1. Depression Among People with HIV Infection Francine Cournos, M.D. Professor of Clinical Psychiatry, Columbia University Principal Investigator, New York/New Jersey AETC fc15@columbia.edu There are no relationships to disclose. June 2009

2. Depression: Dante vs. the DSM IV Dante : “I did not die But yet I lost life’s breath Imagine for yourself what I became Deprived at once of both my life and death” Dante’s Inferno Translation by John Ciardi

3. 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

4. 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 www.psych.org

5. 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.

6. 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

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

8. 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 in HIV+ Women

9. 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 )

10. 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 Progression

11. Over the last two weeks how often have you been bothered by any of the following problems: uLittle interest or pleasure in doing things. – 0=Not at all – 1=Several days – 2=More than half the days – 3=Nearly every day uFeeling 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 disorder Kroenke et al, Med Care, 2003 Screening for Depression: PRIME-MD PHQ2

12. Completed Suicide: A Fatal Outcome of Depression (General Population) Lifetime rate of completed suicide for major affective disorders = 10-15% Risk Factors u White, male, older, single, unemployed, recent loss, access to lethal weapons u Previous history of suicide attempts, family history of suicide, victim of abuse u In addition to depressive symptoms, severe anxiety, psychotic symptoms, personality disorders, substance use, poor impulse control, detailed suicide plan u Severe medical illness especially with loss of functioning or intractable pain American Psychiatric Association Practice Guidelines and other reference documents www.psych.org www.psych.org

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

14. TREATING DEPRESSION

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

16. Treatment of Depression in People with HIV uModify contributing factors uPsychotherapies uPsychopharmacology uInpatient care (suicide risk, medical work-up, grave disability) uECT uExperimental brain stimulation treatments American Psychiatric Association Practice Guidelines and other reference documents www.psych.org www.psych.org

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

18. 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 www.psych.org

19. 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

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

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

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

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

24. Tricyclic Antidepressants: Potential Useful Properties Anti-diarrhea Sedation Anti-neuropathic pain Can monitor correct dose by blood levels: – imipramine, desipramine, nortriptyline American Psychiatric Association Practice Guidelines and other reference documents www.psych.orgwww.psych.org

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

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

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

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

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

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

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

32. Educational Resources on HIV and Mental Health Local and national AETCs NYS AIDS Institute: www.hivguidelines.org www.hivguidelines.org American Psychiatric Association Office of HIV Psychiatry: www.psych.org/AIDS www.psych.org/AIDS

33. 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

34. To schedule a Psychiatric Consultation please contact James Satriano, PhD, at SATRIAN@PI.CPMC.COLUMBIA.EDU OR 212/543-5591 To schedule a Training Activity, please contact Dusty Hackler, MA, at DRA2107@COLUMBIA.EDU OR 212/543-6537 OR visit us on the web at: www.columbia.edu/~fc15/