1. 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

2. 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

3. Update on Bipolar Disorder Update on Bipolar basics STEP-BD LiTMUS

4. Lizzie Simon Time Magazine Aug 11, 2002 "Everything was perfect... and then I went insane"

5. Goya Portrait of Don Gaspar Melchor de Jovellanos

6. 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.

7. 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.

8. 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

9. Collaborative Care and Concordance

11. 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

12. 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

13. Key STEP-BD Baseline Findings

14. STEP-BD: Bipolar Onset > 18 13 to 18 < 13 Perlis RH for the STEP-BD group, Biol Psych 2004;55:875-881

15. Lifetime Anxiety Comorbidity Simon N, et al. Am J Psychiatry. 2004;161:2222-2229. * 0 10 20 30 40 50 60 AnyPanic ± Agor Agor Without Panic SADOCDPTSDGAD BP IBP II * * * * †

16. Key STEP-BD Long-Term Findings

17. With systematic treatment, 30% of STEP-BD participants achieved recovery and then stayed recovered over 1 year

18. Anxiety: more difficult to recover from bipolar depressive episode Otto et al., Br J Psychiatry 2006 Jul;189:20-5. without anxiety with anxiety

19. Anxiety: higher risk of depressive relapse Otto et al., Br J Psychiatry 2006 Jul;189:20-5. without anxiety with anxiety

20. 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

21. No benefit with antidepressants for bipolar depression with manic symptoms Goldberg et al. Am J Psychiatry 2007:164:1348-1355

22. STEP-BD Randomized Trials

23. Antidepressants or placebo added to mood stabilizers for bipolar depression Sachs G et al. N Engl J Med 2007;10.1056/NEJMoa064135 %

24. Treatment Resistant Bipolar Depression: Lamotrigine Added Might Help Nierenberg et al., Am J Psychiatry 2006;163;1-8

25. Adjunctive Psychosocial Interventions Collaborative Care Plus Cognitive-Behavioral Therapy (CBT) Family-Focused Therapy (FFT) Interpersonal and Social Rhythm Therapy (IPSRT)

26. Intensive psychotherapy: remission 110 days earlier 110 Days Miklowitz et al., Arch Gen Psychiatry. 2007 Apr;64(4):419-26.

27. LiTMUS Lithium Moderate Dose Use Study A NIMH Bipolar Trials Network Contract

28. Problem: Long term outcomes suboptimal for Bipolar Disorder and Lithium is under used

29. Can tolerable doses of lithium added to other medications improve 6 month outcomes?

30. LiTMUS Compare strategies of treatment –Optimized treatment with lithium –Optimized treatment without lithium 6 month outcomes Open treatment Blinded outcomes

31. Update on Bipolar Disorder Update on Bipolar basics STEP-BD LiTMUS