Mood and Women

8/12/2019 Mood and Women

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Mood Disorders in Womenwith Epilepsy

Cynthia Harden, MDLaura Ponticello, RN

Comprehensive Epilepsy Center

Department of Neurology and NeuroscienceWeill Medical College of Cornell University

New York, NY


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Prevalence ofPsychiatric Disorders in Epilepsy

1Kanner AM. Biol Psychiatry.2003;54:388-398. 2Ettinger A, et al. Neurology.2004;63:1008-1014.3Wrench J, et al. Epilepsia.2004;45:534-543.4Weissman MM, et al. J Clin Psychiatry.1986;47(suppl 6)11-17.

5

Blum D, et al. In: Program and abstracts of the 54th Annual Meeting of the AAN; April 13-20, 2002.6Kessler RC, et al.Arch Gen Psychiatry. 1994;51:8-19, 7Ettinger AB, et al Neurology.2005;65:535-40.

Prevalence, %

Epilepsy Patients General Population

Depression1-3 20-55 2-4

Anxiety/Panic Disorder4 19-45 2.5-6.5

Bipolar Disorder5 8-12 1-2

Psychosis6 2-8 0.5-0.7


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Prevalence of Depression in Epilepsy

0

10

20

30

40

50

60

%D

epres

sedPatients

Pharmacoresistant Epilepsy

Controlled Epilepsy

Gen. Population (Annual)

Gen. Population (Lifetime)

1Kanner AM. Biol Psychiatry.2003;54:388-398. 2Ettinger A, et al. Neurology.2004;63:1008-1014.3

Wrench J, et al. Epilepsia.2004;45:534-543.4

Waraich P, et al. Can J Psychiatry.2004;49:124-138.5Boylan LS, et al. Neurology. 2004;62:258-261.

Population


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Gilliam F, et al. Neurology.2002;58(suppl 5):S9-S19.

Depression Correlates With Quality of Life in

Pharmacoresistant Epilepsy

0

20

40

60

80

100

Beck Depression Inventory Score

QOLIE-89TotalScore

r = -0.73

P


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Risk of Suicidal Ideation and Attempt in

People With Epilepsy

1Boylan LS, et al. Neurology. 2004;62:258-261.2

Jones JE, et al. Epilepsy Behav. 2003;4:S31-S38.Publishers; 1997:2141-2151.

Behavior/Attempts

People WithEpilepsy

General Population

Ideation1,2

25

20

15

10

5

0

19%

1%

14%

5%%o

fPopulation


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Depression in women with epilepsy

Being female is a risk factor for depression inepilepsy (Ettinger et al, 2004)

642 consecutive women of childbearing age with

epilepsy were evaluated with the HamiltonDepression Scale and HRQOL (Beghi et al., 2004)

Depression of any severity was present in 38%

Mild 19% Moderate 9% Major 10% Severe


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Risk Factors for Depression in

Women with Epilepsy(Beghi et al., 2004)Any depression, or moderate to severe

depression*

Concurrent disability Treatment for associated conditions (neurologic,

endocrine, cardiovascular, orthopedic)*

Seizures in past 6 months* Being a housewife or unemployed*

Depression was associated lower HRQOL scores


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1Thase ME, Rush AJ. In: Bloom FE, Kupfer DF, eds. Psychopharmacology:

The Fourth Generation of Progress. New York, NY: Raven Press, Ltd.; 1995:1082-1097.

Defining Treatment Resistant Depression

Similar criteria to pharmacoresistant epilepsy

Lack of adequate clinical response after 2

well-delivered treatments at adequate dose and

duration from 2 different classes of treatment1


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Two-Question Screening Procedure

During the past month, have you

often been bothered by feeling

down, depressed, or hopeless?

During the past month, have you

often been bothered by having little

interest or pleasure in doing things?

If no to both, major depression is unlikely

May inquire about intermittent symptoms proximal to seizures in PWE toassess atypical manifestation of depression.

If yes to either, proceed with the follow-up clinical interviewor administerscreening instrument

Adapted in part from: Whooley MA, Simon GE. N Engl J Med. 2000;343:1942-1950.

Diagnostic Algorithm for

Major Depression


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Follow-Up Clinical Interview

Adapted in part from: Whooley MA, Simon GE. N Engl J Med. 2000;343:1942-1950.American Psychiatric Association. DSM-IV-TR. R.R American Psychiatric Association: Washington, DC; 2000.

Five or More Symptoms for Major Depression

Depressed mood Anhedonia Weight change Suicidal ideation Sleep disturbance Poor concentration Psychomotor problems Excessive guilt Lack of energy

Consider referral to Psychiatry for further evaluation of depression

Diagnostic Algorithm for

Major Depression (Contd)


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Screening Instruments for Evaluating Depression

Instrument Items Time, min Reliability*

BDI-II1 21 5-10 .94

IDS2 30 5-10 .92

QIDS2 16


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Hellerstein DJ, et al. J Affective Disord. 2002;71:85-96.

Psychometric Properties of the Cornell

Dysthymia Rating Scale

20-item clinician-administered instrument Collateral and patient-based ratings

High interrater reliability

Excellent internal consistency and sensitivity Total scores correlate well with depressive

subtypes of various intensity-mild depressive

symptoms rather than major depression


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Seizure Focus and Risk of Depression

Frontal and temporal lobe dysfunction1-6

Appears to be associated with bilateralreduction in inferofrontal metabolism7and

mesial temporal sclerosis8

Risk of depression is elevated withinvolvement of limbic structures7

Patients with psychic auras are more likelyto experience depression than those

without auras or with somatosensory

auras7

1Victoroff JI, et al.Arch Neurol.1994;51:155-163. 2Perini GI, et al. J Neurol NeurosurgPsychiatry.1996;61:601-605.3Gilliam F, et al. Epilepsia.2000;41(suppl 7):54. Abstract 1.193. 4Bromfield EB, et al.Arch Neurol.1992;49:617-623.

5Mayberg HS, et al.Ann Neurol.1990;28:57-64. 6Eison MS. J Clin Psychopharmacol.1990;10(suppl 3):26S-30S.7Kanner A. Epilepsy Behav.2003;4:S11-S19. 8Quiske A, et al. Epilepsy Res.2000;39:121-125.


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Neuroanatomic Mechanisms of

Depression in Epilepsy

Hecimovic H, et al. Epilepsy Behav.2003;4;S25-S30.

Brain regions commonlyaffected in epilepsy may lead

to clinical expressions of

depressionHippocampus

Prefrontal cortexAmygdala

Research suggests a bi-directional relationship

between epilepsy and depression


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Hecimovic H, et al. Epilepsy Behav. 2003;4;S25-S30.

Neurobiological Aspects of Depression

Monoaminergic theory

Depression is associated with abnormal monoaminergic transmission Alleviation of symptoms via reconstitution of normal 5-HT and NE

transmission

Other neurotransmitters such as DA and GABA, have been implicatedas well

Potential mechanisms of structural changes in primary depression

Deficiencies in neurotrophic support have been postulated as apotential pathogenic mechanism mediating hippocampal atrophy

and frontal lobe changes Deficiencies may be reversed by antidepressant treatment High cortisol secretion has also been suspected to mediate

hippocampal atrophy

C


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Potential Common Pathogenic Mechanisms

of Depression and Epilepsy

Depression

NeurotransmitterAbnormalities

(Animal Models and

Pharmacology)

Gliosis and Neuronal Cell

Loss (Neuropathologic

Studies)

Decreased 5HT-1A

Receptor Binding in

Temporal Lobe and Raphe

Hippocampal and

Frontal Lobe Atrophy

(MRI)


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Considerations in the Treatment of EpilepticPatients With Depressed Mood

LEV, PB, PRM, TGB, TPM, or VGB: lower dose or

discontinue that AED If culprit agent provides best seizure control, counteract negative

psychotropic effects with an antidepressant

Kanner AM, et al. Epilepsy Behav.2003;4:S11-S19.Kanner AM, et al. Epilepsy Behav.2000;1:37-51.

Did the depressive episode follow the discontinuation of anAED possessing mood-stabilizing properties?

CBZ, VPA, or LTG: reintroduction of that AED oranother mood-stabilizing agent may be sufficient

Did the depressive episode follow the introduction or doseincrement of an AED with negative psychotropic properties?


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Postictal depression usually responds poorly toantidepressant therapy; consider an optimal prophylactic AED

Considerations in the Treatment of Epileptic

Patients With Depressed Mood(Cont'd)

Did the depression/depressive symptoms follow suddencessation of seizures in a previously intractable epilepsy?

Consider impact of forced normalization

Treatment with antidepressant can be considered

Do depressive symptoms have a temporal relationship withthe occurrence of seizure frequency?

Kanner AM, et al. Epilepsy Behav.2003;4:S11-S19.

Kanner AM, et al. Epilepsy Behav.2000;1:37-51.


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Treatment Options forDepression in Epilepsy

SSRIs

citalopram (Celexa),escitalopram(Lexapro)f

luoxetine (Prozac),

paroxetine (Paxil),

sertraline (Zoloft)

Norepinephrine/serotonin

reuptake inhibitors

venlafaxine (Effexor) Tricyclics

imipramine (Tofranil),nortriptyline (Pamelor)


MAO inhibitors

Only to be used bypsychiatrists

AEDs (prophylactic agents) VPA, CBZ, LTG

Lithium

Can worsen seizures

VNS Electroconvulsive Therapy

Not contraindicated inseizure disorders


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Antidepressants With Low

Proconvulsant Activity

Harden CL, Goldstein MA. CNS Drugs.2002;16:291-302.

Percentage of Patients Experiencing Seizures: (0.1%)

Drug Percentage

imipramine*(Tofranil) 0.1 at 200 mg/day

doxepin*(Sinequan) 0.1

paroxetine(Paxil) 0.1

amitriptyline*(Elavil) 0.06

desipramine*(Norpramin)/nortriptyline*(Pamelor) 0.05-0.1 (unknown)

mirtazapine(Remeron) 0.04

phenelzine(Nardil)/ tranylcypromine(Parnate)trazodone(Desyrel)/nefazodone (Serzone)

Rare (unknown)Rare (unknown)

*TCA, SSRI, NE/5HT modulator, MAOI, Serotonin modulator.


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Antidepressants With Relatively Moderate and

High Proconvulsant Activity1,2

Percentage of Patients Experiencing Seizures (>0.1%)Drug Percentage

maprotiline (Ludiomil) 3.3 and 15.6

amoxapine(Asendin) >1.0

bupropion(Wellbutrin/XL) 0.44 at 450 mg/day

2.2 at >450 mg/day

clomipramine*(Anafranil) 0.5 at 250 mg/day1.66 at >250 mg/day

imipramine*(Tofranil) 0.6 at >200 mg/day

citalopram(Celexa) 0.3

venlafaxine (Effexor/XR) 0.26

fluvoxamine(Luvox)/fluoxetine(Prozac) 0.2

1Adapted from Harden CL, Goldstein MA. CNS Drugs.2002;16:291-302. 2American Psychiatric

Association. http://www.psych.org/psych_ pract/treatg/pg/

Practice%20Guidelines8904/MajorDepressiveDisorder_2e.pdf.

*TCA, SSRI, SNRI, tetracyclic, DNRI.


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Some SSRIs May Inhibit

CytochromeP450 Enzymes

Fluoxetine

Fluvoxamine Nefazodone Sertraline Paroxetine Venlafazine

Psychiatric Drugs and AEDsDrug-Drug Interactions

AEDs that may have levelsincreased by SSRI use

AEDs

Phenytoin

Barbiturates Carbamazepine

Tiagabine

Zonisamide



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Nemeroff CB, et al. Proc Natl Acad Sci U S A.2003;100:14293-14296; Swartz HA, et al. Psychiatr Serv.

2004;55:448-450; Lisanby SH, et al. CNS Spectr.2003;8:529-536; Morris GL III, et al. Neurology.

1999;53:1731-1735; Cyberonics, Inc. Depression Physicians Manual.Houston, Tex; 2005; Henry TR.

Neurology.2002;59(suppl 4):S3-S14; Krishnamoorthy ES. Epilepsy Behav. 2003;4:S46-S54.

Nonpharmacologic Options for Treatment of

Depression in Patients With Epilepsy

Psychotherapy Cognitive behavioral therapy (CBT) Interpersonal psychotherapy (IPT)

ECT

Patients with severe functional impairment and/ortreatment resistant depression

Psychiatrists are reluctant to use in patients withpharmacoresistant epilepsy

Vagus nerve stimulation (VNS)

Indicated for treating pharmacoresistant epilepsy Does not exacerbate depression, anxiety, or psychosis


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Case 1

Woman in her early 40s with intractable partialepilepsy since age 14 Nocturnal and diurnal convulsive seizures Multiple medication failures of all available AEDs

mostly due to non-serious side effects; now backto old standbys phenytoin and phenobarbital No risk factors for epilepsy Video-EEG shows interictal independent temporal

spikes, left more frequent than right; no seizuresrecorded

MRI shows cerebellar atrophy


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Case 1, contd

Assessment of seizure frequency and severitycompromised during office visits by tearfulness,excessive sensitivity during discussions andtangential ideation

Social status: recent divorce and subsequentfinancial and insurance issues, two small childrenat home, low educational level, not employed

Coping with all issues is marginal as per patientreport

Is it likely that she is depressed? (yes or no byresponse buttons)


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What would you do?

A. Refer for psychiatric evaluation (in light of

social and financial issues)?

B. Start antipressant?

C. Refer for psychotherapy?

D. All of the above?


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What we did

Added Celexa 10 mg per day

Referred for home care for help with children

Referred for psychotherapy with our social

worker-patient kept appointments sporadically

Implanted VNS for seizure control


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How patient did

Depression much improved with interventions as

above

Coping skills have become much more stabilized

Seizures not improved with VNS according to

patient, although she seems better, and she has

some somatic complaints related to VNS

Will refer for investigational drug study orepilepsy surgery

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