1. 1 Key Psychiatric Aspects of AIDS Sari Gilman Aronson, M.D.

2. 2 HIV And The Nervous System Readily enters the brain through macrophages Leads to neuronal damage and loss Neurobiological pathway similar to that seen in stroke and trauma Activation of NMDA-glutamate receptors and voltage-dependent calcium channels

3. 3 Psychosis Early in the course of HIV infection: may be the initial manifestation of HIV but more likely to be from another cause (often substance intoxication/withdrawal) Later onset: direct damage of the CNS from the HIV virus or herald of an underlying secondary CNS disorder Patients with psychosis have a higher mortality rate

4. 4 Delirium Common in hospitalized patients Large differential diagnosis including HIV infection, opportunistic infection, neoplasm, medication side effects, substance intoxication/withdrawal Eliminate inciting factors

5. 5 Antipsychotic Medications Higher incidence of extrapyramidal side effects in this population (seen with both high and low potency medications) May be due to underlying neuronal damage in the basal ganglia Neuroleptic Malignant Syndrome can occur Tardive Dyskinesia may onset in as little as 6 weeks

6. 6 Antipsychotic Medications Newer antispychotic medications are associated with fewer serious side effects Clozapine blood levels may be increased by ritonavir, increasing the risk of seizures and hypotension Coadministration of pimozide and protease inhibitors is contraindicated due to risk of arrhythmia

7. 7 Substance Use Disorders Identify patients who are HIV- positive and have a substance use disorder Higher incidence of dementia and HIV medication non-compliance

8. 8 Substance Use Disorders Higher incidence of other psychiatric disorders in this population including manic-depressive disorder, depression, anxiety disorders, psychotic disorders, personality disorders Higher incidence of incarceration for drug-related crimes Treatment and supportive community services can assist a patient in attaining sobriety

9. 9 HIV and Sexual Abuse Sexual abuse is associated with an increased risk of HIV infection 43% of women (Zirler et al. 1996) and 35% of homosexual/bisexual men (Lenderking et al. 1997) who were either HIV positive or at risk of infection had a history of sexual abuse Adolescents who have been sexually abused are less likely to use condoms

10. 10 Depression Not a normative response to seroconversion or to living with HIV Prior depression is a robust risk factor for development of depression during the course of HIV Early episodes of depression usually reflect a premorbid mood disorder Prevalence is 4-22% in HIV-positive men and 2- 18% HIV-positive women

11. 11 Depression Rates of depression increase to about 25% in later symptomatic stages of AIDS (when complex immune dysregulation is present) Not necessarily associated with HIV dementia May reflect psychoactive effects of immune compounds on brain function

12. 12 Consequences of Depression Mental anguish, impaired quality of life, comorbid substance use disorders, suicide Continued risk behaviors for transmission of HIV Predictor of poor adherence to HIV treatment regimen Depression, independent of the severity of illness, predicts death in medically ill patients

13. 13 Is It Depression or Grief? Grieving patients do not feel worthless, guilty, or suicidal (they may have a passive wish for death) Grieving patients usually retain the capacity for pleasure Grief comes in waves rather than being more constant and unremitting Grieving patients can look forward to the future

14. 14 Diagnosis of Depression Single Question Screening Tool: Are you depressed?

15. 15 Diagnosis of Depression Two Question Screening Tool: 1.During the past month, have you felt down, depressed or hopeless? 2.During the past month, have you noticed that you have little interest or find little pleasure in doing things?

16. 16 Diagnosis of Depression Psychological symptoms: dysphoria, depressed mood, sadness, tearfulness, irritability, lack of pleasure, hopelessness, helplessness, worthlessness, social withdrawal, guilt, suicidal ideation Other indicators: intractable pain, excessive somatic preoccupation, disproportionate disability, poor cooperation or refusal of treatment Physician indicators: feelings of hopelessness, aversion, or lack of interest about the patient

17. 17 Treatment of Depression 16 weeks of Interpersonal Psychotherapy was as effective as Supportive Psychotherapy and imiprimine Antidepressant treatment improves symptoms in 70-80% patients with uncomplicated depression and 40-50% patients with depression complicated by psychiatric comorbidity and advanced AIDS (Lyketsos et al. 2001) SSRIs and bupropion better tolerated than tricyclic antidepressants

18. 18 Treatment of Depression Aggressively treat HIV infection, other underlying medical conditions, substance use disorders Select an antidepressant that has minimal drug-drug interactions and medication side effects Adherence to psychiatric care predicts better outcome

19. 19 Treatment of Depression SSRI metabolism, especially fluoxetine, can be inhibited by ritonavir, indinavir, and grapefruit juice Mediated by CYP2D6 2D6 deficiency identified in 8.5% African Americans, 5-8% Caucasians, and 2-10% Asians Serotonin syndrome can result from elevated SSRI levels

20. 20 Treatment of Depression Easiest SSRIs to use in this population are sertraline and citalopram Mirtazapine has few drug-drug interactions but is more difficult to tolerate Bupropion useful in patients with low seizure risk Nortriptylline has a clinically useful therapeutic window Stimulants may be used in terminally ill patients

21. 21 Anxiety disorders Anxiety disorders are less well studied than mood disorders in this population “Screening diagnoses”: 11% with panic disorder and 26% with generalized anxiety disorder in 2,864 patients with HIV (Sherbourne CD et al. 2000) Important to distinguish anxiety related to an unresolved issue or problem from an anxiety disorder (treatment may differ)

22. 22 Treatment of Anxiety An unresolved issue may give rise to anxiety until an individual faces and begins to address the problem. A referral for psychotherapy is appropriate when the problem is complex or the patient has few skills and strengths to draw upon. Medication treatment can include antidepressants, buspirone, and benzodiazepines with the choice depending on the specific circumstances and concerns.

23. 23 Psychological Issues Importance of the physician-patient relationship Getting tested Emotional responses to diagnosis Fear of disability, suffering and death Who to tell (loved ones, children, sexual partners, friends, coworkers)

24. 24 Psychological Issues How and when to break the news to others Living with a terminal disease Searching for more meaning in life, including relationships, work, and activities Facing the possibility of death Planning for death