Glenn Treisman MD PhDJohns Hopkins University

Disclosure of things that may have affected my views and this presentation

I have accepted honoraria from Boehringer-Ingelheim for I have accepted honoraria from Boehringer-Ingelheim for talks related to HIV and Psychiatrytalks related to HIV and Psychiatry

I have been kicked off all the other drug company speakers I have been kicked off all the other drug company speakers lists because I will not use their slideslists because I will not use their slides

I still think this “Conflicts of Interest” thing is ridiculous, I still think this “Conflicts of Interest” thing is ridiculous, along with HIPAA and the insanity at the airportsalong with HIPAA and the insanity at the airports

I regularly accept payments from Johns Hopkins I regularly accept payments from Johns Hopkins UniversityUniversity

I think doctors are obligated to think criticallyI think doctors are obligated to think critically

Objectives

Is HIV a psychiatric epidemic?Is HIV a psychiatric epidemic? Can we treat the psychiatric disorders that Can we treat the psychiatric disorders that

complicate the HIV epidemic?complicate the HIV epidemic? Can clinicians integrate psychiatric Can clinicians integrate psychiatric

treatment in to HIV treatment?treatment in to HIV treatment?

Prior research has shown that psychiatric patients Have increased risk of HIVHave increased risk of HIV Are less likely to receive HAARTAre less likely to receive HAART Are less likely to stay on HAARTAre less likely to stay on HAART Are less likely to get an undetectable viral Are less likely to get an undetectable viral

loadload Are more likely to dieAre more likely to die

More Rapid Discontinuation of ART in Depressed Persons

Bangsberg DR et al. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; December 16-21, 2001; Chicago, Ill. Abstract 1721.

BDI15BDI15-censored

BDI<15BDI<15-censored

Months on highly active ART706050403020100

Cumulative survival

1.0

.8

.6

.4

.2

0.0P = 0.0001

Depression Decreases AIDS-Free Survival in Patients on ART

HERS cohort: 765 participantsHERS cohort: 765 participants Longitudinal depression Longitudinal depression

(CES-D): none, (CES-D): none, intermittent, chronicintermittent, chronic

Mortality predictors: Mortality predictors: depression, CD4 cell depression, CD4 cell count, ART duration, agecount, ART duration, age

Ickovics JR et al. JAMA. 2001;285:1466-1474.Reprinted with permission.

Total time in study (years)

Cumulative survival

0 1 2 3 4 5 6 70.7

0.8

0.9

1.0HIV-related mortality

DEFINITION OF GROUPSExcludedExcluded

Mental Mental DisorderDisorder

No MentalNo MentalDisorderDisorder

Mental DisorderMental DisorderMet 1 or 2 of 3 Met 1 or 2 of 3

CriteriaCriteria

PsychiatricPsychiatricDiagnosisDiagnosis PsychiatricPsychiatricMedicationMedication PsychiatricPsychiatricEvaluationEvaluation

Himelhoch S, et al. J Acquir Immune Defic Syndr. 2004;37:1457-1463.

ASSOCIATION BETWEEN MENTAL D/O AND TIME TO HAART

TIME IN YEARS

PR

OB

AB

ILIT

Y O

F H

AA

RT

TH

ER

AP

Y

P=0.05

No Mental Disorder

Mental Disorder

2 4 60

Himelhoch S, et al. J Acquir Immune Defic Syndr. 2004;37:1457-1463.

ASSOCIATION BETWEEN MENTAL DISORDER AND SURVIVAL

TIME IN YEARS

PR

OB

AB

ILIT

Y O

F S

UR

VIV

AL

No Mental Disorder

Mental Disorder

P=0.10

Himelhoch S, et al. J Acquir Immune Defic Syndr. 2004;37:1457-1463.

Mental Illness

depressiondemoralizationsubstance abuse

cognitive impairment

AIDS

impulsivitydepression

demoralizationsubstance abuse

cognitive impairment

HIV IS A PSYCHIATRIC EPIDEMIC

• HIV increases risk for psychiatric illness

• psychiatric illness increases risk for HIV

• effective treatment for psychiatric illness can improve patient outcome

• effective treatment for psychiatric illness can decrease HIV transmission

Psychiatric disorders in new medical intakes

Overall Axis I Overall Axis I (non-substance abuse)(non-substance abuse) 54 %54 % Major depressionMajor depression 20 %20 % Adjustment disorderAdjustment disorder 18 %18 %

Substance AbuseSubstance Abuse 74 %74 % Cognitive ImpairmentCognitive Impairment 18 %18 % Personality disorderPersonality disorder 26 %*26 %*

* unpublished observation

Lyketsos, C.G., Hutton, H., Fishman, M., Schwartz, J., Treisman, G. J., Psychiatric morbidity on entry to an HIV primary care clinic. AIDS: 1996: 20(3): 131-144

The Four Perspectives McHugh and

Slavney

DiseaseDiseaseTemperamentTemperamentBehaviorBehaviorLife StoryLife Story

Mental Illness

depressiondemoralizationsubstance abuse

cognitive impairment

AIDS

impulsivitydepression

demoralizationsubstance abuse

cognitive impairment

Problems of life story

An “assumptive” worldAn “assumptive” world Assumptions provoke experienceAssumptions provoke experience Experience shapes assumptionsExperience shapes assumptions The medium of analysis of these The medium of analysis of these

experiences is “meaning”experiences is “meaning” Provides the “software operating system” Provides the “software operating system”

for data and actionfor data and action Can be “rescripted” or rewrittenCan be “rescripted” or rewritten

Experience

Meaning

Assumption

Behavior

Major Depression Demoralization

(Depression in remission)

Sub-syndromal Major Depression

Dysthymia

“Minor Depression”

“Depressive Personality”

Differential Diagnosis of Depression

DEPRESSIONDELIRIUMDEMENTIADEMORALIZATION

Depression diminishes

Mood-the sense of baseline state of Mood-the sense of baseline state of happiness that is usually presenthappiness that is usually present

Vital sense-the sense of being well, healthy, Vital sense-the sense of being well, healthy, energetic, alert and ableenergetic, alert and able

Self Attitude-the sense of being good, of Self Attitude-the sense of being good, of doing well, of effectiveness and utility to doing well, of effectiveness and utility to othersothers

Anhedonia Loss of reward Loss of reward (pleasure, satiation or satisfaction)(pleasure, satiation or satisfaction) associated with associated with

behaviorsbehaviors Appetite Directed BehaviorsAppetite Directed Behaviors

Sleeping Sleeping Eating Eating SexSex

Function Directed BehaviorsFunction Directed Behaviors Work Work HobbiesHobbies ExerciseExercise

Disturbance of Neurophysiology

SleepSleep

EARLY MORNING AWAKENINGEARLY MORNING AWAKENING Difficulty falling asleepDifficulty falling asleep Disrupted sleep architectureDisrupted sleep architecture

AppetiteAppetite

Change in food tasteChange in food taste Weight loss or gainWeight loss or gain Immune functionImmune function

G.I. functionG.I. function

Depression

stressdemoralization

CNS inflammationsubstance abusesubcortical injury

cognitive impairment

HIV

impulsivityhopelessnesscarelessness

demoralizationsubstance abuse

cognitive impairment

TIME OF AIDS

DEPRESSION AS AIDS DEVELOPS

MONTHS BEFORE AND AFTER AIDS

PERCENT DEPRESSED

0

10

20

-48 -36 -24 -12 6 18

Lyketsos CG, et al. Am J Psychiatry. 1996;153:1430-1437.

Differential Diagnosis of Depression

DEPRESSIONDELIRIUMDEMENTIADEMORALIZATION

Pharmacotherapy

• poor sleep

• weight loss

• anxiety

• G.I. disturbance

DesipramineNortriptyline

• hypersomnia

• weight gain

• suicide potential

• chronicity

CitalopramEscitalopram FluoxetineParoxetineSertralineVenlafaxineDesvenlafaxine

Failure from side effects

Lithium augmentationCombination Antidepressants

Thyroid, Pindolol, Antipsychotic augmentation

Failure after adequate trial

NEXT DRUG

BupropionNefazodoneMAOI'sTrazodoneMirtazepineAtomoxetine??

0

100

DEMENTIA SUBSTANCEUSE

PERSONALITYDISORDER

COMPLIANT OVERALL

Full

Partial

None

Treatment of DepressionOutcome by Diagnosis

Lyketsos, C. G., Fishman, M., Hutton, H., Cox, T., Hobbs, S., Spoeler, C., Hunt, W., Driscoll, J., Treisman, G. J., The effectiveness of psychiatric treatment for HIV infected patients, Psychosomatics: 1997: 38:423-432

Mania

HIV

CASE STUDY OF PATIENTS WITH HIV AND MANIA

NEGATIVEHISTORY

(N=7)

33.6

7 male

4 gay/2 IDU

6/6

all AIDS

all

POSITIVEHISTORY

(N=7)

36.0

5 male

4 IDU/3 gay

2/7

2 AIDS/5 HIV+

none

AGE

SEX

RISK FACTOR

CD4<100 *

STAGE *

DEMENTIA ** p<0.05 by fisher's exact test

The Four Perspectives McHugh and

Slavney

DiseaseDiseaseTemperamentTemperamentBehaviorBehaviorLife StoryLife Story

It is much more important to It is much more important to know what sort of patient know what sort of patient has a disease than what sort has a disease than what sort of disease a patient has.of disease a patient has.

William OslerWilliam Osler

Simplified model of disposition

Percent of population

IntroversionIntroversion

Punishment avoidant Punishment avoidant Future directedFuture directedFunction directedFunction directed

ExtraversionExtraversion

Reward directed Reward directed Present directedPresent directedFeeling directedFeeling directed

• Population-Disposition

Introversion-Extroversion

Stability-Instability

introversion extroversion

stable

unstable

sanguine

choleric

phlegmatic

melancholy

Motivated Behavior The cycle of driveThe cycle of drive

CravingCraving BehaviorBehavior ReinforcementReinforcement SatiationSatiation

Environmental ExposureEnvironmental Exposure

Parental and societal inputParental and societal input Biological FactorsBiological Factors

genetic contributiongenetic contribution ? errors in drive, object specificity, or gross pathology? errors in drive, object specificity, or gross pathology

Law of effect

……probability of a behavior can be probability of a behavior can be increased or decreased depending on its increased or decreased depending on its immediate consequence.immediate consequence.Thorndyke 1913Thorndyke 1913

Behaviorenvironmental exposure environmental response

Behavior

positiveincrease

negativedecrease

Internal “drive” (craving)

Behavior

Reward-Reinforcement

Satiation

environmental exposure environmental response

temperamentlife experience

disease

Motivated Behavior

Internal “drive” (craving)

Behavior

Satiation

environmental exposure environmental response

temperamentlife experience

disease

Motivated Behavior

Reward-Reinforcement