depression as a medical co-morbidity of hiv infection francine cournos, m.d. professor of clinical...

Depression as a Medical Depression as a Medical Co-morbidity of HIV Co-morbidity of HIV

InfectionInfection

Francine Cournos, M.D.Francine Cournos, M.D.Professor of Clinical Psychiatry (in Epidemiology), Professor of Clinical Psychiatry (in Epidemiology),

Columbia UniversityColumbia University

[email protected]@columbia.edu

June 12, 2012June 12, 2012

Based on a review of studies prevalence rates for depression Based on a review of studies prevalence rates for depression range from 12% to 71%. range from 12% to 71%.

Studies use different measurement tools and cut-off points.Studies use different measurement tools and cut-off points.

In the largest study of 1113 people, the rate of depression In the largest study of 1113 people, the rate of depression was 42% (using the HSCL-25) for symptoms compatible with was 42% (using the HSCL-25) for symptoms compatible with major depression. major depression.

Depression is often comorbid with other psychiatric Depression is often comorbid with other psychiatric disorders including alcohol and substance use as well as the disorders including alcohol and substance use as well as the neuropsychiatric complications of HIV.neuropsychiatric complications of HIV.

Sherr, et. al., Psychology Health & Medicine, 2011Sherr, et. al., Psychology Health & Medicine, 2011

Depression Among HIV+ PeopleDepression Among HIV+ People

Major Depression—the most common form of severe Major Depression—the most common form of severe depression; may have psychotic featuresdepression; may have psychotic features

Dysthymia—symptoms are milder than major depression Dysthymia—symptoms are milder than major depression but often still debilitating; by definition symptoms have but often still debilitating; by definition symptoms have persisted for more than two yearspersisted for more than two years

Bipolar depression—part of the cycling mood disorder Bipolar depression—part of the cycling mood disorder known as bipolar disorder or manic-depressive diseaseknown as bipolar disorder or manic-depressive disease

The primary focus of this talk is major depression.The primary focus of this talk is major depression.

Common Depressive DisordersCommon Depressive Disorders

““We got out of my friend’s car and walked for We got out of my friend’s car and walked for almost 15 minutes, and then I couldn’t go any almost 15 minutes, and then I couldn’t go any farther. I lay down fully dressed in nice farther. I lay down fully dressed in nice clothes, in the mud. ‘Please let me stay here,’ clothes, in the mud. ‘Please let me stay here,’ I said, and I didn’t care about standing up ever I said, and I didn’t care about standing up ever again.” again.”

Major Depression Is As Much a Physical Major Depression Is As Much a Physical Disorder As It Is a Mental DisorderDisorder As It Is a Mental Disorder

Anatomy of Melancholy by Andrew SolomonAnatomy of Melancholy by Andrew Solomon

The New Yorker, 1/12/98The New Yorker, 1/12/98

RateRates of severe depression are higher among s of severe depression are higher among medically ill people than among physically healthy medically ill people than among physically healthy people.people.

The presence of severe depression is associated The presence of severe depression is associated with increased morbidity and mortality among with increased morbidity and mortality among medically ill people.medically ill people.

Major Depression is Associated with Poorer Major Depression is Associated with Poorer Physical Health and Health OutcomesPhysical Health and Health Outcomes

Diagnosis of Major Depression: Diagnosis of Major Depression: Affective vs. Somatic SymptomsAffective vs. Somatic Symptoms

AFFECTIVEAFFECTIVE Depressed moodDepressed mood Loss of interestLoss of interest Guilt, worthlessnessGuilt, worthlessness HopelessnessHopelessness Suicidal ideationSuicidal ideation

SOMATICSOMATIC Appetite/Weight lossAppetite/Weight loss Sleep disturbanceSleep disturbance Agitation/retardationAgitation/retardation FatigueFatigue Loss of concentrationLoss of concentration

There aren’t enough of them—even if psychiatrists did There aren’t enough of them—even if psychiatrists did nothing else, depression is too common to be treated just by nothing else, depression is too common to be treated just by them.them.

Most patients don’t want to see them—it’s less stigmatizing Most patients don’t want to see them—it’s less stigmatizing to get treatment from someone in medical practice.to get treatment from someone in medical practice.

Why Can’t Psychiatrists (or Others Mental Why Can’t Psychiatrists (or Others Mental Health Practitioners) Just Take Care of Health Practitioners) Just Take Care of

Depression?Depression?

Screening for and Treating Uncomplicated Screening for and Treating Uncomplicated Depression is Relatively StraightforwardDepression is Relatively Straightforward

There are simple, valid, reliable screening toolsThere are simple, valid, reliable screening tools

Rule out bipolar disorder which requires different Rule out bipolar disorder which requires different medication strategies than depression.medication strategies than depression.

Newer antidepressants are easier to use; many are Newer antidepressants are easier to use; many are generic so costs have gone down.generic so costs have gone down.

Psychiatrists and other MHPs could concentrate on Psychiatrists and other MHPs could concentrate on depressed patients who are bipolar, suicidal, depressed patients who are bipolar, suicidal, psychotic, refractory, or have significant psychotic, refractory, or have significant comorbidities.comorbidities.

PHQ-2 and PHQ-9 Screening Tools PHQ-2 and PHQ-9 Screening Tools for Depressionfor Depression

Readily available online at no chargeReadily available online at no charge

Already translated into multiple languages (but not Already translated into multiple languages (but not necessarily validated)necessarily validated)

Well studied in general medical populationsWell studied in general medical populations

Easy to administer or self administerEasy to administer or self administer

Can be used to screen and/or make a diagnosisCan be used to screen and/or make a diagnosis

Can be used to follow patient’s progressCan be used to follow patient’s progress

Over the last two weeks how often have you been bothered Over the last two weeks how often have you been bothered by any of the following problems:by any of the following problems:

Little interest or pleasure in doing things.Little interest or pleasure in doing things.• 0=Not at all0=Not at all

• 1=Several days1=Several days

• 2=More than half the days2=More than half the days

• 3=Nearly every day3=Nearly every day

Feeling down, depressed or hopelessFeeling down, depressed or hopeless• 0=Not at all0=Not at all

• 1=Several days1=Several days

• 2=More than half the days2=More than half the days

• 3=Nearly every day3=Nearly every day

If the score is 3 or more, move to the PHQ9. If the score is 3 or more, move to the PHQ9.

Screening for Depression:Screening for Depression:PRIME-MD PHQ2PRIME-MD PHQ2

LittleLittle interest or pleasure in doing things interest or pleasure in doing things Feeling down, depressed, or hopeless Feeling down, depressed, or hopeless Trouble falling or staying asleep, or sleeping too much Trouble falling or staying asleep, or sleeping too much Feeling tired or having little energyFeeling tired or having little energy Poor appetite or overeatingPoor appetite or overeating Feeling bad about yourself — or that you are a failure orFeeling bad about yourself — or that you are a failure or

have let yourself or your family downhave let yourself or your family down Trouble concentrating on things, such as reading the Trouble concentrating on things, such as reading the

newspaper or watching televisionnewspaper or watching television Moving or speaking so slowly that other people could haveMoving or speaking so slowly that other people could have

noticed? Or the opposite — being so fidgety or restlessnoticed? Or the opposite — being so fidgety or restless

that you have been moving around a lot more than usualthat you have been moving around a lot more than usual Thoughts that you would be better off dead or of hurtingThoughts that you would be better off dead or of hurting

yourself in some way yourself in some way

Diagnostic Instrument for Depression:Diagnostic Instrument for Depression:PHQ9 – Items Rated from 0-3PHQ9 – Items Rated from 0-3

Treating Severe Depression as a Treating Severe Depression as a Medical Co-morbidity of HIVMedical Co-morbidity of HIV

There is an increased understanding that There is an increased understanding that

severe depression is associated with severe depression is associated with

increased morbidity and mortality from HIV increased morbidity and mortality from HIV

infection, and might best be conceptualized infection, and might best be conceptualized

as a medical co-morbidity of HIV infection.as a medical co-morbidity of HIV infection.

Numerous studies across many countries Numerous studies across many countries demonstrate the association of depression with demonstrate the association of depression with increased morbidity and mortality among people increased morbidity and mortality among people with HIV infection.with HIV infection.

Contributing factors include the association of Contributing factors include the association of depression withdepression with

• Failure to access HIV care and treatmentFailure to access HIV care and treatment

• Failure to adhere to antiretroviral medication Failure to adhere to antiretroviral medication once it has been startedonce it has been started

• Possible direct effects of depression on the Possible direct effects of depression on the immune systemimmune system

Depression and HIV-related Depression and HIV-related Morbidity/MortalityMorbidity/Mortality

Mortality predictors: chronic depression, CD4 count, Mortality predictors: chronic depression, CD4 count, HAART duration, ageHAART duration, age

After adjusting for all other variables, women with After adjusting for all other variables, women with chronic depressive symptoms were twice as likely to chronic depressive symptoms were twice as likely to die as women with limited or no depressive die as women with limited or no depressive symptoms.symptoms.


HERS cohort: 765 HIV+ women at 4 sites in U.S. HERS cohort: 765 HIV+ women at 4 sites in U.S. followed for up to 7 yearsfollowed for up to 7 years

Ickovics et al., JAMA, 2001Ickovics et al., JAMA, 2001

WIHS cohort: 2,059 HIV + women in U.S.WIHS cohort: 2,059 HIV + women in U.S.

Replicated HERS results: Chronic depressive symptoms Replicated HERS results: Chronic depressive symptoms associated with AIDS mortalityassociated with AIDS mortality

(N = 1,761)(N = 1,761)


Cook et al., Am J Public Health, 2004Cook et al., Am J Public Health, 2004

996 HIV+ pregnant women in Tanzania followed for 996 HIV+ pregnant women in Tanzania followed for 6-8 years without HAART (vitamin supplementation 6-8 years without HAART (vitamin supplementation study, 1995 – 2003)study, 1995 – 2003)

WHO clinical stage I (82%) and stage II (17%)WHO clinical stage I (82%) and stage II (17%)

31% died during follow-up31% died during follow-up

Depression associated with Depression associated with

• A 60% increase risk of progressing to clinical stage III/IV A 60% increase risk of progressing to clinical stage III/IV disease disease

• A greater than two-fold increased risk of deathA greater than two-fold increased risk of death


Antelman et al., JAIDS, 2007Antelman et al., JAIDS, 2007

198 HIV+ HAART-naive patients in U.S.198 HIV+ HAART-naive patients in U.S.

Probable depression associated with slower Probable depression associated with slower rate of virilogic suppressionrate of virilogic suppression

Probable alcohol and drug Probable alcohol and drug abuse/dependence associated with faster abuse/dependence associated with faster virilogic failurevirilogic failure

Associations Between Associations Between Psychiatric/Substance Use DisordersPsychiatric/Substance Use Disorders

and HAARTand HAART

Pence et al., JAIDS, 2007Pence et al., JAIDS, 2007

Associations Between DepressionAssociations Between DepressionTreatment and HAART Use and OutcomesTreatment and HAART Use and Outcomes

Use of antidepressants + MH therapy, or MH therapy Use of antidepressants + MH therapy, or MH therapy alone, associated with increased HAART utilization alone, associated with increased HAART utilization (N = 1,371)(N = 1,371)

Compliant SSRI use associated with improved HIV Compliant SSRI use associated with improved HIV adherence and laboratory parameters (CD4 cell adherence and laboratory parameters (CD4 cell count and viral load)count and viral load)

Cook et al., AIDS Care, 2006Cook et al., AIDS Care, 2006 Horberg et al., JAIDS, 2008Horberg et al., JAIDS, 2008

Community-based prospective cohort studyCommunity-based prospective cohort study

158 HIV+ homeless/marginally housed people 158 HIV+ homeless/marginally housed people followed every 3 months between 2002-2007followed every 3 months between 2002-2007

Antidepressant treatment associated withAntidepressant treatment associated with• 4 times the likelihood of accepting HAART4 times the likelihood of accepting HAART

• 2 times the likelihood of achieving viral suppression2 times the likelihood of achieving viral suppression

Associations Between Depression Associations Between Depression Treatment and HAART Use and OutcomesTreatment and HAART Use and Outcomes

Tsai et al. Arch Gen Psych, 2010Tsai et al. Arch Gen Psych, 2010

Associations Between Treatment for Mental Associations Between Treatment for Mental Disorders and HAART Use and OutcomesDisorders and HAART Use and Outcomes

HIV Research Network study: Five U.S. sites, 4989 HIV+ HIV Research Network study: Five U.S. sites, 4989 HIV+ people, predominantly minority men.people, predominantly minority men.

Odds of discontinuing HAART by mental health Odds of discontinuing HAART by mental health visits/yearvisits/year

# Visits Adjusted Odds Ratio P Value# Visits Adjusted Odds Ratio P Value

00 1.01.0 Referent Referent

11 1.361.36 0.0013 0.0013

2-52-5 0.930.93 0.43 0.43

6-116-11 0.780.78 0.052 0.052

≥ ≥ 1212 0.600.60 <0.001 <0.001

HimelhochHimelhoch, AIDS, 2009, AIDS, 2009

Interventions for HIV+ People with Interventions for HIV+ People with Depression: A Review of StudiesDepression: A Review of Studies

83 interventions with a placebo/control group 83 interventions with a placebo/control group

Mostly in U.S., mostly conducted with gay menMostly in U.S., mostly conducted with gay men

Reduce depression +/- other endpointsReduce depression +/- other endpoints

Varying measures of depression Varying measures of depression

Diverse strategiesDiverse strategies

Often small sample sizesOften small sample sizes



Usually effective for depression, especially Usually effective for depression, especially those that incorporate a cognitive behavioral those that incorporate a cognitive behavioral (CB) component(CB) component

Cognitive behavioral stress management Cognitive behavioral stress management (CBSM) is particularly effective (CBSM) is particularly effective


Psychological InterventionsPsychological Interventions


Antidepressants are generally effectiveAntidepressants are generally effective

Correcting testosterone deficiency with Correcting testosterone deficiency with replacement hormone treatment has been replacement hormone treatment has been shown to improve mood shown to improve mood


Pharmacological InterventionsPharmacological Interventions


Treatments that combine psychological and Treatments that combine psychological and pharmacologic treatment appear to be the most pharmacologic treatment appear to be the most effective.effective.

Treatments that appear to be ineffective Treatments that appear to be ineffective include non-specific coping interventions and include non-specific coping interventions and herbal/vitamin supplements.herbal/vitamin supplements.

Sherr, et. al.Sherr, et. al., Psychology Health & Medicine, 2011Psychology Health & Medicine, 2011

Other InterventionsOther Interventions

Interventions for HIV+ People with Interventions for HIV+ People with DepressionDepression

Many brief evidence-based psychotherapies Many brief evidence-based psychotherapies have been manualized.have been manualized.

Manualized interventions may be targeted to Manualized interventions may be targeted to individuals or groups.individuals or groups.

Manualized interventions can be taught to Manualized interventions can be taught to providers with limited mental health providers with limited mental health background.background.

Antiretrovirals and Psychotropics:Antiretrovirals and Psychotropics:General PointsGeneral Points

Psychotropic medications maintain efficacy in the HIV+ Psychotropic medications maintain efficacy in the HIV+ population.population.

Overlapping metabolic pathways in cytochrome P-450 system Overlapping metabolic pathways in cytochrome P-450 system (3A4 and 2D6) (3A4 and 2D6) drug interactions (often theoretical). drug interactions (often theoretical).

May facilitate or inhibit one another’s metabolism. Websites, May facilitate or inhibit one another’s metabolism. Websites, online resources are available for information.online resources are available for information.

Overlapping toxicities, especially liver toxicity among patients Overlapping toxicities, especially liver toxicity among patients co-infected with hepatitis viruses. co-infected with hepatitis viruses.

But most psychotropics can be used safely if start low, go But most psychotropics can be used safely if start low, go slow.slow.

American Psychiatric Association Practice Guidelines and other reference documents www.psych.org/aids

Somatic Treatments for DepressionSomatic Treatments for Depression

Caution with use of antidepressants among Caution with use of antidepressants among adolescents and young adults under 24-y.o.: warning adolescents and young adults under 24-y.o.: warning about increased suicide riskabout increased suicide risk

SSRIs (easiest to use in primary care)SSRIs (easiest to use in primary care) SNRIsSNRIs TricyclicsTricyclics Other antidepressantsOther antidepressants Atypical antipsychotics/mood stabilizers for bipolar Atypical antipsychotics/mood stabilizers for bipolar

depressiondepression Brain stimulation treatments (includes ECT but many Brain stimulation treatments (includes ECT but many

new approaches are being studied)new approaches are being studied) Light therapy for seasonal depressionLight therapy for seasonal depression Avoid St. John’s Wort—lowers antiretroviralsAvoid St. John’s Wort—lowers antiretrovirals

American Psychiatric Association Practice Guidelines and other reference documents www.psych.org/aids

Antidepressant Studies in HIV: Antidepressant Studies in HIV: Another SummaryAnother Summary

> 1000 patients treated in clinical trials> 1000 patients treated in clinical trials Antidepressants 50-90% effective and superior to Antidepressants 50-90% effective and superior to

placeboplacebo Placebo response rates as high as 48%Placebo response rates as high as 48% Average # concurrent HIV medications = 4Average # concurrent HIV medications = 4 Women and IDUs underrepresentedWomen and IDUs underrepresented Depression diagnoses and outcome criteria varyDepression diagnoses and outcome criteria vary HIV illness stage variesHIV illness stage varies Duration varies (4 weeks-1 year)Duration varies (4 weeks-1 year) High attrition rates (19-55%)High attrition rates (19-55%)

Reported Neuropsychiatric Adverse Reported Neuropsychiatric Adverse Effects of Medications Commonly Used Effects of Medications Commonly Used

in HIV Infectionin HIV Infection

depression as a medical co-morbidity of hiv infection francine cournos, m.d. professor of clinical...

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uncomplicated depression

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diagnosis of major depression

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rate s of severe depression

bipolar disorder