An Update on Bipolar Disorder NARSAD 2008

Andrew A. Nierenberg, MD

Medical Director

Harvard Bipolar Clinic and Research Program,

Massachusetts General Hospital

Director, NIMH Bipolar Trials Network

Professor of Psychiatry, Harvard Medical School

Thank you NARSAD

• Thilo Deckersbach, PhD

• Christina Dording, MD

• Aude Henin, PhD

• Dan Iosifescu, MD

• Andrew A. Nierenberg, MD

• Michael J. Ostacher, MD, MPH

• Janet Witte, MD

Update on Bipolar Disorder

• Update on Bipolar basics

• STEP-BD

• LiTMUS

Lizzie SimonTime Magazine Aug 11, 2002

"Everything was perfect...and then I went insane"

Goya Portrait of Don Gaspar Melchor de Jovellanos

Bipolar Disorder• Prevalence:

– BPI and II: • 1.1% of the workforce• 2.6% of the general population

• Mean age of onset: 17.4 years

Kessler et al. Arch Gen Psychiatry. 2005;62:617-627.Kessler et al. Am J Psychiatry. 2006;163:1561-1568.

Bipolar Disorder• Recurrent and chronic disorder

– Manic or hypomanic episodes– Major depressive episodes and symptoms

• Major burden– Inter-episodic symptoms

• Dysfunction: – 65.5 lost days of work per year

Kessler et al. Arch Gen Psychiatry. 2005;62:617-627.Kessler et al. Am J Psychiatry. 2006;163:1561-1568.

STEP-BD

• Systematic Treatment Enhancement Program for Bipolar Disorder

• www.stepbd.org• Evidence guided treatment• Specialty bipolar clinics• Integration of measurement and management• Embedded randomized trials

Collaborative Careand

Concordance

Collaborative Care: Integration of Measurement and Management

• Shared measurement– Symptoms

• Depression

• Mania/hypomania

• Anxiety

• Irritability

– Stress, alcohol, weight– Side effects– Functioning

Nierenberg AA. J Clin Psychiatry. 2006;67 Suppl 11:3-7.www.manicdepressive.org (see Resources section)

Clinical Self-report Form

Clinical Monitoring Form

Collaborative Care: Integration of Measurement and Management

• Mood monitoring• Medication concordance

• Non-concordance open for discussion

• Negotiate– Goals– Medication changes

• Menu of reasonable choices

• Collaborative Care Workbook

Key STEP-BD Baseline Findings

STEP-BD: Bipolar Onset

28%

37%

35%> 18

13 to 18

< 13

Perlis RH for the STEP-BD group, Biol Psych 2004;55:875-881

Lifetime Anxiety Comorbidity

Simon N, et al. Am J Psychiatry. 2004;161:2222-2229.

*

0

10

20

30

40

50

60

Any Panic±

Agor

Agor Without

Panic

SAD OCD PTSD GAD

BP I BP II

*

*

* *

†

Key STEP-BD Long-Term Findings

With systematic treatment, 30% of STEP-BD participants

achieved recovery and

then stayed recovered over 1 year

Anxiety: more difficult to recover from bipolar depressive episode

Otto et al., Br J Psychiatry 2006 Jul;189:20-5.

without anxiety

with anxiety

Anxiety: higher risk of depressive relapse

Otto et al., Br J Psychiatry 2006 Jul;189:20-5.

without anxiety

with anxiety

Higher bipolar relapse rate with residual symptoms

Perlis et al., Am J Psychiatry. 2006 Feb;163(2):217-24.

Without residual symptoms

With residual symptoms

Without residual symptoms

With residual symptoms

No benefit with antidepressants for bipolar depression with manic

symptoms

Goldberg et al. Am J Psychiatry 2007:164:1348-1355

STEP-BD Randomized Trials

Antidepressants or placebo added to mood stabilizers for bipolar

depression

0

5

10

15

20

25

30

35

40

Durable recovery TreatmentEffectiveness

Response

Affective Switch

Sachs G et al. N Engl J Med 2007;10.1056/NEJMoa064135

%

Treatment Resistant Bipolar Depression: Lamotrigine Added Might Help

Nierenberg et al., Am J Psychiatry 2006;163;1-8

Adjunctive Psychosocial Interventions

• Collaborative Care Plus

• Cognitive-Behavioral Therapy (CBT)

• Family-Focused Therapy (FFT)

• Interpersonal and Social Rhythm Therapy (IPSRT)

Intensive psychotherapy: remission 110 days earlier

110 Days

Miklowitz et al., Arch Gen Psychiatry. 2007 Apr;64(4):419-26.

LiTMUSLithium Moderate Dose Use Study

A NIMH Bipolar Trials Network Contract

Problem:Long term outcomes suboptimal for

Bipolar Disorderand

Lithium is under used

Can tolerable doses of lithium added to other medications improve 6

month outcomes?

LiTMUS

• Compare strategies of treatment– Optimized treatment with lithium– Optimized treatment without lithium

• 6 month outcomes

• Open treatment

• Blinded outcomes

Update on Bipolar Disorder

• Update on Bipolar basics

• STEP-BD

• LiTMUS