Bipolar Disorder and Bipolar Disorder and Alcohol Use DisordersAlcohol Use Disorders

Marcy Verduin, M.D.Marcy Verduin, M.D.

University of Central FloridaUniversity of Central Florida

1© AMSP 2010

Challenging to TreatChallenging to Treat

Lack of treatment researchLack of treatment research

Dx challenge = symptom overlapDx challenge = symptom overlap

Rx challenges = toxicity & nonadherenceRx challenges = toxicity & nonadherence

Integrated Rx difficult to findIntegrated Rx difficult to find

2© AMSP 2010

This Lecture ReviewsThis Lecture Reviews

DefinitionsDefinitions

Prevalence, course, & causesPrevalence, course, & causes

TreatmentTreatment

3© AMSP 2010

Bipolar DisorderBipolar Disorder

1+ manic episode:1+ manic episode: 1+ week euphoric or irritable mood1+ week euphoric or irritable mood 3+ (or 4+ if irritable):3+ (or 4+ if irritable):

4© AMSP 2010

self-esteemself-esteem

need for sleepneed for sleep

talkativenesstalkativeness

Racing thoughtsRacing thoughts

DistractibilityDistractibility

goal-directed activitygoal-directed activity

pleasurable activitiespleasurable activities

Depressive EpisodesDepressive Episodes

Major depression = 5 lasting 2+ weeks:Major depression = 5 lasting 2+ weeks:

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Depressed moodDepressed mood

SSleepleep or or

IInterest nterest

GGuilt uilt or worth or worth

EEnergy nergy

CConcentration oncentration

AAppetite ppetite or or

PPsychomotor sychomotor or or

SSuicidal thoughts/attemptuicidal thoughts/attempt

Abuse & DependenceAbuse & Dependence

Abuse 1+ of:Abuse 1+ of:

ObligationsObligations

Hazardous useHazardous use

LegalLegal

Interpersonal Interpersonal

problemsproblems

Dependence 3+ of:Dependence 3+ of: ToleranceTolerance

WithdrawalWithdrawal

Amounts or more timeAmounts or more time

Desire or unable cut downDesire or unable cut down

time get, use, or recovertime get, use, or recover

non-drug activitiesnon-drug activities

Physical/psychological Physical/psychological

problemsproblems

6© AMSP 2010

Symptom OverlapSymptom Overlap

Alc Alc → symptoms of BP→ symptoms of BP

BP → symptoms of AUDBP → symptoms of AUD

Use timing of sx’s to clarifyUse timing of sx’s to clarify

Mania before AUDMania before AUD

Mania during sobrietyMania during sobriety7© AMSP 2010

BP dx

Time Line ApproachTime Line Approach

8© AMSP 2010

18 20 23 28 32 37 42Grad HS

Married Son born

AUD Mania

This Lecture ReviewsThis Lecture Reviews

Definitions Definitions ✓✓

Prevalence, course, & causesPrevalence, course, & causes

Treatment Treatment

9© AMSP 2010

PrevalencePrevalence

10© AMSP 2010

Prevalence of BP + AUDsPrevalence of BP + AUDs

Alc Dep 6 x Alc Dep 6 x mania mania

BP 6 x BP 6 x AUDs AUDs

BP = #1 BP = #1 ΨΨ disorder assoc with AUDs disorder assoc with AUDs11© AMSP 2010

AUDs Impact BP SymptomsAUDs Impact BP Symptoms

3 x 3 x onset < 20 onset < 20

4 x 4 x comorbid dx comorbid dx

2-3 x 2-3 x sx of: sx of:

ImpulsivityImpulsivity

ViolenceViolence

Suicide attempt Suicide attempt

12© AMSP 2010

AUDs Impact RecoveryAUDs Impact Recovery

risk risk ΨΨ hospitalization (45% vs 15%)hospitalization (45% vs 15%)

~4 x faster relapse to mania~4 x faster relapse to mania

Slower mood episode recovery by ~2 wksSlower mood episode recovery by ~2 wks

13© AMSP 2010

Order of Onset MattersOrder of Onset Matters

Alc 1Alc 1stst::

Older BP onset by ~10 yearsOlder BP onset by ~10 years

Longer time in mood recoveryLonger time in mood recovery

BP 1BP 1stst::

time in mood episodestime in mood episodes

Longer time with AUD sxLonger time with AUD sx

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AUD Impact AdherenceAUD Impact Adherence

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70%

40%

Shared Genetic Risk FactorsShared Genetic Risk Factors

~2 x ~2 x SUDs if relatives with BP or MDD SUDs if relatives with BP or MDD

Common chromosomal regions:Common chromosomal regions:

Chr 9 Chr 9 BP risk BP risk

effect in AUD familieseffect in AUD families16© AMSP 2010

Dysfunctional NTsDysfunctional NTs

Dopamine (DA)Dopamine (DA) Norepinephrine (NE)Norepinephrine (NE)

17© AMSP 2010

How Risk Factors How Risk Factors → BP + AUD→ BP + AUD

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BP risk

No BP

BP

No Alc

Alc

How Risk Factors How Risk Factors → BP + AUD→ BP + AUD

BP → mania → all acts done to excessBP → mania → all acts done to excess

Excess → Excess → drink drink

drink → AUDdrink → AUD

Mania resolves, but AUD remainsMania resolves, but AUD remains

19© AMSP 2010

Self-MedicationSelf-Medication

Theory:Theory:

Alc to Alc to BP sx BP sx

But prior MDD But prior MDD → → AUD AUD

Alc Alc → → dep sxdep sx

Alc Alc → → maniamania20© AMSP 2010

This Lecture ReviewsThis Lecture Reviews

Definitions Definitions ✓✓

Prevalence, course, & causes Prevalence, course, & causes ✓✓

Treatment Treatment

21© AMSP 2010

What We KnowWhat We Know

BP + AUD excluded from studiesBP + AUD excluded from studies

Joint BP + AUD difficult to studyJoint BP + AUD difficult to study

Joint dx often mixed episodesJoint dx often mixed episodes

Are dangers to use antidepressantsAre dangers to use antidepressants

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Recall Clinical VignetteRecall Clinical Vignette

42 yo man42 yo man

History of BP and Alc DepHistory of BP and Alc Dep

Residential rehabResidential rehab

30 days sober30 days sober

Not taking medsNot taking meds

Mania + depressionMania + depression23© AMSP 2010

Initial AssessmentInitial Assessment

Medical & Medical & ΨΨ issues issues, rx plan, rx plan

Most immediate need – rx withdrawalMost immediate need – rx withdrawal

Consider Consider Ψ Ψ emergenciesemergencies

Suicide Suicide

ViolenceViolence

PsychosisPsychosis

Self-neglectSelf-neglect24© AMSP 2010

Rx SettingRx Setting

25© AMSP 2010

Alc DetoxAlc Detox

Standard rx = bzStandard rx = bz

Lorazepam (AtivanLorazepam (Ativan): 2-4mg qid day 1): 2-4mg qid day 1

Taper over ~ 5 daysTaper over ~ 5 days26© AMSP 2010

Also for DetoxAlso for Detox

+/- Anticonvulsants+/- Anticonvulsants

side-effects & side-effects & costcost

Valproate (Depakote): Valproate (Depakote):

20mg/kg/day (20mg/kg/day ( bid) day 1 bid) day 1

Taper over ~ 5 daysTaper over ~ 5 days27© AMSP 2010

Rx Mood Sx in BPRx Mood Sx in BP

Mood stabilizer +/- adjunctive medsMood stabilizer +/- adjunctive meds

LithiumLithium

Anticonvulsants (e.g., valproate)Anticonvulsants (e.g., valproate)

Antipsychotics (e.g., olanzapine)Antipsychotics (e.g., olanzapine)28© AMSP 2010

Lithium (Lithobid)Lithium (Lithobid)

Dose 600-1200mg/day Dose 600-1200mg/day (( bid) bid)

Rx & prevent maniaRx & prevent mania

Blood levels: 0.6-1.2 mEq/LBlood levels: 0.6-1.2 mEq/L

Side effects (SE): Side effects (SE): thirst/urination, tremor, thirst/urination, tremor,

nausea, birth defectsnausea, birth defects29© AMSP 2010

AnticonvulsantsAnticonvulsants

Often used + LiOften used + Li

Interactions with alc = dangerousInteractions with alc = dangerous

Most common:Most common:

Valproate (Depakote)Valproate (Depakote)30© AMSP 2010

ValproateValproate

Usual dose = 1000-1500mg/day (Usual dose = 1000-1500mg/day ( bid) bid)

Mixed mania & rapid cyclingMixed mania & rapid cycling

Blood levels: 50-100 Blood levels: 50-100 μμg/mLg/mL

SE: GI upset, tremor, SE: GI upset, tremor, weight, birth weight, birth

defectsdefects31© AMSP 2010

Atypical AntipsychoticsAtypical Antipsychotics

Often temporary for acute maniaOften temporary for acute mania

Olanzapine (Zyprexa): 10-20mg/dayOlanzapine (Zyprexa): 10-20mg/day

Many SE: Many SE: weight, sedation, dry mouth, weight, sedation, dry mouth,

glucose, glucose, lipidslipids32© AMSP 2010

Rx in BP + AUDRx in BP + AUD

VPA > Li for mood stabilizationVPA > Li for mood stabilization

Mixed mania & rapid cyclingMixed mania & rapid cycling

AdherenceAdherence

Beware: Beware: risk lethal OD with alc risk lethal OD with alc

Avoid antidepressantsAvoid antidepressants

Choose mood stabilizer effective in w/dChoose mood stabilizer effective in w/d

33© AMSP 2010

AUD MedicationsAUD Medications

Disulfiram (Antabuse)Disulfiram (Antabuse)

Naltrexone (Revia)Naltrexone (Revia)

Acamprosate (Campral)Acamprosate (Campral)34© AMSP 2010

Disulfiram (Antabuse)Disulfiram (Antabuse)

Sensitizing agent to alcSensitizing agent to alc

Few controlled trials in AUDFew controlled trials in AUD

Too dangerous in BP?Too dangerous in BP?

Many SE: depression, psychosisMany SE: depression, psychosis

Usual dose 250mg/dayUsual dose 250mg/day35© AMSP 2010

Naltrexone (Revia)Naltrexone (Revia)

rewarding effects of alcrewarding effects of alc

No data in BPNo data in BP

Blocks opioid receptor → Blocks opioid receptor → DA DA

2 formulations:2 formulations:

Oral – usual dose 50-100mg/dayOral – usual dose 50-100mg/day

Depot (Vivitrol) – 380mg IM/month Depot (Vivitrol) – 380mg IM/month

36© AMSP 2010

Acamprosate (Campral)Acamprosate (Campral)

Improves abstinenceImproves abstinence

No data in BPNo data in BP

Stabilizes glutamate in protracted w/dStabilizes glutamate in protracted w/d

Usual dose ~2g/dayUsual dose ~2g/day37© AMSP 2010

PsychotherapyPsychotherapy

Cognitive-Behavioral Therapy (CBT)Cognitive-Behavioral Therapy (CBT)

Individual & groupIndividual & group

Effective for both BP and AUDEffective for both BP and AUD

For BP: For BP: adherence, monitor relapse, adherence, monitor relapse,

communicationcommunication

For AUD: behavior change, prevent For AUD: behavior change, prevent

relapse, self-help groupsrelapse, self-help groups38© AMSP 2010

Clinical Vignette - OutcomeClinical Vignette - Outcome

Valproate: Valproate: mood sx, mood sx, liver enzymes liver enzymes

Lithium: Lithium: mania, no effect depression mania, no effect depression

Depression Depression → → craving craving

Antidepressant + naltrexone Antidepressant + naltrexone → → stablestable

CBT + Alc AnonCBT + Alc Anon

39© AMSP 2010

Summary of BP + AUD RxSummary of BP + AUD Rx

Initial assessment: safety, dxInitial assessment: safety, dx

Determine rx settingDetermine rx setting

Stabilize moodStabilize mood

Add meds for AUDAdd meds for AUD

PsychotherapyPsychotherapy40© AMSP 2010

This Lecture ReviewsThis Lecture Reviews

Definitions Definitions ✓✓

Prevalence, course, & causes Prevalence, course, & causes ✓✓

Treatment Treatment ✓✓

41© AMSP 2010