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Clinical Data and Best Practices for Managing Depression in HCV-Infected Patients Treated With Peginterferon and Ribavir PowerPoint Presentation
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Clinical Data and Best Practices for Managing Depression in HCV-Infected Patients Treated With Peginterferon and Ribavir

Clinical Data and Best Practices for Managing Depression in HCV-Infected Patients Treated With Peginterferon and Ribavir

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Clinical Data and Best Practices for Managing Depression in HCV-Infected Patients Treated With Peginterferon and Ribavir

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  1. Clinical Data and Best Practices for Managing Depression in HCV-Infected Patients Treated With Peginterferon and Ribavirin Martin Schaefer, MD Associate Professor of Psychiatry Charité University of Medicine Berlin, Germany Head, Department of Psychiatry, Psychotherapy and Addiction Medicine Kliniken-Essen-Mitte Essen, Germany This program is supported by an educational grant from

  2. About These Slides Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent These slides may not be published or posted online without permission from Clinical Care Options We are grateful to Martin Schaefer, MD, Kliniken-Essen-Mitte, Essen, Germany, who aided in the content creation of these slides DisclaimerThe materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.

  3. Summary of HCV Epidemiology and Treatment

  4. Epidemiology of HCV Infection • Nearly 170 million persons infected with HCV worldwide • Represents 2.5% of world population • Approximately 3-4 million new cases each year • 80% of new cases become chronic • HCV infection responsible for • Up to 76% of all HCC cases • 65% of liver transplantations in developed world • Cirrhosis develops in 20% to 30% over 20-30 years • 5% annual incidence of HCC World Health Organization. Available at: http://www.who.int/mediacentre/factsheets/fs164/en/.

  5. Common Adverse Effects of HCV Infection Lang CA, et al. J Pain Sym Manage. 2006;31:335-344.

  6. Current HCV Standard of Care Current standard of care for hepatitis C Combination therapy with pegIFN plus RBV Treatment length dependent on viral genotype and virologic response on therapy Response rates vary according to genotype SVR > 50% overall in clinical trials 42% to 46% for genotype 1 infection 76% to 82% for genotype 2/3 infection NIH Consens State Sci Statements. 2002;19:1-46. Manns M, et al. Lancet. 2001;358:958-965. Fried MW, et al. N Engl J Med. 2002;347:975-982.

  7. Relationship Among Depression, HCV, and HCV Treatment

  8. Depression significantly more prevalent in chronically HCV-infected patients than in the general population[1] Reported prevalence rates for MDD (according to DSM-IV)[2-4] 6% to 10% for the general population 24% to 70% for HCV-infected patients Depression More Common in HCV Patients vs General Population 1. Coughlan B, et al. Br J Health Psychol. 2002;7:105-116. 2. Lang CA, et al. J Pain Sym Manage. 2006;31:335-344. 3. Lee D, et al. Dig Dis Sci. 1997;42:186-191. 4. World Health Organization. http://www.who.int/mediacentre/factsheets/fs265/en/.

  9. Variation Among Results of Studies Examining IFN-Related Depression Systematic review analyzed 21 clinical trials of HCV-infected patients experiencing IFN-related depression Definition of depression, treatment strategy, and duration differed among trials 100 82 80 60 Patients With Depression (%) 44 41 37 36 35 34 33 40 26 24 24 23 20 20 17 17 16 20 0 0 Hunt 1997 Davis 1998 Kraus 2005 Kraus 2003 Scalori 2005 Scalori 2000 Mulder 2000 Hauser 2002 Renault 1987 Schafer 2003 Castera 2002 Pariente 1999 Miyaoka 1999 Bernstein 2002 Horikawa 2003 Bonaccorso 2002 Reichenberg 2005 McHutchinson 1998 Schafer A, et al. Int J Methods Psychiatr Res. 2007;16:186-201.

  10. 32 HCV-infected patients randomized to no treatment or pegIFN alfa-2a/2b + RBV Depression and fatigue evaluated at baseline and at ~ 12 weeks HCV treatment associated with development of depressive symptoms, fatigue Worsened Depression and Fatigue Scores Following HCV Treatment PegIFN + RBV (n = 20) Control (n = 12) P < .01 19.2 20 15 P < .01 10 8.1 5 Mean Change at Follow-up 0 -0.9 -5 -4.0 Depression (MADRS) Fatigue (MFI) -10 Majer M, et al. Brain Behav Immun. 2008;22:870-880.

  11. De NovoDepression in Patients Treated With PegIFN + RBV 176 HCV-infected patients beginning pegIFN alfa-2a + RBV therapy evaluated for depressive and anxiety disorders at baseline and throughout treatment Patients with baseline mood disorders excluded (n = 30) High incidence of depression and anxiety syndromes during treatment Martin-Santos R, et al. Alimen Pharmacol Ther. 2008;27:257-265.

  12. Time Course of Mood Changes in Patients Treated With PegIFN + RBV • 17 patients without psychiatric diseases or drug addiction treated with pegIFN + RBV • Majority of depressive symptoms occurred during first 1-3 months of HCV therapy 30 25 20 16.94 Mean MADRS Score 13.12* 15 12.88 10 *P < .001 vs baseline. 3.65 5 0 Baseline 1 Month 3 Months 6 Months Schaefer M, et al. Hepatology. 2007; 46:991-998.

  13. Risk of Suicide During Antiviral Therapy Treatment with IFN + RBV reported to be associated with suicidal thoughts, suicide attempts, and successfully completed suicides No robust estimates of suicide rates in IFN-exposed and untreated hepatitis C population Most data from case reports Relative risk associated with treatment is unknown Specific risk factors for suicide during IFN/RBV therapy are unknown Consider risks associated with antidepressant use Dieperink E, et al. Gen Hosp Psychiatry. 2004;26:237-240.

  14. Risk Factors for Depression During IFN-Based Therapy Key risk factor for depression during HCV therapy is presence of depressive symptoms before or during treatment Other factors that may be associated History of drug abuse HIV coinfection Older age Organic brain impairment Genetic risk factors in the serotonergic system Sex is risk factor for depression in the general population but is not risk factor for IFN-induced depression Raison CL, et al. J Clin Psychiatry. 2005;66:41-48. 40. Capuron L, et al. N Engl J Med. 1999;340:1370. Kraus MR, et al. Gastroenterology. 2007;132:1279-1286. Martin-Santos R, et al. Aliment Pharmacol Ther. 2008; 27:257-265.

  15. Depressive Symptoms and Viral Clearance at 24 Weeks PegIFN alfa-2b 1.5 µg/kg/week + fixed-dose (800 mg/day) or weight-based (800-1400 mg/day) RBV Higher baseline SDS depression scores associated with lower rates of HCV RNA negativity at Week 24 (P < .05) Raison CL, et al. Brain Behav Immun. 2005;19:23-27.

  16. Antidepressant Use May Improve SVR Rates Following HCV Therapy 39 patients received IFN alfa-2b + RBV for 24-48 weeks Assessed with BDI and SCID throughout treatment for development of major depression SVR attained by 38.5% of patients who developed major depression vs only 11.5% of patients without depression All patients who developed depression initiated antidepressants Ongoing prospective CIPPAD trial of 100 patients pretreated with antidepressants vs 100 patients receiving placebo should offer more definitive conclusions regarding interrelationships of depression, antidepressant use, and virologic outcomes Loftis JM, et al. Neurosci Lett. 2004;365:87-91.

  17. Pretreatment Assessment and Pharmacologic Treatment for HCV Treatment–Related Depression

  18. Approach to Managing Psychiatric Issues During HCV Treatment Education, monitoring, and support Information and psychoeducation before and during treatment Monitoring of patients and past and current psychiatric issues Assessment of current or previous substance abuse Supportive psychotherapy and counseling Regulation of sleep Pharmaceutical strategies Antidepressant treatment Other treatments: antipsychotics, benzodiazepines (mood stabilizers, amphetamines, naltrexone, tryptophan, etc) Antiviral therapy dose reduction, discontinuation if needed Schaefer M, et al. Current Drug Abuse Reviews. 2008;1:177-187.

  19. Depression Rating Scales Depression scales can be used before and during treatment to assess baseline, changes in symptoms Self-rating scales BDI (Becks Depression Inventory) Z-SDS (Zung Self-Rating Depression Scale) HADS (Hospital Anxiety and Depression Scale) Rating scales HAMD (Hamilton Depression Scale) MADRS (Montgomery-Åsberg Depression Scale)

  20. How to Use Diagnostic Scales • BDI, Z-SDS, HADS, HAMD, or MADRS • Show changes in depressive symptoms over time • Try to quantify the severity of depressive symptoms • Diagnosis of a “major depression” must be confirmed by diagnostic criteria • DSM-IV • Or using the SCID as a diagnostic interview • To diagnose major depression–specific symptoms, they must be present over a period of ≥ 14 days APA. Diagnostic and statistical manual of mental disorders revision IV-TR, 4th ed. 2000. Iannuzzo RW, et al. Psychiatry Res. 2006;145:21-37. Shafer AB. J Clin Psychol. 2006;62:123-146.

  21. When to Use Diagnostic Depression Scales During HCV Treatment Early diagnosis Required symptom duration of 14 days for MD diagnosis should not prevent initiation of clinical management of HCV-associated or treatment-associated depression Early intervention When depressive symptoms appear or a significant increase in depression scores occurs over several days May prevent development of severe depressive symptoms

  22. Use of Antidepressants for IFN-Induced Depression Initiate antidepressants at lowered doses to reduce adverse events and increase adherence Therapeutically relevant antidepressive effect can be expected at Day 8 to 14 of treatment Adverse effects generally appear in first 8 days In case of nonresponse Assess adherence Monitor serum levels to determine if dose escalation is needed Switch or add if current drug found to be ineffective Combination of 2 antidepressants with a different profile can be considered (eg, citalopram and mirtazapine) Raison C, et al. CNS Drugs. 2005;19:105-123. 61. Schaefer M, et al. Neuropsychobiology. 2000;42(suppl 1):43-45.

  23. Treatment for Depression Associated With HCV Therapy Open trials/case series/case reports Fluoxetine[1] Nortriptyline[2] Trimipramine/nefazodone[3] Sertraline[4] Paroxetine[5-7] Citalopram[8,9] Prospective controlled trial for acute treatment Citalopram[10] 1. Levenson JL, et al. Am J Gastroenterol. 1993;88:760-761. 2. Valentine AD, et al. Psychosomatics. 1995;36:418-419. 3. Schafer M, et al. Neuropsychobiology. 2000;42(suppl 1):43-45. 4. Schramm TM, et al. Med J Aust. 2000;173:359-361. 5. Kraus MR, et al. Aliment Pharmacol Ther. 2002;16:1091-1099. 6. Kraus MR, et al. N Engl J Med. 2001;345:375-376. 7. Capuron L, et al. Neuropsychopharmacology. 2002;26:643-652. 8. Gleason OC, et al. J Clin Psychiatry. 2002;63:194-198. 9. Schaefer M, et al. J Hepatol. 2005;42:793-798. 10. Kraus MR, et al. Gut. 2008;57:531-536.

  24. Antidepressant Efficacy in Patients Receiving HCV Treatment Efficacy with SSRIs across multiple studies *In the case of nonresponse to the antidepressant, citalopram dose was elevated to 40 mg/day or citalopram up to 30 mg/day was combined with mirtazapine. 1. Gleason OC, et al. Prim Care Companion J Clin Psychiatry. 2005;7:225-230. 2. Schaefer M, et al. J Hepatol. 2005;42:793-798. 3. Hauser P, et al. Mol Psychiatry. 2002;7:942-947. 4. Kraus MR, et al. Aliment Pharmacol Ther. 2002;16:1091-1099.

  25. Improved Depression Scores With Citalopram During HCV Treatment First prospective, controlled trial of citalopram 20 mg/day vs placebo for depression during HCV treatment with pegIFN + RBV Citalopram (n = 14) Placebo (n = 14) 14 P = .025 P = NS 12 P = .016 10 HADS Depression Score 8 6 4 2 Baseline Depression diagnosis 1 wk f/u 2 wks f/u 4 wks f/u After IFN therapy Citalopram Treatment Period Kraus MR, et al. Gut. 2008;57:531-536.

  26. Safety Considerations When Prescribing Antidepressants Hansen RA, et al. Ann Intern Med. 2005;143:415-426. Stahl SM, et al. CNS Spectr. 2005;10:732-747. Hanje AJ, et al. Clin Gastroenterol Hepatol. 2006;4:912-917. Montgomery SA, et al. Int J Clin Pract. 2005;59:1435-1440. Edwards IR, et al. Lancet. 2003;361:1240.

  27. Selecting an Antidepressant: Potential for Drug-Drug Interactions Antidepressants can interact with the cytochrome P450 enzyme in the liver and, therefore, interfere with the metabolism of other medications Weak P450 Blockers:Likely to have little impact on metabolism of other drugs Citalopram Escitalopram Mirtazapine Venlafaxine Bupropion Duloxetine Modafinil Sertraline Potent P450 Blockers: Potential for strong impact on metabolism of other drugs Methylphenidate Nefazodone 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.

  28. Special Safety Considerations With SSRIs SSRIs considered safe in patients without liver cirrhosis, thrombocytopenia, or other contraindications No differences in serum levels or adverse effects in HCV-infected patients without cirrhosis treated with citalopram vs non-HCV–infected individuals SSRIs associated with risk of GI bleeding in setting of hepatitis C Potential for bleeding should be noted in particular for cirrhotic patients Gleason OC, et al. J Clin Psychiatry. 2002; 63:194-198. Gleason OC, et al. Prim Care Companion J Clin Psychiatry. 2005; 7:225-230. Schaefer M, et al. Hepatology. 2003; 37:443-451. Schaefer M, et al. J Hepatol. 2005; 42:793-798. Weinrieb RM, et al. J Clin Psychiatry. 2003; 64:1502-1510.

  29. Antidepressant Treatment Before HCV Therapy

  30. Early Studies: Benefit of Prophylactic Treatment for IFN-Induced Depression 40 malignant melanoma patients received paroxetine or placebo starting 2 weeks before IFN therapy and continuing throughout treatment Reduced incidence of depression (P = .04), fewer cases of depression requiring HCV treatment discontinuation (P = .03) with paroxetine Pretreatment with paroxetine associated with lower incidence of fear, cognitive impairment, and pain Paroxetine did not reduce or prevent symptoms such as fatigue, sleeping disturbances, anhedonia, or irritability Musselman DL, et al. N Engl J Med. 2001;344:961-966. Capuron L, et al. Neuropsychopharmacology. 2002;26:643-652.

  31. Prophylactic Treatment Reduced Depression Symptom Severity • Prospective, double-blind trial of 61 HCV-infected patients randomized to paroxetine vs placebo for 2 weeks before IFN + RBV therapy • No difference in rates of major depression with paroxetine (13%) vs placebo (21%); P = .71 • Depression symptom severity reduced during treatment with use of paroxetine among patients with elevated baseline depressive symptoms 100 Rates of Mild, Moderate, Severe, Depression During IFN/RBV Therapy 80 Paroxetine* (n = 28) Placebo (n = 33) 57 60 55 Patients (%) 40 35 21 17 20 7 9 0 0 Moderate (MADRS ≥ 25) Severe (MADRS ≥ 31) Normal (MADRS < 15) Mild (MADRS ≥ 15) *P = .02 Raison CL, et al. Aliment Pharmacol Ther. 2007;25:1163-1174.

  32. No Reduction in IFN-Induced Depression With Pretreatment 33 HCV-infected patients randomized to paroxetine vs placebo before HCV treatment[1] 35.7% vs 31.6% of the paroxetine and placebo groups developed depression In rescue arm of study, 10 of 11 patients receiving paroxetine experienced reductions in depressive symptoms 133 patients received either escitalopram or placebo before pegIFN alfa-2a + RBV[2] 2% vs 8% of patients in placebo and escitalopram arms developed depression during first 12 weeks of treatment Patients with previous psychiatric risk factors or preexisting depression excluded 1. Morasco BJ, et al. J Affect Disord. 2007;103:83-90. 2. Diez-Quevedo C, et al. 2007 AASLD. Abstract 347.

  33. Use of SSRI Pretreatment in Patients Receiving HCV Retreatment • Patients experiencing major depression during first course of HCV treatment received SSRI pretreatment when retreated for HCV (N = 8) • Reduced depressive symptoms severity with retreatment First therapy P = .036 14 Retreatment with SSRI 12 10 8 HADS Depression Score 6 4 2 0 t1 t2 t3 t4 t5 Time Point of Examination Kraus MR, et al. J Viral Hepatitis. 2005;12:96-100.

  34. Patients With Psychiatric Problems: During and After HCV Therapy Psychiatric visits Every 2-4 weeks for first 3 months Then every 4-8 weeks Encourage patient and confidant (relative, friend, etc) to look for psychiatric changes and in self-rating scores Continue antidepressant treatment ≥ 3 months after the end of HCV treatment Reduce the dosage of antidepressant slowly Attend to mental changes ≥ 6 months after end of HCV treatment Loftis J, et al. Drugs. 2006;66:155-174. Raison C, et al. CNS Drugs. 2005;19:105-123.

  35. Cognitive Function, HCV, and HCV Therapy

  36. Cognitive Disturbances in HCV Infection Cognitive disturbances associated with both HCV infection and IFN-based therapy Psychomotor slowing, poor concentration and memory may occur independently or as part of depressive mood changes Cognitive changes compared in HCV-infected patients with minimal liver disease (n = 37) vs uninfected controls (n = 46) HCV group showed marginally poorer learning efficiency Valentine AD, et al. Semin Oncol. 1998;25(1 suppl 1):39-47. McAndrews MP, et al. Hepatology. 2005;41:801-808. Weissenborn K, et al. J Hepatol. 2004;41:845-851.

  37. Cognitive Disturbances in HCV Infection (cont’d) HCV-infected patients with normal liver function, mild fatigue (n = 15) vs HCV-infected patients with normal liver function, moderate-to-severe fatigue (n = 15) vs healthy matched volunteers (n = 15) Greater cognitive impairment in HCV-infected patients vs controls Poorer attention levels, higher executive functions, higher levels of anxiety and depression, impaired quality of life Deficits more marked in patients with moderate vs mild fatigue Valentine AD, et al. Semin Oncol. 1998;25(1 suppl 1):39-47. McAndrews MP, et al. Hepatology. 2005;41:801-808. Weissenborn K, et al. J Hepatol. 2004;41:845-851.

  38. Conflicting Results: Cognitive Impairment During HCV Therapy Fontana and colleagues’ HALT-C subanalysis IFN nonresponders retreated with pegIFN alfa-2a + RBV for 24 weeks (n = 177) or 48 weeks (n = 57) Cognitive impairment: 32% at baseline vs 34% through Week 24 (P = .64) No increase in overall cognitive impairment in patients receiving 48 weeks of treatment (P = .48) Significant increases in difficulty concentrating, emotional distress, and symptoms of depression (BDI) in patients receiving 48 weeks of treatment Fontana RJ, et al. Hepatology. 2007;45:1154-1163.

  39. Conflicting Results: Cognitive Impairment During HCV Therapy (cont’d) Kraus and colleagues 70 patients received IFN alfa-2b or pegIFN alfa-2b + RBV Poorer reaction times (P < .001), alertness (P < .001), divided attention (P < .001), vigilance (P < .001) after 3 months of HCV therapy vs baseline Performance returned to pretreatment levels after treatment cessation Lieb and colleagues 38 HBV- or HCV-infected patients treated for 12 weeks with low-dose IFN Decreased immediate recall (P = .015) and reduction in words recited (P = .034) Cognitive impairment not correlated with depressive symptoms or anxiety May be caused by disturbances in prefrontal cortex, hippocampus Kraus MR, et al. Clin Pharmacol Ther. 2005;77:90-100. Lieb K, et al. Eur Psychiatry. 2006;21:204-210.

  40. Cognitive Disturbances May Appear Late in Therapy, Persist After 50 patients receiving pegIFN/RBV treatment assessed at baseline,14 times during a 48-week course of treatment, and 4 times during 24 weeks of follow-up 30% of patients experienced cognitive problems during therapy 37% of patients who complained of cognitive disturbances during treatment still suffered from cognitive disturbances 8 weeks after treatment end 3 patients first reported cognitive disturbances after the end of IFN treatment Highest incidence of cognitive symptoms between Weeks 12-20 of treatment Reichenberg A, et al. AIDS. 2005;(19 suppl 3):S174-S178.

  41. How Does HCV Impair Cognitive Function? HCV infection leads to changes in brain metabolism and in the serotonin-dopamine transporter[1-5] Significant decrease in N-acetyl-aspartate/creatinine ratio[5] Increased choline and decreased N-acetyl-aspartate levels[3] Hypometabolism in the prefrontal cortex[6] Significant reduction of regional cerebral blood flow in areas associated with memory and language function[7] 1. Forton DM, et al. AIDS. 2005;19:S53-S63. 2. Forton DM, et al. 2007 Hepatology. 2002;45;433-439. 3. McAndrews MP, et al. Hepatology. 2005;41:801-808. 4. Weissenborn K, et al. Metab Brain Dis. 2000;15:173-178. 5. Weissenborn K, et al. J Hepatol. 2004;41:845-851. 6. Juengling FD, et al. Psychopharmacology. 2000;152:383-389. 7. Tanaka H, et al. Clin Exp Med. 2006;6:124-128.

  42. Risk Factors for Cognitive Impairment During HCV Therapy Neurocognitive problems may occur independently from dose and duration of HCV treatment Risk factors Pretreatment with neurotoxic medication Diabetes, vascular disease, older age, early vegetative symptoms Fatigue, severe depression, history of severe psychiatric adverse effects with IFN Abuse of benzodiazepines or alcohol; methadone treatment Concomitant cirrhosis, hepatic encephalopathy, or depression Fattovich G, et al. J Hepatol. 1996;24:38-47. Jaubert D, et al. Presse Med. 1991;20:221-222. Reichenberg A, et al. AIDS. 2005;(19 suppl 3):S174-S178. 96. Wichers MC, et al. Psychol Med. 2005;35:433-441. Wichers MC, et al. Mol Psychiatry. 2005;10:538-544. Weissenborn K, et al. J Hepatol. 2004;41:845-851. Weissenborn K, et al. Metab Brain Dis. 2000;15:173-178.

  43. Sleep disturbances Administration of sleep medications (eg, benzodiazepines) or sedative antidepressants (eg, mirtazapine) may be indicated Irritability Antidepressants, mood stabilizers, or antipsychotics may be indicated depending on etiology Fatigue Thyroid dysfunction and anemia must be ruled out SSRIs may be indicated Psychotic symptoms Psychiatric monitoring indicated Suicidal symptoms Dose reductions or treatment interruptions may be indicated Other Symptoms During IFN Treatment Dieperink E, et al. Gen Hosp Psychiatry. 2004;26:237-240. Constant A, et al. J Clin Psychiatry. 2005;66:1050-1057. Schaefer M, et al. Fortschr Neurol Psychiatr. 2003;71:469-476. Sockalingam S, et al. Int Clin Psychopharmacol. 2005;20:289-290. Schaefer M, et al. Current Drug Abuse Reviews. 2008;1:177-187.

  44. HCV Patients With Psychiatric Disorders in the Setting of Drug Addiction

  45. HCV Prevalence by Selected Groups, United States: High Rates in IDUs Hemophilia 87.0 Injection Drug Users 79.0 Hemodialysis 10.0 STD Clients 6.0 Gen Population, Adults 3.5 Surgeons, PSWs 2.0 Pregnant Women 1.0 Military Personnel 0.3 0 10 20 30 40 50 60 70 80 90 100 Mean Percentage Anti-HCV Positive Prevalence of hepatitis C in patients with psychiatric disorders: 6% to 9% Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/101/101_hcv.ppt. Dinwiddie SH, et al. Am J Psychiatry. 2003;160:172-174. Chang TT, et al. J Med Virol. 1993;40:170-173. Cividini A, et al. J Hepatol. 1997;27:455-463.

  46. Duration of Injection Drug Use and Prevalence of Blood-Borne Viruses 100 80 HCV 60 HBV Estimated Seroprevalence (%) HIV 40 HTLV 20 0 0-4 5-8 9-12 13-24 25-36 37-48 49-60 61-72 Duration of Injection Drug Use (Months) Garfein RS, et al. Am J Public Health. 1996;86:655-661.

  47. Psychiatric, Drug, Alcohol Disorders Often Coexist in HCV Patients 33,824 HCV-infected patients admitted to VA hospitals during 1992-1999 31% had “active disorders” defined as hospitalization for psychiatric or drug detoxification disorders 86% had past or present psychiatric, drug, or alcohol use disorder 100 HCV (n = 22,341) Controls (n = 43,267) 80 69 P < .0001 for all between-arm comparisons 60 50 Patients (%) 41 39 34 40 33 31 25 24 21 16 20 13 0 Depression PTSD Psychosis Bipolar Anxiety Drug Use El-Serag HB, et al. Gastroenterology. 2002;123:476-482.

  48. Prevalence of Psychiatric Disorders and Substance Abuse in HCV Medical records review of past and present DSM-IV–based psychiatric disorders (N = 306) 100 86 80 60 Prevalence (%) 38 40 30 28 19 17 20 9 0 PTSD IV Drug Use Mood Disorders Psychotic Disorders Alcohol Use Disorders Personality Disorders Other Anxiety Disorders Yovtcheva SP, et al. Psychosomatics. 2001;42:411-415.

  49. Management of Hepatitis C: NIH Consensus Conference Statement All patients with chronic hepatitis C are potential candidates for antiviral therapy HCV therapy has been successful even when the patients have not abstained from continued drug or alcohol use . . . . Thus, it is recommended that treatment of active injection drug use be considered on a case-by-case basis and that active injection drug use in and of itself not be used to exclude such patients from antiviral therapy. • Treatment is recommended for patients with an increased risk of developing cirrhosis NIH Management of Hepatitis C Consensus Conference Statement. Available at: http://consensus.nih.gov/2002/2002HepatitisC2002116html.

  50. NIH Recommendations on Treating Injection Drug Users Management of HCV is enhanced by linking to drug-treatment programs Methadone is not a contraindication to HCV treatment HCV treatment of active injection drug users should be considered on a case-by-case basis Active injection drug use in and of itself should not exclude such patients from antiviral therapy NIH Management of Hepatitis C Consensus Conference Statement. Available at: http://consensus.nih.gov/2002/2002HepatitisC2002116html.