New Treatments

For Bipolar Disorder

Po W. Wang, MD
Clinical Associate Professor
Bipolar Disorders Clinic
Stanford University School of Medicine

Abbott Laboratories
AstraZeneca
Bristol-Myers Squibb
Corcept Therapeutics
Eisai Inc.
Elan Pharmaceuticals
Eli Lilly and Company
GlaxoSmithKline

Janssen Pharmaceutica
Novartis Pharmaceuticals
Pfizer
Repligen
Sanofi-Aventis
Shire Pharmaceuticals
Solvay Pharmaceuticals
Wyeth Pharmaceuticals

 Why understanding pharmacology is

important to you
Current approved treatments
Bipolar Depression - Unmet needs
Current Research
Additional Areas for Breakouts

Own your care and collaborate with your doctor.

Target symptoms
Potentially useful medications
Potential side effects

Be hopeful about the possibilities!

Brand Name
Abilify
Equetro, Tegretol
Thorazine
Depakote
Lamictal
Eskalith, Lithobid
Zyprexa
Symbyax
Seroquel
Risperdal
Geodon
Saphris

Generic Name
.
.
.
.
.
.
.
.
.
.
.
.

Aripiprazole
Carbamazepine
Chlorpromazine
Divalproex
Lamotrigine
Lithium
Olanzapine
Olanzapine-fluoxetine
Quetiapine
Risperidone
Ziprasidone
Asenapine

Yellow font indicates generic available

Acute Mania

Acute Depression

Longer-Term

Year Drug

Year Drug

Year Drug

1970 Lithium

1974 Lithium

1973 Chlorpromazine

2003 Olanzapine+fluoxetine
combination

1994 Divalproex, ER (2005)

2006 Quetiapine, XR (2008)

2004 Olanzapine

2003 Lamotrigine

2000 Olanzapine*

2005 Aripiprazole

2003 Risperidone*

2008 Quetiapine, XR (adjunct)

2004 Quetiapine, XR (2008)*

2009 Risperidone LAI*

2004 Ziprasidone
2004 Aripiprazole*

Unmet
Need

2004 Carbamazepine ERC

2009 Asenapine
*Adjunctive and monotherapy; LAI = Long-Acting Injectable formulation

2009 Ziprasidone (adjunct)

Unmet
Need

Acute Mania

Acute Depression
Response

Response

Maintenance
Relapse

60
50

58%
50%

57%
24%

23%

34%

34%

685

1597

20%

40
30

30%
20
10
0

2109
Medication

1639
Placebo

730
Medication

Placebo

Medication

946

=N

Placebo

16 Monotherapy Studies (N ~ 3750)

Improved due to other reasons

Not Improved

Improved due to drug

4 Monotherapy / Combination Therapy Studies (N ~ 1400)

Improved due to other reasons

Improved due to drug

Not Improved

6 Monotherapy Studies (N ~ 2500)

Still well due to

other reasons

Well due
to drug

Relapsed

% of Weeks
Asymptomatic
Depressed
Manic/hypomanic/cycling/mixed

3%

15%
53%
32%

50%

47%

Anticonvulsants

Lithium

Valproate (Depakote)
Carbamazepine (Equetro, Tegretol)
Lamotrigine (Lamictal)
Oxcarbazepine (Trileptyl)
Topiramate (Topamax)
Gabapentin (Neurontin)
Zonisamide (Zonegran)

New Antipsychotics
Olanzapine (Zyprexa)
Risperidone (Risperidal)
Quetiapine (Seroquel)
Ziprasidone (Geodon)
Aripiprazole (Abilify)
Asenapine (Saphris)
Clozapine (Clozaril)

Antidepressants
Prozac+Zyprexa (Symbyax)
Fluoxetine (Prozac)
Sertraline (Zoloft)
Paroxetine (Paxil)
Citalopram (Celexa)
Tricyclic Antidepressants
Monoamine Oxidase Inhibitors

Miscellaneous
Benzodiazepines (Klonapin, Ativan, etc.)
Typical Antipsychotics (Haldol, Thorazine)
Thyroid Hormone
Nutriceuticals
ECT, TMS, VNS

Large yellow font indicates approved treatments

Small italic font indicates unapproved treatments

Armodafinil (Nuvigil)
Background
Cephalon Pharma
Nuvigil - a right-hand version of Provigil
Narcolepsy, excessive daytime sleepiness with sleep apnea
Provigil efficacious in Bipolar I or II depression (85 patients)
Nuvigil efficacious in Bipolar I depression (257 patients)

Study Design
Nuvigil added to mood stabilizers for Bipolar I depression
Gold-standard designed (randomized, placebo-controlled), 8-week study
Beginning September 2010 June 2012

Lurasidone
Background
Dainippon Sumitomo Pharma
New antipsychotic medication
Blocks Dopamine-2 receptors
Blocks Serotonin-2A receptors

Study Design
Bipolar I Depression
Gold-standard designed, 6-week study
Evaluate efficacy, safety, and tolerability of Lurasidone
Beginning September 2010 September 2011

L-Methylfolate (Deplin)
Background
Pamlab, L.L.C. type of folic acid (a vitamin) that enters brain
Folate to L-methylfolate conversion limited with
Depression, certain medical disorders, poor nutrition
Lithium, anticonvulsants, birth control pills, alcohol, tobacco
Controls creation of chemicals involved in depression
Can accelerate antidepressant response

Study Design
Deplin added to other medicines (no antidepressants) in Bipolar I depression
Gold-standard designed, 8-week study
Evaluate efficacy, safety, and tolerability of Deplin
Beginning September 2010 - September 2011

Lithium versus Quetiapine (Seroquel)

Background
Federally funded Agency for Healthcare Research and Quality (AHRQ)
Clinical and Health Outcomes Initiative in Comparative Effectiveness (CHOICE)
Lithium classical treatment for bipolar disorder
Seroquel major newer treatment for bipolar disorder
Combination treatments are often used in bipolar disorder

Study Design
Bipolar I or II Disorder, with at least mild symptoms
6-month, randomized, single-blind rater study
Evaluate effectiveness, safety, tolerability of adding Lithium vs. Seroquel
Beginning September 2010 - September 2013

 Combination Therapy
Duration of Therapy
Drug Interactions
Managing Adverse Effects

Be active in your own treatment

Bipolar depression - a current research priority
New research is always on the horizon

Bipolar Research at Stanford

Contact Shelley Hill at

(650) 498-4801
or
shill@stanford.edu
or visit
www.bipolar.org