The Treatment of Mood and Anxiety Disorders in HIV

Marshall Forstein, MDAssociate Professor of Psychiatry

Harvard Medical SchoolChair, Steering Committee on HIV Psychiatry

American Psychiatric Association

Disclosures

• Nothing to disclose

Mood Disorder due to a General Medical ConditionSubstance-Induced Mood DisorderMajor Depression

DemoralizationAdjustment Disorder

Sub-syndromal Major Depression

Dysthymia

“Minor Depression”“Depressive Personality”

Grief SadnessDisillusionmentDespondency

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 60%Substance Use Disorders 50%Dysthymic Disorder 25%Anxiety Disorders 25%

McDaniel et al., 1999

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

TIME OF AIDS

MONTHS BEFORE AND AFTER AIDS

0

10

20

-48 -36 -24 -12 6 18

Depression as AIDS DevelopsPE

RC

ENT

DEP

RES

SED

Lyketsos et. al., 1995

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 GenPsychiatry 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 Pract2003, 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 Pract2003, 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 high-

risk behaviors and antiretroviral non-adherence.

• 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):S5-47-S5-50.  

• 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 12.3 %–PTSD 10.4 %–GAD 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 anxiety-inducing 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 Activities0= 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= None1= 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