Depression and ptsd treatments improve hiv treatment outcome
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Depression and PTSD Treatments Improve HIV Treatment Outcome. Eric Avery, MD Assistant Clinical Professor of Psychiatry Director, HIV Psychiatry Services The University of Texas Medical Branch Galveston, Texas. Objectives.

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Depression and ptsd treatments improve hiv treatment outcome

Depression and PTSD Treatments Improve HIV Treatment Outcome

Eric Avery, MD

Assistant Clinical Professor of Psychiatry

Director, HIV Psychiatry Services

The University of Texas Medical Branch

Galveston, Texas


Objectives

Objectives

1. To understand the relationship between the increasing prevalence of psychiatric disorders in HIV patients and the changing epidemiology of the epidemic.

2. To review Depression and Post Traumatic Stress Disorder (PTSD):

Prevalence

Diagnosis

Impact on adherance and mortality

Treatment of Depression and PTSD

3. To review HIV and psychiatric drug/drug interactions.


Hiv is a psychiatric epidemic

HIV is a Psychiatric Epidemic

  • Psychiatric illness increases risk for HIV.

  • HIV increases risk for psychiatric illness.

  • Effective treatment for psychiatric illness can improve patient outcome.

  • Effective treatment for psychiatric can decrease HIV transmission.


Psychiatric illness increases risk of hiv infection

Psychiatric Illness Increases Risk of HIV Infection

  • Substance Abuse.

  • Mood Disorders (Major Depression, Bipolor D/O)

  • Post Traumatic Stress Disorder (PTSD)

  • Psychotic Disorders

  • Impulsive behavior and personality factors


Hiv increases risk for psychiatric illness

HIV Increases Risk for Psychiatric Illness

  • Increased major depression.

  • Increased mania.

  • HIV dementia (AIDS Dementia Complex).

  • Increased psychosocial stressors.


Depression

Depression

1. Prevalence

2. Diagnosis

3. Impact on ARV Treatment:

  • Initiation

  • Discontinuation

  • Adherance

    4. Impact on HIV Mortality

    5. Treatment of Depression


100 patients with hiv how many are depressed

100 Patients with HIVHow many are depressed?


Depression and ptsd treatments improve hiv treatment outcome

Depressed Mood and HIV:

Name the 11 types:

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

Why is the diagnosis important?


Differential diagnosis of depressed moods in hiv patients

Differential Diagnosis of Depressed Moods in HIV Patients

  • Despondency/demoralization.

  • Dysthymia (chronic low mood).

  • Adjustment disorder/minor depression.

  • Major depression, recurrent major depression.

  • General anxiety disorder.

  • Bipolar disorder -- depressed phase.

  • Organic mood disorder “secondary depression” (infections, medication side-effects, and mass lesions of CNS).

  • Malnourishment/weight loss associated with HIV.

  • Sleep disorder.

  • Psychoactive substance abuse.

  • Bereavement.


Depression and ptsd treatments improve hiv treatment outcome

Depression: Multicenter AIDS Cohort Study

% Depressed

Time of AIDS Onset

55- 49- 43- 37- 31- 25- 19- 13- 7-12 0-6 0-6 7-12 13- 19-

60 54 48 42 36 30 24 18 mo mo mo mo 18 24

mo mo mo mo mo mo mo mo mo mo

Percentages of Multicenter AIDS Cohort Study participants who met syndromal criteria for depression, or who had a score of 22 or greater on the Center for Epidemiologic Studies Depression scale (CES-D) or 14 or greater on the CES-D minus its “somatic” items (CES-D-NS), as AIDS developed.

Lyketos et al, Psych Ann 31: 1 Jan 01


Depression and progression to aids prehaart lyketos hoover guccione et al jama 1993

Depression and Progression to AIDS – PreHAARTLyketos, Hoover, Guccione et al JAMA 1993

  • MACS Cohort: 1718 participants

  • 21% depressed at baseline

  • Cox proportional hazards analysis controlling for sociodemographics, CD4, AIDS related symptoms

  • Depression did not predict AIDS or death


Depression and progression to death prehaart burack barret stall chesney estrand coates jama 1993

Depression and Progression to Death – PreHAARTBurack, Barret, Stall, Chesney, Estrand, Coates JAMA 1993

  • San Francisco Men’s Health Study: 277 participants

  • 20% depressed at baseline

  • Cox proportional hazards analysis of progression to death

  • Depression predicted ARV use but not mortality


Depression and ptsd treatments improve hiv treatment outcome

Depression and Progression to AIDS – PreHAARTMayne, Vittinghoff, Chesney, Barrett, Coates Arch Int Med 1996

  • SF Men’s Cohort: 1032 participants over 102 months

  • Cox proportional hazards with time dependent variables

  • 58% had significant depressive symptoms (CES-D)

  • Longitudinal measurement of depression every 6 months

  • Predictors of Mortality

    • CD4 cell count

    • B2 microglobulin

    • P24 antigen

    • WHO HIV stage

    • Depression (RR=1.67 P<0.05)


Depression and progression to aids post haart ickovics hamburger vlahov et al jama 2001

Depression and Progression to AIDS: Post-HAARTIckovics, Hamburger, Vlahov et alJAMA 2001

  • HERS Cohort: 765 Participants

  • Longitudinal depression (CES-D)

    • 42% chronic

    • 35% intermittent

    • 23% none

  • Mortality predictors: depression (RR=2), CD4, HAART duration, age


Depression mortality by cd4 and viral load post haart ickovics hamburger vlahov et al jama 2001

Depression, Mortality by CD4 and Viral load: Post-HAARTIckovics, Hamburger, Vlahov et alJAMA 2001


Why does depression speed progression to aids and death

Why Does Depression Speed Progression to AIDS and Death?

  • Stress alters cellular and humoral immune response

    • Kieclot-Glaser Proc Nat Acad Sci 1996

    • Vedhara Lancet 1999

    • Glaser Psychosom Med 1992

    • Jabaaij J Psychosom Res 1993

    • Glaser Ann NY Acad Sci 1998

    • Azciati Psychosomatics 2001

  • Delay in HAART initiation

  • Early HAART Discontinuation

  • Sub-optimal adherence to HAART


  • Depression and delay in haart initiation fairfield jgim 1999

    Factor

    Hazard

    95% CI

    p Value

    CD4 cell count

    <200

    1.00

    200-500

    2.63

    1.61, 4.17

    <.001

    >500

    11.11

    3.57, 33.33

    <.001

    Tenfold increase in initial        elevated viral load

    0.66

    0.45, 0.98

    .038

    History of pneumocystis

    0.57

    0.37, 0.90

    .016

    Depression (53%)

    1.49

    1.03, 2.13

    .032

    History of injection drug use

    2.70

    1.35, 5.56

    .005

    Model adjusted for calendar date of first elevated viral load.

    Depression and Delay in HAART InitiationFairfield JGIM 1999

    199 Patients New England Deaconnes with VL>10,000


    What degree of adherence is needed to prevent drug resistant virus

    What Degree of AdherenceIs Needed to PreventDrug-Resistant Virus

    Adherence to a PI-Containing Regimen CorrelatesWith HIV RNA Response at 3 Months

    100

    80

    60

    Patients With HIV RNA <400 (%)

    40

    20

    0

    <70

    70-80

    80-90

    90-95

    >95

    PI Adherence (%) (MEMScaps)

    Paterson. 6th CROI; 1999; Chicago. Abstract 92.


    Depression predicts adherence to non hiv treatment

    Amiodarone

    Irvine

    Psychosom Med

    1999

    General medicine

    Botelho

    J Fam Pract

    1992

    Aspirin for angina

    Carney

    Behavioral Med

    1998

    Renal diet

    De-Nour

    Transplantation

    1993

    ESRD Diet

    Katz

    Psychol Reports

    1998

    ESRD Diet

    Schnieder

    Health psychol

    1991

    ESRD Medical Regimen

    Brownbridge

    Ped Neph

    1994

    Cyclosporine Renal Transplant

    Kiley

    Transplantation

    1993

    Cyclosporine Renal Transplant

    Rodriguez

    Trans Proc

    1991

    Rheum arthritis treatment plan

    Taal

    Pt Ed Counsel

    1992

    Oral cytoxan

    Lebovits

    Cancer

    1990

    Asthma

    Cochrane

    Drugs

    1996

    Depression Predicts Adherence to Non-HIV Treatment


    Depression and hiv medication adherence

    Depression and HIV Medication Adherence

    • Singh AIDS Care 1996

    • Holzmer AIDS Patient Care STDs 1999

    • Peterson Annals Int Med 2000

    • Schulz 38th ICAAC 1998

    • Bangsberg #1721 41st ICAAC 2001


    Depression is under treated

    Depression is Under-Treated

    • 475 HIV+ men

    • 37% moderate-severe depressive symptoms

      • 40% of depressed received mental health care (12 mo)

      • 3.4% of depressed received antidepressant medications (12 mo)

        Katz et al AIDS Care 1996


    Depression diagnosis

    Depression: Diagnosis


    Simple depression assessment

    Simple Depression Assessment

    • During the past month, have you often been bothered by feeling down, depressed, or hopeless?

    • Yes No

    • During the past month, have you often been bothered by having little interest or pleasure in doing things?

    • Yes No

    If “no” to both, patient is unlikely to have major depression.

    If “yes” to either, proceed with the follow-up clinical interview.

    Whooley MA, Simon GE. N Engl J Med, 2000.


    Follow up interview for diagnosis sigecapss

    Follow-up Interview for Diagnosis: SIGECAPSS

    SSleepDisruption in sleep patterns nearly every day?

    IInterestsDecreased interest and pleasure in usual activities

    GGuiltFeelings of worthlessness or guilt?

    EEnergyDecreased energy?

    CConcentrationDiminished ability to concentrate?

    AAppetiteChange in appetite or weight?

    PPsychomotorPsychomoror retardation or agitation/irritable?

    SSuicidalRecurrent thought of death or suicide?

    SSex driveDiminished sex drive?


    Depression and ptsd treatments improve hiv treatment outcome

    10I do not feel sad.

    1I feel sad.

    2I am sad all the time and I can’t snap out of it.

    3I am so sad or unhappy that I can’t stand it.

    20I am not particularly discouraged about the future.

    1I feel discouraged about the future.

    2I feel I have nothing to look forward to.

    3I feel that the future is hopeless and that things cannot improve.

    30I do not feel like a failure.

    1I feel I have failed more than the average person.

    2As I look back on my life, all I can see is a lot of failures.

    3 I feel I am a complete failure as a person.

    80 I don’t feel I am any worse than anybody else.

    1 I am critical of myself for may weaknesses or mistakes.

    2 I blame myself all the time for my faults.

    3 I blame myself for everything bad happens.

    90 I don’t have any thoughts of killing myself.

    1 I have thoughts of killing myself, but I would not carry them out.

    2 I would like to kill myself.

    3 I would kill myself if I had the chance.

    100 I don’t cry any more than usual.

    1 I cry more now than I used to.

    2 I cry all the time now.

    3 I used to be able to cry, but now I can’t cry even though I want to.

    To order forms: 1-800-228-0752

    Beck Depression Inventory Date__________________Name:__________________________________________________ Marital Status:_______ Age:____ Sex:___Occupation:_____________________________________________ Education:___________________________This questionnaire consists of 21 groups of statements. After reading each group of statements carefully, circle the number (0,1,2 or 3) next to the one statement in each group which best describes the way you have been feeling the past week, including today. If several statements within a group seem to apply equally well, circle each one. Be sure to read all the statements in each group before making your choice.


    Depression treatment

    Depression: Treatment


    Tricyclic antidepressants treatment of depression in hiv individuals

    Medication

    Response

    Author

    Journal

    Year

    Imipramine

    74%

    Rabkin

    Am J Psych

    1994

    Imipramine

    87%

    Elliot

    Am J Psych

    1998

    Desipramine

    50%

    Schwartz

    Dep and Anxiety

    1999

    Tricyclic Antidepressants Treatment of Depression in HIV+ Individuals


    Depression and ptsd treatments improve hiv treatment outcome

    Treatment of Depression With Other Agents

    in HIV+ Individuals

    Drug

    Response

    Author

    Journal

    Year

    Dextroamphetamine

    73%

    Wagner

    J Clin Psych

    1999

    Testosterone

    74%

    Rabkin

    Arch Gen Psych

    2000

    Testosterone (Sx decrease)

    Grinspoon

    J Clin Endo Metab

    2000

    Grinspoon 2000


    Ssri treatment of depression in hiv individuals

    Medication

    Response

    Author

    Journal

    Year

    Fluoxetine

    83%

    Rabkin

    J Clin Psych

    1994

    Fluoxetine

    64%

    Zisook

    J Clin Psych

    1998

    Fluoxetine

    67%

    Elliot

    Am J Psych

    1998

    Fluoxetine

    90%

    Ferrando

    Gen Hosp Psych

    1997

    Fluoxetine

    75%

    Schwartz

    Dep and Anxiety

    1999

    Fluoxetine/

    Sertraline

    78%

    Ferrando

    J Clin Psych

    1999

    Sertraline

    86%

    Ferrando

    Gen Hosp Psyh

    1997

    Nefazodone

    73%

    Elliot

    J Clin Psych

    1999

    Paroxetine

    86%

    Ferrando

    Gen Hosp Psych

    1997

    SSRI Treatment of Depression in HIV+ Individuals


    Side effect toxicity profile tca vs ssri

    TCA

    Narrow therapeutic window

    Requires drug monitoring

    Anticholinergic effects

    Dry mouth, Constipation, dizziness, hypotension

    41% discontinue at 6 months

    (Rabkin Amer J Psych 1994)

    Pill burden

    SSRI

    Mild side effects

    Anticholinergic, agitation/sedation, sexual dysfunction

    Drug interactions (Rx + ritonavir)

    Bupropion - seizures

    Side Effect/Toxicity Profile TCA vs SSRI


    Ssri fda approvals

    SSRI FDA Approvals

    * FDA approved to age 6 years;


    Half lives of 4 ssris

    Half Lives of 4 SSRIs


    Serotonin discontinuation syndrome

    Serotonin Discontinuation Syndrome

    • Somatic symptoms

      • Disequilibrium, dizziness, unsteadiness, vertigo

      • Feeling “spacey”, confusion, memory dysfunction

      • Flulike symptoms (myalgia, chills, fatigue, nausea)

      • Sensations of electric shocks, parethesia, tremor

      • Insomnia, overactivity, vivid dreams

    • Psychological symptoms

      • Agitation, anxiety, irritability

      • Mood lability, crying spells

      • Cognitive fog


    Hepatic isoenzyme inhibition of the ssris cytochrome p450

    Hepatic Isoenzyme Inhibition of the SSRIs (Cytochrome P450)


    Hiv related medications and psychotropic agents involving the cytochrome p450 isoenzyme

    HIV-Related Medications and Psychotropic Agents Involving the Cytochrome P450 Isoenzyme


    Staging hiv and antidepressant treatment treat depression first whenever possible

    Staging HIV and Antidepressant Treatment:Treat Depression First Whenever Possible

    • Depression is common

    • Depression is the strongest modifiable predictor of adherence to all medical therapy

    • Adherence is the strongest predictor of disease progression and death after CD4 cell count

    • Depression should be treated prior to starting antiretroviral therapy

      • Depression screen, CD4, VL

    • Patients with severe HIV disease may need concurrent initiation of antidepressant therapy and antiretroviral therapy

    Bangsberg JGIM 1999;14:446-8


    Comorbid mood and anxiety disorders

    Comorbid Mood and Anxiety Disorders

    Panic Disorder 50% - 65%1

    Generalized Anxiety Disorder 8%- 39%1

    Depression

    Social Anxiety Disorder 70%2

    PTSD 48%4

    OCD 67%3

    1American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC;

    American Psychiatric Press; 1994.

    2 Van Ameringen M et al. J Affect Disord. 1991;21:93-99.

    3 Rasmussen SA, Eisen JL. J Clin Psychiatry. 1992;53(suppl):4-10.

    4 Coryell W Et al. Am J Psychiatry 1988;155:895-898.


    Post traumatic stress disorder

    Post Traumatic Stress Disorder

    • Prevalence

    • Childhood abuse, PTSD and HIV risk behaviors

    • Proposed association between PTSD and HIV treatment nonadherance

    • Treatment of PTSD


    Ptsd prevalence

    PTSD Prevalence

    • Over half the U.S. population has been exposed to a severe trauma

    • 10-20% of trauma survivors will develop PTSD

    • Lifetime prevalence 8% overall. 12% in women (Kessler 1995)

      • Increased rates in HIV +, incarcerated

      • Limited studies:

        • HIV + 30% (1/3 after HIV dx) (Kelly 1998)

        • Incarcerated women lifetime 33%, current 15-22% (Hutton 2001)

    • PTSD is the 5th most prevalent major psychiatric illness


    Most prevalent anxiety disorders in the general population

    Most Prevalent Anxiety Disorders in the General Population

    Lifetime Prevalence (%)

    Kessler et al, National Comorbidity Survey, 1994

    MalesFemales

    Hutton (2001) 177 Prison Women

    Kelly (1998) 61 HIV+ Gay/Bi men


    Comorbidity

    Comorbidity

    • Comorbid psychiatric illness is about 80%

    • Patients with PTSD are 2 - 4X more likely to have depression, anxiety disorders or substance abuse

    • They are 90X more likely to have a somatization disorder


    Common traumatic events

    Common Traumatic Events

    • Witnessing injury/death

    • Sexual molestation/rape

    • Natural disaster/fire

    • Physical attack or abuse/threatened with a weapon

    • Life threatening accident

    • Combat


    Ptsd clinical course

    PTSD - Clinical Course

    • PTSD symptoms usually present within the first 3 months following the trauma

      • Less frequently, symptoms may be delayed for months or years after the traumatic event

      • Symptoms of PTSD may persist for months or years after the trauma

  • Approximately 50% of all cases of PTSD are chronic


  • Connection between childhood abuse and hiv infection

    Connection Between Childhood Abuse and HIV Infection

    Reported Abuse & Survivor Characteristics (N= 52 HIV +Adults Atlanta Social Service Agency)

    Note. Survivor characteristic categories are not independent.

    Allers C. J Counsel Devel. 1991; 70: 309-13


    Frequency of ptsd disorders among 177 women prisoners in an hiv risk behavior study

    Frequency of PTSD Disorders Among 177 Women Prisoners in an HIV Risk Behavior Study

    Compared with participants who did not have PTSD, those with lifetime diagnosis of PTSD were 71% more likely to have engaged in anal sex and 56% more likely to have engaged in prostitution. The association between lifetime PTSD and other HIV risk behaviors were not significant in this study.

    Hutton, Psych Services 2001, 52/4:508-13


    Ptsd predicts adherence to non hiv treatment

    PTSD Predicts Adherence to Non-HIV Treatment

    Survivors of Myocardial Infarction

    • 102 s/p MI

    • 10% PTSD (intrusion/avoidance)

      • significant association with decreased adherence

        Shemesh Gen. Hosp. Psych 2000


    Ptsd is under treated

    PTSD is Under-Treated

    47 HIV+ women

    • 42% full, current PTSD

      • 59% not receiving mental health care

    • 22% partial PTSD

      • 78% not receiving mental health care

        Martinez AIDS Patient Care and STDs 2002


    Ptsd diagnosis

    PTSD: Diagnosis


    Screening questions

    Screening questions

    • Have you ever had anything happen to you where you thought you would be seriously injured or might die?

    • Have you ever been in a life threatening accident? Fire? Disaster?

    • Have you ever been attacked or raped?

    • Have you ever seen these things happen to someone else?


    If the answer to any of these questions is yes

    If the answer to any of these questions is “yes”

    • Do you ever have nightmares about the event, or sometimes feel the same feelings you had when you were in the trauma?

    • Do you startle easily?

    • Do you try hard to avoid situations which remind you of the trauma?

    • How do you feel about your future?


    Depression and ptsd treatments improve hiv treatment outcome

    Yes or No?

      Have you experienced or witnessed a life-

    threatening event that caused intense fear

    Do you re-experience the event in at least one of

    the following ways?

      Repeated, distressing memories and/or

    Yes No dreams?

     Acting or feeling as if the event were

    Yes No happening again (flashbacks or a sense of

    reliving it)?

      Intense physical and/or emotional distress

    Yes No when you are exposed to things that remind

    you of the event?

    Do you avoid reminders of the event and feel numb, compared to

    the way you felt before, in three or more of the following ways?

      Problems concentrating?

    Yes No

      Feeling “on guard”?

    Yes No

      An exaggerated startle response?

    Yes No

      Do your symptoms interfere with your daily life?

    Yes No

      Have you symptoms lasted at least 1 month?

    Yes No

    Having more than one illness at the same time can make it more

    difficult to diagnose and treat the different conditions. Illnesses

    that sometimes complicate PTSD include depression and

    substance abuse. To see if you have other problems that may

    need treatment, please complete the following questions.

    HOW CAN I TELL IF I HAVE PTSD?PTSD is a serious, yet treatable medical disorder. It is not a sign of personal weakness. If you think you may have PTSD, answer the following questions and show this checklist to your health care professional

    Consensus Guidelines: J Clin Psych 1999


    Ptsd treatment

    PTSD: Treatment


    Psychotherapeutic interventions

    Psychotherapeutic Interventions

    • Acute PTSD

      • mild: Psychotherapy

      • severe: Psycho therapy and medication

    • Chronic PTSD

      • mild:Psychotherapy first or + medication

      • severe:Psychotherapy first or + medication

        If comorbid (eg: depression / bipolor / other anxiety DO)

      • medication plus psychotherapy

    • Most effective: cognitive behavioral therapy (CBT) and exposure therapy

    • Patients are encouraged to confront anxiety provoking triggers, decrease avoidance, and practice stress reducing strategies

    • When referring patients, seek therapists with expertise in CBT and BT

      Consensus Guidelines J. Clin. Psychiatry 1999


    Pharmacological interventions antidepressants

    Pharmacological Interventions:Antidepressants

    Positive Controlled Trials:

    TCAs

    • amitryptaline (Elavil)

    • imipramine ((Tofranil)

      MAOIs

    • phenelzine (Nardil)

      SSRIs

    • fluoxetine (Prozac): civilians only

    • sertraline (Zoloft): (Paxil): FDA indication

    • paroxetine (Paxil)


    Benzodiazepines

    Benzodiazepines

    • Should NOT be first line

    • May exacerbate

      • Dissociation

      • Substance abuse

      • Disinhibition

    • Best used as an augment


    Pharmacological steps for ptsd

    Pharmacological Steps for PTSD

    • Start with and SSRI

    • Initiate with a low dose, half of what would start for depression

    • Titrate to a high dose

    • Once patient improves, maintain dosage for at least a year


    Pharmacotherapy steps for ptsd

    Pharmacotherapy Steps for PTSD

    • If no response or intolerant to SSRI:

      • Venlafaxine

      • Nefazadone

      • A tricyclic antidepressant

    • If all else fails, consider a monoamine oxidase inhibitor


    Reasonable augmentations

    Reasonable augmentations

    • Anticonvulsants: for dissociation, explosiveness, mood lability

    • Autonomic blockers: for SNS overactivity

    • Benzodiazepines or Buspirone: for excessive anxiety

    • Neuroleptics: for poor impulse control

    • Sedating antidepressants (Trazadone): for insomnia


    Summary

    Summary

    • Psychiatric disorders, especially depression and PTSD are common in HIV patients.

    • Depression is the strongest modifiable predictor of adherence to all medical therapy.

    • Adherence is the strongest predictor of disease progression and death after CD4 count.

    • Depression should be treated prior to starting antiretroviral therapy. When in doubt, treat.

    • The behavioral manifestations of PTSD contribute to problems of HIV treatment adherance.

      • Difficulty recognizing harm

      • Difficulty developing self protective mechanism

      • Compulsive need to repeat the trauma

      • Sense of foreshortened future


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