December 2014 MRC2.CORP.D.00011

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1 This program is paid for by Otsuka America Pharmaceutical, Inc. and Lundbeck, LLC. The speaker is a paid contractor of Otsuka America Pharmaceutical, Inc. advice or professional diagnosis. Users seeking medical advice should consult with their physician or other healthcare professional.

2 Recognizing and Responding to Inadequately Treated Major Depressive Disorder (MDD) Otsuka America Pharmaceutical, Inc., Rockville, MD advice or professional diagnosis. Users seeking medical advice should consult with their physician or other healthcare professional.

3 Link Between Depression and Other Illnesses High blood pressure 24% Major Depression in the Past Year 3% Stroke Asthma 17% 9% 7% Heart disease Diabetes When these rates were compared with subjects without reported mental illness in the past year, the differences in all chronic health conditions were statistically significantly different at the 0.05 level. Accessed 29 April

4 Burden of Disease to the Individual Physical MDD is a consistent predictor of the subsequent first onset of a variety of chronic physical disorders, including arthritis, asthma, cardiovascular disease, diabetes, chronic pain, and certain types of cancer Financial Incomes of people with MDD are substantially lower than those without depression Education MDD is associated with a 60% elevated risk of failure to complete secondary school than otherwise comparable youth 1. Kessler RC. Psychiatr Clin North Am. 2012;35(1):

5 Total Societal Costs (2000) Type of cost Dollars (in billions) Percentage of Total Cost/Case (in dollars) Total costs* ,118 Direct cost ,309 Inpatient ,127 Outpatient Pharmaceutical ,319 Suicide-related costs Workplace costs ,507 Absenteeism ,169 Presenteeism ,337 *Total costs = direct, suicide-related, and workplace costs. Note: Cost/case may not equal total cost divided by population estimates due to rounding. 1. Greenberg PE et al. J Clin Psychiatry. 2003;64(12):

6 Suicide Risk Patients with MDD are roughly 20 times more likely to commit suicide than the general population Attempts at suicide among patients with MDD are highly associated with the occurrence and overall severity of MDD symptoms Increased time spent depressed is predictive of suicide attempts in this population 1. Sokero TP et al. Br J Psychiatry. 2005;186:

7 Baseline Characteristics Associated With a Poor Response to Antidepressant Treatment Living alone Greater severity of depression Unemployed Lower income Higher neuroticism Anxious features Comorbid medical condition and/or personality disorder Longer duration of illness 1. Trivedi M. Psychiatry Weekly. May 21,

8 Predictors of Relapse and Recurrence in MDD Median Weeks to Relapse* Improved Without Remission (n = 82) Remission (n = 155) *Relapse defined as onset of new major depressive episode. 1. Judd LL et al. J Affect Disord

9 Residual Symptoms and Functioning % of patients with residual symptoms Residual Symptoms 100 Remitters N=412 Non-remitters N=212 Core Insomnia Anxiety Somatic Moderate Pain Normal functioning at endpoint (Month 3) was associated with the absence of core mood symptoms (OR 8.7; 95% CI, ) and insomnia symptoms (OR 1.8; 95% CI, ) CI, confidence interval; OR, odds ratio. 1. Romera I et al. BMC Psychiatry. 2013;13; 51. 9

10 Remission as Goal of Treatment Only approximately 28% of patients treated for MDD achieve remission* following treatment with a single antidepressant 1 Partial response (indicated by a 25% to 49% reduction in depressive symptoms) is common 2 Patients not achieving a full remission typically suffer from troubling residual symptoms 2 Even patients considered to be fully remitted report experiencing at least one residual symptom 3,4 Ideally, the goal of treatment for MDD is for patients to achieve full remission 5 *Remission defined as a score of 5 on the Hamilton Depression Rating Scale. 1. Trivedi MH et al. Am J Psychiatry. 2006;163:28-40; 2. Fava M. J Psychopharm. 2006;20(3):29-34; 3. Paykel ES et al. Psychol Med. 1995;25(6): ; 4. Nierenberg AA et al. Psychol Med. 2010;40(1):41-50; 5. Trivedi M. Psychiatry Weekly. May 21,

11 Nonpharmacologic Therapies for MDD Categories of Care Care Strategies Psychotherapy Cognitive Behavioral Therapy (CBT) 1 Alternative Mind-Body Therapy Family/Caregiver Involvement Web-Based Intervention Interpersonal Therapy 1 Group Therapy 1 Problem Solving Therapy 1 Future Directed Therapy (FDT) 2 Relaxation techniques (breathing exercises, meditation, etc.) 3 Yoga, tai chi, qigong 3 Family/caregiver involvement in the patient treatment plan facilitates day to day management of chronic difficulties of depression 4 Deprexis (an interactive program that integrates multiple therapeutic approaches to depression) 5 1. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder. 3rd ed. Arlington, VA: American Psychiatric Association; 2010; 2. Vilhauer JS et al. Innov Clin Neurosci. 2013;10(3):12-2; 3. Bertisch SM et al. J Psychosom Res. 2009;66(6): ; 4. Justin RG. Prim Care Companion. J Clin Psychiatry. 2001;3(6):267; 5. Meyer B et al. J Med Internet Res. 2009;11(2):e15. 11

12 Significant Challenges Exist Surrounding the Treatment of MDD There is significant unmet need in the treatment of MDD: under-treatment due to misdiagnosis or underdiagnosis 1 low rates of adherence and persistence to therapy, 2 potentially influenced by: slow onset of action: antidepressants require 4 6 weeks to achieve full therapeutic effect 3 lack of efficacy: a significant proportion of patients fail to remit or only partially remit despite adequate therapy 4,5 poor tolerability: adverse events associated with pharmacologic agents may reduce adherence and persistence 3 low rates of guideline-concordant follow up 6 1. Nierenberg. Am J Manag Care. 2001(suppl 11):353-66; 2. Cantrell, et al. Med Care. 2006;44(4): ; 3. Gelenberg, et al. American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder. 2010; 4. Olchanski, et al. Clin Ther. 2013;35(4):512-22; 5. Nierenberg, et al. Psychol Med. 2010;40(1):41-50; 6. Chen, et al. Gen Hosp Psych. 2010;32:

13 For more information or to request a live presentation from your local Medical Science Liaison, please visit advice or professional diagnosis. Users seeking medical advice should consult with their physician or other healthcare professional.

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