Chronic Care Models

- Clinic-based tools to promote self-management and continuity of care for chronic illnesses
- VA CSP #430
- Self-management (Life Goals Program - group sessions)
- Delivery system/clinical information system redesign
- Decision support (Clinical Practice Guidelines)

## VA CSP #430 Chronic Care Model for Bipolar Disorder

**VA CSP #430 Chronic Care Model for Bipolar Disorder**

**Self-Management**
**(Life Goals)**

**Decision Support**
**(Guidelines)**

**Delivery System**
**(Care Manager)**

## Life Goals Program

- Education, group interaction and support
- Personal symptom profile(s), warning signs
- Triggers and coping resources
- Personal cost-benefit analysis
- Action plan / personal care plan
- Destigmatization

## Responding to Depression/Stress by Drinking Alcohol

- I can finally sleep
- I don’t get panic attacks
- I don’t feel so down
- It gets me out of the house, and when I socialize, I forget my troubles

- My wife gets mad at me
- Sometimes, it makes me not care & feel like killing myself
- I feel terrible the next morning

- Good Effects

- Bad Effects

## Medications for the Management of Bipolar Disorder

- Lithium
- Anticonvulsants
- Antipsychotics
- Antidepressants
- Benzodiazepines

## Medications for the SUD Treatment

- Acamprosate
- Amantadine
- Buprenorphine/Naloxone
- Bupropion

## Medications for SUD Treatment

- Disulfiram
- Methadone
- Naltrexone
- Nicotine replacement

## Inadequacy of Treatment

- Only 59% of patients with BD-SUD were on adequate mood stabilizing regimens
- Only 0.4% were receiving substance abuse-specific medications

**Notes:**
Simon, NM, Otto, MW, Weiss, RD et al. for STEP-BD Investigators. Pharmacotherapy for Bipolar Disorder and Comorbid Conditions: Baseline Data From STEP-BD. J Clin Psychopharmacol. 2004; 24: 512-520.

## Reasons for Non-Response

- Non-adherence
- Inadequate dosing
- Relapse to substance use
- Incorrect diagnosis/indication
- Drug interactions
- Adverse drug reactions

**Notes:**
Alcohol + psych meds Disulfiram-acetaldehyde (death?), MAOI-tyramine (hypertensive crisis), TCA- acute, inhibit metabolism; chronic, induce metabolism
Neuroleptics- CNS (akathisia, dystonia)
Barbs – enzyme induction, resp depression
Bz’s and opiates – resp depression 
Stimulants – exacerbation of psychosis
Nicotine – enzyme induction; stop smoking – enzyme revert to nl and levels may rise

## Strength of Evidence

- Study design
- Randomized controlled trials
- Open-label trials
- Retrospective studies
- Case series/reports
- Outcome measures

## Lithium

- 2 open-label 12 week studies
- Cocaine dependent patients
- N=16
- 3/16 decreased craving
- N=10
- 5/10 decreased craving
- 3/10 cocaine free x 3 wks

**Notes:**
Gawin FH, Kleber HD. Cocaine abuse treatment. Open pilot trial with desipramine and lithium carbonate. Arch Gen Psychiatry. 1984;41:903-9.

## Lithium

- 6 wk, Randomized, Double Blind, Placebo Controlled, Parallel group
- Adolescent outpts (BD I, II or MD; N=25)
- Alcohol, marijuana, inhalant, cough syrup
- Percentage of positive urine drug screens decreased in the lithium group (p=0.028)

**Notes:**
Geller B, Cooper TB, Sun K, et al. Double-blind and Placebo-controlled Study of Lithium for Adolescent Bipolar Disorders With Secondary Substance Dependency. Acad Child & Adolesc Psychiatry. 1998; 37:171-178.

## Valproate 

- 24 wk, open-label study in alcohol, cocaine or SUD outpts (N=9)
- Decreased days of substance used (p<0.005)

**Notes:**
Brady KT, Sonne SL, Anton R et al. Valproate in the Treatment of Acute Bipolar Affective Episodes Complicated by Substance Abuse. A Pilot Study. et al  J Clin Psychiatry 1995

## Valproate 

- 24 wk, RCT, in BD I pts with alcohol dependence receiving lithium (N=59)
- Fewer heavy drinking days (p=0.02)
- Higher serum concentration correlated with improved alcohol use outcomes
- No significant changes in mood symptoms

**Notes:**
Salloum IM, Cornelius JR, Daley DC et al. Efficacy of Valproate Maintenance in Patients with Bipolar Disorder and Alcoholism.  Arch Gen Psychiatry 2005;62:37-45.

## Lithium and Valproate

- 24 wk, open-label, in 56 with alcohol, cannabis, and/or cocaine dependent outpts
- 14 pts met DSM-IV criteria for full remission of alcohol or drug use disorder after 6 months

**Notes:**
Calabrese JR, Shelton MD, Bowden CL et al. Bipolar Rapid Cycling: Focus on Depression as Its Hallmark. J Clin Psychiatry 2001;62:34-41.

## Carbamazepine

- 12 wk, placebo controlled, outpts with cocaine dependence (N=139)
- N=57 cocaine dependent with mood d/o
-  N=82 without mood d/o
- Decreased drug craving
- Significantly longer time to first cocaine use in pts with mood disorders
- No difference in cocaine use in pts without mood disorders

**Notes:**
Brady KT, Sonne SC, Malcolm RJ, et al. Carbamazepine in the treatment of cocaine dependence: subtyping by affective disorder. Exp Clin Psychopharmacol. 2002: 10:276-85.

## Gabapentin

- 43 pts with bipolar disorder resistant to standard treatment received gabapentin adjunctively for 8 wks (case series)
- 18/43 (42%) responded
- Alcohol abuse was associated with positive response

**Notes:**
Perugi G, Toni C, Frare F et al. Effectiveness of Adjunctive Gabapentin in Resistant Bipolar Disorder: Is It Due to Anxious-Alcohol Abuse Comorbidity? J Clin Psychopharmacol 2002;22:584-591.

## Lamotrigine 

- 12 wk, open-label, in 30 cocaine dependent outpts
- Decreased craving and NS decrease days of use and money spent on cocaine
- No change in positive urine drug screens

**Notes:**
Brown ES, Jeffress J, Liggin JEM et al, Switching Outpatients with Biplar or Schizoaffective Disorders and Substance Abuse from their current antipsychotic to Ariprazole. J Clin Psychiatry 2003

## Aripiprazole 

- 20 antipsychotic-treated pts with bipolar or schizoaffective d/o and substance abuse switched to open-label aripiprazole for 12 wks
- 17 with alcohol dependence showed a reduction in dollars spent (p=0.042) and craving (p=0.003)
- 9 with cocaine-related d/o showed a reduction in craving (p=0.014) but not in use

**Notes:**
Brown ES, Jeffress J, Liggin JDM et al, Switching Outpatients with Biplar or Schizoaffective Disorders and Substance Abuse from their current antipsychotic to Aripiprazole. J Clin Psychiatry 2005; 66:767-760.

## Quetiapine 

- 12 wk, open-label, outpts with cocaine dependence (N=17)
- Decreased craving and NS decrease in days of cocaine use and money spent on cocaine
- Slight increase in positive urine drug screens
- Subset with alcohol use (N=14)
- Decrease in craving
- Decrease in days of alcohol use/wk but not drinks/wk

**Notes:**
Brown ES, Mejtek VA, Perantie DC et al. Quetiapine in bipolar disorder and cocaine dependence.  Bipolar Disord 2002;4:407-11.

## Ongoing RCTs

- Quetiapine vs risperidone in bipolar disorder with stimulant dependence
- Divalproex ER vs risperidone in BD-SUD

**Notes:**
www.clinicaltrials.gov

## Summary of Medications for Management of Bipolar Disorder

- Few randomized controlled trials
- Most data with valproate and carbamazepine
- Trials are short duration (no long term trials)
- Small samples
- Comorbid substances vary in studies
- Definition of response
- Further research is needed

## Use Caution When Treating  BD-SUD

- Impulsivity/Toxicity
- Tricyclics
- MAOIs
- Abuse
- Opiates
- Stimulants
- Barbiturates
- BZDs

## VANTS Call

- May 30, 2006
- 2:00 pm Eastern
- 1-800-767-1750
- Access Code 14945