depression: dante vs. the dsm iv

Depression Among People with HIV Infection

Francine Cournos, M.D.Professor of Clinical Psychiatry, Columbia UniversityPrincipal Investigator, New York/New Jersey AETC

[email protected]

There are no relationships to disclose.

June 2009

Depression: Dante vs. the DSM IV

Dante:

“I did not dieBut yet I lost life’s breathImagine for yourself what I becameDeprived at once of both my life and death”

Dante’s InfernoTranslation by John Ciardi

Depression: Dante vs. the DSM IV

DSM IV Categories:

• Major depression – severe sx + ≥ 2 weeks • Dysthymic disorder – moderate sx ≥ 2 years • Bipolar disorders

- Bipolar 1 – Major depression + mania- Bipolar 2 – Major depression + hypomania- Related disorders

- Cyclothymia- Borderline Personality Disorder?

• Adjustment disorder with depressed mood• Sub-threshold depressive symptoms

Major Depression: Key Points

• Depression is a physical and a mental illness

• Depression frequently presents in primary care

• Depression is very common among HIV+ people

• Depression is associated with increased morbidity and mortality among HIV+ people (and for other illnesses)

• There are effective treatments for depression, but many depressed HIV+ people never receive them

American Psychiatric Association Practice Guidelines and other reference documents www.psych.org

RAND HCSUS Study:2,864 HIV-positive Medical Patients

Any Psychiatric Disorder: 48%• Major depression 36% • Dysthymia 27%• Generalized anxiety disorder 16%• Panic attack 11%• Drug dependence 13%• Problematic alcohol use 19%

Bing et al Arch. Gen. Psych. 2001

Later studies showed elevated rates of PTSD. Israelski et al, AIDS Care, 2007.

RAND HCSUS Study:1,489 HIV-positive Medical Patients

• 27% took psychotropic medication :

– 21% antidepressants– 17% anxiolytics– 5% antipsychotics– 3% psychostimulants

• About half of patients with depressive disorders did not receive antidepressants—African-Americans were overrepresented.

• Depression is therefore common and undertreated among HIV positive people in medical treatment.

Vitiello, et al, AJP, 2003

– Mortality predictors: chronic depression, CD4 count, HAART duration, age

– After adjusting for all other variables, women with chronic depressive symptoms were twice as likely to die as women with limited or no depressive symptoms

Depression and Mortality inDepression and Mortality inHIV+ WomenHIV+ Women

HERS cohort (Ickovics et al JAMA 2001): 765 HIV+ women at 4 HERS cohort (Ickovics et al JAMA 2001): 765 HIV+ women at 4 sites followed for up to 7 yearssites followed for up to 7 years

WIHS cohort: 2,059 HIV + women

• Replicated HERS results: Chronic depressive symptoms associated with AIDS mortality (N = 1,716; Cook et al, AJPH, 2004)

• Depression + illicit drug use, or recent drug use alone, associated with decreased HAART utilization (N = 1,668; Cook et al, JAIDS, 2002; N=1710; Cook, et al, Drug and Alcohol Dependence, 2007)

Depression and Mortality inDepression and Mortality inHIV+ WomenHIV+ Women

The Effect of Depression Treatment on HIV Medical Outcomes

• Use of antidepressants + MH therapy, or MH therapy alone, associated with increased HAART utilization (N = 1,371; Cook, et al, AIDS Care, 2006)

• Depression significantly worsens HAART adherence and HIV viral control. Compliant SSRI use is associated with improved HIV adherence and laboratory parameters (CD4 cell count and viral load). (N= 3,359; Horberg, et al, JAIDS, 2008)

• Depression (and substance use disorders) are associated with non-adherence to HAART

• Controlling for adherence, depression remains associated with more rapid progression of HIV and increased morbidity and mortality

• The treatment of depression improves medical outcomes

• The diagnosis and treatment of depression is an essential component of HIV care

Summary: Depression and HIV Summary: Depression and HIV ProgressionProgression

Over the last two weeks how often have you been bothered by any of the following problems:

Little interest or pleasure in doing things.– 0=Not at all– 1=Several days– 2=More than half the days– 3=Nearly every day

Feeling down, depressed or hopeless– 0=Not at all– 1=Several days– 2=More than half the days– 3=Nearly every day

The higher the score the more likely the patient has depressive disorderKroenke et al, Med Care, 2003

Screening for Depression:Screening for Depression:PRIME-MD PHQ2PRIME-MD PHQ2

Completed Suicide: A Fatal Outcome of Depression(General Population)

Lifetime rate of completed suicide for major affective disorders = 10-15%

Risk Factors White, male, older, single, unemployed, recent loss, access to lethal weapons

Previous history of suicide attempts, family history of suicide, victim of abuse

In addition to depressive symptoms, severe anxiety, psychotic symptoms, personality disorders, substance use, poor impulse control, detailed suicide plan

Severe medical illness especially with loss of functioning or intractable pain


Qestions for Discussing Suicide

Questions:-Do you feel unhappy and hopeless?-Do you feel unable to face each day?-Do you feel life is a burden?-Do you feel life is not worth living?-Do you feel like committing suicide?

Further questions:

-Have you made any plans to end your life?-How are you planning to do it?-Do you have the means to carry out suicide in your possession (pills/guns/other method)?-Have you considered when to do it?


TREATING DEPRESSION

Barriers to Treating Depression

• Patient Level: stigma of mental illness; desire to be strong and tough; there’s nothing wrong

• Intervention Level: the side effects of antidepressants manifest before the therapeutic effects

• Provider Level: failure to screen, detect, discuss, treat

• System Level: limited funding/availability of mental health services; lack of provider training


Treatment of Depression inPeople with HIV

Modify contributing factors

Psychotherapies

Psychopharmacology

Inpatient care (suicide risk, medical work-up, grave disability)

ECT

Experimental brain stimulation treatmentsAmerican Psychiatric Association Practice Guidelines and other reference documents www.psych.org

Depression:Modify Contributing Factors

• Diagnose and treat underlying medical illness

• Attempt to reduce the impact of medication side effects and use of substances

• Address psychosocial problemsAmerican Psychiatric Association Practice Guidelines and other reference documents www.psych.org

Brief Manualized Evidenced-Based Psychotherapies for Depression

• Cognitive behavioral therapy (CBT) (negative automatic thoughts)

• Interpersonal psychotherapy (IPT)(interpersonal difficulties)

• Others (some include psychodynamic strategies)American Psychiatric Association Practice Guidelines and other reference documents www.psych.org

Depression: When to Refer for Urgent Psychiatric Evaluation

• Patient is suicidal and/or has just made a suicide attempt

• Patient has symptoms of psychosis or severe agitation (but rule out delirium)

• Patient has mixed depression and mania

Agents Used for Depression in Patients with HIV

• Antidepressants– SSRIs– SNRIs– TCA (tricyclic antidepressants ) – Other antidepressants

• Psychostimulants

• Hormonal treatment—check for / treat testosterone levels in men and women


Antidepressants: SSRIs

• In general, SSRIs are well tolerated, safe, and have lower rates of drug discontinuation in studies with HIV-infected patients – all have equal efficacy

• SSRIs have proven efficacy in clinical trials with HIV+ depressed patients

• Drug interactions need to be considered with fluoxetine and paroxetine

• Side effects: nausea, jitteriness, weight loss, insomnia, sexual dysfunction


Antidepressants: SSRIs

• Sertraline (Zoloft) 25 - 200 mg/day• Escitalopram (Lexapro) 10 – 20 mg/day• Citalopram (Celexa) 20 - 40 mg/day)• Fluoxetine (Prozac)* 10 - 60 mg/day• Paroxetine (Paxil)* 10 - 60 mg/day

*More likely to cause drug interactions


Antidepressants: SNRIs

• Venlafaxine (Effexor) XR 75-300 mg qd– useful in SSRI nonresponders – extended release form preferable– may decrease indinavir levels - significance unknown

• Mirtazapine (Remeron) 15-45 mg qHS– very useful in patients with insomnia

• Duloxetine (Cymbalta) 20-60 mg qd– effective for symptoms of physical pain associated with depression– indicated for diabetic neuropathy

• Desvenlafaxine (Pristiq) 50mg- extended release


Wainberg, et al. Psychiatric Medications and HIV Antiretrovirals: A Guide to Interactions for Clinicians, second edition, New York/New Jersey AIDS Education & Training Center, HRSA, 2008.

Tricyclic Antidepressants: Potential Useful Properties

• Anti-diarrhea

• Sedation

• Anti-neuropathic pain

• Can monitor correct dose by blood levels: – imipramine, desipramine, nortriptyline


Tricyclic Antidepressant / Antiretroviral Drug Interactions

• Tricyclics (TCAs) are metabolized principally by CYP 2D6

• Ritonavir is a moderate inhibitor of CYP 2D6 & and may cause higher blood levels of TCAs

• TCAs can delay cardiac conduction and cause arrhythmias, especially at high levels

• EKG and plasma TCA monitoring is recommended when these drugs are co-

administered with ritonavir or other inhibitors of 2D6

• TCAs are dangerous in overdose--avoid giving large quantities to suicidal patients


Other Antidepressants

• Trazadone (Desyrel)– good in low doses for sleep– infrequently, arrhythmias and priaprism occur– levels may be elevated by PIs

• Bupropion (Wellbutrin, Zyban)– often chosen for low sexual side effects– may cause anxiety or insomnia– levels may be increased by efavirenz and protease inhibitors



Bipolar Depression

• Check for history of mania or hypomania (elevated/irritable mood, decreased need for sleep, high energy, racing thoughts, pressured speech, self-importance, risk taking behavior)

• Mood stabilizers are the treatment of choice

• Giving antidepressants alone can precipitate mania


Mood Stabilizers: Lithium and Anticonvulsants with an Approved Indication

• Lithium carbonate (Eskalith, Lithobid)– Use in lower doses or avoid with renal disease

• Divalproex sodium (Depakote)– Can cause severe liver toxicity– Can increase zidovudine levels – dosage change not recommended but monitor for toxicity

• Valproic acid (Depakene)– Can cause severe liver toxicity– Can increase zidovudine levels – dosage

change not recommended but monitor for toxicity



Mood Stabilizers: Anticonsulsants with an Approved Indication

• Lamotrigine (Lamictal)– Lamotrigine levels may be markedly decreased by lopinavir/ritonavir

• Oxcarbazepine (Trileptal)

• Carbamazepine (Tegretol + others)– Avoid: may lower levels of PIs and NNRTIs

• Other anticonvulsants have been used but do not have an approved indication


Mood Stabilizers: Atypical Antipsychotics with an Approved Indication for Bipolar

Disorder

• Aripiprazole (Abilify)

• Olanzapine (Zyprexa)

• Quetiapine (Seroquel)

• Risperidone (Risperdal)

• Ziprasidone (Geodon)

Cautions: Interactions with PIs; metabolic complications


HIV and Depression: Other Considerations

• St. John’s Wort may lower levels of NNRTIs and protease inhibitors – caution patients (it’s natural, but so is arsenic)

• HCV is a common comorbidity in HIV infected people; HCV treatment (peginterferon alpha 2b + ribavirin) is associated with depression.



Educational Resources on HIV and Mental Health

• Local and national AETCs

• NYS AIDS Institute: www.hivguidelines.org

• American Psychiatric Association Office of HIV Psychiatry:www.psych.org/AIDS

AETC National Programs

• National Resource Center (FXB/UMDNJ)– Provides virtual library of online training resources

for adaptation to meet local training needs– www.aidsetc.org

• Warmline/PEPline (UCSF)– Telephone consultation for HIV clinical

management and post-exposure prophylaxis management

– Warmline: 800-933-3413 PEPline: 888-448-4911

To schedule a Psychiatric Consultation please contact James Satriano, PhD, [email protected]

OR 212/543-5591

To schedule a Training Activity, please contact Dusty Hackler, MA, at

[email protected] OR 212/543-6537

OR visit us on the web at:www.columbia.edu/~fc15/

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