Depression%20and%20PTSD%20Treatments%20Improve%20HIV%20Treatment%20Outcome

1
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

2
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.

3
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.

4
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

5
HIV Increases Risk for Psychiatric Illness

• Increased major depression.
• Increased mania.
• HIV dementia (AIDS Dementia Complex).
• Increased psychosocial stressors.

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Depression

• 1. Prevalence
• 2. Diagnosis
• 3. Impact on ARV Treatment
• Initiation
• Discontinuation
• Adherance
• 4. Impact on HIV Mortality
• 5. Treatment of Depression

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100 Patients with HIVHow many are depressed?
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• Depressed Mood and HIV
• Name the 11 types
• 1.
• 2.
• 3.
• 4.
• 5.
• 6.
• 7.
• 8.
• 9.
• 10.
• 11.
• Why is the diagnosis important?

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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.

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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
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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

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

• San Francisco Mens Health Study 277
  participants
• 20 depressed at baseline
• Cox proportional hazards analysis of progression
  to death
• Depression predicted ARV use but not mortality

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

• SF Mens 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 (RR1.67 Plt0.05)

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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 (RR2), CD4,
  HAART duration, age

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

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Depression and Delay in HAART InitiationFairfield
JGIM 1999
199 Patients New England Deaconnes with VLgt10,000
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What Degree of AdherenceIs Needed to Prevent
Drug-Resistant Virus
Adherence to a PI-Containing Regimen
CorrelatesWith HIV RNA Response at 3 Months
100
80
60
Patients With HIV RNA lt400 ()
40
20
0
lt70
70-80
80-90
90-95
gt95
PI Adherence () (MEMScaps)
Paterson. 6th CROI 1999 Chicago. Abstract 92.
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Depression Predicts Adherence to Non-HIV Treatment
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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

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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

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Depression Diagnosis
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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.
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Follow-up Interview for Diagnosis SIGECAPSS

• S Sleep Disruption in sleep patterns nearly
  every day?
• I Interests Decreased interest and pleasure in
  usual activities
• G Guilt Feelings of worthlessness or guilt?
• E Energy Decreased energy?
• C Concentration Diminished ability to
  concentrate?
• A Appetite Change in appetite or weight?
• P Psychomotor Psychomoror retardation or
  agitation/irritable?
• S Suicidal Recurrent thought of death or
  suicide?
• S Sex drive Diminished sex drive?

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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.

• 1 0 I do not feel sad.
• 1 I feel sad.
• 2 I am sad all the time and I cant snap out of
  it.
• 3 I am so sad or unhappy that I cant stand it.
• 2 0 I am not particularly discouraged about the
  future.
• 1 I feel discouraged about the future.
• 2 I feel I have nothing to look forward to.
• 3 I feel that the future is hopeless and that
  things cannot improve.
• 3 0 I do not feel like a failure.
• 1 I feel I have failed more than the average
  person.
• 2 As 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.

• 8 0 I dont 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.
• 9 0 I dont 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.
• 10 0 I dont 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 cant cry
  even though I want to.
• To order forms 1-800-228-0752

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Depression Treatment
27
Tricyclic Antidepressants Treatment of Depression
in HIV Individuals
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• Treatment of Depression With Other Agents
• in HIV Individuals

Grinspoon 2000
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SSRI Treatment of Depression in HIV Individuals
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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

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SSRI FDA Approvals
FDA approved to age 6 years
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Half Lives of 4 SSRIs
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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

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Hepatic Isoenzyme Inhibition of the SSRIs
(Cytochrome P450)
35
HIV-Related Medications and Psychotropic Agents
Involving the Cytochrome P450 Isoenzyme
36
(No Transcript)
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Staging HIV and Antidepressant TreatmentTreat
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 199914446-8
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Comorbid Mood and Anxiety Disorders
Panic Disorder 50 - 651
Generalized Anxiety Disorder
8- 391
Depression
Social Anxiety Disorder 702
PTSD 484
OCD 673
1 American 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. 19912193-99. 3 Rasmussen SA, Eisen JL.
J Clin Psychiatry. 199253(suppl)4-10. 4
Coryell W Et al. Am J Psychiatry 1988155895-898.
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Post Traumatic Stress Disorder

• Prevalence
• Childhood abuse, PTSD and HIV risk behaviors
• Proposed association between PTSD and HIV
  treatment nonadherance
• Treatment of PTSD

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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

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Most Prevalent Anxiety Disorders in the General
Population
Lifetime Prevalence ()
Kessler et al, National Comorbidity Survey, 1994
Males Females
Hutton (2001) 177 Prison Women
Kelly (1998) 61 HIV Gay/Bi men
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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

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Common Traumatic Events

• Witnessing injury/death
• Sexual molestation/rape
• Natural disaster/fire
• Physical attack or abuse/threatened with a weapon
• Life threatening accident
• Combat

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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

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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
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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, 52/4508-13
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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

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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

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PTSD Diagnosis
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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?

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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?

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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

• 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

• ? ? 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

Consensus Guidelines J Clin Psych 1999
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PTSD Treatment
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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

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Pharmacological InterventionsAntidepressants

• Positive Controlled Trials
• TCAs
• amitryptaline (Elavil)
• imipramine ((Tofranil)
• MAOIs
• phenelzine (Nardil)
• SSRIs
• fluoxetine (Prozac) civilians only
• sertraline (Zoloft) (Paxil) FDA indication
• paroxetine (Paxil)

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Benzodiazepines

• Should NOT be first line
• May exacerbate
• Dissociation
• Substance abuse
• Disinhibition
• Best used as an augment

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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

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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

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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

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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