RESOURCE GUIDE CHAPTER THREE PSYCHIATRY AND HIV/AIDS 52 MENTAL HEALTH, HIV/AIDS AND HCV COINFECTION Psychiatric Disorders Fact Sheet4 Psychiatric disorders are a barrier to medical care and adherence to medications, and several studies When it comes have found that depression, stress and trauma can lead to disease progression and increased to HIV/AIDS, mortality.5,6,7,8 The power of mental health mental health treatment to reduce depression and anxiety, improve adherence and HIV health outcomes and, matters. in turn, reduce the likelihood of death from AIDS- related causes speaks to the vital role of mental Diagnosis and health care in the web of HIV care. 8.9.10.11 treatment of People with serious mental illness are particularly mental health vulnerable to HIV infection as a result of the higher prevalence among this group of a variety of factors, issues are essential including poverty, homelessness, high-risk sexual to the physical activities, drug abuse, sexual abuse, and social marginalization. Estimates of HIV infection rates health and quality among people with mental illness in the United States vary widely from 3 percent to 23 percent; life for PWAs. of the average is about 7 percent. Their health outcomes remain poor.12 4 Information for this section is from: http://hab.hrsa.gov/publications/may2009/default.htm 5 Treisman GJ, Angelino AF, Hutton HE. Psychiatric issues in the management of patients with HIV infection. JAMA. 2001;286:2857–64. 3Lesser, 2008. 6 Lesser, 2008. 7 Starace F, Ammassari A, Trotta MP, et al. Depression is a risk factor for suboptimal adherence to highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2002;31(Suppl 3):S136–9. 8 Whetten K, Reif S, Whetten R, et al. Trauma, mental health, distrust, and stigma among HIV-positive persons: implications for effective care. Psychosom Med. 2008;70:531–8. 8. Cook JA, Grey D, Burke J, et al. Depressive symptoms and AIDS-related mortality among a multisite cohort of HIV- positive women. Am J Public Health. 2004;94:1133–40. 9. Kalichman SC. Co-occurrence of treatment nonadherence and continued HIV transmission risk behaviors: implications for positive prevention interventions. Psychosom Med. 2008;70:593–7. 10. Carrico AW, Antoni MH. Effects of psychological interventions on neuroendocrine hormone regulation and immune status in HIV-positive persons: a review of randomized controlled trials. Psychosom Med. 2008;70:575–84. 11. Horberg MA, Silverberg MJ, Hurley LB, et al. Effects of depression and selective serotonin reuptake inhibitor use on adherence to highly active antiretroviral therapy on clinical outcomes in HIV-infected patients. J Acquir Immun Defic Syndr. 2008;47:384–90. 12. Weiser SD, Wolfe WR, Bangsberg DR. The HIV epidemic among individuals with mental illness in the United States. Curr Infect Dis Rep. 2004;6:404–10 53 RESOURCE GUIDE HIV/AIDS PSYCHIATRY A Review of Syndromes and Treatment Stephen J. Fitzpatrick MD, FRCPC HIV/AIDS PSYCHIATRY Consultation-Liaison Psychiatry A Review of Syndromes St. Paul’s Hospital, Vancouver, BC and Treatment: Presentation Clinical Associate Professor Department of Psychiatry as presented by Stephen Faculty of Medicine Fitzpatrick as the Keynote University of British Columbia Address Director Program of Consultation-Liaison Psychiatry Department of Psychiatry University of British Columbia 54 MENTAL HEALTH, HIV/AIDS AND HCV COINFECTION •TO UNDERSTAND THE •HUMAN RETROVIRUS IDENTIFIED IN BIOLOGY OF HIV IN THE CNS 1984 •RNA PLUS REVERSE TRANSCRIPTASE •TO REVIEW COMMON ENZYME PSYCHIATRIC DISORDERS ASSOCIATED WITH HIV •RAPID REPLICATION AND GENETIC MUTATION DISEASE AND THEIR TREATMENT •INFECTS BLOOD T-HELPER (CD4) LYMPHOCYTES, •TO REVIEW IMPORTANT LYMPHOID TISSUE AND CNS INTERACTIONS BETWEEN PSYCHOTROPIC AND ANTIRETROVIRAL MEDICATIONS 1 2 •PSYCHIATRIC •SEXUAL BEHAVIOURS WITH MOOD DISORDERS EXCHANGE OF BODY BIPOLAR, DEPRESSION, DYSTHYMIA FLUIDS PSYCHOTIC DISORDERS SCHIZOPHRENIA, SCHIZOAFFECTIVE •INJECTION DRUG USE PERSONALITY DISORDERS •BLOOD TRANSFUSION BNOARRCDIESRSLISINTEIC, ,H DISETPREINODNEICN,T , ANTISOCIAL •PERINATAL •SUBSTANCE USE / ABUSE / DEPENDENCE •SOCIAL / GEOGRAPHICAL / FINANCIAL FACTORS 3 4 55 RESOURCE GUIDE •3-6 WEEKS AFTER INFECTION •USUALLY LASTS FOR YEARS •BURST OF REPLICATION AND WIDE •BALANCE BETWEEN VIRUS DISSEMINATION OF VIRUS REPLICATION/INFECTION OF NEW CD4 CELLS VS PRODUCTION OF NEW CD4 CELLS •NON-SPECIFIC FLU-LIKE SYMPTOMS • 10 BILLION VIRUS PARTICLES PRODUCED •BODY MOUNTS MASSIVE IMMUNE RESPONSE DHOAIULYRS- PLASMA VIRUS HALF-LIFE OF 6 PRODUCES ANTIBODIES POSITIVE SEROCONVERSION AND POSITIVE HIV TEST •NOT A DORMANT STATE 5 6 Biology HIV creates chronic, progressive, inflammatory CNS disease Viral load, CD4 count provide a ‗cross-sectional •PRODUCTION CANNOT KEEP UP WITH snapshot‘ DESTRUCTION AND REPLICATION Serum and CSF viral dynamics may differ •FATIGUED IMMUNE RESPONSE SYSTEM Neuronal dysfunction –neurotoxins, chronic inflammatory state, cytokine and chemokine •CD4 < 200 release Apoptosis ( programmed cell death ) in sub-cortical •OPPORTUNISTIC INFECTIONS ARISE white matter, basal ganglia and frontal lobes 7 8 56 MENTAL HEALTH, HIV/AIDS AND HCV COINFECTION ANTIVIRAL THERAPY TARGETS DURING THE HIV REPLICATION CYCLE •EARLY PENETRATION INTO CNS (DAY 16) VIA MACROPHAGES ACROSS BLOOD-BRAIN BARRIER • VIRUS INFECTS MACROPHAGES AND MICROGLIAL CELLS, NOT NEURONS •NEUROTOXINS AND CHRONIC INFLAMMATORY RESPONSE NEURONAL DYSFUNCTION/DEATH •CNS IS A RESERVOIR WITH SEPARATE VIRAL DYNAMICS FROM PERIPHERAL BLOOD •BRAIN/LIMBIC SYSTEM DYSFUNCTION MOOD SYMPTOMS, SLEEP DISTURBANCE, MEMORY AND CONCENTRATION COMPLAINTS, MENTAL SLOWING, AGITATION 9 10 • DRUG-DRUG INTERACTIONS • NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS NRTI’s •LIVER TOXICITY • NUCLEOTIDE REVERSE TRANSCRIPTASE •DEGREE OF DRUG CNS PENETRATION INHIBITORS NtRTI’s •CO-INFECTION WITH HEPATITIS C • PROTEASE INHIBITORS INTERFERON TREATMENT PI’s •SIDE EFFECTS OF ARV THERAPY • NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS NNRTI’s • RIBONUCLEOTIDE REDUCTASE INHIBITORS 11 12 57 RESOURCE GUIDE  Combination therapy most popular One pill = 3 or 4 ARV’s Atripla Truvada Kivexa Raltegravir Maraviroc Etravirine 12 14 Challenges -PROTEASE INHIBITORS GENERALLY INHIBIT METABOLISM OF  What am I treating? PSYCHOTROPIC MEDS, ESPECIALLY BUPROPRION,  What does the patient report as a problem? BENZODIAZEPINES AND CLOZAPINE  What do other people report as a problem? -MONITOR DOSES, SIDE-EFFECTS, CLINICAL RESPONSE  Adherence to ARV RX -RITONAVIR (NORVIR)) AND RITONAVIR / LOPINAVIR (KALETRA)  Substances REQUIRES MOST MONITORING  Drug interactions -EFAVIRENZ (SUSTIVA) HAS UP TO 34% CNS PENETRATION  Delirium –-FREQUENT CNS / PSYCHIATRIC MANIFESTATIONS –-CAN HAVE ACUTE ONSET OF MOOD SHIFT, AGITATION,  Vague symptoms SUICIDALITY  What is the problem? 15 16 58 MENTAL HEALTH, HIV/AIDS AND HCV COINFECTION – SLEEP DISORDERS – ADJUSTMENT DISORDERS – COGNITIVE DISORDERS – ANXIETY DISORDERS •HIV -ASSOCIATED MINOR COGNITIVE MOTOR DISORDER H-MCMD – MOOD DISORDERS •HIV -ASSOCIATED DEMENTIA COMPLEX H-ADC •DEPRESSION – SUBSTANCE ABUSE / DEPENDENCE •MANIA / HYPOMANIA – DELIRIUM – PSYCHOTIC DISORDERS •SCHIZOPHRENIA •SCHIZOAFFECTIVE •BRIEF PSYCHOSIS 17 18 - VERY COMMON - FREQUENT CO-MORBIDITY - ELEVATED PREVALENCE OF PSYCHIATRIC DISORDERS - POLYPHARMACY PRE-HIV INFECTION - DYNAMICS OF ACUTE AND CHRONIC MEDICAL DISEASE -ALL PERSONS WITH HIV WILL DEVELOP AT LEAST ONE PSYCHIATRIC DISORDER OVER COURSE OF DISEASE -SOCIALLY MARGINALIZED, LIMITED SUPPORT, ISOLATION FROM FAMILY - BIO-PSYCHO-SOCIAL MODEL 19 20 59 RESOURCE GUIDE –EDUCATE RE: – IMPROVE QUALITY OF LIFE •RISK REDUCTION •SEXUAL BEHAVIOURS – FACILITATE ADHERENCE •CO-INFECTION – ADVOCATE RE: – INCREASE LEVEL OF FUNCTION •DISABILITY •FAMILY – DECREASE HEALTH CARE COSTS •BUREAUCRACY – IMPROVE RELATIONSHIPS – ADDRESS DEATH AND DYING ISSUES 21 22 Depression  Most common disorder –THINK GERIATRIC BRAIN •START LOW, GO SLOW  Cascade of negative consequences  Under recognized, under treated –BALANCE RISKS AND BENEFITS  Normalization of Sx by others –POLYPHARMACY  Overlap of HIV physical Sx with mood Sx –REVIEW CD4, VIRAL LOAD, ANTIRETROVIRAL (ARV)  Anhedonia, diurnal variation, early cognitive decline MEDS, OTHER MEDICATIONS, LFTS  Responsive to Rx 23 24 60 MENTAL HEALTH, HIV/AIDS AND HCV COINFECTION Depression Rx Augmentation  SRI’s  Common  SSNRI’s  Effective  Buproprion  Multiple choices –other AD’s, Lithium, T3 (Cytomel),  Psychostimulants psychostimulants, atypicals  Mirtazepine  Caution -Drug-drug interations  ECT  No TCA’s, MAOI’s –exceptions include  Pain  Sleep  Augmentation 25 26 MEDICATIONS FOR BIPOLAR DISORDERS BIPOLAR DISORDERS  lithium  PRE-EXISTING BIPOLAR DISORDER BECOMES MORE FRAGILE WITH  valproic acid (EPIVAL) HIV  gabapentin (NEURONTIN)  NEW ONSET MORE LIKELY ASSOCIATED WITH CNS HIV DISEASE OR SUBSTANCE USE THAN FAMILY/PERSONAL HISTORY  atypical antipsychotics  ? RECENT CHANGE IN ARVs  avoid carbamazepine (TEGRETOL) and clozapine  bone marrow suppression  MAY DO WELL WITH SUBTHERAPEUTIC DOSES  ? lamotrigine (LAMICTAL) - Steven’s-Johnson Syndome  ? topiramate (TOPAMAX) 27 28 61