Charles B. Nemeroff, M.D., Ph.D.

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1 CASE STUDY 2 Charles B. Nemeroff, M.D., Ph.D. Leonard M. Miller Professor and Chairman Department of Psychiatry and Behavioral Sciences Director, Center on Aging University of Miami Miller School of Medicine Miami, Florida 33136

2 CASE STUDIES ADAA, Miami, FL 9 April 2015 W. Edward Craighead, Ph.D. J. Rex Fuqua Professor and Vice Chair Emory University Psychiatry/Psychology

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4 CHARLES B. NEMEROFF, M.D., PH.D. DISCLOSURES Research/Grants: National Institutes of Health (NIH), Agency for Healthcare Research and Quality (AHRQ) Speakers Bureau: None Consultant: Xhale, Takeda, SK Pharma, Shire, Roche, Lilly, Allergan Stockholder: CeNeRx BioPharma, Inc., PharmaNeuroBoost, Revaax Pharma, Xhale Other Financial Interest: CeNeRx BioPharma, PharmaNeuroBoost Patents: Method and devices for transdermal delivery of lithium (US 6,375,990B1), Method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (US 7,148,027B2) Scientific Advisory Board: American Foundation for Suicide Prevention (AFSP), CeNeRx BioPharma, National Alliance for Research on Schizophrenia and Depression (NARSAD), PharmaNeuroBoost, Anxiety Disorders Association of America (ADAA), Skyland Trail Board of Directors: AFSP, Gratitude America, Skyland Trail, ADAA

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6 Financial Disclosures W. Edward Craighead Dr. Craighead receives support from the NIH for his research, and he receives book royalties from John Wiley & Sons. He is a Senior Fellow, Center for the Study of Law and Religion, Emory University. He is an officer of Hugarheill ehf, an Icelandic company dedicated to prevention of depression. His participation is supported by the Mary and John Brock Foundation and the Fuqua Family Arnarson & Craighead Foundations.

7 CASE STUDY 3 A 64-year-old male, CFO of a large health care company is referred to you for evaluation of depression after discharge from a step-down cardiology unit. He had suffered his first myocardial infaction 10 days ago and was admitted to the CCU for 3 days followed by a week long stay in a monitored hospital unit. Family history is positive for both depression and heart disease. He admits to consuming 2 packs per day of cigarettes and moderate daily alcohol intake.

8 CASE STUDY 3 (cont.) He had a stent placed in his left anterior descending coronary artery after treatment with a thrombolytic in the Emergency Room. He is discharged on ASA, Plavix, an ACE inhibitor, nifedipine and propranolol. On MSE he fills criteria for severe non-psychotic MDD. He is hopeless and anhedonic with almost delusional thoughts of his imminent demise. He wants to return to work immediately, but is concerned about whether his concentration or energy level is sufficient.

9 CASE STUDY 3: Question 1 Of the medications he is currently being treated with by his cardiologist, the most likely contributors to his depression are: A. ACE inhibitor and Plavix B. Nifedipine and propranolol C. ASA and ACE inhibitor D. All of these drugs can cause depression E. None of the above

10 CASE STUDY 3 (cont.) You discuss with your patient s cardiologist the likelihood that nifedipine and propranolol may be contributing to the severe depression. Together you agree that a β-blocker that does not cross the blood-brain barrier is less likely to produce depression. He is switched to naldolol. The patient insists that he has no time for psychotherapy and prefers pharmacotherapy for his depression.

11 CASE STUDY 3: Question 2 Your recommendation for antidepressant therapy is: A. St. John s wort B. Bupropion C. Paroxetine D. Escitalopram E. Venlafaxine

12 CASE STUDY 3: Question 3 Your recommendation for concurrent psychotherapy is: A. Intensive daily CBT B. Interpersonal Psychotherapy C. Short term supportive therapy D. Group therapy with other cardiology patients with depression related disorders E. No Psychotherapy until the delusional thoughts are significantly decreased

13 CASE STUDY 3 (cont.) The patient is treated with escitalopram 10 mg po q am. After 3 weeks, he is only approximately 20% improved. He has been unable to return to work and is ruminating about his cardiac status and his longevity, which he perceives is markedly reduced. He has no interest in usual activities and is also fearful of engaging in sexual activity for fear of inducing another cardiac event.

14 CASE STUDY 3: Question 4 At this point you decide to: A. Add bupropion 150 mg XL q am B. Switch to duloxetine 30 mg po q am C. Add olanzapine 10mg po qhs D. Increase the escitalopram dose to 20 mg E. Add aripiprazole 5 mg po qhs

15 CASE STUDY 3 (cont.) His dose of escitalopram was increased to 20 mg and 2 weeks later little improvement is noted; the dose is increased to 30 mg per day. Two weeks later, he is approximately 40% improved, but still anxious, back at work but fatigued, and still ruminating about his health. He has had 2 episodes of sexual activity in which he failed to perform adequately in his view unable to ejaculate.

16 CASE STUDY 3: Question 5 He has now been treated for 7 weeks with escitalopram and is somewhat improved, but has not achieved a clinical response (<50% improvement). You discuss the options with him and: A. Increase the escitalopram dose to 40 mg q am B. Discontinue escitalopram and begin bupropion XL 150 mg po q am C. Taper escitalopram and begin venlafaxine 75 mg po q am D. Taper escitalopram and begin mirtazapine 15 mg po q am E. Reduce escitalopram to 30 mg q am and add bupropion XL 150 mg q am

17 CASE STUDY 3 (cont.) You chose to reduce escitalopram to 30 mg po qhs and add bupropion XL 150 mg po q am. After 3 weeks the patient shows no improvement. In fact, he seems more agitated and ruminative and complains of insomnia. He admits to thoughts of suicide and is having extreme difficulty at work. His wife who accompanies him, for the first time, expresses her concerns about his pervasive depressed mood and negative thoughts.

18 CASE STUDY 3: Question 6 At this point you recommend: A. rtms after taper and discontinuation of both escitalopram and bupropion B. Clomipramine 75 mg po qhs after taper and discontinuation of escitalopram and bupropion C. ECT after taper and discontinuation of both escitalopram and bupropion D. Aripiprazole 10 mg po qhs augmentation after bupropion discontinuation E. Quetiapine 100 mg po qhs after bupropion discontinuation

19 CASE STUDY 3: Question 7 At this point you also recommend: A. CBT to focus on his cognitive distortions and his underlying schema B. Behavior Therapy for his addictive patterns of behavior C. IPT to focus on his work situation D. Group supportive therapy for other patients who have had similar post MI interpersonal problems

20 CASE STUDY 3 (cont.) Together with the patient and his wife, you opt for the aripiprazole augmentation strategy. After 2 weeks on escitalopram (30 mg po q am) and aripiprazole (10 mg po qhs), he reports an absolute inability to sit still. He finds this particular curious in that he believes that his depression is finally getting better. He has renewed interest in hobbies and is now more sexually active.

21 CASE STUDY 3: Question 8 You now recommend that he: A. Add alprazolam 0.25 mg po bid B. Add buspirone 5 mg po tid C. Discontinue all meds and begin ECT D. Discontinue all meds and refer for VNS E. Reduce the aripiprazole dose to 5 mg po qhs

22 CASE STUDY 3: Question 9 You also recommend that he: A. Continue CBT and focus on his underlying schema B. Add Behavior Therapy to address addictive behaviors C. Refer to a sex therapist to assure continuation of adaptive intimacy D. Both A & B E. Both A & C

23 CASE STUDY 3 (cont.) With the reduction in aripiprazole dose, the akathisia disappears and he continues to improve attaining remission 16 weeks after initiation of treatment.

24 CASE STUDY 3 Questions or comments.

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Charles B. Nemeroff, M.D., Ph.D.

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