Bipolar Disorder: Psychological Treatment

1
Bipolar Disorder Psychological Treatment
2
Role of Adjunctive Psychotherapy in Bipolar I
Disorder

• Increase adherence to medication
• Address residual symptoms
• Enhance social and occupational functioning
• Improve detection of early warning signs of
  impending recurrence

Keck PE Jr. Biol Psychiatry. 200048430-432.
3
Bipolar-Specific Psychotherapy Common Strategies

• Psychoeducation about illness and medications
• Careful review of medication side effects
• Promote regular sleep-wake cycle
• Daily monitoring of mood states
• Collaborative management strategies, including
  engagement of wide social support system

Frank E et al. J Abnorm Psychol.
1999108579-587. Miklowitz DJ et al. Biol
Psychiatry. 200048582-592. Perry A et al. BMJ.
1999318149-153. Scott J et al. Psychol Med.
200131459-467.
4
Bipolar-Specific Adjunctive Psychotherapies

• Psychoeducation
• Cognitive-behavioral psychotherapy
• Psychodynamic psychotherapy
• Marital/family therapy
• Interpersonal psychotherapy

Frank E et al. J Abnorm Psychol.
1999108579-587. Miklowitz DJ et al. Biol
Psychiatry. 200048582-592. Perry A et al. BMJ.
1999318149-153. Scott J et al. Psychol Med.
200131459-467.
5
Individual Psychoeducation vs Treatment as Usual
(TAU) Time to Manic Relapse
70
Psychoeducation (n 34)
60
Cumulative Events
TAU (n 35)
50
P .008
40
30
20
10
0
10
20
30
40
50
60
70
Weeks
Perry A et al. BMJ. 1999318149-153.
6
Individual Psychoeducation vs TAUTime to
Depressive Relapse
60
Psychoeducation (n 34)
50
TAU (n 35)
P .19
40
Cumulative Events
30
20
10
0
10
30
40
50
60
70
20
Weeks
TAU treatment as usual
Perry A et al. BMJ. 1999318149-153.
7
Family-Focused Treatment (FFT) Study Results

• Assignment to FFT was associated with
  significantly fewer relapses and longer time to
  relapse (P .04)
• FFT was associated with greater improvement of
  depressive (but not manic) symptoms (P .04)

Miklowitz DJ et al. Biol Psychiatry.
200048582-592.
8
Group Psychoeducation in the Prophylaxis of
Recurrences in Bipolar Patients
16
14
12
14.83
10
Number of Days of Hospitalization per Patient
8
6
4
4.75
2
0
Adapted from Colom F et al. Arch Gen Psychiatry.
200360402-407.
9
Bipolar Disorder Treatment Goals

• Relieve acute symptoms
• Prevent suicide
• Prevent/reduce recurrences
• Achieve maximum drug efficacy with minimum side
  effects and medication
• Promote adherence to medication regimen
• Improve quality of life    

Bowden CL. J Am Acad Psychoanal. 199220477-486.
Goodwin FK, Jamison KR. Manic-Depressive
Illness. Oxford University Press New York, NY
1990.
10
Why Are Patients Nonadherent?

• Denial of illness
• Side effects
• Belief of recovery
• Lack of control over life
• Lapsed prescription
• Cost of medication
• Missing euphoria

Keck PE Jr et al. Psychopharmacol Bull.
19973387-91.
11
Treatment Guidelines and Their Implications for
Practice

• APA treatment guidelines
• New data on bipolar disorder epidemiology
• Managing acute mood episodes
• Managing maintenance therapy
• Formulations, combination therapy considerations

Sachs GS. J Clin Psychiatry. 200364(suppl
8)35-40.
12
APA Bipolar 2002 Treatment Guidelines

• Goals of psychiatric management
• Establish and maintain therapeutic alliance
• Monitor the patients psychiatric status
• Provide education about bipolar disorder
• Enhance treatment compliance
• Promote regular patterns of activity and sleep
• Anticipate stressors
• Identify new episodes early
• Minimize functional impairments

American Psychiatric Association. Practice
Guideline for the Treatment of Patients with
Bipolar Disorder. 2nd ed. Washington, DC 2002.
13
Acute Mania Standard Care Pathway
Meets acute mania criteria
Mood stabilizer antipsychotic
Mood stabilizer
Antipsychotic
Continuation
Recovering
Mood stabilizer antipsychotic
Add newmood stabilizer
Continuation
Recovering
ECT
Sachs GS. J Clin Psychiatry. 200364(suppl
8)35-40.
14
Initial Decision Point Mood Elevation Pathway
1. Determine clinical status
Meets acute mania criteria
2. Ensure safety
Choose appropriate treatment venue, initiate
medical work-up
Review indications for antipsychotic medication
3. Restore behavioral control
Go to mood stabilizer menu of reasonable choices
4. Initiate/optimize mood stabilizer
5. Determine indication for antipsychotic
medication
Review indications for antipsychotic medication
6. Determine need for additional antimanic
treatment
Review putative antimanic agents
7. Determine indication for ECT
Review indication for ECT
Sachs GS. J Clin Psychiatry. 200364(suppl
8)35-40.
15
Treatments for Acute Mania

• FDA-approved
• Lithium
• Valproate
• Olanzapine
• Chlorpromazine
• Risperidone
• Quetiapine

• Trial data available
• Carbamazepine
• Conventional antipsychotics
• Ziprasidone
• Aripiprazole
• Electroconvulsive therapy

16
Treatments for Acute Mania (cont.)

• Limited trial data available
• Other atypical antipsychotics
• Clozapine
• New antiepileptic drugs
• Topiramate
• Lamotrigine
• Gabapentin
• Other compounds
• Calcium channel blocker
• Benzodiazepine
• Omega-3

17
Treatments for Acute Mania (cont.)

• Monotherapy
• Lithium
• Valproate
• Olanzapine
• Chlorpromazine
• Risperidone
• Quetiapine
• Ziprasidone
• Aripiprazole

• Monotherapy (cont.)
• Carbamazepine
• Oxcarbazepine
• Gabapentin
• Topiramate
• Combination therapy
• Various combinations

18
Summary of Recommended Doses of MedicationsUsed
for Acute Phase Treatment of Mania/Hypomania

• Type/Class Medication Usual Target Dose
  Usual Max Dose (level) Schedule
• Lithium (0.81.0 mEq/L) (1.2 mEq/L) BID or
  QHS
• Anticonvulsant Oxcarbazepine 6002100
  mg/day 2400 mg/day BID or TID
• Divalproex sodium (80 ?g/mL) (125
  ?g/mL) BID or QHS
• Atypical Aripiprazole 15 mg/day 30 mg/day QD
• Antipsychotics
• Clozapine 100300 mg/day 900 mg/day QHS
• Olanzapine 1015 mg/day 20 mg/day BID or QHS
• Risperidone 2 mg/day 6 mg/day BID or QHS
• Quetiapine 400800 mg/day 800 mg/day BID or
  QHS
• Ziprasidone 40160 mg/day 160 mg/day BID

Doses used for maintenance treatment may be
lower Adapted from Suppes T, Dennehy B. Texas
Implementation of Medication AlgorithmsBipolar
Disorder Algorithms. August 27, 2002. Data
courtesy of GS Sachs. Jones M et al. Presented
at the Fifth International Conference on Bipolar
Disorder. Pittsburgh, PA June 12-14, 2003.
19
Doses of Medications Used for Acute Phase
Treatment of Bipolar Depression
Risk of serious side effects associated with
rapid titration Doses used for maintenance
treatment may be lower Suppes T, Dennehy B. Texas
Implementation of Medication AlgorithmsBipolar
Disorder Algorithms. August 27, 2002.
20
Psychotic Mania Acute Phase Stratified Approach

• Ensure safety, rule out life-threatening
  conditions
• Eliminate mood-elevating substances and
  psychotomimetics
• Implement therapies to allow behavioral control
• Start mood stabilizer

Atypical antipsychotic
( benzodiazepine)
Divalproex, or lithium (or carbamazepine)
Bilateral ECT
Sustained Remission
Sachs GS. J Clin Psychiatry. 200364(suppl
8)35-40.
21
Continuation Phase Mania

• Begins with remission of acute symptoms
• Continue successful acute therapies at full dose
• To maintain effective serum levels
• Consistent with ability to tolerate medication
• Often must reduce lithium
• Often must reduce divalproex
• Often must increase carbamazepine
• Choose duration of 8 weeks, unless
• Documented natural course is longer
• Documented history of early affective switch

Sachs GS. J Clin Psychiatry. 200364(suppl
8)35-40.
22
Maintenance/Discontinuation Phase

• Begins with declaration of recovery
• Sustained remission gt 8 weeks
• Maintain prophylactic therapies
• Gradual taper of acute treatments
• Monitor clinical/laboratory
• Follow-up monthly x 1 yr
• Adverse effects
• Therapeutic range
• Cycle length (mood chart)
• Roughening

Sachs GS. J Clin Psychiatry. 200364(suppl
8)35-40.
23
Treatment of Pediatric Mania

• Taper stimulants and antidepressants, re-evaluate
  mood and behavior
• Still with mood symptoms and nonpsychotic
• Atypical ? mood stabilizer (MS)
• Psychosis or partial or nonresponse ? atypical
  MS
• gt 4 weeks
• Once stable, re-evaluate attention-deficit
  hyperactivity disorder (ADHD)
• Still with ADHD symptoms?
• Low-dose stimulants, longer acting with less
  rebound
• Mood stabilization is necessaryfirst step!

Biederman J et al. J Am Acad Child Adolesc
Psychiatry. 1998371091-1096.
24
New Antiepileptic Drugs (AED)

• Lamotrigine, gabapentin, topiramate used in adult
  acute mania studies
• Gabapentin and topiramate have not shown
  differentiation from placebo in the treatment of
  acute mania
• Bipolar depression
• Lamotrigine
• Bipolar disorder plus anxiety
• Gabapentin
• Weight loss
• Topiramate and zonisamide
• Awaiting controlled data for pediatric bipolar
  disorder
• Topiramate

Slide courtesy of MP DelBello.
25
Pediatric Bipolar DisorderSummary

• Pediatric BP resembles severe form of adult BP
• Taper antidepressants and stimulants
• Atypical antipsychotics are advantageous for
  pediatric BP
• No serum monitoring
• Probable equal efficacy and improved tolerability
• Combination pharmacotherapy may be necessary

Slide courtesy of MP DelBello.
26
Treatment of Bipolar DepressionCategory I
Recommendations

• Initiate lithium
• Augment with lamotrigine for breakthrough
  depression
• Antidepressant monotherapy should be avoided
• Psychotic depressions usually require adjunctive
  antipsychotics
• ECT if life-threatening, treatment-resistant,
  psychotic, or catatonic

Recommended with substantial clinical confidence
American Psychiatric Association. Practice
Guideline for the Treatment of Patients with
Bipolar Disorder. 2nd ed. Washington, DC 2002.
27
Treatment of Bipolar DepressionCategory II
Recommendations

• Initiate lamotrigine as alternative first-line
  treatment
• If maintenance phase, optimize dose of
  maintenance medication
• Add interpersonal or cognitive therapy to
  medication
• Augment with bupropion, paroxetine, other SSRIs,
  venlafaxine, or an MAOI for breakthrough
  depression
• Antidepressants recommended earlier for bipolar II

Recommended with moderate clinical
confidence MAOI monoamine oxidase inhibitors
American Psychiatric Association. Practice
Guideline for the Treatment of Patients with
Bipolar Disorder. 2nd ed. Washington, DC 2002.
28
Bipolar Depression APA Guidelines Executive
Summary

• First-line for new episodes
• Lithium or lamotrigine
• In more severely ill patient, consider lithium
  plus antidepressant
• Consider ECT if life-threatening inanition,
  suicidality, psychosis
• Breakthrough episodes
• Optimize primary agent
• Add lamotrigine, bupropion, or paroxetine
• Alternatives another SSRI, venlafaxine, or MAOI

American Psychiatric Association. Practice
Guideline for the Treatment of Patients with
Bipolar Disorder. 2nd ed. Washington, DC 2002.
29
Risks of Standard Antidepressant Use in Bipolar
Patients

• Induction of mania or cycle acceleration1,2
• Delayed introduction of mood stabilizers may
  worsen outcome, suicide risk3
• Debated efficacy above antidepressant effects of
  mood stabilizers4
• Possibly less efficacious in bipolar depression
  than unipolar depression
• Few standard antidepressants have been studied in
  bipolar depression

1. Wehr TA et al. Arch Gen Psychiatry.
197936555-559. 2. Altshuler LL et al. Am J
Psychiatry. 19951521130-1138. 3. Goldberg JF et
al. J Clin Psychiatry. 200263985-991. 4. Moller
HJ et al. J Affect Disord. 200167141-146.
30
Risk Factors for Antidepressant-Induced Mania

• Prior antidepressant-induced switches
• Substance abuse
• Multiple antidepressant trials
• Hyperthymic temperament
• Genetic predispositions
• Early age at onset

Goldberg JF, Truman CJ. Bipolar Disord.
20035407-420.
31
Bipolar Depression and AntidepressantsGeneral
Guidelines

• Always use a mood stabilizer for the bipolar I
  patient, even while depressed
• In patients who readily relapse into depression
  after discontinuing the antidepressant, use the
  antidepressant at the lowest
  effective dosage
• Promptly wean the antidepressant if evidence of
  hypomania or mania emerges

Frances AJ et al. J Clin Psychiatry.
199657(suppl 12A)3-88.Dantzler A, Osser DN.
Psychiatr Ann. 199929270-284.
32
Rapid Cycling Treatment Guidelines

• Is a predictor of positive response to treatment
  with valproate
• Appears to neutralize lithiums antidepressant
  efficacy
• Avoid antidepressants in bipolar II
• First-line therapy
• Start with valproate in bipolar I
• Start with lamotrigine in bipolar II
• Move quickly to combination therapy if first-line
  therapy is not efficacious
• Add lithium, etc

Calabrese JR, et al. J Clin Psychiatry.
200162(suppl 14)34-41.
33
Managing Maintenance Treatment

• Preventing Episode Relapse

34
Long-Term Treatment GoalsBipolar Depression

• Remission of symptoms of major depression and a
  return to normal levels of psychosocial
  functioning
• Therapy should NOT precipitate mania, mixed
  states, or rapid cycling
• Eliminate frequent breakthrough of depressive
  symptoms

American Psychiatric Association. Practice
Guideline for the Treatment of Patients with
Bipolar Disorder. 2nd ed. Washington, DC 2002.
35
Comorbid Bipolar DisorderTreatment
36
Comorbid Bipolar DisorderTreatment Guidelines

• Start with mood stabilizers that might be
  effective for the comorbid disorder(s)
• Depending on severity of bipolarity and
  comorbidity, consider monotherapy vs combination
  therapy with mood stabilizers
• Li or VPA with an atypical antipsychotic, Li
  VPA, Li CBZ
• Use patient education, supportive therapy, CBT as
  initial and/or maintenance adjunctive treatment
  for substance use, anxiety, eating, and impulsive
  disorder comorbidity

Li lithium VPA valproate CBZ
carbamazepine CBT cognitive behavior therapy
Cassano GB et al. J Affect Disord. 200059(suppl
1)S69-S79.
37
Comorbid Bipolar DisorderTreatment Guidelines
(cont.)

• For combination medical treatment of comorbid
  conditions, use agents that are mood stabilizing
  or mood neutral before those that are mood
  destabilizing
• Avoid treatments of comorbid conditions that are
  mood destabilizing (eg, antidepressants,
  stimulants, uncovering psychotherapies) until
  mood stabilization and/or pure depression has
  occurred
• Various combinations of treatments often
  necessary
• Always assess affective and comorbid symptoms
  concurrently

Cassano GB et al. J Affect Disord. 200059(suppl
1)S69-S79.
38
Atypical Antipsychotics

• Advantages
• Low EPS and TD liability
• Prolactin sparing with most
  drugs
• Improvement in cognitive deficits
• Advantages in some refractory patients

• Limitations
• Metabolic side effects with some (eg, weight
  gain)
• EPS liability with some drugs at high doses
• Somnolence
• Inadequate response in many
  patients

EPS extrapyramidal symptoms TD tardive
dyskinesia
Meltzer HY. Neuropsychopharm. 199921(suppl)106S-
115S.