統合失調症における認識機能障害治療動向

Overview

Introduction

Cognitive impairment is regarded as a core deficit of schizophrenia; the primary unmet need is the availability of an effective drug for the treatment of cognitive impairment in schizophrenia (CIS). However manufacturers will need to carefully consider how to develop and market such a drug, and increase awareness of the disorder in patients, carers and prescribers.

Scope

• Analysis of a survey of 185 prescribing psychiatrists in the seven major markets as well as in-depth interviews with CIS Key Opinion Leaders
• Detailed treatment trees showing the prevalence,diagnosis and treatment rates of CIS across the seven major markets
• Analysis of specific treatment strategies to improve cognition once CIS has been diagnosed
• Insight into diagnostic and therapeutic unmet needs, and recommendations to aid market penetration and maximize prescription rates

Report Highlights

According to Datamonitor Primary Physician Research (PPR) CIS is perceived to be prevalent in 60% of the schizophrenia population, although the rate is likely to be even higher. However, CIS is currently diagnosed in fewer than 40% of patients, with a treatment rate which is even lower.

Manufacturers need to increase physician awareness of specifically testing for cognitive impairment during or soon after the initial diagnosis schizophrenia, in order to maximize long-term CIS drug revenues.

In the absence of an approved drug therapy for CIS, treatment primarily consists of atypical antipsychotic therapy. However, numerous drugs are in development for CIS utilizing a variety of drug mechanisms, although Datamonitor believes that it is unlikely that a drug will be approved for CIS in the next five years.

Reasons to Purchase

• Understand the diagnosis and treatment pathways in CIS and asses differential treatment and unmet needs in CIS
• Design patient and physician awareness campaigns based upon patient and advocacy response and commercial analysis
• Enhance development and market penetration strategies of CIS drugs

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

• About the CNS pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

• Scope of the analysis
• Datamonitor insight into the CIS market
• Key metrics

CHAPTER 2 INTRODUCTION AND SCOPE

• Coverage of the Stakeholder Insight Survey
  • Epidemiology and diagnosis of CIS
  • Treatment of CIS
  • Drug profiles

CHAPTER 3 COUNTRY TREATMENT TREES

• US
• Japan
• France
• Germany
• Italy
• Spain
• UK

CHAPTER 4 EPIDEMIOLOGY & PATIENT SEGMENTATION

• Key findings
• Cognitive impairment in schizophrenia: definition andclassification
  • Diagnostic criteria of schizophrenia
    • A - Characteristic symptoms
    • B - Social/occupational dysfunction
    • C - Duration
    • D - Schizoaffective and mood disorder exclusion
    • E - Substance/general medical condition exclusion
    • F - Relationship to a pervasive developmental disorder
  • The seven domains of cognitive impairment in schizophrenia
  • CIS affects patients quality of life - improvement ofwhich may prove to be a useful endpoint in clinical trials
• Epidemiology of CIS
  • Prevalence of CIS
    • Schizophrenia affects 1% of the population
    • CIS is stated as affecting 60% of patients withschizophrenia, although the true rate is likely to be higher
  • Half of CIS patients suffer from mild cognitive impairment
  • CIS is almost equally prevalent in males and females
  • More than one-third of CIS patients suffer from one ormore comorbidities
    • Anxiety is the most prevalent comorbidity CIS
    • Substance and alcohol abuse is frequently observed in CIS
    • Depression affects one-third of CIS patients
    • Oppositional defiant disorder and conduct disorder isreported in one in five CIS patients
    • Speech/language disorder is reported in 13% of CISpatients
    • Autism and Aspergers disorder affects only 6% of CISpatients
    • Tic disorders and Tourettes syndrome are not frequentlyseen in CIS patients
  • Psychiatrists reported that prevalence of CIS increasewith age, although this is not supported by clinical data
  • One-third of patients with CIS develop dementia in laterlife
  • Data suggests that onset of dementia occurs 10 yearsearlier in patients with CIS
  • Black box warnings restrict off-label antipsychotic use inelderly patients with dementia

CHAPTER 5 DIAGNOSIS AND TREATMENT OPTIONS

• Key findings
• Schizophrenia diagnostic guidelines
  • Summary of the diagnostic criteria for schizophrenia
• Numerous cognitive tests are used by psychiatrists toassess cognitive impairment in schizophrenia
  • MiniMental State Examination
  • Positive and Negative Syndrome Assessment
  • Wechsler Memory Scale
  • Wisconsin Card Sorting Test
  • Neuropsychological Assessment Battery
  • Alzheimers Disease Assessment Scale
• There is insufficient physician awareness of CIS and theavailable assessment tools
  • MATRICS program provides consensus on clinical trialendpoints
  • Strategic trial design can support demonstration of drugefficacy in CIS
    • MATRICS recommendations for the clinical trial design forcognition enhancing drugs in schizophrenia
    • Treatment Units for Research on Neurocognition andSchizophrenia encourage scientific research into CIS
• Less than 40% of patients with CIS are diagnosed
• CIS is detected early during the course of schizophreniain Japan, France and Germany
• Positive symptoms remain the priority treatment domain ofschizophrenia
• Social cognition, attention and executive function are themost clinically important domains of CIS to treat
• Guidelines for the treatment of schizophrenia providelittle information on treating cognitive deficits
• Pharmacological treatments for schizophrenia and CIS
  • Atypical antipsychotics
    • Olanzapine
    • Risperidone
    • Quetiapine
    • Aripiprazole
    • Ziprasidone
    • Amisulpride
    • Perospirone
    • Sertindole
    • Zotepine
    • Clozapine
  • Typical neuroleptics
  • Alzheimers and dementia drugs
    • Donepezil
    • Rivastigmine
    • Galantamine
    • Memantine
  • Other drugs
    • Buflomedil
    • Citicoline
    • Benzodiazepines
• Non-pharmacological therapy
  • Psychosocial therapy
    • Acute phase
    • Stabilization phase
    • Stable phase
• CIS increases the already high economic burden ofschizophrenia

CHAPTER 6 PRESCRIBING TRENDS AND INFLUENCING FACTORS

• Key findings
• Prescribing trends
  • Atypical antipsychotics form more than 90% ofschizophrenia maintenance treatment strategies
    • Zyprexa and Risperdal are the most frequently usedantipsychotics in schizophrenia maintenance therapy
  • Only one-third of patients receive specific therapy forthe treatment of cognitive impairment
  • Time restrictions, and limited finances and resources,curtail the use of psychosocial therapy in CIS
  • A variety of non-pharmacological therapeutic strategiesare employed in the treatment of CIS
  • Four strategies predominate for improving cognitivefunctioning in schizophrenia
  • Switching from one atypical antipsychotic to another isthe most frequently employed strategy to improve cognitive functioning
    • Switching atypical antipsychotics is employed intwo-thirds of antipsychotic switching strategies
    • Risperdal and Zyprexa are the most frequent antipsychoticsswitched-to across the seven major markets
    • Abilify and Geodon are the most frequent antipsychoticsswitched-to in the US
    • Risperdal and Zyprexa are the most common antipsychoticsswitched-to in Europe and Japan
  • Addition of an adjunctive non-antipsychotic drug is thethird most frequently implemented strategy to improve cognitivefunctioning
    • Addition of an anti-Alzheimers drug is the most frequentadjunctive non-antipsychotic therapy employed to improve cognitivefunctioning
    • Aricept is the most frequent non-antipsychotic drugadded-on to schizophrenia maintenance therapy to improve cognitivefunctioning
    • Aricept is the most frequent non-antipsychotic drugadded-on to schizophrenia maintenance therapy in the US
    • Aricept is the most frequent non-antipsychotic drug statedto be added-on to schizophrenia maintenance therapy in Europe and Japan
  • Addition of an adjunctive antipsychotic drug is the fourthmost frequently implemented strategy to improve cognitive functioning
    • Addition of atypical antipsychotics is the most frequentantipsychotics adjunctive therapy employed to improve cognitivefunctioning
    • Seroquel and Abilify are the most frequent antipsychoticsadded-on to schizophrenia maintenance therapy in the US
    • Zyprexa and Risperdal are the most frequent antipsychoticsadded-on to schizophrenia maintenance therapy in Europe and Japan
  • Patients remain on CIS therapy for approximately fourmonths before switching to a second-line strategy
  • Switching to an alternative antipsychotic is the mostfrequently employed second-line strategy to improve cognitive functioning
• Factors influencing physician decision making
  • Efficacy in improving the cognitive functioning inpatients with CIS is the most likely attribute to influence physician drugchoice
  • Abilify rated most highly for the treatment of cognitivesymptoms of schizophrenia
    • Abilify rated most highly for the treatment of cognitivesymptoms of schizophrenia in the US
    • Zyprexa rated most highly for the treatment of globalsymptoms of schizophrenia in Japan
    • Abilify rated most highly for the treatment of globalsymptoms of schizophrenia in France
    • Abilify rated most highly for the treatment of globalsymptoms of schizophrenia in Germany
    • Clozapine rated most highly for the treatment of globalsymptoms of schizophrenia in Italy and Spain
    • Clozapine rated most highly for the treatment of globalsymptoms of schizophrenia in the UK

CHAPTER 7 IMPROVING TREATMENT OUTCOMES

• Key findings
• The primary unmet need is the availability of a drug forthe treatment of CIS
  • Improved efficacy in multiple domains of cognitiveimpairment is desirable
  • Greater efficacy without compromising upon side-effectprofiles
    • Increased public, patient and physician awareness andeducation
    • Improved cognitive assessment and diagnosis will drivephysician prescribing
• Numerous drugs with differing mechanisms of action are indevelopment because the cause of CIS remains unknown
  • Psychiatrists are relatively unaware of the key drugs indevelopment which show the greatest propensity to treat CIS
    • Top five drugs listed by interviewed psychiatrists indevelopment with potential for the treatment of CIS
    • Other pipeline drugs with the potential for treatment ofCIS
• The future of CIS therapy
  • Adjunctive therapy offers the greatest potential
  • Approved drugs will be prescribed for CIS, newly diagnosedschizophrenia and off-label in other psychiatric disorders
  • It is unlikely that a drug will be approved for CIS withinthe next five years

• APPENDIX A
  • Bibliography
  • Websites
• APPENDIX B
  • Physician sample breakdown
  • Physician research methodology
• APPENDIX C
  • Physician questionnaire
  • SECTION 1 Epidemiology and diagnosis of CIS
  • Section 2 Treatment
  • Section 3 Drug profiles
  • Report methodology
    • Date of research completion
  • About Datamonitor
    • About Datamonitor Healthcare
    • Datamonitor Healthcares research and analysismethodologies
  • Datamonitor Healthcares therapy area capabilities
    • About the CNS analysis team
    • Key therapy team members
      • Lynda Lynch, Director CNS
      • David Abramson, Therapeutic Lead Consultant
  • Disclaimer

List of Tables

• Table 1: Prevalence (%) of CIS across the seven majormarkets
• Table 2: CIS severity categorization
• Table 3: Severity of cognitive impairment in CISpatients (%)
• Table 4: Proportion (%) of males versus female patientswith CIS across the seven major markets
• Table 5: Prevalence (%) of patients with CIS exhibitingcomorbid psychiatric disorders across the seven major markets
• Table 6: Proportion (%) of patients with schizophreniawho suffer from CIS, across the seven major markets
• Table 7: Proportion of CIS patients developing dementiain later life (%)
• Table 8: Age (years) of onset of dementia in CISpatients versus the general population, across the seven major markets
• Table 9: Diagnostic criteria for schizophrenia and itssubtypes
• Table 10: Physician usage of tools for the assessment ofcognitive impairment (%)
• Table 11: MATRICS CCB for clinical trials
• Table 12: MATRICS community functioning measures
• Table 13: Proportion of patients with CIS diagnosedacross the seven major markets (%)
• Table 14: Time period from schizophrenia diagnosis whenCIS is diagnosed in schizophrenia patients across the seven major markets(% patients with CIS diagnosed at time points)
• Table 15: Treatment priority for the primary domains ofschizophrenia - rated by dividing 100 points across five domains, withincreasing importance recognized by increased number of points
• Table 16: Treatment priority for the primary domains ofcognitive impairment in schizophrenia - rated by dividing 100 pointsacross five domains, with increasing importance recognized by increasednumber of points
• Table 17: Selecting antipsychotics for patients withcomplicating problems
• Table 18: Drugs prescribed for the treatment of CIS
• Table 19: Drug classes prescribed for schizophreniamaintenance therapy
• Table 20: Drug classes prescribed for schizophrenia,2004
• Table 21: Proportion of patients receiving drugs forschizophrenia maintenance therapy (%)
• Table 22: Top five drugs prescribed for schizophreniamaintenance therapy across the seven major markets
• Table 23: Proportion of patients with schizophreniaspecifically treated to improve cognitive functioning (%)
• Table 24: Proportion of patients receiving each therapytype used in the treatment of CIS across the seven major markets (%)
• Table 25: Non-pharmacological therapies used in thetreatment of CIS (% of patients receiving psychosocial therapy thatreceive each intervention)
• Table 26: Treatment strategies employed to improvecognitive functioning, across the seven major markets (%)
• Table 27: Antipsychotic switch strategies for thetreatment of CIS across the seven major markets (% of patients switched)
• Table 28: Antipsychotics switched-to for the treatmentof CIS across the seven major markets (% of patients switched to therapy)
• Table 29: Top antipsychotic switching strategies for CISacross the seven major markets (% of patient switches)
• Table 30: Top six antipsychotics switched-to for thetreatment of CIS across the seven major markets (% of patients switched totherapy)
• Table 31: Top antipsychotic switching strategies for CISacross the seven major markets (%)
• Table 32: Add-on strategies for the treatment of CISacross the seven major markets (% of patients that receivenon-antipsychotic adjunctive therapy)
• Table 33: Non-antipsychotic drugs added-on for thetreatment of CIS across the seven major markets (% of non-antipsychoticadd-on strategies)
• Table 34: Top non-antipsychotic add-on strategies forCIS across the seven major markets (% of antipsychotic plusnon-antipsychotic strategies)
• Table 35: Top six non-antipsychotic drugs added-on forthe treatment of CIS across the seven major markets (% of patientsreceiving non-antipsychotic add-on therapy)
• Table 36: Top non-antipsychotic add-on strategies forCIS across the seven major markets (% of antipsychotic plusnon-antipsychotic strategies)
• Table 37: Antipsychotic add-on strategies for thetreatment of CIS across the seven major markets (% of patients who receivean additional antipsychotic)
• Table 38: Antipsychotics added-on for the treatment ofCIS across the seven major markets (% of antipsychotic add-on strategies)
• Table 39: Top antipsychotic add-on strategies for CISacross the seven major markets (% of patients who receive an additionalantipsychotic)
• Table 40: Top six adjunctive antipsychotics for thetreatment of CIS across the seven major markets (% of patients receivingantipsychotic add-on therapy)
• Table 41: Top antipsychotic add-on strategies for CISacross the seven major markets (% of patients receiving antipsychoticadd-on therapy)
• Table 42: Duration of time before patients progress tosecond-line therapy, across the seven major markets (weeks)
• Table 43: Second line therapeutic strategies in thetreatment of CIS (% of patients that have progressed to second linetherapy)
• Table 44: Key drug attributes most likely to influencephysician drug choice (%)
• Table 45: Top five drugs in each country as rated byinterviewed psychiatrists for the treatment of positive and negative,cognitive and global symptoms of schizophrenia
• Table 46: Pipeline drugs reported (unprompted) byinterviewed psychiatrists
• Table 47: Other pipeline drugs with potential for thetreatment CIS, not reported by interview psychiatrists
• Table 48: US physician sample breakdown, 2005
• Table 49: Japanese physician sample breakdown, 2005
• Table 50: French physician sample breakdown, 2005
• Table 51: German physician sample breakdown, 2005
• Table 52: Italian physician sample breakdown, 2005
• Table 53: Spanish physician sample breakdown, 2005
• Table 54: UK physician sample breakdown, 2005

List of Figures

• Figure 1: Prevalence, diagnosis and drug treatment ratesof CIS across the seven major markets.
• Figure 2: Prevalence and diagnosis rates of CIS in theUS
• Figure 3: Drug treatment patterns of schizophrenia andCIS in the US
• Figure 4: Prevalence and diagnosis rates of CIS in Japan
• Figure 5: Drug treatment patterns of schizophrenia andCIS in Japan
• Figure 6: Prevalence and diagnosis rates of CIS inFrance
• Figure 7: Drug treatment patterns of schizophrenia andCIS in France
• Figure 8: Prevalence and diagnosis rates of CIS inGermany
• Figure 9: Drug treatment patterns of schizophrenia andCIS in Germany
• Figure 10: Prevalence and diagnosis rates of CIS inItaly
• Figure 11: Drug treatment patterns of schizophrenia andCIS in Italy
• Figure 12: Prevalence and diagnosis rates of CIS inSpain
• Figure 13: Drug treatment patterns of schizophrenia andCIS in Spain
• Figure 14: Prevalence and diagnosis rates of CIS in theUK
• Figure 15: Drug treatment patterns of schizophrenia andCIS in the UK
• Figure 16: Prevalence of CIS across the seven majormarkets (%)
• Figure 17: Severity of cognitive impairment in CISpatients
• Figure 18: Proportion of males versus female patientswith CIS across the seven major markets (%)
• Figure 19: Prevalence of anxiety disorders in CIS acrossthe seven major markets (%)
• Figure 20: Prevalence of substance and alcohol abuse inCIS across the seven major markets (%)
• Figure 21: Prevalence of depression in CIS across theseven major markets (%)
• Figure 22: Prevalence of oppositional defiant disorderand conduct disorder in CIS across the seven major markets
• Figure 23: Prevalence of speech and language disordersin CIS across the seven major markets (%)
• Figure 24: Prevalence of autism and Aspergers disordersin CIS across the seven major markets (%)
• Figure 25: Prevalence of tic disorder/Tourettessyndrome disorders in CIS across the seven major markets (%)
• Figure 26: Proportion (%) of patients with schizophreniawho suffer from CIS, across the seven major markets
• Figure 27: Spectrum of CIS
• Figure 28: Cognitive impairment in schizophrenia overtime
• Figure 29: Proportion of CIS patients developingdementia in later life (%)
• Figure 30: Age of onset of dementia in CIS patientsversus the general population, across the seven major markets
• Figure 31: Atypical antipsychotic black-box warningagainst usage in elderly patients with dementia related psychosis.
• Figure 32: Proportion of patients with CIS diagnosedacross the seven major markets
• Figure 33: Time period from schizophrenia diagnosis whenCIS is diagnosed in schizophrenia patients across the seven major markets
• Figure 34: Correlation of perceived prevalence and earlydiagnosis of CIS
• Figure 35: Treatment priority for the primary domains ofschizophrenia - rated by dividing 100 points across five domains, withincreasing importance recognized by increased number of points
• Figure 36: Treatment priority for the primary domains ofcognitive impairment in schizophrenia - rated by dividing 100 pointsacross five domains, with increasing importance recognized by increasednumber of points
• Figure 37: Drug classes prescribed for schizophreniamaintenance therapy
• Figure 38: Proportion of patients receiving drugs forschizophrenia maintenance therapy (%)
• Figure 39: Proportion of patients with schizophreniaspecifically treated to improve cognitive functioning
• Figure 40: Therapy types used in the treatment of CISacross the seven major markets
• Figure 41: Non-pharmacological therapies used in thetreatment of CIS
• Figure 42: Treatment strategies employed to improvecognitive functioning, across the seven major markets
• Figure 43: Antipsychotic switch strategies for thetreatment of CIS across the seven major markets (% of patients switched)
• Figure 44: Antipsychotics switched-to for the treatmentof CIS across the seven major markets (%)
• Figure 45: Add-on strategies for the treatment of CISacross the seven major markets (%)
• Figure 46: Correlation of frequency of non-antipsychoticadjunctive usage and response of "other/not stated"
• Figure 47: Non-antipsychotic drugs added-on for thetreatment of CIS across the seven major markets (%)
• Figure 48: Antipsychotic add-on strategies for thetreatment of CIS across the seven major markets (%)
• Figure 49: Antipsychotics added-on for the treatment ofCIS across the seven major markets (%)
• Figure 50: Duration of time before patients progress tosecond-line CIS therapy, across the seven major markets
• Figure 51: Second line therapeutic strategies
• Figure 52: Key drug attributes most likely to influencephysician drug choice for the treatment of CIS
• Figure 53: Psychiatrist rating of drugs used for thetreatment of CIS
• Figure 54: Unmet needs in the treatment of CIS
• Figure 55: Physician awareness of pipeline drugs
• Figure 56: Use of cognitive enhancing drugs inschizophrenia and other psychiatric disorders