hcvdep_2008_schaefer_downloadable.ppt
http://www.100md.com
参见附件(630KB)。
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
Summary of HCV Epidemiology and Treatment
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
Common Adverse Effects of HCV Infection
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
Relationship Among Depression, HCV, and
HCV Treatment
Depression More Common in HCV Patients vs General Population
* 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
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
Worsened Depression and Fatigue Scores Following HCV Treatment
* 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
De Novo Depression 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
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
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
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
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)
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
Pretreatment Assessment and Pharmacologic Treatment for HCV Treatment-Related Depression
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
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-?sberg Depression Scale)
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......（后略) ......
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
Summary of HCV Epidemiology and Treatment
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
Common Adverse Effects of HCV Infection
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
Relationship Among Depression, HCV, and
HCV Treatment
Depression More Common in HCV Patients vs General Population
* 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
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
Worsened Depression and Fatigue Scores Following HCV Treatment
* 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
De Novo Depression 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
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
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
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
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)
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
Pretreatment Assessment and Pharmacologic Treatment for HCV Treatment-Related Depression
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
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-?sberg Depression Scale)
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......（后略) ......