1. Mood, Behavior, and Medications in MS Mitchell T. Wallin, MD, MPH MS Clinic Director Department of Veterans Affairs Medical Center Washington, DC Assistant Professor of Neurology Georgetown University Medical School 1

2. Topical Outline I. Depression II. Mood Swings III. Anxiety Disorders IV. Case study and Conclusions 2

3. Emotional Disorders in MS  Disturbances of affect  Most common conditions (DSM IV):  Major depression  Dysthymic disorder & Bipolar Disorder  Panic disorder  Generalized anxiety disorder  Relationship to MS is multi-factorial and complex but good response to standard treatment Minden, 2000 3

4. Depression in MS  Lifetime prevalence 40-60% for major depression (Sadovnik, 1996)  Point prevalence 15-30%  Increased risk of suicide: 3% of 295 patients over a six year period (Kahana, 1971; Stenager, 1992)  Possible MRI correlate: frontal, parietal and arcuate fasciculus lesions (Berg, 2000; Pujol, 1997) 4

5. Depression scores from a community sample of MS patients (Chwastiak, 2002) 5

6. DSM-IV Criteria for Major Depression S Sleep-Insomnia/hypersomnia A Appetite or weight changes D Dysphoria- “bad mood”, irritable, sad A Anhedonia- lack of interest/pleasure F Fatigue A Agitation/psychomotor retardation C Concentration E Esteem (low) or guilt S Suicide/thoughts of death Montano, 1994 Montano, 1994 6

7. Risk Factors for Suicide in MS  Severity of depression  Alcohol abuse  Living alone Feinstein, 2002 Feinstein, 2002 7

8. Differential Diagnosis of Depression in MS  MS Cognitive Dysfunction  Fatigue  Medications  Interferon-beta  Thyroid dysfunction (Kreisler, 2003)  Possible direct effect (CHAMPS) 8

9. Treatment of Depression in MS  Medications  Tricyclic antidepressants (Nortriptyline)  SSRIs (Sertraline, Paroxetine)  SNRIs (Venlafaxine)  NDRI (Buproprion)  Stimulants (Methylphenidate HCl, Modafinil) 9

10. Non-pharmacologic Treatment of Depression in MS  Exercise  Psychotherapy  Electroconvulsive Therapy 10

11. Mood Swings  Emotional lability: rapid oscillations in mood  Affective release: unpredictable fits of crying or laughing  Euphoria: exaggerated happiness and optimism 11

12. Treatment of emotional lability in MS  Hypomania during pulsed steroid therapy  Dose reduction & slow taper with corticosteroids  Divalproex Sodium (Depakote)  Lithium Carbonate  Cyclothymia or Bipolar disorder  Divalproex Sodium (Depakote)  Lithium Carbonate  Carbamazepine (Tegretol) 12

13. Treatment of emotional lability in MS  Pathologic laughing or crying:  Tricyclic antidepressants (Amitriptyline)  SSRIs (Sertraline)  Agitation and rage  Haloperidol or Quetiapine  Benzodiazepines (Clonazepam) 13

14. Assessment of Mood Swings in MS  Evaluate the following with any report of any mood swings:  Context and timing  Stress  Untoward effects of medications  Infection  Unclear to what extent mood changes are related to MS pathology 14

15. Anxiety Disorders and MS  Panic attacks  Generalized Anxiety Disorder  Anxiety symptoms associated with depression 15

16. Treatment of Anxiety Disorders in MS  Panic Disorder  TCAs (Imipramine)  SSRIs (Paroxetine)  Benzodiazepines (Clonazepam)  Depakote (Marazziti, 1996) 16

17. Treatment of Anxiety Disorders in MS  Generalized Anxiety Disorder  Buspirone HCl (Buspar)  Imipramine HCl (Tofranil)  Venlafaxine HCl (Effexor)  Benzodiazepines (Lorazepam) 17

18. Screening for Emotional Disorders in MS  Depression questions (USPSTF, 2002)  Have you been feeling sad or angry lately?  Have you lost interest in or stopped enjoying the things that usually give you pleasure?  Beck Depression Inventory  Beck Anxiety Inventory  Identify patients at high risk for suicide Nicholl, 2001 Nicholl, 2001 18

19. Case 38 yr old AA female with SP MS, migraine headaches, and history of depression presented to the clinic with four days of agitation, poor attention, racing thoughts, and inappropriate laughter. EDSS 7.0 38 yr old AA female with SP MS, migraine headaches, and history of depression presented to the clinic with four days of agitation, poor attention, racing thoughts, and inappropriate laughter. EDSS 7.0 Medications: Glatiramer acetate, ITB (stable dose), Gabapentin, Topiramate, Sumatriptan (sc), Fioricet, Diazepam, Sertraline Medications: Glatiramer acetate, ITB (stable dose), Gabapentin, Topiramate, Sumatriptan (sc), Fioricet, Diazepam, Sertraline 19

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21. Emotional Disorders and MS Conclusions  Depression and mood in MS patients fluctuate over time  Screen for mood disorders at each clinic visit  Become familiar with a medication in each of the major treatment classes  Utilize referral networks of mental health professionals, social workers, and community resources to assist individual patients 21