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

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

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)

a.       EtOH use → sxs 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 sxs 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

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 sxs to clarify dx

E. Consider clinical vignette to illustrate dx principles (slide 8)

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 sxs when quit

d. Now sober x 30 days

e. Med non-compliant

f. Presenting sxs:

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: (slide 9)

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 10)

III. Prevalence, course, & causes

A.    Prevalence from 3 national face-to-face studies (slide 11)

1.                  National Epidemiologic Survey on EtOH & Related Conditions (NESARC)8

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 12)

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 13)

1.                  AUDs → negative impact BP outcomes

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

1. ~ 2 x ↑ mixed episodes12

2. 3 x ↑ mood sxs 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 14)

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 15)

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 sxs: ~ 20% vs 10% follow-up weeks18

3.                  BP + AUDs ↑ medication non-adherence: ~ 70% vs 40%6 (slide 16)

(Note: study included illicit drug use disorders)

F.      Causes reasons for co-occurrence not well understood19,20 (slide 17)

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 18)

a. Dopamine (DA)

1. Reward pathway for AUDs24

2. Role in mania25

a. e.g., L-dopa: precursor of DA used for rx Parkinsons

b. → manic sxs 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 19)

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

b. Biologic risk may → BP; BP behavior → drink23 (slide 20)

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 sxs (slide 21)

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

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 sxs with EtOH use, but EtOH:

1. depressive sxs3

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 sxs3

a. Expect EtOH to improve insomnia or calm manic sxs

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 22)

IV. Rx of BP + AUDs (slide 23)

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

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 24)

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 25)

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 26)

1. Hospitalization if:

a. Severe w/d

b. Severe mood sxs

c. Suicidality/violence risk

d. Psychosis

e. Inability to care for self

2. Outpatient for:

a. Mild/moderate mood sxs

b. Can adhere to rx recommendations

c. Strong social support

3. In clinical vignette:

a. Residential program provides strong support & structure

b. Mood sxs problematic but not severe

c. Current rx setting is appropriate

E. Considerations when EtOH detox required (slide 27)

1. Standard rx benzodiazepines (bz) to prevent & manage w/d sxs

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

3. +/- evidence re: anticonvulsants (with adjunctive bzs) for EtOH w/d30 (slide 28)

a. Have more side effects & cost vs bzs

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 29)

1. Some BP pts need mood stabilizer +/- adjunctive meds

a. Lithium (Lithobid) 600-1200mg/day bid (slide 30)

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 31)

1. Valproate (Depakote) 1000-1500mg/day bid (slide 32)

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 33)

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 34)

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:

1. Use bzs 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 35)

1. Disulfiram (Antabuse) sensitizing agent to EtOH (slide 36)

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 37)

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 38)

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 sxs (mood & w/d) stable, need use cognitive-behavioral rx (CBT) (slide 39)

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 40)

1. Started VPA → significant ↑ in liver enzymes

2. Discontinued VPA & started Li

3. Manic sxs resolved, but not depression

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

5. Added antidepressant & naltrexone → stabilization of sxs

6. Throughout rx received psychotherapy (individual & group)

J. Now completed rx review. Summary: (slide 41)

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 42)

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

2. Given significant impairment typical of initial presentation, very gratifying to observe patients make substantial improvements & stabilize

 


References:

1. Verduin ML, Tolliver BK, Brady KT. Substance abuse and bipolar disorder. MedScape, posted December 5, 2005.

2. Cardoso BM, Sant Anna MK, Dias VV, Andreazza AC, Ceresr KM, Kapczinski F. The impact of co-morbid alcohol use disorder in bipolar patients. Alcohol. 2008;42:451-7.

3. Raimo EB and Schuckit MA. Alcohol dependence and mood disorders. Addict Behav. 1998;23:933-46.

4. Frye MA, Salloum IM. Bipolar disorder and comorbid alcoholism: prevalence rate and treatment considerations. Bipolar Disord. 2006;8:677-85.

5. Sajatovic M, Valenstein M, Blow FC, Ganoczy D, Ignacio RV. Treatment adherence with antipsychotic medications in bipolar disorder. Bipolar Disord. 2006;8:232-41.

6. Keck PE, McElroy SL, Strakowski SM, West SA, Sax KW, Hawkins JM, Bourne ML, Haggard P. 12-Month outcome of patients with bipolar disorder following hospitalization for a manic or mixed episode. Am J Psychiatry. 1998;155:646-52.

7. Ziedonis DM. Integrated treatment of co-occurring mental illness and addiction: clinical intervention, program, and system perspectives. CNS Spectr. 2004;9:892-904.

8. Grant BF, Stinson FS, Dawson DA, Chou SP, Dufour MC, Compton W, Pickering RP, Kaplan K. Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2004;61:807-16.

9. Regier DA, Farmer ME, Rae DS, Locke BZ, Keith SJ, Judd LL, Goodwin FK. Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiologic Catchment Area (ECA) study. JAMA. 1990;264:2511-8.

10. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51:8-19.

11. Frye MA, Altshuler LL, McElroy SL, Suppes T, Keck PE, Denicoff K, Nolen WA, Kupka R, Leverich GS, Pollio C, Grunze H, Walden J, Post RM. Gender differences in prevalence, risk and clinical correlates of alcoholism comorbidity in bipolar disorder. Am J Psychiatry. 2003;160:883-9.

12. Sonne SC, Brady KT, Morton WA. Substance abuse and bipolar affective disorder. J Nerv Ment Disease. 1994;182:349-52.

13. Salloum IM, Cornelius JR, Mezzich JE, Kirisci L. Impact of concurrent alcohol misuse on symptom presentation of acute mania at initial evaluation. Bipolar Disord. 2002;4:418-21.

14. Morrison JR. Bipolar affective disorder and alcoholism. Am J Psychiatry. 1974;131:1130-3.

15. Hoblyn JC, Balt SL, Woodard SA, Brooks JO. Substance use disorders as risk factors for psychiatric hospitalization in bipolar disorder. Psychiatr Serv. 2009;60:50-5.

16. Tohen M, Waternaux CM, Tsuang MT. Outcome in mania: a 4-year prospective follow-up of 75 patients using survival analysis. Arch Gen Psychiatry. 1990;47:1106-11.

17. Tohen M, Zarate CA, Zarate SB, Gebre-Medhin P, Pike S. The McLean/Harvard First Episode Mania Project: pharmacologic treatment and outcome. Psychiatric Ann. 1996;26:S444-8.

18. Strakowski SM, DelBello MP, Fleck DE, Adler CM, Anthenelli RM, Keck PE Jr, Arnold LM, Amicone J. Effects of co-occurring alcohol abuse on the course of bipolar disorder following a first hospitalization for mania. Arch Gen Psychiatry. 2005;62:851-8.

19. Brown ES, Suppes T, Adinoff B, Thomas NR. Drug abuse and bipolar disorder: comorbidity or misdiagnosis? J Affect Disord. 2001;65:105-15.

20. Strakowski SM, DelBello MP. The co-occurrence of bipolar and substance abuse disorders. Clin Psychol Rev. 2000;20:191-206.

21. Ingraham LJ, Wender PH. Risk for affective disorder and alcohol and other drug abuse in the relatives of affectively ill adoptees. J Affect Disord. 1992;26:45-51.

22. Saunders EFH, Zhang P, Copeland JN, McInnis MG, Zllner S. Suggestive linkage at 9p22 in bipolar disorder weighted by alcohol abuse. Am J Med Genet B Neuropsychiatr Genet. 2009.

23. Schuckit MA, Kelsoe JR, Braff DL, Wilhelmsen KC. Some possible genetic parallels across alcoholism, bipolar disorder, and schizophrenia. J Stud Alcohol. 2003;64:157-9.

24. Weiss F, Lorang MT, Bloom FE, Koob GF. Oral alcohol self-administration stimulates dopamine release in the rat nucleus accumbens: genetic and motivational determinants. J Pharmacol Exp Ther. 1993;267:250-8.

25. Murphy DL, Brodie HK, Goodwin FK, Bunney WE Jr. Regular induction of hypomania by L-dopa in bipolar manic-depressive patients. Nature. 1971;229:135-6.

26. Markou A, Kosten TR, Koob GF. Neurobiological similarities in depression and drug dependence: a self-medication hypothesis. Neuropsychopharmacology. 1998;18:135-74.

27. Rao U, Ryan ND, Birmaher B, Dahl RE, Williamson DE, Kaufman J, Rao R, Nelson B. Unipolar depression in adolescents: clinical outcome in adulthood. J Am Acad Child Adolesc Psychiatry. 1995;34:566-78.

28. Harrington R, Fudge H, Rutter M, Pickles A, Hill J. Adult outcomes of childhood and adolescent depression. Arch Gen Psychiatry. 1990;47:465-73.

29. Wilens TE, Biederman J, Kwon A, Ditterline J, Forkner P, Moore H, Swezey A, Snyder L, Henin A, Wozniak J, Faraone SV. Risk of substance use disorders in adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2004;43:1380-6.

30. Ait-Daoud N, Malcolm RJ, Johnson BA. An overview of medications for the treatment of alcohol withdrawal and alcohol dependence with an emphasis on the use of older and newer anticonvulsants. Addict Behav. 2006;31:1628-49.

31. Bowden CL. Clinical correlates of therapeutic response in bipolar disorder. J Affect Disord. 2001;67:257-65.

32. Weiss RD, Greenfield SF, Najavits LM, Soto JA, Wyner D, Tohen M, Griffin ML. Medication compliance among patients with bipolar disorder and substance use disorder. J Clin Psychiatry. 1998;59:172-4.

33. Goldberg JF, Whiteside JE. The association between substance abuse and antidepressant-induced mania: a preliminary study. J Clin Psychiatry. 2002;63:791-5.

34. Garbutt JC. The state of pharmacotherapy for the treatment of alcohol dependence. J Subst Abuse Treat. 2009;36:S15-23.

35. Fountoulakis KN, Vieta E. Treatment of bipolar disorder: a systematic review of available data and clinical perspectives. Int J Neuropsychopharmacol. 2008;11:999-1029.