Siddhartha S. Nadkarni, M.D.

F.A.C.E.S. Conference

May 5, 2013

DIAGNOSIS AND TREATMENT OF MOOD DISORDERS IN EPILEPSY

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)

• Dysthymia

• Major Depression

• Bipolar Disorder

• Mania

• Depression

• Mixed States

• Bipolar I, Bipolar II

HOW TO DIAGNOSE MOOD DISORDERS

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

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

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

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

DEPRESSION AND EPILEPSY

• 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

• Increased Suicide attempts related to interictal psychopathology (borderline p.d., psychosis) rather than sz frequency, medications, psychosocial stressors (Mathews and Barabas, 1981; Medez et al., 1989)

• Biological Factors contributing to interictal depression:• Family History of Mood Disorders• Left Sided Sz focus• Bilateral Frontal Hypometabolism

DEPRESSION AND EPILEPSY

• WAY UNDERRECOGNIZED AND UNDERTREATED (BOYLAN, 2004).

• May be different than “major depression.”

TREATMENTS FOR DEPRESSION IN EPILEPSY• Antidepressants

• Anti-Epileptic Drugs

• Vagus Nerve Stimulation

• Cognitive Behavioral Therapy

• Transcranial Magnetic Stimulation

• Future Directions and Alternative Treatments

MAJOR NEUROTRANSMITTERSType Major Transmitters

Amines AcetylcholineCatecholamines (DA, NE)SerotoninHistamine

Amino Acids GlutamateGABA (γ-aminobutyric acid)Glycine

Other Small Molecules ATP

Neuropeptides Angiotensin IIβ-endorphinCholecystokininCRFEnkephalinNeuropeptide YOrexinSomatostatinSubstance PMany others

NOREPINEPHRINE

SEROTONIN

ANTIDEPRESSANTS

RISPERDAL

Karen Blair has Schizophrenia. “The magnificent Circus”

SIDE EFFECTS

• 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.

AED’S

• Depression

• Phenobarbital

• Zonegran

• Depakote

• Dilantin

• Keppra

• Anxiety

• Keppra

• Lamictal

• Felbatol

ZYPREXA

“She Likes You”

POSITIVE SIDE EFFECTS

• Mood Stabilization:

• Tegretol

• Depakote

• Lamictal

• Antidepressant

• Lamictal

• Stimulant

• Lamictal

• Anxiolytic

• N eurontin

• Phenobarbital

SEROQUEL

“What Jack Saw”

Neuropsychopharmacology, April 2001

• 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

Biological Psychiatry 2005

• 222 patients

• 15% responded in active treatment

• 10% responded in sham arm

• 1% dropped out for non-tolerabilty

• No evidence of short term efficacy

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

TREATMENT TIPS• 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.