The Treatment of Mood and
Anxiety Disorders in HIV
Marshall Forstein, MD
Associate Professor of Psychiatry
Harvard Medical School
Chair, Steering Committee on HIV Psychiatry
American Psychiatric Association
Disclosures
• Nothing to disclose
Mood Disorder due
to a General
Medical Condition
Substance-Induced
Mood Disorder
Major Depression
Demoralization
Adjustment Disorder
Grief
Sadness
Disillusionment
Despondency
Dysthymia
“Depressive Personality”
“Minor Depression”
Sub-syndromal Major Depression
Mood Disorders
Mood disorders are the most frequent psychiatric
complication associated with HIV disease
Mood disorders may be more prevalent in people
at risk for HIV infection
Mood disorders may be secondary to HIV
complications or its treatment
Prevalence of Axis I Disorders in
Multi-site HIV/AIDS Mental Health
Demonstration Project
Major Depression
Substance Use Disorders
Dysthymic Disorder
Anxiety Disorders
McDaniel et al., 1999
60%
50%
25%
25%
Impact of depression
• Depression causes biologic changes in
endocrine and immune function that may
contribute to disease progression and
mortality
• Impacts readiness for ART and adherence
with treatment
DSM IV Depressive Disorders
• Major depression (can include psychotic
features)
• Dysthymia ( long standing low mood)
• Bipolar depression ( manic-depression)
– Type I, Type II
• Substance induced mood disorders
• Mood disorder due to general medical
condition
• Cyclothymia ( frequent ups and downs)
Differential Diagnosis
• Mood disorder due to a general medical
condition: Diabetes, cardiac disease
• CNS HIV cognitive disorders
• CNS opportunistic illnesses and cancers
• Medication effects
• Other medical & endocrine abnormalities
Impact of depression in HIV
• Depressive symptoms and
psychological stress associated with:
– More rapid progression of illness
– Higher mortality rates
– Poor adherence with treatment
• Increased risk for secondary transmission
– Greater impairments in psychosocial
function
PERCENT DEPRESSED
Depression as AIDS Develops
20
10
TIME OF AIDS
Lyketsos et. al.,
1995
0
-48
-36
-24
-12
6
MONTHS BEFORE AND AFTER AIDS
18
Prevalence of Depression
• Epidemiologic study of 2864 HIV +
– Almost 50% identified as having a psychiatric
disorder
– >1/3 were positive for major depression
– >1/4 were positive for dysthymia
Bing EG, Burnam MA, Longshore D, et al.: Psychiatric disorders and drug use among
human immunodefi ciency virus-infected adults in the United States. Arch Gen
Psychiatry 2001, 58:721–728.
HIV+ women and depression
• May be more vulnerable than men as in
the general population
• Study of 765 HIV + women
– 42% had chronic depressive symptoms
– 35% had intermittent depressive symptoms
• HIV+ women 4x more likely to be
depressed than HIV- women [Morrison et al ]
Kaiser Permanente and Group
Health Cooperative
• 42 % had a depression diagnosis
– only 15 % used SSRIs.
– Depression without SSRI use significantly
decreased the odds of achieving 90 percent
or greater adherence to ART
• Risk for mutation and secondary transmission of
resistant virus
Affective vs. Somatic Symptoms:
Depressive Symptoms
AFFECTIVE
• Depressed mood
• Loss of interest
• Guilt, worthlessness
• Hopelessness
• Suicidal ideation
SOMATIC
• Appetite/Weight loss
• Sleep disturbance
• Agitation/retardation
• Fatigue
• Loss of
concentration
Treatment of Depression
• Antidepressant Agents
–No one drug has clear superiority
over others
–Chosen on the basis of
• Side effect profile
• Drug-drug interaction
Other treatments for mood disorders
• Testosterone
–Evidence for improvement of mood
in hypogonadism
• Psychostimulants
–Methylphenidate
–Dextroamphetamine
–Modafinil
Psychotherapy for depression
• Best evidence is for combination of
CBT and medication
• Few randomized studies
– Interpersonal psychotherapy (IPT)
– New evidence based meta-analysis of
dynamic therapies
– Group , psycho educational or
therapeutic
Rule out medical co-morbidity
• Hepatitis C infection (independent of HIV
coinfection and interferon/ribavirin therapy) )
– Fatigue 97% of patients
– Depression 25 % current
• Up to 70% have elevated scores on
depression rating scales
– cognitive dysfunction
• (up to 82% impairment on some measures).
Crone C, Gabriel GM: Comprehensive review of hepatitis C for psychiatrists: risks, screening,
diagnosis, treatment and interferon-based therapy complications. J Psychiatr Pract
2003, 9:93–110.
Depression and adherence
• Depression is an independent predictor of
adherence and mortality in women.
• Antiretroviral adherence did not predict
antidepressant adherence
• antidepressant adherence did predict antiretroviral
adherence
•
•
•
Villes V et al, The effect of depressive symptoms at ART initiation on HIV clinical progression and
mortality: implications in clinical practice. Antivir Ther 2007; 12(7): 1067-74. ;
Lima VD, et al, The effect of adherence on the association between depressive symptoms and mortality
among HIV-infected individuals first initiating HAART. AIDS, 2007 May 31; 21(9): 1175-83
Bottonari KA, Tripathi, SP, Fortney JC, Rimland D, Rodriguez-Barradas M, Gifford AL, Pyne JA,
Correlates of Antiretroviral and Antidepressant Adherence Among Depressed HIV-Infected Patients,
AIDS PATIENT CARE and STDs Volume 26, Number 5, 2012
Endocrine dysfunction
and mental dysfunction
• Clinical and subclinical hypothyroidism
– 16% prevalence
• Beltran S, Lescure F-X, Desailloud R, et al.: Increased
prevalence of hypothyroidism among human immunodefi
ciency virus infected patients: a need for screening. Clin
Infect Dis 2003, 37:579–583.
• Hypogonadism
– Up to 50% in symptomatic HIV
• Mylonakis E, Koutkia P, Grinspoon S: Diagnosis and
treatment of androgen deficiency in human immunodefi
ciencyvirus-infected men and women. Clin Infect Dis 2001,
33:857–864.
Rule out medical co-morbidity
• Hepatitis C infection (independent of HIV
coinfection and interferon/ribavirin therapy) )
– Fatigue 97% of patients
– Depression 25 % current
• Up to 70% have elevated scores on
depression rating scales
– cognitive dysfunction
• (up to 82% impairment on some
measures).
Crone C, Gabriel GM: Comprehensive review of hepatitis C for psychiatrists: risks, screening,
diagnosis, treatment and interferon-based therapy complications. J Psychiatr Pract
2003, 9:93–110.
Endocrine dysfunction
and mental dysfunction
• Clinical and subclinical hypothyroidism
– 16% prevalence
• Beltran S, Lescure F-X, Desailloud R, et al.: Increased
prevalence of hypothyroidism among human immunodefi
ciency virus infected patients: a need for screening. Clin
Infect Dis 2003, 37:579–583.
• Hypogonadism
– Up to 50% in symptomatic HIV
• Mylonakis E, Koutkia P, Grinspoon S: Diagnosis and
treatment of androgen deficiency in human immunodefi
ciencyvirus-infected men and women. Clin Infect Dis 2001,
33:857–864.
Endocrine dysfunction
and mental dysfunction
• Adrenal insufficiency
– 50% in severely ill HIV
• Mayo J, Callazos J, Martinez E, Ibarra S: Adrenal function in
the human immunodefi ciency virus-infected patient. Arch
Intern Med 2002, 162:1095–1098.
• Graves disease
• Chen F, Day SL, Metcalfe RA, et al.: Characteristics of
autoimmune thyroid disease occurring as a late complication
of immune reconstitution in patients with advanced human
immunodefi ciency virus (HIV) disease. Medicine (Baltimore)
2005, 84:98–106.
Endocrine dysfunction
and mental dysfunction
• Adrenal insufficiency
– 50% in severely ill HIV
• Mayo J, Callazos J, Martinez E, Ibarra S: Adrenal function in
the human immunodefi ciency virus-infected patient. Arch
Intern Med 2002, 162:1095–1098.
• Graves disease
• Chen F, Day SL, Metcalfe RA, et al.: Characteristics of
autoimmune thyroid disease occurring as a late complication
of immune reconstitution in patients with advanced human
immunodefi ciency virus (HIV) disease. Medicine (Baltimore)
2005, 84:98–106.
Symptoms of Endocrine Dysfunction
• Fatigue, low mood, low libido, and loss of
lean body mass
• Acute-stage Graves’ disease presents with
activation symptoms such as anxiety,
irritability, insomnia, weight loss, mania,
and agitation.
– symptoms may be ameliorated by correction
of the deficiency state.
Confounding Dx’s
• Increasing prevalence of neurocognitive
disorders
• CNS inflammation in both Primary HIV
neurocognitive disorders and depression
• Co- occurring HCV
• Substance use
– Especially Methamphetamine- neurotoxic
Anxiety and HIV
• Importance of identifying anxiety
– evidence linking these disorders to both highrisk behaviors and antiretroviral nonadherence.
•
•
Hilerio CM, Martínez J, Zorrilla CD, et al. Posttraumatic stress disorder symptoms
and adherence among women living with HIV. Ethn Dis. 2005;15(4 Suppl 5):S5-47S5-50.
Roux P, Carrieri MP, Michel L, et al. Effect of anxiety symptoms on adherence to
highly active antiretroviral therapy in HIV-infected women. J Clin Psychiatry.
2009;70:1328-1329.
A diagnosis of an anxiety disorder
is a diagnosis of exclusion
• Anxiety symptoms (Somatic complaints)
– shortness of breath,
– chest pain,
– racing/pounding heart,
– dizziness,
– diaphoresis, (sweatiness)
– numbness or tingling,
– nausea,
– sensation of choking
A diagnosis of an anxiety disorder
is a diagnosis of exclusion
• Anxiety symptoms (psychological)
– fear, worry,
– insomnia,
– impaired concentration and memory,
– diminished appetite,
– ruminations,
– compulsive rituals,
– avoidance of situations that make them
anxious.
Anxiety Sensitivity (AS)
• AS is operationally defined as the fear of
anxiety and arousal-related sensations.
McNally RJ. Anxiety sensitivity and panic disorder. Biol Psychiatry
2002;52:938–946
Anxiety Sensitivity
• conceptualized as a relatively stable
cognitive factor that is conceptually and
empirically distinct from the actual
experience of (negative) emotional states.
Bernstein A, Zvolensky MJ. Anxiety sensitivity: Selective review of
promising research and future directions. Expert Rev Neurother
2007;7:97–101.
Anxiety Sensitivity
• AS is incrementally related to greater
anxiety, somatization, and depression
symptoms among persons with HIV/AIDS
Gonzalez A, Zvolensky MJ, Solomon SE, Miller CT. Exploration of the
relevance of anxiety sensitivity among adults living with HIV/AIDS for
understanding anxiety vulnerability. J Health Psychol 2010;15:138–146.
Anxiety Sensitivity
• When anxious or experiencing somatic
symptoms, individuals high in AS may
become more acutely fearful due,
specifically, to beliefs that these anxiety
and related bodily sensations (e.g., rapid
heartbeat) have harmful personal
consequences (e.g.,‘‘I am going crazy’’).
Symptom Distress and AS:
interactive model of anxiety
• HIV symptom distress and AS may interact to
confer greater risk for anxiety symptoms.
• higher levels of HIV symptom distress may be
exacerbated by an individual’s level of AS, and
thereby may be associated with higher anxiety
symptoms
• individual’s HIV symptom distress level may trigger
more AS-specific cognitive reactions
The following questions may help
determine if anxiety is present
• Are you anxious?
• Are you fearful or afraid?
• Do you worry a lot?
• Are you tense or irritable?
• Are you restless?
• Do you have difficulty sleeping?
Anxiety in HIV+
• Anxiety symptoms are commonly
experienced during periods of illness and
may be a response to stressful situations.
Anxiety Disorder Present if Symptoms:
• Interfere with a patient’s daily function
(e.g., the patient is unable to work, leave
home, attend to medical care)
• Interfere with personal relationships
• Cause marked subjective distress
Anxiety Disorders in HIV +
people in medical care
• Anxiety disorder
20.3%
–Panic disorder
–PTSD
–GAD
12.3 %
10.4 %
2.8 %
Vitiello B, Burnam MA, Bing EG, et al. Use of psychotropic
medications among HIV-infected patients in the United
States. Am J Psychiatry,2003;160:547-554.
Underlying medical conditions may
also cause anxiety symptoms:
• CNS pathologies: HIV-related
infections, neoplasms, dementia, or
delirium
• Systemic or metabolic illness:
hypoxia, sepsis, electrolyte imbalance
• Endocrinopathies: thyroid disease,
hypoglycemia, pheochromocytoma,
Cushing’s syndrome
Underlying medical conditions may
also cause anxiety symptoms:
• Respiratory conditions: pneumonia
• Cardiovascular conditions:
arrhythmias, pulmonary embolus
• Substance intoxication/withdrawal:
from alcohol, nicotine, caffeine,
opiates, methadone, buprenorphine,
cocaine, and amphetamines
MANAGEMENT OF ANXIETY DISORDERS
• Referral to Mental Health Provider for
Diagnosis and Treatment when:
– Mild anxiety symptoms do not respond to
psychosocial interventions in the primary care
setting
– Anxiety symptoms are persistent or severe
– Intrusive or disturbing obsessive thoughts or
compulsive rituals are present
– Anxiety symptoms are occurring in patients with a
current or past history of substance use disorders
Psychosocial Intervention for Mild Anxiety
Symptoms in the Primary Care Setting
• Express empathy
• Educate patients about anxiety
• Identify the psychosocial factors that
contribute to patients’ anxiety symptoms,
including financial and housing instability,
social isolation, and conflict in key
relationships, and refer patients for
supportive services
Psychosocial Intervention for Mild Anxiety
Symptoms in the Primary Care Setting
• Prepare patients for stressful situations and
assist in development of coping strategies and
interventions
• Counsel patients to reduce intake of anxietyinducing substances such as caffeine and
nicotine
• Teach patients simple relaxation exercises.
Slow, deep abdominal breathing can be useful
when patients practice for 1 minute three times
a day, increasing to 5 minutes, if possible
• Patients who do not respond to basic
psychosocial interventions, and patients
with more severe anxiety symptoms or a
possible anxiety disorder, may require
psychopharmacologic treatment and/or
specialized psychotherapeutic treatment.
Assessing Depression
•
PHQ-9
PHQ-9 #10
PHQ-9 — Nine Symptom Checklist
2) If you checked off any problem on this questionnaire
so far, how difficult have these problems made it for
you to do your work, take care of things at home, or
get along with other people?
–
Not Difficult at All (0)
–
Somewhat Difficult (1)
–
Very Difficult (2)
–
Extremely Difficult (3)
Assessing Anxiety
HAD-D -6
• Hamilton Depression Scale
– Administered by health care professional
– Six items from the longer HAD-D 17, 21
scales
– Very sensitive to depression
– Useful for monitoring change and progress of
treatment
The Hamilton Rating Scale for Depression
• Patient name:
• Date of Assessment:
• To rate the severity of depression in
patients who are already diagnosed as
depressed, administer this questionnaire.
The higher the score, the more severe the
depression.
1. Depressed Mood
[sadness, hopeless, helpless, worthless]
0= absent
1= These feeling states indicated only on questioning
2= These feeling states spontaneously reported
verbally
3= Communicates feeling states non verbally- i.e.
through facial expression, posture, voice and
tendency to weep
4= Patient reports VIRTUALLY ONLY these feeling
states in his spontaneous verbal and non-verbal
communication
2. Feelings of guilt
0= absent
1= Self reproach, feels he has let people down
2= Ideas of guilt or rumination over past errors or
sinful deeds
3= Present illness is a punishment. Delusions of guilt
4= Hears accusatory or denunciatory voices and /or
experiences threatening visual hallucinations
7. Work and Activities
0= No difficulty
1= Thoughts and feelings of incapacity, fatigue or
weakness related to activities; work or hobbies
2= Loss of interest in activity; hobbies or work- either
directly reported by patient, or indirect in
listlessness, indecision and vacillation (feels he has
to push self to work or activities
3= Decrease in actual time spent in activities or
decrease in productivity
4= Stopped working because of present illness
8. Retardation: psychomotor
[slowness of thought and speech; impaired ability to
concentration decreased motor activity]
0= Normal speech and thought
1= Slight retardation at interview
2= Obvious retardation at interview
3= Interview difficult
4= Complete stupor
Anxiety (psychological)
0= No difficulty
1= Subjective tension and irritability
2= Worrying about minor matters
3= Apprehensive attitude apparent in face or speech
4= Fears expressed without questioning
Somatic Symptoms General
0= None
1= Heaviness in limbs, back or head.
Backaches headache, muscle aches. Loss
of energy and fatigability
2= any clear cut symptom rates 2
NOTE: this item may be less useful in
symptomatic HIV patients
Set protocol
• Give scale before starting treatment
• Give scale at intervals after starting
antidepressants and /or psychotherapy