Paul E Keck Jr MD Lindner Center of HOPE University of Cincinnati College of Medicine Key Recommendations Realize that comorbidity is the rule not the exception in bipolar disorder BP ID: 298280
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Slide1
Principles of Treating Individuals with Complex Co-Morbidity
Paul E. Keck, Jr., MD
Lindner Center of HOPE
University of Cincinnati College of MedicineSlide2
Key Recommendations
Realize that co-morbidity is the rule, not the exception, in bipolar disorder (BP)2. Assess affective and co-morbid symptoms concurrently
Focus pharmacotherapy on achieving mood stabilization. Use psychological treatments–eg
., patient education or illness management–to address co-morbidity issues.Slide3
Key Recommendations (continued)
Know the evidence–or the lack thereof–for the therapies used to treat BP with co-morbiditiesAvoid prematurely treating co-morbidities with mood-destabilizing agents
Before using antidepressants to treat anxiety disorders co-morbid with BP, consider mood stabilizers and atypical antipsychotics with demonstrated efficacy in anxiety
Rethink requiring active alcoholics to “stop drinking” before treating their BP, and select BP therapies accordinglySlide4
Key Recommendation 1
Realize that co-morbidity is the rule, not the exception, in bipolar disorder (BP)Slide5
National Co-morbidity Survey
1
2
≥ 3
# Lifetime
DSM-III Disorders
21
13
14
% General
Population*
0
100
96
% Sample
With BP I
†
*N=8098;
†
Percentage of patients with
euphoric-grandiose subtype of BP I with
comorbidities
(N=29).Kessler RC, et al. Arch Gen Psychiatry.1994;51:8-19; Kessler RC, et al. Psychol Med. 1997;27:1079-1089.Slide6
Prevalence of Selected Co-morbidities with BP I* (N=29)
*Euphoric-grandiose subtype.
Kessler RC, et al. Psychol Med. 1997;27:1079-1089.
Patients (%)Slide7
Odds Ratio for Anxiety Disorders in Bipolar vs Unipolar
Disorders*Epidemiologic Catchment Area (ECA) Survey.†P<.0001.
PD=panic disorder; OCD=obsessive-compulsive disorder.Chen YW, et al. Am J Psychiatry. 1995;152:280-282; Chen YW, et al. Psychiatry Res. 1995;59:57-64.
Odds
Ratio
20.8
PD
†
OCD
†Slide8
BP and Mental and Medical Disorder Co-morbidity—Clinical Studies
Eating disorders
Impulse control disorders
Tourette
syndrome
Attention-deficit/ hyperactivity disorder
Conduct disorder
Sexual disorders
Migraine
Other chronic pain syndromes?
Obesity
Type II diabetes mellitus
Kruger S et al.
Int
J Eat
Disord
. 1996;19:45-52; McElroy SL et al.
Compr
Psychiatry
. 1996; 37:229-240;
Comings BG et al.
Am J Hum Genet
. 1987;41:804-821;
Biederman
J et al.
Biol
Psychiatry.
2000;48:458-466; Frazier JA et al.
Am J Psychiatry
. 2002;159:13-21; McElroy SL et al.
J
Clin
Psychiatry
. 1999;60:414-420;
Merikangas
KR et al.
Arch Gen Psychiatry
. 1990;47:849-853;
Elmslie
JL et al.
J
Clin
Psychiatry. 2000;61:179-184; McElroy SL et al. J Clin Psychiatry. 2002;63:207-213; Regenold WT et al. J Affect Disord. 2002;70:19-26.Slide9
Key Recommendation 2
Assess affective and co-morbid symptoms concurrentlySlide10
Affective and Comorbid Symptoms of BP
Affective Manic Depressive
Mixed Cycling
Psychotic
Co-morbid
Obsessive-compulsive
Panic/agoraphobia
Generalized anxiety
Phobia
Alcohol use
Substance use
Binge eating Slide11
Key Recommendation 3
Focus pharmacotherapy on achieving mood stabilization. Use psychological treatments–eg, patient education or illness management–to address co-morbidity issues.Slide12
Comorbid BP: Treatment Guidelines
First goal of pharmacotherapy is mood stabilizationStart with medications that might be effective for both BP and the co-morbid disorder(s)Weigh the severity of bipolarity and co-morbidity when considering
monotherapy vs combination therapy
Monitoring patients through daily mood charting helps recognition of mood states, co-morbidities, their relation with one another, Rx response
Freeman MP, et al.
J Affect
Disord
.
2002;68:1-23.Slide13
Goals of Psychotherapy for BP Patients
Modify social risk factors toEnhance protective effects of patient’s social environmentImprove patient’s abilities to manage effects of stressorsEnhance medication adherence
Increase patient’s and family’s willingness to accept the reality of the disorderReduce risk for suicideIdentify, understand, and manage co-morbid disorders
Miklowitz
DJ.
J
Clin
Psychopharmacol
.
1996;16(
suppl
1):S56-S66.Slide14
Psychotherapy for BP Patients:Clinical Trial of Integrated Group Therapy
Integrated group therapy (IGT): manual-based group psychotherapy integrating treatment for 2 disorders6-month pilot study for outpatients (N=45) with BP and substance abuse
Compared outcomes in patients receiving IGT (12 or 20 weekly sessions) or not receiving IGTResults: Patients receiving IGT had
Significantly better outcomes on Addiction Severity Index (
P
<.03), percentage of months abstinent (
P
<.01), likelihood of achieving 3 consecutive abstinent months (
P
<.004)
Significantly greater improvement on YMRS (
P
<.04), but no difference on HAM-D
Weiss RG, et al.
J
Clin
Psychiatry.
2000;61:361-367.Slide15
Key Recommendation 4
Know the evidence–or the lack thereof–for the therapies used to treat BP with co-morbidities Know the evidence–or the lack thereof–for mood stabilizers/atypical antipsychotics in treating conditions commonly co-morbid with BP when those conditions
do not occur with BSlide16
Lithium in Co-morbid Conditions: Randomized Placebo-controlled Trials
Condition
Alcohol
dependence
Anorexia
nervosa
Conduct
disorder
Impulsive
aggression
OCD
Outcome
(# studies)
+
+
+
–
+
+
+
+
–
–
Judd JL, et al.
Am J Psychiatry
. 1984;141:1517-1521; Kline NS, et al.
Am J Med Sci
. 1974;268:15-22;
Fawcett J, et al.
Arch Gen
Psychiatry.
1987;44:248-256;
McDougle
CJ, et al.
J
Clin
Psychopharmacol
.
1991;11:175-184;
Pigott
TA, et al.
J
Clin
Psychopharmacol
.
1991;11:242-248; Gross HA, et al.
J
Clin
Psychopharmacol
. 1981;1:376-381; Campbell M, et al.
J Am
Acad
Child
Adolesc
Psychiatry.
1995;34:445-453; Malone RP, et al.
Arch Gen Psychiatry.
2000;57:649-654;
Sheard
MH, et al.
Am J Psychiatry
. 1976;133:1409-1413;
Dorus
W, et al.
JAMA
. 1989; 262:1646-1652.
The FDA has not approved the use of lithium for any of these disorders.Slide17
Divalproex in Co-morbid Conditions: Randomized Placebo-controlled Trials
Brady KT, et al.
Drug & Alcohol Dependence.
2002;67:323-330;
Lum
M, et al.
Prog
Neuropsychopharmacol
Biol
Psychiatry.
1991;15:269-273; Hollander E, et al.
Neuropsychopharmacology
. 2003;28:1186-1197; Hollander E, et al.
J
Clin
Psychiatry.
2001;62:199-203; Freitag FG, et al. Neurology. 2002;58:1652-1659.
Condition
Alcohol
dependence
(relapse to prevention)The FDA has approved the use of
divalproex for migraine prophylaxis but has not approved any of the other disorders.Panicdisorder
Borderline
personality
disorder
Migraine
(prophylaxis)
Intermittent explosive disorder (modified)
Outcome
(# studies)
+
+
+
+
+
+
+
+
+
–
Posttraumatic stress disorder (modified)
+
–Slide18
Carbamazepine in Co-morbid Conditions: Randomized Placebo-controlled Trials
Malcolm R, et al.
Am J Psychiatry
. 1989;146:617-621;
Bjorkqvist
SE, et al.
Acta
Psychiatr
Scand
. 1976;53:333-342;
Uhde
TW, et al.
Am J Psychiatry
. 1988;145:1104-1119; Kaplan AS, et al.
Am J Psychiatry
. 1983;140:1225-1226;
Cowdry
RW, et al. Arch Gen Psychiatry. 1988;45:111-119.
Condition
Alcohol withdrawal
The FDA has not approved the use of carbamazepine for any of these disorders.
AlcoholdependenceBorderline
personality disorder
Panic
disorder
Bulimia
nervosa
Outcome
(# studies)
+
+
+
+
+
+
+
–
–Slide19
Atypical Antipsychotics in Co-morbid Conditions: Placebo-controlled Trials
RIS=
risperidone
; OLZ=
olanzapine
McDougle
CJ, et al.
Arch Gen Psychiatry
. 2000;57:794-801;
Brawman-Mintzer
O, et al. Unpublished data;
Shapira
NA, et al. American College of
Neuropsychopharmacology
; 2002; San Juan, Puerto Rico;
Findling
RL, et al.
J Am
Acad Child Adolesc Psychiatry. 2000;39:509-516; Snyder R, et al. J Am Acad Child
Adolesc Psychiatry. 2002;41:1026-1036; Dion Y, et al.
J Clin Psychopharmacol. 2002;22:31-39; McDougle CJ, et al. Arch Gen Psychiatry. 1998;55:633-641; Grabowski J, et al. J Clin Psychopharmacol. 2000;20:305-310.Condition
OCD
The FDA has not approved the use of olanzapine or risperidone for any of these disorders.
Conduct
disorder
Tourette
syndrome
Autism
+
(RIS)
Cocaine
dependence
Outcome
(Agents)
+
(RIS)
+/–
(OLZ)
+
(RIS)
+
(RIS)
+
(RIS)
–
(RIS)
GAD
+
(RIS)Slide20
Key Recommendation 5
Avoid prematurely treating co-morbidities with mood-destabilizing agentsSlide21
Co-morbid BP: Treatment Guidelines
Avoid treatments that destabilize moodAntidepressants, stimulants may precipitate hypomania, mania, mixed states, rapid cycling“Uncovering” psychotherapies may increase psychological stress
Destabilization of mood often worsens co-morbid conditionsConcentrate initial therapies on producing mood stability or pure depression; once a patient is depressed, antidepressants usually can be addedSlide22
Key Recommendation 6
Before using antidepressants to treat anxiety disorders co-morbid with BP, consider mood stabilizers and atypical antipsychotics with demonstrated efficacy in anxietySlide23
Mood Stabilizers and Atypical Antipsychotics with Efficacy in Anxiety
Mood stabilizers: valproate/divalproex for
panic disorderAtypical antipsychotics: risperidone for generalized anxiety and obsessive-compulsive disordersSlide24
Key Recommendation 7
Rethink requiring active alcoholics to “stop drinking” before treating their BP, and select BP therapies accordinglySlide25
Treating Co-morbid Alcohol Abuse
Alcoholic, bipolar patients should not be refused treatment for BP Do not postpone therapy until patients achieve sobrietyPatients denied therapy for BP until they stop drinking very often never return for treatmentMany problems of co-morbid alcohol abuse occur with other addictive substances
Consider adjunctive psychological treatment
Bipolar Care OPTIONS Southeast Regional Working Group; June 6-7, 2003; Atlanta, GA.Slide26
Effects of BP Treatments on Comorbid Alcohol Abuse
Divalproex: may be effective in preventing relapseCarbamazepine: effective in alcohol withdrawal
Lithium: may be effective but need to monitor electrolytes and hydration when taken in combination with alcoholSlide27
Topiramate in Alcohol Dependence
Study Weeks
Placebo (n=48)
Topiramate
(n=55)
-9
-8
-7
-6
-5
-4
-3
-2
-1
0
0 4 8 12
Drinks/d
-6.24 ± 1.23
-3.36 ± 1.04
Mean Change ± 95% CI From Baseline on Drinks/Day
P
<.0001
Baseline: 7.78 (
topiramate
)
vs
6.52 (placebo).
Johnson BA, et al.
Lancet
. 2003;361:1677-1685.
The FDA has not approved this use.Slide28
Key Recommendations: Summary
Realize that co-morbidity is the rule, not the exception, in bipolar disorder (BP)Assess affective and co-morbid symptoms concurrently
Focus pharmacotherapy on achieving mood stabilization. Use psychological treatments–eg
, patient education or illness management–to address co-morbidity issues.Slide29
Key Recommendations: Summary
Know the evidence–or the lack thereof–for the therapies used to treat BP with co-morbiditiesAvoid prematurely treating co-morbidities with mood-destabilizing agents
Before using antidepressants to treat anxiety disorders co-morbid with BP, consider mood stabilizers and atypical antipsychotics with demonstrated efficacy in anxiety
Rethink requiring active alcoholics to “stop drinking” before treating their BP, and select BP therapies accordinglySlide30
Q & ASlide31
888-536-HOPE (4673)
lindnercenterofhope.org