1. Bipolar Disorder and Alcohol Use Disorders Marcy Verduin, M.D. University of Central Florida 1 © AMSP 2010

2. Challenging to Treat Lack of treatment research Lack of treatment research Dx challenge = symptom overlap Dx challenge = symptom overlap Rx challenges = toxicity & nonadherence Rx challenges = toxicity & nonadherence Integrated Rx difficult to find Integrated Rx difficult to find 2 © AMSP 2010

3. This Lecture Reviews Definitions Definitions Prevalence, course, & causes Prevalence, course, & causes Treatment Treatment 3 © AMSP 2010

4. Bipolar Disorder 1+ manic episode: 1+ manic episode: 1+ week euphoric or irritable mood 1+ week euphoric or irritable mood 3+ (or 4+ if irritable): 3+ (or 4+ if irritable): 4 © AMSP 2010  self-esteem  self-esteem  need for sleep  need for sleep  talkativeness  talkativeness Racing thoughts Racing thoughts Distractibility Distractibility  goal-directed activity  goal-directed activity  pleasurable activities  pleasurable activities

5. Depressive Episodes Major depression = 5 lasting 2+ weeks: Major depression = 5 lasting 2+ weeks: 5 © AMSP 2010 Depressed mood Depressed mood Sleep  or  Sleep  or  Interest  Interest  Guilt  or worth  Guilt  or worth  Energy  Energy  Concentration  Concentration  Appetite  or  Appetite  or  Psychomotor  or  Psychomotor  or  Suicidal thoughts/attempt Suicidal thoughts/attempt

6. Abuse & Dependence Abuse 1+ of: Abuse 1+ of: Obligations Obligations Hazardous use Hazardous use Legal Legal Interpersonal problems Interpersonal problems Dependence 3+ of: Dependence 3+ of: Tolerance Tolerance Withdrawal Withdrawal  Amounts or more time  Amounts or more time Desire or unable cut down Desire or unable cut down  time get, use, or recover  time get, use, or recover  non-drug activities  non-drug activities Physical/psychological problems Physical/psychological problems 6 © AMSP 2010

7. Symptom Overlap Alc → symptoms of BP Alc → symptoms of BP BP → symptoms of AUD BP → symptoms of AUD Use timing of sx’s to clarify Use timing of sx’s to clarify Mania before AUD Mania before AUD Mania during sobriety Mania during sobriety 7 © AMSP 2010 BP dx

8. Time Line Approach 8 © AMSP 2010 18 20 23 28 32 37 42 Grad HS MarriedSon born AUD Mania

9. This Lecture Reviews Definitions ✓ Definitions ✓ Prevalence, course, & causes Prevalence, course, & causes Treatment Treatment 9 © AMSP 2010

10. Prevalence 10 © AMSP 2010

11. Prevalence of BP + AUDs Alc Dep 6 x  mania Alc Dep 6 x  mania BP 6 x  AUDs BP 6 x  AUDs BP = #1 Ψ disorder assoc with AUDs BP = #1 Ψ disorder assoc with AUDs 11 © AMSP 2010

12. AUDs Impact BP Symptoms 3 x  onset < 20 3 x  onset < 20 4 x  comorbid dx 4 x  comorbid dx 2-3 x  sx of: 2-3 x  sx of: Impulsivity Impulsivity Violence Violence Suicide attempt Suicide attempt 12 © AMSP 2010

13. AUDs Impact Recovery  risk Ψ hospitalization (45% vs 15%)  risk Ψ hospitalization (45% vs 15%) ~4 x faster relapse to mania ~4 x faster relapse to mania Slower mood episode recovery by ~2 wks Slower mood episode recovery by ~2 wks 13 © AMSP 2010

14. Order of Onset Matters Alc 1 st : Alc 1 st : Older BP onset by ~10 years Older BP onset by ~10 years Longer time in mood recovery Longer time in mood recovery BP 1 st : BP 1 st :  time in mood episodes  time in mood episodes Longer time with AUD sx Longer time with AUD sx 14 © AMSP 2010

15. AUD Impact Adherence 15 © AMSP 2010 70% 40%

16. Shared Genetic Risk Factors ~2 x  SUDs if relatives with BP or MDD ~2 x  SUDs if relatives with BP or MDD Common chromosomal regions: Common chromosomal regions: Chr 9  BP risk Chr 9  BP risk  effect in AUD families  effect in AUD families 16 © AMSP 2010

17. Dysfunctional NTs Dopamine (DA) Reward Pathway Mania Norepinephrine (NE) 17 © AMSP 2010 WithdrawalDepression

18. How Risk Factors → BP + AUD 18 © AMSP 2010 BP risk No BP BP No Alc Alc

19. How Risk Factors → BP + AUD BP → mania → all acts done to excess BP → mania → all acts done to excess Excess →  drink Excess →  drink  drink → AUD  drink → AUD Mania resolves, but AUD remains Mania resolves, but AUD remains 19 © AMSP 2010

20. Self-Medication Theory: Theory:  Alc to  BP sx  Alc to  BP sx But prior MDD →  AUD But prior MDD →  AUD Alc →  dep sx Alc →  dep sx Alc →  mania Alc →  mania 20 © AMSP 2010

21. This Lecture Reviews Definitions ✓ Definitions ✓ Prevalence, course, & causes ✓ Prevalence, course, & causes ✓ Treatment Treatment 21 © AMSP 2010

22. What We Know BP + AUD excluded from studies BP + AUD excluded from studies Joint BP + AUD difficult to study Joint BP + AUD difficult to study Joint dx often mixed episodes Joint dx often mixed episodes Are dangers to use antidepressants Are dangers to use antidepressants 22 © AMSP 2010

23. Recall Clinical Vignette 42 yo man 42 yo man History of BP and Alc Dep History of BP and Alc Dep Residential rehab Residential rehab 30 days sober 30 days sober Not taking meds Not taking meds Mania + depression Mania + depression 23 © AMSP 2010

24. Initial Assessment Medical & Ψ issues, rx plan Medical & Ψ issues, rx plan Most immediate need – rx withdrawal Most immediate need – rx withdrawal Consider Ψ emergencies Consider Ψ emergencies Suicide Suicide Violence Violence Psychosis Psychosis Self-neglect Self-neglect 24 © AMSP 2010

25. Rx Setting Hospital Severe w/d Severe mood sx Suicide/ violence Psychosis Self- neglect Outpatient Mild/mod mood sx Compliant Social support 25 © AMSP 2010

26. Alc Detox Standard rx = bz Standard rx = bz Lorazepam (Ativan): 2-4mg qid day 1 Lorazepam (Ativan): 2-4mg qid day 1 Taper over ~ 5 days Taper over ~ 5 days 26 © AMSP 2010

27. Also for Detox +/- Anticonvulsants +/- Anticonvulsants  side-effects & cost  side-effects & cost Valproate (Depakote): Valproate (Depakote): 20mg/kg/day (  bid) day 1 Taper over ~ 5 days Taper over ~ 5 days 27 © AMSP 2010

28. Rx Mood Sx in BP Mood stabilizer +/- adjunctive meds Mood stabilizer +/- adjunctive meds Lithium Lithium Anticonvulsants (e.g., valproate) Anticonvulsants (e.g., valproate) Antipsychotics (e.g., olanzapine) Antipsychotics (e.g., olanzapine) 28 © AMSP 2010

29. Lithium (Lithobid) Dose 600-1200mg/day (  bid) Dose 600-1200mg/day (  bid) Rx & prevent mania Rx & prevent mania Blood levels: 0.6-1.2 mEq/L Blood levels: 0.6-1.2 mEq/L Side effects (SE):  thirst/urination, tremor, nausea, birth defects Side effects (SE):  thirst/urination, tremor, nausea, birth defects 29 © AMSP 2010

30. Anticonvulsants Often used + Li Often used + Li Interactions with alc = dangerous Interactions with alc = dangerous Most common: Most common: Valproate (Depakote) Valproate (Depakote) 30 © AMSP 2010

31. Valproate Usual dose = 1000-1500mg/day (  bid) Usual dose = 1000-1500mg/day (  bid) Mixed mania & rapid cycling Mixed mania & rapid cycling Blood levels: 50-100 μg/mL Blood levels: 50-100 μg/mL SE: GI upset, tremor,  weight, birth defects SE: GI upset, tremor,  weight, birth defects 31 © AMSP 2010

32. Atypical Antipsychotics Often temporary for acute mania Often temporary for acute mania Olanzapine (Zyprexa): 10-20mg/day Olanzapine (Zyprexa): 10-20mg/day Many SE:  weight, sedation, dry mouth,  glucose,  lipids Many SE:  weight, sedation, dry mouth,  glucose,  lipids 32 © AMSP 2010

33. Rx in BP + AUD VPA > Li for mood stabilization VPA > Li for mood stabilization Mixed mania & rapid cycling Mixed mania & rapid cycling Adherence Adherence Beware:  risk lethal OD with alc Beware:  risk lethal OD with alc Avoid antidepressants Avoid antidepressants Choose mood stabilizer effective in w/d Choose mood stabilizer effective in w/d 33 © AMSP 2010

34. AUD Medications Disulfiram (Antabuse) Disulfiram (Antabuse) Naltrexone (Revia) Naltrexone (Revia) Acamprosate (Campral) Acamprosate (Campral) 34 © AMSP 2010

35. Disulfiram (Antabuse) Sensitizing agent to alc Sensitizing agent to alc Few controlled trials in AUD Few controlled trials in AUD Too dangerous in BP? Too dangerous in BP? Many SE: depression, psychosis Many SE: depression, psychosis Usual dose 250mg/day Usual dose 250mg/day 35 © AMSP 2010

36. Naltrexone (Revia)  rewarding effects of alc  rewarding effects of alc No data in BP No data in BP Blocks opioid receptor →  DA Blocks opioid receptor →  DA 2 formulations: 2 formulations: Oral – usual dose 50-100mg/day Oral – usual dose 50-100mg/day Depot (Vivitrol) – 380mg IM/month Depot (Vivitrol) – 380mg IM/month 36 © AMSP 2010

37. Acamprosate (Campral) Improves abstinence Improves abstinence No data in BP No data in BP Stabilizes glutamate in protracted w/d Stabilizes glutamate in protracted w/d Usual dose ~2g/day Usual dose ~2g/day 37 © AMSP 2010

38. Psychotherapy Cognitive-Behavioral Therapy (CBT) Cognitive-Behavioral Therapy (CBT) Individual & group Individual & group Effective for both BP and AUD Effective for both BP and AUD For BP:  adherence, monitor relapse, For BP:  adherence, monitor relapse,  communication For AUD: behavior change, prevent relapse, self-help groups For AUD: behavior change, prevent relapse, self-help groups 38 © AMSP 2010

39. Clinical Vignette - Outcome Valproate:  mood sx,  liver enzymes Valproate:  mood sx,  liver enzymes Lithium:  mania, no effect depression Lithium:  mania, no effect depression Depression →  craving Depression →  craving Antidepressant + naltrexone → stable Antidepressant + naltrexone → stable CBT + Alc Anon CBT + Alc Anon 39 © AMSP 2010

40. Summary of BP + AUD Rx Initial assessment: safety, dx Initial assessment: safety, dx Determine rx setting Determine rx setting Stabilize mood Stabilize mood Add meds for AUD Add meds for AUD Psychotherapy Psychotherapy 40 © AMSP 2010

41. This Lecture Reviews Definitions ✓ Definitions ✓ Prevalence, course, & causes ✓ Prevalence, course, & causes ✓ Treatment ✓ Treatment ✓ 41 © AMSP 2010