Diagnosis and Treatment of Mood Disorders in Epilepsy

1. Diagnosis and Treatment of Mood Disorders in Epilepsy Siddhartha S. Nadkarni, M.D. F.A.C.E.S. Conference May 5, 2013

5. What is Mood? • Emotional State or Frame of Mind • Not an Emotion, less specific • A Weather • Not Temperament or Personality (which are more like a climate)

6. Dysthymia • Major Depression • Bipolar Disorder • Mania • Depression • Mixed States • Bipolar I, Bipolar II

7. How To Diagnose Mood Disorders

9. Dysthymia • Chronic Depression • More days than not for at least 2 years • In kids can be irritability for at least 1 year • Never goes more than 2 months without experiencing: • Poor appetite or overeating • Insomnia or hypersomnia • Low energy or fatigue • Low self esteem • Poor concentration or difficulty making decisions • Feelings of hopelessness

10. Depression • 5 Symptoms for at least 2 weeks: • Depressed Mood* • Sleep Disturbance • Interest Loss (“Anhedonia”)* • Guilty Ruminations • Energy loss • Concentration Loss • Appetite Changes • Psychomotor Changes • Suicidal Thinking • * One has to be depressed mood or loss of pleasure

11. Mania • 1 Week of persistently elevated, expansive, or irritable mood (or any duration if hospitalization required) • During this time at least 3 of the following: • Inflated self-esteem or grandiosity • Decreased need for sleep • More talkative or pressured speech • Flight of ideas or racing thoughts • Distractibility • Increased goal-directed activity or psychomotor agitation • Excessive involvement in pleasurable activities that have a high potential for painful consequences

13. Bipolarity and Dysthymia • Bipolar I is diagnosed by the presence of a manic episode • Bipolar II is diagnosed by the presence of depression and hypomania • Mixed state is when one meets criteria for both a depressive and manic episode • Schizoaffective Disorder is characterized by psychosis between mood episodes • Outside post-ictal or prodromal mood states, Depression is far and away the most common mood disorder in Epilepsy

14. Up to 80% of Epilepsy patients have depression (50% - 80%). Suicide attempts may be 4 times that of a control group with chronic neurologic illnesses. Depression was the only correlating factor in a recent study in terms of quality of life for a wide range of seizure patients (Boylan, 2004) including sz type/frequency/location/medications, etc. Depression and Epilepsy

15. Increased Suicide attempts related to interictal psychopathology (borderline p.d., psychosis) rather than sz frequency, medications, psychosocial stressors (Mathews and Barabas, 1981; Medezet al., 1989) Biological Factors contributing to interictal depression: Family History of Mood Disorders Left Sided Sz focus Bilateral Frontal Hypometabolism Depression and Epilepsy

16. WAY UNDERRECOGNIZED AND UNDERTREATED (BOYLAN, 2004). May be different than “major depression.” Depression and Epilepsy

17. Treatments for Depression in Epilepsy • Antidepressants • Anti-Epileptic Drugs • Vagus Nerve Stimulation • Cognitive Behavioral Therapy • Transcranial Magnetic Stimulation • Future Directions and Alternative Treatments

19. Major Neurotransmitters

20. Norepinephrine

21. Serotonin

22. Antidepressants

25. Risperdal Karen Blair has Schizophrenia. “The magnificent Circus”

26. All Anti-Epileptic Drugs (AED’s) have side effects. In a given patient these effects may be problematic or helpful. The Goal of Epilepsy treatment is to obtain seizure freedom without untoward side effects. A note about the PDR. Side Effects

27. Depression Phenobarbital Zonegran Depakote Dilantin Keppra Anxiety Keppra Lamictal Felbatol AED’s

28. Zyprexa “She Likes You”

29. Mood Stabilization: Tegretol Depakote Lamictal Antidepressant Lamictal Stimulant Lamictal Anxiolytic N eurontin Phenobarbital Positive Side Effects

30. Seroquel “What Jack Saw”

36. Neuropsychopharmacology, April 2001

37. Open Pilot Study of 60 patients with treatment resistent depression • 2 weeks single blind recovery (no stimulation) followed by 10 weeks of VNS • 59 completers because one person improved during recovery period (no stim) • Conclusions: • 30.5% responder rate for HRSD • 30% responder rate for the MADRS • 37.3% responder rate for the Clinical Global Impression-Improvement Score • Of those who had received 7 or more antidepressants, none responded • 39% of the rest responded • Those who never had ECT were 3.9 X more likely to respond • Most Common Side Effect was Hoarseness in 55% • Good for low to moderate antidepressant resistence

38. Biological Psychiatry 2005

39. 222 patients • 15% responded in active treatment • 10% responded in sham arm • 1% dropped out for non-tolerabilty • No evidence of short term efficacy

42. Electroconvulsive Therapy • ECT is likley the most effective treatment we have for Depression • ECT is not contraindicated in Epilepsy • In fact ECT came into use due to “forced normalization.” • ECT can be used to abort Status Epilepticus

43. First step is diagnosis. We don’t do as good a job as we should in asking about these symptoms. You may need to tell us. Remove inciting AED’s. Antidepressants, may respond to lower doses in this population. Antipsychotics as needed or in low doses. Stimulants. Anti-anxiety medications may treat both seizrues and anxiety but tolerance and withdrawal are worries. Treatment tips