MULTIPLE SCLEROSIS AND DEPRESSION. Michael Racke, MD The Ohio State University Meera Narasimhan, MD University of South Carolina

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1 MULTIPLE SCLEROSIS AND DEPRESSION Michael Racke, MD The Ohio State University Meera Narasimhan, MD University of South Carolina

2 MICHAEL RACKE, MD Disclosures!! Research/Grants: National Institute of Neurologic Disorders; National Multiple Sclerosis Society!! Speakers Bureau: None!! Consultant: Eli Lilly and Company!! Stockholder: None!! Other Financial Interest: Receives honoraria for serving on the editorial boards of Archives of Neurology and The Neurologist!! Advisory Board: None

3 MEERA NARASIMHAN, MD Disclosures!! Research/Grants: Bristol-Myers Squibb Company; Forest Laboratories, Inc.; Janssen, L.P.; National Institute of Health; Otsuka America Pharmaceutical, Inc.!! Speakers Bureau: AstraZeneca Pharmaceuticals LP; Bristol-Myers Squibb Company; Eli Lilly and Company!! Consultant: None!! Stockholder: None!! Other Financial Interest: None!! Advisory Board: None

4 LEARNING OBJECTIVE Design strategies to recognize and manage depression in patients with multiple sclerosis

5 DEPRESSION!! Mood disorders (major depression, dysthymia, bipolar, panic, and generalized anxiety) are common in multiple sclerosis!! Relationship between mood disorders and MS is multifactorial and complex!! It is unclear whether mood disorders are direct consequences of the disease process or psychological reactions to it!! Mood disorders in MS are no different from mood disorders more generally, and they respond similarly to standard treatments Minden SL. J Neurovirol 2000;6:S160-S167.

6 FATIGUE AND DEPRESSION!!Pathogenesis - uncertain 1-3!!Weakly associated with overall neurologic impairment!!no anatomic markers of fatigue!!temperature - Uhthoff s phenomenon!!immune factors!!cytokines, IL-6, IL-1, and TNF IL = interleukin; TNF = tumor necrosis factor 1. Ziemssen T. J Neurol Sci 2009;277:S37-S Rocca MA, et al. J Neuroimaging 2007;17:S36-S Gold SM, et al. Neurol Clin 2006;24:

7 FATIGUE AND DEPRESSION!!Pathogenesis - uncertain 1,2!!Infection!!Altered cerebral metabolism!!fmri shows increased brain activation!!disruption in neurotransmitter systems!!serotonergic pathway!!psychological factors fmri = functional magnetic resonance imaging 1. Ziemssen T. J Neurol Sci 2009;277:S37-S Rocca MA, et al. J Neuroimaging 2007;17:S36-S41.

8 IMPLICATIONS FOR CLINICAL PRACTICE!!Initial questions!!are there signs of an impending relapse?!!is there an infection present or has there been increased heat exposure?!!have medications been changed or added that could increase fatigue?!!anti-spasticity agents, ß-blockers, TCAs, benzo, AEDs ß = beta; TCA = tricyclic antidepressants; benzo = benzodiazepine; AED = antiepileptic drug

9 IMPLICATIONS FOR CLINICAL PRACTICE!!Questions regarding pain, sleep, and depression!!other fatigue-producing conditions!!lab screen: TFT, CBC, Lytes/glu, LFT, ESR, UA, vitamin B-12!!Psychiatric referral!!overwhelming fatigue with severe depression!!refractory to treatment of fatigue TFT = thyroid function test; LFT = liver function test; CBC = complete blood count; ESR = erythrocyte sedimentation rate; UA = urinalysis; Lytes = electrolytes; glu = blood glucose

10 DEPRESSION AND FATIGUE Nonpharmacologic Approaches!!Education and support!!exercise (graded, not overexertion)!!multidisciplinary rehabilitation program!!behavioral therapy

11 DEPRESSION AND FATIGUE Pharmacologic Approaches!!Modafinil* 1-3!!Reduces excessive sleepiness associated with sleep disorders!!promotes wakefulness with fewer adverse effects and less abuse potential than stimulants!! mg/day * Approved by the FDA to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy, shift work sleep disorder, and patients optimally managed with CPAP 1. Brown JN, et al. Ann Pharmacother 2010;44: Brioschi A, et al. Eur Neurol 2009;62: Fava M, et al. Ann Clin Psychiatry 2007;19:

12 DEPRESSION AND FATIGUE Pharmacologic Approaches!! Fluoxetine* 1-3 /protriptyline* 3!! Amantadine* 2,3!! Methylphenidate* 2,3 and dextroamphetamine* 3!! 4-aminopyridine (4-AP) K channel blocker, improve nerve conduction 2!! 4AP (dalfampridine*): 10 mg bid; paresthesias, abdominal pain, confusion, and seizure!! Cooling devices!! Active!! Cooling suits or liquid-cooled garments!! Passive!! Ice or gel packs; cooling a garment * NOT approved by the US FDA for treatment of depression and fatigue in MS 1. Romani A, et al. Mult Scler 2004;10: ; 2. Hadjimichael O, et al. Health Qual Life Outcomes 2008;6:100; 3. Fawcett J. Merck Manual. Home Edition

13 AN OPEN-LABEL, 8-WEEK, FLEXIBLE- DOSE TRIAL OF ESCITALOPRAM IN PATIENTS WITH COMORBID MAJOR DEPRESSION AND MULTIPLE SCLEROSIS

14 MEAN CHANGE IN BECK DEPRESSION INVENTORY In Patients with Comorbid MDD and MS Mean Score (BDA) SD = SD = p =.001; N = 15 Baseline Week 8 Paired t-test (12) Narasimhan M, et al. Presented at the 2010 Annual Meeting of the American Psychiatric Association, New Orleans, LA. Abstract: NR3-49.

15 MEAN CHANGE IN HAM-D-17 In Patients with Comorbid MDD and MS Mean Score (HAM-D-17) p =.0002; N = SD = SD = 6.98 Baseline Week 8 Paired t-test (12) Narasimhan M, et al. Presented at the 2010 Annual Meeting of the American Psychiatric Association, New Orleans, LA. Abstract: NR3-49.

16 TRIAL OF ESCITALOPRAM IN COMORBID MAJOR DEPRESSION WITH MS Study Results!!Responders showed statistically significant improvement in depressive symptoms on the HAM-D-17 (p =.000) and the BDI (p =.001)!!CGI-S showed significant symptom reduction (p ".003) and CGI-I was also statistically significant (p =.002)!!Quality of life improvements were significant for MQOL Global rating (p =.022) and also for scaled scores (p =.003) Narasimhan M, et al. Presented at the 2010 Annual Meeting of the American Psychiatric Association, New Orleans, LA. Abstract: NR3-49.

17 TRIAL OF ESCITALOPRAM IN COMORBID MAJOR DEPRESSION WITH MS Study Results!!Changes in anxiety symptoms were not statistically significant!!4 subjects dropped out due to occurrence of nausea or diarrhea that did not resolve within 2 weeks!!study demonstrates that escitalopram* may be a viable treatment option for this population * Escitalopram is approved by the FDA for acute and maintenance treatment of MDD in adults and adolescents aged years, and for the acute treatment of GAD in adults Narasimhan M, et al. Presented at the 2010 Annual Meeting of the American Psychiatric Association, New Orleans, LA. Abstract: NR3-49.

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