Bipolar Disorder and Alcohol Use Disorders

Marcy Verduin, M.D.

University of Central Florida College of Medicine

(slide 1)

©AMSP 2010

I. Introduction

A. Bipolar disorder (BP) & Alcohol Use Disorders (AUDs) challenging to treat

(slide 2)

1. Lack of treatment (rx) research in co-occurring BP & AUDs1

a. Most studies of BP exclude AUD patients (pts)1

b. AUDs & illicit drug use disorders combined despite key differences2

1’. Alcohol (EtOH) different effects than other drugs2

2’. EtOH legal & ↑ available vs illegal drugs2

3’. EtOH most common substance used in BP2

2. Diagnostic (dx) & rx challenges for those with both AUDs & BP

a. Dx challenge: symptom (sx) overlap between AUDs & BP3

(e.g., sadness episodes)

b. Rx challenges:

1’. Potential hepatic toxicity if combine BP meds & EtOH4

2’. Rx nonadherence ~70% if both BP & AUDs5,6

(Note: study included illicit drug use disorders)

3. Integrated rx for both disorders is difficult to find7

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B. This lecture reviews: (slide 3)

1. Definitions (BP, abuse, dependence [dep])

2. Prevalence, course, & causes

3. Rx of BP & AUDs

II. Definitions

A. BP disorder – focus on DSM-IV BP I for this talk

1. > 1 manic episode required (slide 4)

2. Manic episode

a. > 1 week of euphoric, expansive, or irritable mood

b. > 3 of the following (> 4 if mood is only irritable):

1’. ↑ self-esteem or grandiosity

2’. ↓ need for sleep

3’. ↑ talkativeness (ex: talking fast/pressured & difficult to interrupt)

4’. Racing thoughts

5’. Distractibility

6’. ↑ goal-directed activity (ex: working several jobs for ↑↑↑ # hours)

7’. ↑ pleasurable activities with problems (ex: promiscuity)

3. BP I patients can have depressive episodes (slide 5)

4. Major depressive episode

a. > 5 in a 2 week period:

1’. Depressed mood

2’. Loss of interest

3’. ↓ or ↑ appetite

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4’. ↓ or ↑ sleep

5’. ↓ or ↑ psychomotor behavior (movement associated with mental

processes)

6’. ↓ energy

7’. ↓ worth or ↑ guilt

8’. ↓ concentration

9’. Suicidal thoughts/attempt

B. EtOH abuse – repeated problems in same 12 months with ≥ 1 of: (slide 6)

1. Inability to fulfill role obligations

2. Recurrent use in hazardous situations

3. Recurrent legal problems

4. Ongoing use despite social or interpersonal problems

5. Not meet criteria for dep

C. EtOH dep – repeated problems in same 12 months with ≥ 3 of:

1. Tolerance: ↑ use to get same effect; ↓ effect with same amount used

2. Withdrawal (w/d) syndrome or receive rx to avoid w/d

3. Use larger amounts/longer time than intended

4. Desire or unsuccessful efforts to cut down

5. ↑ time spent to get, use & recover

6. Give up important activities

7. Ongoing use despite problems

D. Apply definitions if co-occurring BP & AUDs is challenging

1. Sx overlap (slide 7)

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a. EtOH use → sx’s suggestive of BP

1’. Heavy EtOH use → impulsivity, irritability, mood swings, poor

judgment & insomnia

2’. May be incorrectly attributed to hypomania3

b. BP leading to sx’s suggestive of AUD

1’. Temporary ↑ in EtOH during mania

2’. May be incorrectly attributed to AUD3

c. True BP disorder suggested by:

1’. Mania before AUD

2’. Mania during extended sobriety

3’. Mania only when actual AUD unlikely BP

2. Use timeline approach in diagnostic interviewing3 (slide 8)

a. Draw horizontal line on sheet of paper

b. Mark ages of SUD onset & periods of abstinence

c. Mark ages of major mood episodes

d. Use major life events as anchors to help with recall

e. Use timing of sx’s to clarify dx

E. Consider clinical vignette to illustrate dx principles

1. 42 year old man with history of BP and EtOH dep

a. In residential rehab program

b. Usual 12 beers/day

c. Intoxicated most of day; w/d sx’s when quit

d. Now sober x 30 days

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e. Med non-compliant

f. Presenting sx’s:

1’. Depression: score mod/severe on depression rating scale

2’. Hopeless

3’. Low self-worth

4’. Irritable

5’. ↓ sleep

6’. Racing thoughts

7’. Restless

8’. Talkative

9’. Not suicidal

2. Timeline approach:

a. AUD onset age 23

b. 1st manic episode age 20

c. 3 sober periods x 6-8 months following tx, ages 32, 37, 40

d. Manic episode during sobriety at ages 32 and 40

3. Diagnosis = BP disorder, mixed episode & EtOH dep

F. Completed definitions of BP (mania, depression) & AUDs (EtOH abuse & dep).

Now move on to prevalence, course, & causes. (slide 9)

III. Prevalence, course, & causes

A. Prevalence from 3 national face-to-face studies (slide 10)

1. National Epidemiologic Survey on EtOH & Related Conditions

(NESARC)8

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a. More recent (2001-2002)

b. ~43,000 age 18+

c. All in community (no hospitals, jails, or prisons)

2. Epidemiologic Catchment Area (ECA) study9

a. Older (1980-1984) in 5 cities

b. ~ 20,000 age 18+

c. Included institutionalized individuals

3. National Comorbidity Survey (NCS)10

a. Older survey (1990-1992)

b. ~8000 age 15-5411

c. All in community

B. Lifetime prevalence of BP I disorder ~ 1%9

C. Lifetime prevalence of AUDs ~ 14%9

D. Prevalence of BP I & AUDs

1. ~ 50% with BP ever have AUD; EtOH dep > abuse (30% vs 15%)9

2. EtOH dep 6 x ↑ mania vs those without EtOH dep8 (slide 11)

3. BP 6 x ↑ AUD vs those without BP9

4. BP is major Ψ disorder most likely associated with AUDs8,9

5. Gender & comorbidity11

a. If BP: ♂ (50%) > ♀ (30%) ever AUD

b. BP ♀ 7 x ↑ AUD vs general population

c. BP ♂ 3 x ↑ AUD vs general population

E. Co-occurring AUDs impact BP course (slide 12)

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1. AUDs → negative impact BP outcomes

a. Effect AUDs on psychiatric sx’s (from 4 studies; 1 with illicit drugs)

1’. ~ 2 x ↑ mixed episodes12

2’. 3 x ↑ mood sx’s before age 2012

3’. 4 x ↑ other comorbid disorders (#1 = PTSD)12

4’. ~ 3 x ↑ mood swings13

5’. ~ 3 x ↑ impulsivity (e.g., reckless driving)13

6’. ~ 2 x ↑ violence (e.g., bar fights)13

7’. ~ 2 x ↑ suicide attempt14

b. BP + AUDs →: (slide 13)

1’. ↑ risk Ψ hospitalization (43% vs 15%)15

2’. ~ 4 x faster relapse to mania16

3’. Slower recovery from mood episode: 55 days vs 43 days17

(Note: study included illicit drug use disorders)

2. Order of onset affects course of both conditions (slide 14)

a. EtOH 1st:

1’. Older BP onset (by ~ 10 years)18

2’. ↑ time in BP episode recovery: ~ 30% vs 50% follow-up weeks18

b. BP 1st:

1’. ↑ time spent in mood episodes: 35% vs 15% follow-up weeks18

2’. ↑ time spent AUD sx’s: ~ 20% vs 10% follow-up weeks18

3. BP + AUDs ↑ medication non-adherence: ~ 70% vs 40%6 (slide 15)

(Note: study included illicit drug use disorders)

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F. Causes – reasons for co-occurrence not well understood19,20 (slide 16)

1. Shared genetic risk factors

a. ~2 x ↑ SUDs in relatives of kids with mood disorders21

b. BP + AUDs – common chromosomal associations (9, 13, 22)22,23

1’. Ex: Chr 9 – genetic risk for BP

2’. Risk for BP ↑ in families with AUDs

2. Dysfunctional neurotransmitters (NT) in BP + AUDs (slide 17)

a. Dopamine (DA)

1’. Reward pathway for AUDs24

2’. Role in mania25

a’. e.g., L-dopa: precursor of DA used for rx Parkinson’s

b’. → manic sx’s in BP

b. Other monoamines (e.g., norepinephrine [NE]) 23

1’. NE dysregulation seen in major depression

2’. Abruptly stop EtOH → sympathetic hyperactivity (↑ NE)

3. How might chromosomes and NTs → co-occurrence? (slide 18)

a. EtOH might precipitate BP in those predisposed (genetic or NT)26

b. Biologic risk may → BP; BP behavior → ↑ drink23 (slide 19)

1’. In mania, all acts done to excess

2’. Could develop AUD

3’. When mania gone, AUD might stay

4. Self-medication: ↑ drink to ↓ BP sx’s (slide 20)

a. If true, expect ↑ AUD if prior mood disorders, but:

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1’. No ↑ risk of AUD if prior major depression in some studies3

a’. Teen with new depression → no ↑ risk AUD as adult27

b’. Child/adolescent depression → no ↑ risk AUD 18 yrs later28

2’. Risk of SUD associated with teen BP onset/severity29

a’. 3x ↑ risk of SUD if severe vs moderate BP

b’. BP onset typically precedes SUD onset

b. Also expect ↓ mood sx’s with EtOH use, but EtOH:

1’. → ↑ depressive sx’s3

a’. EtOH = CNS depressant

b’. Heavy EtOH use → intense depression in 3 lab studies

c’. If AUD, depression often resolves with sobriety

2’. Not ↓ manic sx’s3

a’. Expect EtOH to improve insomnia or calm manic sx’s

b’. No evidence that EtOH has these effects

c’. EtOH may worsen mood or ↑ mood episode frequency

G. Summary – completed prevalence, course, & causes. Now move on to rx.

(slide 21)

IV. Rx of BP + AUDs (slide 22)

A. Both disorders studied extensively alone, but limited data on rx of comorbidity1

1. BP + AUDs often excluded from studies for:

a. Scientific reasons (e.g., want only “pure” disorder)

b. Safety reasons (e.g., risk interaction EtOH with antidepressants, etc.)

2. Joint BP + AUD patients difficult to study: poor adherence with rx

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3. Knowing impact of AUDs on BP helpful in guiding rx decisions, ex:

a. Know ↑ risk of mixed episodes in BP + AUDs, so choose meds

effective for mixed mania

b. Know ↑ risk for antidepressant-induced mania, so try to avoid

antidepressants

B. Recall clinical vignette to illustrate rx principles (slide 23)

1. 42 year old man with history of BP & EtOH dep

a. In residential rehab program

b. Now sober x 30 days

c. Med non-compliant

d. Symptoms of mania + depression

C. Initial assessment – establish: dx; safety; medical & Ψ issues; develop rx plan

(slide 24)

1. Most immediate need – treat EtOH w/d3

2. Next consider potential Ψ emergencies3

a. Risk of harm to self/others (suicidality/violence)

b. Psychosis (usually = hearing voices & believe people want to harm)

c. Inability to care for self

3. In clinical vignette:

a. Diagnosis = BP disorder, mixed episode & EtOH dep

b. Not at risk for EtOH w/d (despite low BAC, vital signs not ↑↑)

c. Not currently at risk to self/others, not psychotic

D. Determine appropriate rx setting. Consider: (slide 25)

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1. Hospitalization if:

a. Severe w/d

b. Severe mood sx’s

c. Suicidality/violence risk

d. Psychosis

e. Inability to care for self

2. Outpatient for:

a. Mild/moderate mood sx’s

b. Can adhere to rx recommendations

c. Strong social support

3. In clinical vignette:

a. Residential program provides strong support & structure

b. Mood sx’s problematic but not severe

c. Current rx setting is appropriate

E. Considerations when EtOH detox required (slide 26)

1. Standard rx – benzodiazepines (bz) to prevent & manage w/d sx’s

2. Ex: lorazepam (Ativan) – usual dose 2-4mg qid on day 1

3. +/- evidence re: anticonvulsants (with adjunctive bz’s) for EtOH w/d30

(slide 27)

a. Have more side effects & ↑ cost vs bz’s

b. But do work; may consider if other reason to rx (e.g., vital signs)

c. Valproate (Depakote) – 20mg/kg/day (divided bid) on day 1

F. Considerations when stabilizing mood (slide 28)

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1. Some BP pt’s need “mood stabilizer” +/- adjunctive meds

a. Lithium (Lithobid) –600-1200mg/day bid (slide 29)

1’. Best studied med to rx & prevent mania in BP

2’. Blood levels must be between 0.6 and 1.2mEq/L

3’. Side effects (SEs): ↑ thirst/urination, tremor, nausea, birth defects

b. Anticonvulsants (often + Li) (slide 30)

1’. Valproate (Depakote) –1000-1500mg/day bid (slide 31)

a’. Especially good for mixed or frequent episodes

b’. Blood levels must be between 50 and 100mg/mL

c’. SEs include GI upset, tremor, weight gain, birth defects

2’. Interact with EtOH dangerous

c. Atypical antipsychotics (often temporary for acute mania) (slide 32)

1’. Ex: olanzapine (Zyprexa) –10-20mg/day

2’. Many SEs: weight gain, sedation, dry mouth, ↑ glucose & lipids

2. Treating BP in someone who also has an AUD: (slide 33)

a. Valproate (VPA) is preferred over lithium (Li) as a mood stabilizer

1’. Better for mixed episodes & frequent mood change31

2’. Better med compliance than Li32

3’. Beware of ↑ overdose lethal if mixed with EtOH

b. Avoid antidepressants

1’. BP + SUD at ↑ risk for antidepressant-induced mania33

2’. If must use, monitor for mania

c. If treating for EtOH w/d while stabilizing mood:

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1’. Use bz’s as standard of care for w/d, &

2’. Choose mood stabilizer effective in w/d rx (ex: valproate)

G. Use of meds to treat AUDs (slide 34)

1. Disulfiram (Antabuse) – sensitizing agent to EtOH (slide 35)

a. No data on safety in BP (some think too dangerous)

b. Few controlled trials in AUD

c. Many side effects (e.g., depression, psychosis)

d. Usual dose 250mg per day

2. Naltrexone (Revia) for ~ 6 months (slide 36)

a. Might ↓ rewarding effects of EtOH

b. No data on use if also BP

c. Opioid receptor antagonist → ↓ dopamine release in brain

d. ↓ reinforcing, pleasurable effects of EtOH

e. Two formulations (oral & depot) available

1’. Oral tablet: usual dose 50-100mg per day

2’. Long-acting injectable (Vivitrol) – usual dose 380mg IM monthly

3. Acamprosate (Campral) – improves abstinence (slide 37)

a. No data on safety in BP

b. Glutamate receptor modulator

c. Stabilizes glutamate in protracted w/d34

d. Usual dose ~ 2g per day

H. Once acute sx’s (mood & w/d) stable, need use cognitive-behavioral rx (CBT)

(slide 38)

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1. CBT → focuses on relationship between thoughts, feelings, and behavior

2. Individual & group therapy effective for both BP + AUDs

3. Full description beyond scope of this lecture, but know:

a. For BP - ↑ rx adherence, learning to monitor warning signs of relapse,

& improving communication35

b. For AUD - ↑ recognition of need to change, learning skills to prevent

relapse, & engaging in self-help groups

I. In clinical vignette: (slide 39)

1. Started VPA → significant ↑ in liver enzymes

2. Discontinued VPA & started Li

3. Manic sx’s resolved, but not depression

4. Maximized Li dose, but depression persisted & pt began craving EtOH

5. Added antidepressant & naltrexone → stabilization of sx’s

6. Throughout rx received psychotherapy (individual & group)

J. Now completed rx review. Summary: (slide 40)

1. Initial assessment: safety issues (ex: w/d, suicide) & establish dx

2. Determine rx setting (inpatient vs outpatient)

3. Stabilize mood with meds

4. Add meds for AUD

5. Engage in psychotherapy

K. Take home message: (slide 41)

1. BP + AUDs complicate each other → ↓ threshold for ↑ing intensity &

structure of care

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2. Given significant impairment typical of initial presentation, very

gratifying to observe patients make substantial improvements & stabilize

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