principles of treating individuals with complex co-morbidity paul e. keck, jr., md lindner center of...
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Principles of Treating Individuals with Complex Co-Morbidity
Paul E. Keck, Jr., MD
Lindner Center of HOPEUniversity of Cincinnati College of
Medicine
Key Recommendations
1. Realize that co-morbidity is the rule, not the exception, in bipolar disorder (BP)
2. Assess affective and co-morbid symptoms concurrently
3. Focus pharmacotherapy on achieving mood stabilization. Use psychological treatments–eg., patient education or illness management–to address co-morbidity issues.
Key Recommendations (continued)4. Know the evidence–or the lack thereof–for the therapies
used to treat BP with co-morbidities
5. Avoid prematurely treating co-morbidities with mood-destabilizing agents
6. Before using antidepressants to treat anxiety disorders co-morbid with BP, consider mood stabilizers and atypical antipsychotics with demonstrated efficacy in anxiety
7. Rethink requiring active alcoholics to “stop drinking” before treating their BP, and select BP therapies accordingly
Key Recommendation 1
• Realize that co-morbidity is the rule, not the exception, in bipolar disorder (BP)
National Co-morbidity Survey
1
2
≥ 3
# LifetimeDSM-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.
Prevalence of Selected Co-morbidities with BP I* (N=29)
93
71
61
41
59
29
0
10
20
30
40
50
60
70
80
90
100
Any AnxietyDisorder
AnySubstance
Abuse
AlcoholDependence
DrugDependence
ConductDisorder
AdultAntisocialBehavior
*Euphoric-grandiose subtype.Kessler RC, et al. Psychol Med. 1997;27:1079-1089.
Patie
nts
(%)
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.
3.21.6
10.0
0
2
4
6
8
10
12
14
16
18
20
Bipolar Unipolar Bipolar Unipolar
Odd
s Ra
tio
20.8
PD† OCD†
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.
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
Key Recommendation 3
• Focus pharmacotherapy on achieving mood stabilization. Use psychological treatments–eg, patient education or illness management–to address co-morbidity issues.
Comorbid BP: Treatment Guidelines
• First goal of pharmacotherapy is mood stabilization
• Start 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.
Goals of Psychotherapy for BP Patients
• Modify social risk factors to• Enhance protective effects of patient’s social
environment• Improve patient’s abilities to manage effects of
stressors• Enhance medication adherence• Increase patient’s and family’s willingness to accept the
reality of the disorder• Reduce risk for suicide• Identify, understand, and manage co-morbid disorders
Miklowitz DJ. J Clin Psychopharmacol. 1996;16(suppl 1):S56-S66.
Psychotherapy for BP Patients:Clinical Trial of Integrated Group Therapy• Integrated group therapy (IGT): manual-based group
psychotherapy integrating treatment for 2 disorders
• 6-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 IGT
• Results: 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.
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 B
Lithium in Co-morbid Conditions: Randomized Placebo-controlled Trials
Condition
Alcohol dependence
Anorexianervosa
Conductdisorder
Impulsiveaggression
OCD
Out
com
e(#
stud
ies)
+++–
+ ++
+––
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.
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
Borderlinepersonality
disorder
Migraine(prophylaxis)
Intermittent explosive disorder (modified)
Out
com
e (#
stud
ies) +
+++++
++
+–
Posttraumatic stress disorder (modified)
+ –
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.
Alcoholdependence
Borderlinepersonality disorder
Panicdisorder
Bulimia nervosa
Out
com
e(#
stud
ies) +
++++
+ +––
Atypical Antipsychotics in Co-morbid Conditions: Placebo-controlled Trials
RIS=risperidone; OLZ=olanzapineMcDougle 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
Out
com
e (A
gent
s)
+(RIS)+/–
(OLZ)
+(RIS)
+(RIS)
+(RIS)
–(RIS)
GAD
+(RIS)
Co-morbid BP: Treatment Guidelines
• Avoid treatments that destabilize mood• Antidepressants, stimulants may precipitate
hypomania, mania, mixed states, rapid cycling• “Uncovering” psychotherapies may increase
psychological stress• Destabilization of mood often worsens
co-morbid conditions• Concentrate initial therapies on producing mood
stability or pure depression; once a patient is depressed, antidepressants usually can be added
Key Recommendation 6
• Before using antidepressants to treat anxiety disorders co-morbid with BP, consider mood stabilizers and atypical antipsychotics with demonstrated efficacy in anxiety
Mood Stabilizers and Atypical Antipsychotics with Efficacy in Anxiety
• Mood stabilizers: valproate/divalproex for panic disorder
• Atypical antipsychotics: risperidone for generalized anxiety and obsessive-compulsive disorders
Key Recommendation 7
• Rethink requiring active alcoholics to “stop drinking” before treating their BP, and select BP therapies accordingly
Treating Co-morbid Alcohol Abuse
• Alcoholic, bipolar patients should not be refused treatment for BP • Do not postpone therapy until patients achieve
sobriety• Patients denied therapy for BP until they stop drinking
very often never return for treatment• Many 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.
Effects of BP Treatments on Comorbid Alcohol Abuse
• Divalproex: may be effective in preventing relapse• Carbamazepine: effective in alcohol withdrawal • Lithium: may be effective but need to monitor
electrolytes and hydration when taken in combination with alcohol
Topiramate in Alcohol Dependence
Study WeeksPlacebo (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.
Key Recommendations: Summary
1. Realize that co-morbidity is the rule, not the exception, in bipolar disorder (BP)
2. Assess affective and co-morbid symptoms concurrently
3. Focus pharmacotherapy on achieving mood stabilization. Use psychological treatments–eg, patient education or illness management–to address co-morbidity issues.
Key Recommendations: Summary
4. Know the evidence–or the lack thereof–for the therapies used to treat BP with co-morbidities
5. Avoid prematurely treating co-morbidities with mood-destabilizing agents
6. Before using antidepressants to treat anxiety disorders co-morbid with BP, consider mood stabilizers and atypical antipsychotics with demonstrated efficacy in anxiety
7. Rethink requiring active alcoholics to “stop drinking” before treating their BP, and select BP therapies accordingly