what’s really new in bipolar disorder, october 2005

WHAT’S REALLY NEW IN BIPOLAR WHAT’S REALLY NEW IN BIPOLAR DISORDER, OCTOBER 2005DISORDER, OCTOBER 2005

OR WHAT I THINK IS OR WHAT I THINK IS IMPORTANT AND NEWIMPORTANT AND NEW

(AND SOME OLD STUFF TOO)(AND SOME OLD STUFF TOO)

WHO AM I? WHO AM I? WHERE AM I?WHERE AM I?

MEDICAL DIRECTOR OF DAY HOSPITAL, MEDICAL DIRECTOR OF DAY HOSPITAL, PALOMAR HOSPITAL, ESCONDIDO, PALOMAR HOSPITAL, ESCONDIDO,

CALIFORNIA; PSYCHIATRIST, CALIFORNIA; PSYCHIATRIST, PSYCHIATRIC CENTERS OF SAN DIEGO, PSYCHIATRIC CENTERS OF SAN DIEGO,

ESCONDIDOESCONDIDOPinnacle Of Career: Pinnacle Of Career:

1.1. Admission to Medical SchoolAdmission to Medical School2.2. Joining PCSDJoining PCSD

$$$ DISCLOSURES $$$ $$$ DISCLOSURES $$$ RESEARCH, LECTURES, CONSULTANTRESEARCH, LECTURES, CONSULTANT

• Lilly, Janssen, Wyeth-Ayerst, Servier, Lilly, Janssen, Wyeth-Ayerst, Servier, FHH Foundation, Lundbeck, Organon, FHH Foundation, Lundbeck, Organon, Alberta Heritage Foundation Alberta Heritage Foundation Research, Astra-Zeneca, BiovailResearch, Astra-Zeneca, Biovail

• Inspiration: Dr. Ron Remick, Dr. Ernie Inspiration: Dr. Ron Remick, Dr. Ernie McCrank, My patients McCrank, My patients

MY DAILY AFFIRMATIONSMY DAILY AFFIRMATIONS

• Just for today…I won’t sit in my living Just for today…I won’t sit in my living room all day in my underwear; I’ll room all day in my underwear; I’ll move the computer into the bedroommove the computer into the bedroom

HISTORICAL REVIEWHISTORICAL REVIEW

• AretaeusAretaeus

• KraepelinKraepelin

• LeonhardLeonhard

• GoodwinGoodwin

• AkiskalAkiskal

• Gorman met McCrankGorman met McCrank

WHAT I LEARNED IN MY FIRST WHAT I LEARNED IN MY FIRST RESEARCH PROJECTRESEARCH PROJECT

•NOTHING IN LIFE OCCURS IN NOTHING IN LIFE OCCURS IN A VACUUM, NOT EVEN HEART A VACUUM, NOT EVEN HEART

DISEASEDISEASE

MOOD DISORDERS ARE DISORDERS MOOD DISORDERS ARE DISORDERS WITH CYCLICAL CHANGES IN MOOD, WITH CYCLICAL CHANGES IN MOOD,

ENERGY AND BEHAVIORENERGY AND BEHAVIOR

• It seems to me that it is more likely It seems to me that it is more likely that Mood Disorders are primarily that Mood Disorders are primarily energy disorders with secondary energy disorders with secondary mood and behavior dimensionsmood and behavior dimensions

DIAGNOSTIC ISSUESDIAGNOSTIC ISSUES

• DSM IV puts primary emphasis on polarity DSM IV puts primary emphasis on polarity (i.e. history of mania or hypomania) rather (i.e. history of mania or hypomania) rather than cyclicity or recurrencethan cyclicity or recurrence

• Depressive disorders are thus a Depressive disorders are thus a meaningless category because of: 1. meaningless category because of: 1. Defined by “not bipolar” 2. Too Defined by “not bipolar” 2. Too heterogeneous, patient with 2 episodes in heterogeneous, patient with 2 episodes in lifetime vs. someone with episodes every lifetime vs. someone with episodes every 12 to 24 months 12 to 24 months

HIGHLY RECURRENT UNIPOLAR HIGHLY RECURRENT UNIPOLAR DEPRESSION (Clinical Features)DEPRESSION (Clinical Features)

• Family history of Bipolar Disorder (BD)Family history of Bipolar Disorder (BD)• Bipolar like age of onset (teens and 20’s)Bipolar like age of onset (teens and 20’s)• High episode frequency (every 18-24 mo)High episode frequency (every 18-24 mo)• Represents 25-35% of unipolar casesRepresents 25-35% of unipolar cases• May convert to BD, but many don’t, unless May convert to BD, but many don’t, unless

receiving antidepressants without mood receiving antidepressants without mood stabilizerstabilizer

• Patients respond to Li better than imipraminePatients respond to Li better than imipramine• No category for these patients in DSM IVNo category for these patients in DSM IV

POTENTIAL BIPOLAR DIATHESISPOTENTIAL BIPOLAR DIATHESIS

• Recurrent major depressive episodesRecurrent major depressive episodes• Early age of onset (40% of patients before age 20 Early age of onset (40% of patients before age 20

BD, of remaining 60%, most have highly recurrent BD, of remaining 60%, most have highly recurrent unipolar depression)unipolar depression)

• Family history of BDFamily history of BD• Atypical depressive symptoms Atypical depressive symptoms • Brief depressive episodesBrief depressive episodes• Psychotic Depressive episodesPsychotic Depressive episodes• Post Partum DepressionPost Partum Depression• AD induced hypomania/maniaAD induced hypomania/mania• AD non-response or wear off AD non-response or wear off

PNEMONIC FOR MANIC PNEMONIC FOR MANIC SYMPTOMS - DIGFASTSYMPTOMS - DIGFAST

• Distractibility Distractibility • Indiscretion (pleasurable activities) Indiscretion (pleasurable activities) • Grandiosity Grandiosity • Flight of ideas Flight of ideas • Activity increase Activity increase • Sleep deficit (decreased need) Sleep deficit (decreased need) • Talkativeness (pressured speech)Talkativeness (pressured speech)

ALL QUESTIONS POSED TO ALL QUESTIONS POSED TO BIPOLAR PATIENTS, ARE BIPOLAR PATIENTS, ARE BEST POSED TO THEIR BEST POSED TO THEIR

RELATIVESRELATIVES

……At Least When It Comes To ManiaAt Least When It Comes To Mania

Bipolar Disorder Symptoms areBipolar Disorder Symptoms areChronic and Predominantly Chronic and Predominantly DepressiveDepressive

AsymptomaticDepressedManic/hypomanicCycling / mixed

% of Weeks

146 bipolar I 146 bipolar I patientspatientsfollowed 12.8 yearsfollowed 12.8 years

86 bipolar II 86 bipolar II patientspatientsfollowed 13.4 followed 13.4 yearsyears

53%32%

9%6%

46%50%

1% 2%

Judd et al (2002) Archives of General Psychiatry (59) 530-537

Judd et al (2002) Archives of General Psychiatry (59) 530-537 Judd et al (2003) Archives General

Psychiatry. (60) 261-269Judd et al (2003) Archives General

Psychiatry. (60) 261-269

ANANTIDEPRESSANT (AD) TREATMENT IN BIPOLAR VS.

UNIPOLAR DEPRESSION• Ghaemi SN et. al.; Am J Psychiatry Ghaemi SN et. al.; Am J Psychiatry

161:163-165,2004161:163-165,2004• Long term safety and effectiveness of AD’s Long term safety and effectiveness of AD’s

is well established for unipolar, but not BD is well established for unipolar, but not BD patients. Short term efficacy is clear.patients. Short term efficacy is clear.

• Tricyclic’s are not as effective for Tricyclic’s are not as effective for recurrence as Li has been demonstratedrecurrence as Li has been demonstrated

• This study compared modern and older This study compared modern and older AD’s in Bipolar depression (41 patients) vs. AD’s in Bipolar depression (41 patients) vs. Unipolar depression (37 patients)Unipolar depression (37 patients)

AD TREATMENT TRIAL AD TREATMENT TRIAL COMPARISON CONTINUEDCOMPARISON CONTINUED

• Short term non-response for BD at 51.3% vs. Short term non-response for BD at 51.3% vs. Unipolar at 31.6%Unipolar at 31.6%

• Manic switching less in BD patients taking mood Manic switching less in BD patients taking mood stabilizers (31.6% vs. 84.2%)stabilizers (31.6% vs. 84.2%)

• Cycle acceleration only occurred in BD depression Cycle acceleration only occurred in BD depression (25.6%), with new rapid cycling in 32.1% of (25.6%), with new rapid cycling in 32.1% of patientspatients

• Late response loss, or tolerance was 3.4X’s more Late response loss, or tolerance was 3.4X’s more frequent in BD depressionfrequent in BD depression

• Cycle acceleration, rapid cycling and response Cycle acceleration, rapid cycling and response loss were not prevented by mood stabilizersloss were not prevented by mood stabilizers

• In general, modern AD’s did not have lower In general, modern AD’s did not have lower negative outcomes than Tricyclic'snegative outcomes than Tricyclic's

AD TREATMENT TRIAL AD TREATMENT TRIAL COMPARISON CONCLUSIONCOMPARISON CONCLUSION

• An unfavorable cost/benefit ratio is An unfavorable cost/benefit ratio is indicated for the use of AD therapy in indicated for the use of AD therapy in the treatment of Bipolar depressionthe treatment of Bipolar depression

• This studies distressing numbers are This studies distressing numbers are significant, considering that many significant, considering that many clinicians, and even most guidelines clinicians, and even most guidelines are suggesting both short and long-are suggesting both short and long-term use of AD’s for Bipolar depressionterm use of AD’s for Bipolar depression

A 52 WEEK OPEN-LABEL A 52 WEEK OPEN-LABEL CONTINUATION STUDY OF Ltg. IN THE CONTINUATION STUDY OF Ltg. IN THE TREATMENT OF BIPOLAR DEPRESSIONTREATMENT OF BIPOLAR DEPRESSION

• McElroy SL et. al.; J Clin Psychiatry 65:204-McElroy SL et. al.; J Clin Psychiatry 65:204-210, 2004210, 2004

• Bipolar depression is more frequent, lasts Bipolar depression is more frequent, lasts longer, and is more difficult to treat than longer, and is more difficult to treat than maniamania

• Ltg is a novel anticonvulsant that has been Ltg is a novel anticonvulsant that has been shown to be effective in the acute treatment shown to be effective in the acute treatment of Bipolar depression. This study is a 52 week, of Bipolar depression. This study is a 52 week, open-label continuation of that original trialopen-label continuation of that original trial

A 52 WEEK OPEN-LABEL A 52 WEEK OPEN-LABEL CONTINUATION STUDY OF Ltg. IN THE CONTINUATION STUDY OF Ltg. IN THE TREATMENT OF BIPOLAR DEPRESSION TREATMENT OF BIPOLAR DEPRESSION

CONTINUEDCONTINUED• The study group were BD I patients with an The study group were BD I patients with an

episode of Major Depression that had completed episode of Major Depression that had completed a 7 week dbl. bld. Plc. Controlled Ltg. a 7 week dbl. bld. Plc. Controlled Ltg. intervention, and were then invited to enter this intervention, and were then invited to enter this study, receiving 100-500 mg./day of Ltg.study, receiving 100-500 mg./day of Ltg.

• Of the 135 patients completing the acute study, Of the 135 patients completing the acute study, 124 (92%) entered the continuation study124 (92%) entered the continuation study

• MADRS, CGI measures were applied at 4, 12, 24, MADRS, CGI measures were applied at 4, 12, 24, 36, and 52 weeks36, and 52 weeks

A 52 WEEK OPEN-LABEL A 52 WEEK OPEN-LABEL CONTINUATION STUDY OF Ltg. IN THE CONTINUATION STUDY OF Ltg. IN THE TREATMENT OF BIPOLAR DEPRESSION TREATMENT OF BIPOLAR DEPRESSION

CONTINUEDCONTINUED• Of the 124 patients entered, 77 had received Ltg Of the 124 patients entered, 77 had received Ltg

and 47 had received placebo during the acute and 47 had received placebo during the acute studystudy

• The mean duration of Ltg. exposure was 10.4 The mean duration of Ltg. exposure was 10.4 months, and mean modal dose was 187 mg/d.months, and mean modal dose was 187 mg/d.

• 56% of the patients completed the trial56% of the patients completed the trial• There was a significant and sustained There was a significant and sustained

improvement over time. 84% achieved remission improvement over time. 84% achieved remission by week 4, and episodes of mania/hypomania were by week 4, and episodes of mania/hypomania were reduced from the previous yearreduced from the previous year

• Headache was the most common drug-related Headache was the most common drug-related adverse eventadverse event

A 52 WEEK OPEN-LABEL A 52 WEEK OPEN-LABEL CONTINUATION STUDY OF Ltg IN THE CONTINUATION STUDY OF Ltg IN THE TREATMENT OF BIPOLAR DEPRESSION TREATMENT OF BIPOLAR DEPRESSION

CONCLUSIONCONCLUSION• Ltg was effective in 1 year of open Ltg was effective in 1 year of open

label treatment as adjunctive or label treatment as adjunctive or monotherapy, and provided monotherapy, and provided sustained improvement without sustained improvement without mood destabilizationmood destabilization

• The issue of remission is studied in The issue of remission is studied in many psychiatric disorders, but it many psychiatric disorders, but it may be most critical in BDmay be most critical in BD

LAMOTRIGINE RASHLAMOTRIGINE RASH

• Can cause severe skin reactions (i.e. Can cause severe skin reactions (i.e. Steven Johnson Syndrome SJS, Toxic Steven Johnson Syndrome SJS, Toxic Epidermal Necrolysis TEN)Epidermal Necrolysis TEN)

• Recent data from German Rash Registry Recent data from German Rash Registry show only 1/10,000 (almost all neurology show only 1/10,000 (almost all neurology patients)patients)

• Registry lists many other agents (9 Registry lists many other agents (9 antibiotics, 4 anticonvulsants) ahead of Ltgantibiotics, 4 anticonvulsants) ahead of Ltg

CARDIAC DISEASE AND CARDIAC DISEASE AND DEPRESSIONDEPRESSION

PRELIMINARY RANDOMIZED, DBL BLD, PRELIMINARY RANDOMIZED, DBL BLD, PLACEBO CONTOLLED TRIAL OF PLACEBO CONTOLLED TRIAL OF

PRAMIPEXOLE (MIRAPEX) ADDED TO MOOD PRAMIPEXOLE (MIRAPEX) ADDED TO MOOD STABILIZERS FOR TREATMENT RESISTANT STABILIZERS FOR TREATMENT RESISTANT

BD DEPRESSIONBD DEPRESSION• Goldberg et. al. Am J Psychiatry 161:564-Goldberg et. al. Am J Psychiatry 161:564-

566,2004566,2004• Pramipexole, a dopamine agonist, may Pramipexole, a dopamine agonist, may

have AD properties. Efficacy and safety have AD properties. Efficacy and safety were assessed in this studywere assessed in this study

• 22 depressed outpatients with non-22 depressed outpatients with non-psychotic BD were randomly assigned to psychotic BD were randomly assigned to placebo or Pramipexole at max. dose of placebo or Pramipexole at max. dose of 1.7 mg./d for 6 weeks. HDRS (response at 1.7 mg./d for 6 weeks. HDRS (response at 50% improvement) and CGI were used50% improvement) and CGI were used



BD DEPRESSION CONTINUEDBD DEPRESSION CONTINUED• 83% of Pramipexole and 60% of placebo 83% of Pramipexole and 60% of placebo

patients completed the studypatients completed the study• Response rates in the Pramipexole and Response rates in the Pramipexole and

placebo groups were 67% and 20% placebo groups were 67% and 20% respectivelyrespectively

• Pramipexole patients also had greater Pramipexole patients also had greater mean improvements in CGI scoresmean improvements in CGI scores

• One patient DC’ed Pramipexole because of One patient DC’ed Pramipexole because of the emergence of hypomania (the only the emergence of hypomania (the only adverse effect drop-out)adverse effect drop-out)



BD DEPRESSION CONCLUSIONBD DEPRESSION CONCLUSION• Pramipexole appears to be effective and safe Pramipexole appears to be effective and safe

for the treatment of Bipolar depressionfor the treatment of Bipolar depression

• Bipolar depression has emerged as one of the Bipolar depression has emerged as one of the most important and difficult conditions to treat. most important and difficult conditions to treat. Beyond Ltg., the choices are complex and Beyond Ltg., the choices are complex and poorly supported by sufficient datapoorly supported by sufficient data

• Larger randomized and controlled studies are Larger randomized and controlled studies are now needed to further assess this studynow needed to further assess this study

GENERAL PRINCIPLES OF GENERAL PRINCIPLES OF MANAGEMENTMANAGEMENT

• Use life charts to monitor illnessUse life charts to monitor illness• Remember, it is basically a depressive Remember, it is basically a depressive

disorder, even though all of the new disorder, even though all of the new med’s are anti-manic drugsmed’s are anti-manic drugs

• Issue is preventing recurrenceIssue is preventing recurrence• AD’s can induce mania and/or cyclingAD’s can induce mania and/or cycling• Keep in mind high suicide risk with BDKeep in mind high suicide risk with BD• Never forget the therapeutic Never forget the therapeutic

relationshiprelationship

WHAT IS THE THERAPEUTIC WHAT IS THE THERAPEUTIC RELATIONSHIP?RELATIONSHIP?

• The psychodynamic features of the The psychodynamic features of the pharmacotherapy relationship can never be pharmacotherapy relationship can never be overlookedoverlooked

• Without attention to elements such as Without attention to elements such as transference, pharmacotherapy can have transference, pharmacotherapy can have reduced valuereduced value

• As in all therapeutic relationships, a working As in all therapeutic relationships, a working alliance must be established to allow the alliance must be established to allow the treatment to proceed with greatest treatment to proceed with greatest effectivenesseffectiveness

WHAT IS THE THERAPEUTIC WHAT IS THE THERAPEUTIC RELATIONSHIP, CONTINUED?RELATIONSHIP, CONTINUED?

• The pharmacotherapeutic alliance can be The pharmacotherapeutic alliance can be tested and strengthened when: discussing tested and strengthened when: discussing goals of treatment; discussing side effects; goals of treatment; discussing side effects; the potential for abuse with this patient; the the potential for abuse with this patient; the clinicians availability for the resolution of clinicians availability for the resolution of medication and non-medication difficultiesmedication and non-medication difficulties

• Attention to the therapeutic alliance also Attention to the therapeutic alliance also involves: consistency; availability; willingness involves: consistency; availability; willingness to discuss; and explain alternativesto discuss; and explain alternatives


• Transference issues include: Idealization initially Transference issues include: Idealization initially with the physician being authoritative and with the physician being authoritative and knowledgeable, and a provider of coherent and knowledgeable, and a provider of coherent and non-judgmental explanation, with no non-judgmental explanation, with no confrontation of looking inward or need to face confrontation of looking inward or need to face past and present painful experiencespast and present painful experiences

• Unfortunately, the inconsistent and sometimes Unfortunately, the inconsistent and sometimes limited results of the medication, can be more limited results of the medication, can be more than disappointing to the hopeful patientthan disappointing to the hopeful patient

• Some times the initial positive transference can Some times the initial positive transference can lend itself to the undermining of psychotherapy, lend itself to the undermining of psychotherapy, and even splitting. If under-recognized, it can and even splitting. If under-recognized, it can undermine all of the treatmentundermine all of the treatment


• Counter-transference needs to be Counter-transference needs to be recognized and understoodrecognized and understood

• Issues like: discouragement; the Issues like: discouragement; the desire for treatment to proceed more desire for treatment to proceed more quickly or with less pain; to control quickly or with less pain; to control the patient; or to give some thing the patient; or to give some thing tangible to the patient during a tangible to the patient during a hopeless or helpless impasse.hopeless or helpless impasse.

TREATMENT OF TREATMENT OF BREAKTHROUGH DEPRESSIONBREAKTHROUGH DEPRESSION

• Li has modest effectLi has modest effect

• Lamotrigine (Ltg) has more robust effectLamotrigine (Ltg) has more robust effect

• Olanzapine very small effect (perhaps Olanzapine very small effect (perhaps through non-specific anti-anxiety, ant-through non-specific anti-anxiety, ant-insomnia effect)insomnia effect)

• Quetiapine has large effect, that Quetiapine has large effect, that appears to be specific for depression (?appears to be specific for depression (?study data)study data)

HOW DO YOU DISTINGUISH HOW DO YOU DISTINGUISH BIPOLAR FROM BORDERLINE AND BIPOLAR FROM BORDERLINE AND FACTITIOUS DISORDER?FACTITIOUS DISORDER?

• Bipolar Spectrum Disorder has Bipolar Spectrum Disorder has considerably more denialconsiderably more denial

• Bipolar Spectrum Disorder has much Bipolar Spectrum Disorder has much less interest in any treatment, but less interest in any treatment, but particularly psychotherapyparticularly psychotherapy

WHY IS THERE SO WHY IS THERE SO MUCH DISABILITY MUCH DISABILITY

IN BIPOLAR IN BIPOLAR DISORDER?DISORDER?

Seroquel is not yet Seroquel is not yet indicated in Canada for indicated in Canada for the treatment of bipolar the treatment of bipolar

disorderdisorder

Information presented within may Information presented within may contain data not supported by the contain data not supported by the

current product monograph. Please current product monograph. Please consult the product monograph for consult the product monograph for

prescribing information.prescribing information.

Study OverviewStudy Overview

• Eight-week, multicenter, double-blind, Eight-week, multicenter, double-blind, randomized, fixed-dose, placebo-controlled randomized, fixed-dose, placebo-controlled monotherapy studymonotherapy study

• Study population: outpatients with DSM-IV Study population: outpatients with DSM-IV bipolar I or bipolar II disorder, with or bipolar I or bipolar II disorder, with or without rapid cycling, in a major without rapid cycling, in a major depressive episodedepressive episode

• Study groups: quetiapine 600 mg/d, Study groups: quetiapine 600 mg/d, quetiapine 300 mg/d, placeboquetiapine 300 mg/d, placebo

• Conducted at 39 centers in the United Conducted at 39 centers in the United StatesStates

Calabrese et al, APA 2004

-20

-15

-10

-5

0

§

§

§

§

§ §§

§

§

§

§§

§

§ §§

§p<0.001 vs placebo

1 2 43 65 7 8

MADRS: Change From MADRS: Change From Baseline Baseline MADRS: Change From MADRS: Change From Baseline Baseline

ITT, LOCFCalabrese et al, APA 2004

Study Week

Mea

n C

han

ge

Fro

m B

asel

ine

Quetiapine 600 mg (n=170)Quetiapine 300 mg (n=172)Placebo (n=169)

0

10

20

30

40

50

60

70

1 2 3 4 5 6 7 8

Study Week

% P

atie

nts

†p<0.01 §p<0.001 vs placebo ITT, LOCFCalabrese et al, APA 2004

Response Rate Response Rate ((50% decrease in MADRS)50% decrease in MADRS)Response Rate Response Rate ((50% decrease in MADRS)50% decrease in MADRS)

†

§§


§§

§

§

§ §

§

§§ §

§ §

Remission Rate Remission Rate (MADRS (MADRS 12)12)

0

10

20

30

40

50

60

1 2 3 4 5 6 7 8

Study Week

% P

atie

nts


†p<0.01 §p<0.001 vs placebo ITT, LOCFCalabrese et al, APA 2004

§ §

§§

§

§

§

†

§§ §

§ § §

Effect Size: Change in Effect Size: Change in MADRSMADRS

Quetiapine 600 mgQuetiapine 600 mg

Quetiapine 300 mgQuetiapine 300 mg

Large (0.8)Large (0.8)

Medium (0.5)Medium (0.5)

Small (0.2)Small (0.2)

0.750.75

0.640.64

AstraZeneca data on file

-10

-9

-8

-7

-6

-5

-4

-3

-2

-1

01 2 43 65 7 8

Study Week

HAM-A: Change From HAM-A: Change From BaselineBaselineHAM-A: Change From HAM-A: Change From BaselineBaseline

†

Mea

n C

han

ge

Fro

m B

asel

ine

ITT, LOCFMacfadden et al, APA 2004

§ †

*

*p<0.05 †p<0.01 §p<0.001


§

§

§

§

§

§

§

§ §

§

§

§

-7

-6

-5

-4

-3

-2

-1

0

Mea

n C

han

ge

Fro

m B

asel

ine

Quetiapine600 mgn=170

Placebon=169


Imp

rov

eme

nt

§

§

§p<0.001 vs placebo ITT, LOCFCalabrese et al, APA 2004

Pittsburgh Sleep Quality Index Pittsburgh Sleep Quality Index (PSQI): Change From Baseline(PSQI): Change From BaselinePittsburgh Sleep Quality Index Pittsburgh Sleep Quality Index (PSQI): Change From Baseline(PSQI): Change From Baseline

0

5

10

15

Quality of Life (Quality of Life (Q-LES-Q): Q-LES-Q): Change From BaselineChange From Baseline

§p<0.001 vs placebo

§

Mea

n C

han

ge

Fro

m B

asel

ine

Quetiapine600 mg

PlaceboQuetiapine300 mg

Imp

rov

eme

nt


§

• Quetiapine was found to be effective Quetiapine was found to be effective for a broad range of depressive and for a broad range of depressive and anxiety symptomsanxiety symptoms

• Quetiapine was found to be effective Quetiapine was found to be effective in improving quality of sleepin improving quality of sleep

• Quetiapine was found to be effective Quetiapine was found to be effective in improving quality of lifein improving quality of life

Efficacy SummaryEfficacy SummaryEfficacy SummaryEfficacy Summary

Common Adverse Events Common Adverse Events

(>10% patients and 2x placebo rate)(>10% patients and 2x placebo rate)

AdverseAdverseEventEvent

Quetiapine Quetiapine 600 mg600 mgn=180n=180

Quetiapine Quetiapine 300 mg300 mgn=179n=179

PlaceboPlacebon=180n=180

Dry mouth Dry mouth (%)(%) 40.640.6 44.144.1 7.87.8

Sedation Sedation (%)(%) 32.232.2 29.629.6 6.16.1

Somnolence Somnolence (%)(%) 24.424.4 27.427.4 8.38.3

Dizziness Dizziness (%)(%) 22.822.8 16.816.8 8.38.3

Constipation Constipation (%)(%) 11.111.1 11.711.7 4.44.4

Safety, LOCFCalabrese et al, APA 2004

0

2

4

6

8

10

Treatment-Emergent Treatment-Emergent ManiaMania


Placebon=180


% P

atie

nts

Treatment-emergent mania: adverse event of mania, or YMRS 16 at 2 consecutive visits or last visit


Change in WeightChange in Weight

Quetiapine Quetiapine 600 mg600 mg

Quetiapine Quetiapine 300 mg300 mg PlaceboPlacebo

Mean Mean change (kg)change (kg)

1.61.6 1.01.0 0.20.2

>7% increase>7% increasein weight (%)in weight (%)

1111 1010 33

Safety, LOCF

Serum Glucose (Fasting)Serum Glucose (Fasting)

QuetiapinQuetiapine 600 mge 600 mg

QuetiapiQuetiapine 300 ne 300

mgmgPlaceboPlacebo

Baseline Baseline mg/dLmg/dL

8686 8787 8787

Endpoint Endpoint mg/dLmg/dL

9292 9090 9090

Safety, LOCF

0

5

10

15

20

Sexual Adverse EventsSexual Adverse Events%

Pat

ien

ts


Placebon=180


Safety, LOCF

Safety SummarySafety Summary

• The rate of treatment-emergent mania with The rate of treatment-emergent mania with quetiapine was no greater than with placeboquetiapine was no greater than with placebo

• Common adverse events included dry mouth, Common adverse events included dry mouth, sedation/somnolence, and dizzinesssedation/somnolence, and dizziness

• Quetiapine was associated with minimal Quetiapine was associated with minimal weight changeweight change

• Quetiapine was not associated with significant Quetiapine was not associated with significant change in serum glucose levelschange in serum glucose levels

• The safety profile of quetiapine in this The safety profile of quetiapine in this population was consistent with previous population was consistent with previous studiesstudies

PearlsPearls

• Screen for bipolar disorder in every Screen for bipolar disorder in every depressed and anxious patientdepressed and anxious patient

• Early diagnosis and treatment will lead to Early diagnosis and treatment will lead to improved quality of life and will slow the improved quality of life and will slow the progression ofprogression ofbipolar disorder through the life cycle;bipolar disorder through the life cycle;

• Atypical agents such as quetiapine Atypical agents such as quetiapine (Seroquel) are effective(Seroquel) are effectivemood stabilizersmood stabilizers

• Screen for bipolar disorder in every Screen for bipolar disorder in every depressed and anxious patientdepressed and anxious patient

• Early diagnosis and treatment will lead to Early diagnosis and treatment will lead to improved quality of life and will slow the improved quality of life and will slow the progression ofprogression ofbipolar disorder through the life cycle;bipolar disorder through the life cycle;

• Atypical agents such as quetiapine Atypical agents such as quetiapine (Seroquel) are effective(Seroquel) are effectivemood stabilizersmood stabilizers

EXCELLENT BOOKSEXCELLENT BOOKS

• ““An Unquiet Mind”, by Kay Jamieson, PH.D.An Unquiet Mind”, by Kay Jamieson, PH.D.• ““A Brilliant Madness”, by Patty DukeA Brilliant Madness”, by Patty Duke• ““Plato Not Prozac! Applying Eternal Wisdom Plato Not Prozac! Applying Eternal Wisdom

To Everyday Problems”, by Lou Marinoff To Everyday Problems”, by Lou Marinoff PH.D.PH.D.

• ““The Moral Animal”, by Robert WrightThe Moral Animal”, by Robert Wright• ““Mind Over Mood”, Greenberger et al.Mind Over Mood”, Greenberger et al.• ““Agitated Depression”, Koukopolis, Clinics of Agitated Depression”, Koukopolis, Clinics of

North AmericaNorth America• ““Creating True Peace” Thich Nhat HahnCreating True Peace” Thich Nhat Hahn

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