Stakeholder Insight: Cognitive Impairment in Schizoaffective Disorder - Inevitable or Treatable?

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