Common Mental Health Issues
in Patients with HIV
Francisco Fernandez, MD
Professor and Chair, USF Health Psychiatry
USF Morsani College of Medicine
Faculty, Florida/Caribbean AETC
Disclosure of Financial Relationships
This speaker has no significant financial
relationships with commercial entities to
disclose.
This speaker will discuss off-label use or an
investigational product during the program:
•
Use of stimulants and amantadine in cognitive disorders.
This slide set has been peer-reviewed to ensure that there are no
conflicts of interest represented in the presentation.
Psychiatric Illness in HIV
• Mental disorders are highly prevalent in HIV1 infection and AIDS
– Dual Diagnosis  coexisting substance abuse
and psychiatric disorders
– Triple Diagnosis  coexisting medical illness
with substance abuse and psychiatric disorders
– HIV-Associated Neurocognitive Disorders
(HAND)
DEPRESSION
Epidemiology of Depression in HIV
•
•
•
•
Depression is the most common mental
health disorder in HIV patients1
36% of adults patients receiving medical
care for HIV were depressed in the past 12
months2
Depression is the most common reason for
psychiatric referral
Rates of depression are highest among
injection drug users (IDU) and women
engaging in high risk behaviors3
1. Orlando et al., 2002; Komiti et al., 2003
2. HCSUS Bing et al., 2001;Galvan et al., 2002
3. Goodkin et al., 1996
HIV Mood Disorders: Completed Suicide
Study
Subjects
Findings
________________________________________________________
Marzuk 1992
AIDS vs others
36-66 x increase with AIDS
Kizer 1992
AIDS vs others
17 x increase with AIDS
Cote 1992
72,000 U.S. suicides 7.4 x increase with AIDS
Marzuk 1997
HIV+ vs others
2-3 x increase with HIV <
suicide risk factors (RFs)
Types of Depressive Disorders vs Major
Depressive Disorder (MDD)
• Psychiatric Differential
Diagnoses
– Mild depression (or minor
depression)
– Dysthymia
– Bipolar disorder, currently
depressed
– Adjustment disorder with
depressed mood
• Medical Differential
Diagnoses
– Central Nervous System (CNS)
HIV cognitive disorders [Minor
Cognitive Motor Disorder
(MCMD) & HIV-associated
dementia (HAD)]
– CNS opportunistic illnesses
and cancers
– Substance abuse
– Medication effects
– Endocrine abnormalities
(hypogonadism, adrenal
insufficiency)
How to Identify MDD in a Primary Care Setting?
• Fewer than 50% of patients with MDD are
identified by their primary care providers (PCPs)1
• Two simple questions to ask:
1. During the past two weeks have you felt
sad, down or depressed most of the day,
nearly every day?
2. During the past two weeks have you been
less interested in most things or less able to
enjoy the things that you used to enjoy most of
the time?
1. Asch et al., 2003
Screening and Diagnostic Tools
• Screening: PHQ-2
• Diagnosis: PHQ-9; Depressive disorder module of
the SCID or MINI-6
• PHQ-2 and PHQ-9 readily available at no cost
• PHQ-9 reliable diagnostic tool. Also provides
severity parameters which can help decide the
action plan
PHQ-2: Patient Health Questionaire-2 Kroenke et al. Med Care 2003; 41(11):1284-92
PHQ-9:Patient Health Questionaire-9 Kroenke et al. J GenIntern Med, 2001;16(9)606-13
SCID: Structured Clinical Interview for DSM Disorders www.cumc.columbia.edu/dept/scid/index.html
MINI-6: The Mini-International Neuropyschiatric Interview www.medical-outcomes.com
First Line Treatment for MDD
• Psychotherapies: “talk therapy” like cognitive behavioral
therapy (CBT), interpersonal therapy (IT), psychodynamic
therapy, etc.
• Medications: antidepressants [selective serotonin
reuptake inhibitors (SSRIs), serotonin–norepinephrine
reuptake inhibitors (SNRIs), tricyclic antidepressants
(TCAs), monoamine oxidase inhibitors (MAOIs), others]
• Neurostimulation
– Electroconvulsive therapy (ECT)
– Transcranial Magnetic Stimulation
• Combination of psychotherapy and medication
Selecting an Antidepressant:
Potential for Drug-Drug Interactions
Low P450 blockers:
Likely to have little impact on
metabolism of other drugs
Bupropion
Citalopram
Mirtazapine
Venlafaxine
Sertraline
Potent P450 blockers:
Potential for strong
impact on metabolism of
other drugs
Methylphenidate
Paroxetine
Fluoxetine
Fluvoxamine
Crewe HK, et al. Br J Clin Pharmacol. 1992;34:262-265. Nemeroff CB, et al. Am J Psychiatry. 1996;153:311-320. von Moltke
LL, et al. J Clin Psychopharmacol. 1994;14:1-4. von Motkle LL, et al. Clin Pharmacokinet. 1995;20(suppl 1):33.
When to Refer to a Mental Health Specialist
• Acute risk of suicide
• Psychotic symptoms, signs of dementia
or bipolar disorder
• Patients with limited or non-response to
treatment
• PCP level of comfort
ANXIETY
Prevalence of Anxiety
• Anxiety disorders are the most prevalent
psychiatric disorders in the general population
(Lifetime prevalence 25%)1
• In HIV infected individuals the prevalence rate of
anxiety disorders can be as high as 38%2
• Cohen et al. (2001) found that in an urban U.S.
HIV clinic anxiety was present in up to 70% of
patients
1. Kessler et al., 1994, 2005
2. Elliott, 1998
Anxiety in HIV Patients
• Anxiety as a normal response
• Anxiety as a disorder
– Primary
• Adjustment, panic disorder, post-traumatic stress disorder
(PTSD), generalized anxiety disorder (GAD), social anxiety
disorder (SAD), obsessive compulsive disorder (OCD)
– Secondary Anxiety
• AIDS-associated illness, other medical illnesses
• Anxiety as a side effect
– Secondary to medications
• like HIV or hepatitis C virus (HCV) treatments (e.g.,
efavirenz, steroids, isoniazid, interferon)
– Secondary to street drugs (stimulants, alcohol, etc)
Screening and Diagnostic Tools
• Screening: Hospital Depression and
Anxiety Scale (HADS); Hamilton Anxiety
Scale (HAM-A)
• Diagnosis: Specific modules of the
SCID or MINI-6; specific disorder scales
• Screening questions
Treatment Approaches
• Overall, very similar to major depressive disorder
• Psychotherapies: “talk therapy” like CBT (cognitive
behavioral therapy), IT (interpersonal therapy),
psychodynamic therapy, support groups, etc.
• Medications: antidepressants (SSRIs, SNRIs, TCAs,
MAOIs, other), benzodiazepines.
– In substance use disorders (SUD)  buspirone,
antiepileptic drugs [(AEDs) tiagabine, gabapentin]
• Combination of psychotherapy and medication
SUBSTANCE USE, ABUSE,
DEPENDENCE
Prevalence of Substance Use Disorders (SUD)
in HIV
• SUD have a higher prevalence in HIV patients
compared to the general population
• Bidirectional risk relationship between HIV and
SUD1,2,3,4
• Most prevalent: alcohol (EtOH), cocaine, opiates
– 25-60% life time prevalence of alcohol abuse or
dependence in HIV patients, a 2-4 fold increase
compared to the general population 5,6,7,8
– 23-56 % lifetime prevalence of other drug use
disorders in HIV subjects, a 4-5 fold increase
compared to the general population 5,6,7,8
1. Harvey and Spigner, 1995; 2. Katz et al., 2000; 3. Stall and Purcell, 2000; 4. Wingood and DiClemente,
1998; 5. Rabkin, 1996; 6. Dew et al., 1997; 7. Ferrando et al., 1998; 8. Kessler et al., 1994
Impact of SUD on HIV
• In the U.S., SUD is the main driver of
HIV transmission [intravenous drugs
(IVD) leading]
• If untreated can result in poor treatment
outcomes
• Decreased adherence to combination
antiretroviral therapy (CART)
• Increased risk taking behaviors
• Increased medical and psychiatric
comorbidities
Recognizing SUD
• High suspicion is recommended given high
prevalence and bidirectional risk
– Should be asked at initial visit and at each follow
up
• Use screening instruments
• Use of urine drug screens (UDS)
• Generally more effective to have an open/
nonjudgmental approach when asking patients
• “Many persons who are ill may use drugs or alcohol to get
through tough times. What have you used to cope with
these difficult times?”
Treatment Options for SUD
• Medical treatment
– Detoxification – first step
•
•
•
•
Opiates methadone, buprenorphine, clonidine
Cocaine  symptomatic, dopamine (DA) agonists, naltrexone
ETOH  benzodiazepines, naltrexone
Nicotine  replacement therapy, bupropion, varenicline
– Maintenance: methadone, buprenorphine, DA agonists,
naltrexone, disulfiram, topiramate
• Topiramate  signal across all appetitive drives
• Therapeutic Strategies
– Motivational enhancement therapy, CBT
– 12 Steps facilitation [Alcoholics Anonymous (AA), Narcotics
Anonymous (NA)]
– Residential treatment
HIV Associated Neurocognitive Disorder
(HAND)
• HIV-neurocognitive impairment continues to be an
important problem
• HIV-neurocognitive impairment can be easily
recognized
– Neurodiagnostic tests can improve confidence in the
diagnosis and exclude neoplasms and opportunistic
infections
• HIV-neurocognitive impairment can be treated
– Primary therapy  antiretroviral therapy (ART) that better
distributes into the CNS leads to better outcomes
– Secondary anti-inflammatory therapies
– Palliative therapies
Criteria for HAND
Acquired
Impairment in ≥
2 Cognitive
Abilities
Interferes with
Daily
Functioning
No Preexisting
Cause
Delirium
Absent
Asymptomatic
Neurocognitive
Impairment (ANI)
Mild
No
●
●
Mild Neurocognitive
Disorder (MND)
Mild
Mild
●
●
HIV-Associated
Dementia (HAD)
Marked
Marked
●
●
Changing Prevalence of HAND
•
•
•
•
Highly active antiretroviral therapy (HAART)
HIV-associated dementia (HAD)
Motor neuron disease (MND)
Asymptomatic neurocognitive impairment (ANI)
Modified from Heaton R., et al: HIV-associated neurocognitive disorders (HAND) persist in the era of potent
antiretroviral therapy: The CHARTER Study; and Heaton R., J Int Neuropsychol Soc. May 1995;1(3):231-251.
Screening for HAND by Self Report
Medical Outcomes Study (MOS) HIV Cognitive Functional
Status Scale
1. Difficulty reasoning and solving problems?
2. Forget things that happened recently?
3. Trouble keeping your attention on any activity for long?
4. Difficulty doing activities involving concentration and thinking?
Validated against neuropsychological (NP) overall performance
Knippels, Goodkin, Weiss, et al., AIDS, 2002;16:259-267
Pharmacotherapy of HAND
• Primary Treatments
– Antiretroviral medications
• Secondary Treatments
– Immunostimulants and inflammatory mediators
• Palliative Treatments
– Psychotropic agents
– Nutritional
Neuro-AIDS Can Be Treated Higher CNS PenetrationEffectiveness (CPE) Scores and Lower Viral Loads in
Cerebrospinal Fluid (CSF)
Letendre et al, Archives of Neurology, 2008
Antiretroviral Effectiveness
CNS Penetration-Effectiveness Score
Nucleoside Reverse
Transcriptase Inhibitors
(NRTIs)
Non-Nucleoside Reverse
Transcriptase Inhibitors
(NNRTIs)
Protease Inhibitors (PIs)
Fusion
Inhibitors
Good
Fair
Poor
1
0.5
0
Abacavir
Zidovudine
Emtricitabine
Lamivudine
Stavudine
Delavirdine
Nevirapine
Efavirenz
Indinavir
Indinavir-r
Lopinavir-r
Amprenavir-r
Atazanavir
Atazanavir-r
Darunavir-r
Didanosine
Tenofovir
Zalcitabine
Amprenavir
Nelfinavir
Ritonavir
Saquinavir
Saquinavir-r
Tipranavir-r
Enfuvirtide
LeTendre S., et al, Arch Neurol., 2007
From JC McArthur, MBBS, MPH, at 13th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA.
Relevance of ART, CNS Penetrance &
HAND
• Despite HAART’s effect on incidence, prevalence of
HAND remains high, and pathological evidence of CNS
infection persists
(Heaton R., Neurology, 2010; Vago L., AIDS, 2002)
• HAART can reverse neurocognitive deficits, but at best,
it is usually only partial
– ? Functional performance change
(Tozzi V., AIDS, 2002)
• Long term aviremic HIV+ individuals have high rate of
HAND  MND
(Simioni P., AIDS 2009)
How Best To Treat HAND in 2012
• Primary therapy  suppress HIV RNA viral load
systemically and in CSF
• Consider secondary pharmacotherapy
• Control all controllables
–
–
–
–
Anxiety and depression, drug and alcohol use
Co-infections (HCV)
Medication side-effects
Lab indices (anemia, thyroid, B12, glucose, cholesterol)
• Trial of dopamine agonists
– Stimulants
– Amantadine
Summary
• Depression, anxiety, SUD, HAND, and HIV are highly
comorbid
– Once they combine, there is synergy in the overall effect
on the affected individuals and their treatments
– Careful medical and neurobehavioral evaluation is
required to rule out primary treatable CNS disease and
comorbid psychiatric disorders
– Effective treatment strategies are available for the
primary and secondary HIV manifestations
• The neuropsychiatric complications of the disease deserve
the same aggressive approach as that of the systemic
aspects of the disease
DANIEL
A Neuropsychiatric Case Study
Daniel
• Daniel is a 52-year-old man, HIV+ since 1996. He remains
asymptomatic. He also has hepatitis C.
• 1996: CD4=212, viral load (VL)=182,000
• 1997: HAART – undetectable VL; CD4 ~ 600's.
• Drug holiday – 2004-06, resumed treatment 2007
• Current Meds: darunavir, etravirine, emtricitabine/tenofovir,
ritonavir
• High-level job, he is meticulous and dresses impeccably
• He is a “weekend warrior”
– Uses ecstasy and alcohol.
• For the last 9 months  low energy and some memory difficulties
• He thought this was stress-related; however, a vacation did not
help
Daniel – What is your presumptive diagnosis?
•
•
•
•
•
Adjustment disorder
ART resistance
Substance abuse
Cirrhosis
Depression
What would you like to do next?
A. Cognitive assessment
B. Complete blood count
(CBC), comprehensive
metabolic panel
(CMP), syphilis
serology, CD4, viral
load
C. Endocrine screen
D. CT-brain and/or MRI
E. All of the above
100%
A.
0%
0%
B.
C.
0%
0%
D.
E.
Daniel – Clinical & Lab Findings
• h/o recurrent depressive illness
• h/o relapsing alcoholism and ecstasy
abuse
• Liver enzymes and thyroid labs – within
normal limits (wnl)
• VL and CD4 - no changes
• CT Scan - wnl
• Testosterone – 120 ng/dl
What next?
A. Initiate low dose
citalopram
B. Hormone
replacement
therapy (HRT)
C. PRN lorazepam
D. End of life
Counseling
E. All of the above
100%
0%
A.
0%
B.
C.
0%
0%
D.
E.
Daniel – Recommendations
• Treat alcohol / ecstasy abuse
• HRT
– No improvement with testosterone
replacement in 4 to 6 weeks
• Start formal psychotropic agent
– Which would you choose?
Which psychotropic agent would you
choose?
A. Citalopram
(Celexa®)
B. Quetiapine
(Seroquel®)
C. Venlafaxine
(Effexor XR®)
D. Bupropion
(Wellbutrin XL®)
E. Topiramate
(Topamax®)
0%
A.
0%
0%
B.
C.
0%
0%
D.
E.
Daniel – follow up
• Daniel stops alcohol and ecstasy use
temporarily
• Testosterone replacement continues
• Venlafaxine 150 mg/day
• Initially his energy, memory and concentration
improve
• Complains of feeling depressed, hopeless,
anhedonic, isolates himself, poor appetite,
mild suicidal thoughts, interrupted sleep
What is your diagnosis now?
A. Adjustment disorder
with depressed mood
B. Substance-induced
mood disorder
C. Major depression –
recurrent
D. Bipolar depression
E. Acute stress
reaction/disorder
100%
0%
A.
0%
B.
C.
0%
0%
D.
E.
Daniel – MDD recurrent
• SNRI (liver protection, low drug-drug
interaction potential with ARVs, low
CNS side effects)
– Increase venlafaxine to 300 mg/daily
– Daniel’s depression improves, but
memory and concentration do not
What are his other diagnoses?
A. Residual
depression
B. Relapse on
alcohol and
ecstasy
C. Minor cognitivemotor disorder
D. Acute stress
disorder
E. Neurotoxicity
100%
0%
A.
0%
B.
C.
0%
0%
D.
E.
Daniel – 2 months later …
• Daniel shows very late to his
appointment – unusual for him
• He looks unkempt
• Seems distracted
What do we need to rule out?
A. Residual
depression
B. Relapse on
alcohol and
ecstasy
C. HIV-Associated
Dementia
D. Progression to
AIDS
E. Neurotoxicity
100%
0%
A.
0%
B.
C.
0%
0%
D.
E.
Daniel 2 months later …
•
•
•
•
•
Alcohol? None
Ecstasy? None
Depression? No
Testosterone? Normal
Liver Function Tests (LFTs), Thyroid and
HIV Labs – no changes
Now what?
A. Neuroimaging
B. Lumbar puncture
C. Neuropsychological
testing
D. Psychiatric
consultation
E. All of the above
100%
0%
A.
0%
B.
C.
0%
0%
D.
E.
Daniel – other considerations
•
•
•
•
•
•
Is Daniel taking other medications?
Other drugs?
Over the counter pills or vitamins?
Any new events?
None of these are present?
Now what?
Daniel – Work up results …
• Lumbar Puncture? Mild pleocytosis and elevated
protein.
• Neuro consult “minor cognitive abnormalities without
any focal neurological findings besides mild
neuropathy."
• Psychiatry “no residual depression, no active
substance use, Mini-Mental State Exam (MMSE)
25/30, slowing of information processing”
• Neuropsychological evaluation – attention and working
memory deficits. Slow motor activity and thinking
processes.
• MRI – reported as normal
• What does this mean? Diagnoses?
Daniel – Concluding
• Daniel, besides
– Hepatitis C, HIV, Hypogonadism
– Recurrent Major Depression, Alcohol/ecstasy
• MCMD vs HAD
• Anything else we need to address?
– Adherence
– Medication List
– Psychosocial
• Prognosis?
• What is your personal reaction as Daniel’s provider?
Daniel - Treatment
•
•
•
•
•
•
•
ARV that cross the Blood Brain Barrier
Avoid alcohol, drugs, sedating meds
Stimulants vs DA-agonists
Environmental Interventions
Rehabilitation
Family, work, friends
Support groups, education
Questions
Gracias!
• Francisco Fernandez, M.D.
• ffernand@health.usf.edu
• (813) 974-1437