Cognitive Impairment in Schizoaffective Disorder
Scope
Report Highlights
Reasons to Purchase
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE - page 2
- About the CNS pharmaceutical analysis team - page 2
- CHAPTER 1 EXECUTIVE SUMMARY - page 3
- Scope of the analysis - page 3
- Datamonitor insight into the CIS market - page 5
- Key metrics - page 7
- CHAPTER 2 INTRODUCTION AND SCOPE - page 17
- Coverage of the Stakeholder Insight Survey - page 17
- Epidemiology and diagnosis of CIS - page 17
- Treatment of CIS - page 17
- Drug profiles - page 18
- Coverage of the Stakeholder Insight Survey - page 17
- CHAPTER 3 COUNTRY TREATMENT TREES - page 19
- US - page 20
- Japan - page 22
- France - page 24
- Germany - page 26
- Italy - page 28
- Spain - page 30
- UK - page 32
- CHAPTER 4 EPIDEMIOLOGY & PATIENT SEGMENTATION - page 34
- Key findings - page 34
- Cognitive impairment in schizophrenia: definition and classification - page 35
- Diagnostic criteria of schizophrenia - page 35
- A - Characteristic symptoms - page 36
- B - Social/occupational dysfunction - page 38
- C - Duration - page 38
- D - Schizoaffective and mood disorder exclusion - page 38
- E - Substance/general medical condition exclusion - page 38
- F - Relationship to a pervasive developmental disorder - page 38
- The seven domains of cognitive impairment in schizophrenia - page 38
- CIS affects patient's quality of life - improvement of which may prove to be a useful endpoint in clinical trials - page 40
- Diagnostic criteria of schizophrenia - page 35
- Epidemiology of CIS - page 42
- Prevalence of CIS - page 42
- Schizophrenia affects 1% of the population - page 42
- CIS is stated as affecting 60% of patients with schizophrenia, although the true rate is likely to be higher - page 42
- Half of CIS patients suffer from mild cognitive impairment - page 46
- CIS is almost equally prevalent in males and females - page 48
- More than one-third of CIS patients suffer from one or more comorbidities - page 50
- Anxiety is the most prevalent comorbidity CIS - page 51
- Substance and alcohol abuse is frequently observed in CIS - page 53
- Depression affects one-third of CIS patients - page 55
- Oppositional defiant disorder and conduct disorder is reported in one in five CIS patients - page 57
- Speech/language disorder is reported in 13% of CIS patients - page 58
- Autism and Asperger's disorder affects only 6% of CIS patients - page 59
- Tic disorders and Tourette's syndrome are not frequently seen in CIS patients - page 60
- Psychiatrists reported that prevalence of CIS increase with age, although this is not supported by clinical data - page 61
- One-third of patients with CIS develop dementia in later life - page 67
- Data suggests that onset of dementia occurs 10 years earlier in patients with CIS - page 68
- Black box warnings restrict off-label antipsychotic use in elderly patients with dementia - page 70
- Prevalence of CIS - page 42
- CHAPTER 5 DIAGNOSIS AND TREATMENT OPTIONS - page 74
- Key findings - page 74
- Schizophrenia diagnostic guidelines - page 75
- Summary of the diagnostic criteria for schizophrenia - page 75
- Numerous cognitive tests are used by psychiatrists to assess cognitive impairment in schizophrenia - page 76
- MiniMental State Examination - page 76
- Positive and Negative Syndrome Assessment - page 76
- Wechsler Memory Scale - page 77
- Wisconsin Card Sorting Test - page 77
- Neuropsychological Assessment Battery - page 78
- Alzheimer's Disease Assessment Scale - page 78
- There is insufficient physician awareness of CIS and the available assessment tools - page 79
- MATRICS program provides consensus on clinical trial endpoints - page 82
- Strategic trial design can support demonstration of drug efficacy in CIS - page 84
- MATRICS recommendations for the clinical trial design for cognition enhancing drugs in schizophrenia - page 84
- Treatment Units for Research on Neurocognition and Schizophrenia encourage scientific research into CIS - page 89
- Less than 40% of patients with CIS are diagnosed - page 90
- CIS is detected early during the course of schizophrenia in Japan, France and Germany - page 93
- Positive symptoms remain the priority treatment domain of schizophrenia - page 97
- Social cognition, attention and executive function are the most clinically important domains of CIS to treat - page 100
- Guidelines for the treatment of schizophrenia provide little information on treating cognitive deficits - page 104
- Pharmacological treatments for schizophrenia and CIS - page 107
- Atypical antipsychotics - page 108
- Olanzapine - page 108
- Risperidone - page 109
- Quetiapine - page 110
- Aripiprazole - page 111
- Ziprasidone - page 111
- Amisulpride - page 112
- Perospirone - page 112
- Sertindole - page 112
- Zotepine - page 113
- Clozapine - page 113
- Typical neuroleptics - page 114
- Alzheimer's and dementia drugs - page 114
- Donepezil - page 115
- Rivastigmine - page 116
- Galantamine - page 117
- Memantine - page 117
- Other drugs - page 118
- Buflomedil - page 118
- Citicoline - page 118
- Benzodiazepines - page 118
- Atypical antipsychotics - page 108
- Non-pharmacological therapy - page 119
- Psychosocial therapy - page 119
- Acute phase - page 120
- Stabilization phase - page 121
- Stable phase - page 121
- Psychosocial therapy - page 119
- CIS increases the already high economic burden of schizophrenia - page 121
- CHAPTER 6 PRESCRIBING TRENDS AND INFLUENCING FACTORS - page 124
- Key findings - page 124
- Prescribing trends - page 125
- Atypical antipsychotics form more than 90% of schizophrenia maintenance treatment strategies - page 125
- Zyprexa and Risperdal are the most frequently used antipsychotics in schizophrenia maintenance therapy - page 127
- Only one-third of patients receive specific therapy for the treatment of cognitive impairment - page 130
- Time restrictions, and limited finances and resources, curtail the use of psychosocial therapy in CIS - page 133
- A variety of non-pharmacological therapeutic strategies are employed in the treatment of CIS - page 135
- Four strategies predominate for improving cognitive functioning in schizophrenia - page 138
- Switching from one atypical antipsychotic to another is the most frequently employed strategy to improve cognitive functioning - page 142
- Switching atypical antipsychotics is employed in two-thirds of antipsychotic switching strategies - page 142
- Risperdal and Zyprexa are the most frequent antipsychotics switched-to across the seven major markets - page 145
- Abilify and Geodon are the most frequent antipsychotics switched-to in the US - page 149
- Risperdal and Zyprexa are the most common antipsychotics switched-to in Europe and Japan - page 151
- Addition of an adjunctive non-antipsychotic drug is the third most frequently implemented strategy to improve cognitive functioning - page 155
- Addition of an anti-Alzheimer's drug is the most frequent adjunctive non-antipsychotic therapy employed to improve cognitive functioning - page 155
- Aricept is the most frequent non-antipsychotic drug added-on to schizophrenia maintenance therapy to improve cognitive functioning - page 158
- Aricept is the most frequent non-antipsychotic drug added-on to schizophrenia maintenance therapy in the US - page 162
- Aricept is the most frequent non-antipsychotic drug stated to be added-on to schizophrenia maintenance therapy in Europe and Japan - page 164
- Addition of an adjunctive antipsychotic drug is the fourth most frequently implemented strategy to improve cognitive functioning - page 168
- Addition of atypical antipsychotics is the most frequent antipsychotics adjunctive therapy employed to improve cognitive functioning - page 168
- Seroquel and Abilify are the most frequent antipsychotics added-on to schizophrenia maintenance therapy in the US - page 173
- Zyprexa and Risperdal are the most frequent antipsychotics added-on to schizophrenia maintenance therapy in Europe and Japan - page 174
- Patients remain on CIS therapy for approximately four months before switching to a second-line strategy - page 178
- Switching to an alternative antipsychotic is the most frequently employed second-line strategy to improve cognitive functioning - page 179
- Atypical antipsychotics form more than 90% of schizophrenia maintenance treatment strategies - page 125
- Factors influencing physician decision making - page 182
- Efficacy in improving the cognitive functioning in patients with CIS is the most likely attribute to influence physician drug choice - page 182
- Abilify rated most highly for the treatment of cognitive symptoms of schizophrenia - page 184
- Abilify rated most highly for the treatment of cognitive symptoms of schizophrenia in the US - page 186
- Zyprexa rated most highly for the treatment of global symptoms of schizophrenia in Japan - page 186
- Abilify rated most highly for the treatment of global symptoms of schizophrenia in France - page 187
- Abilify rated most highly for the treatment of global symptoms of schizophrenia in Germany - page 188
- Clozapine rated most highly for the treatment of global symptoms of schizophrenia in Italy and Spain - page 189
- Clozapine rated most highly for the treatment of global symptoms of schizophrenia in the UK - page 190
- CHAPTER 7 IMPROVING TREATMENT OUTCOMES - page 192
- Key findings - page 192
- The primary unmet need is the availability of a drug for the treatment of CIS - page 193
- Improved efficacy in multiple domains of cognitive impairment is desirable - page 193
- Greater efficacy without compromising upon side-effect profiles - page 194
- Increased public, patient and physician awareness and education - page 195
- Improved cognitive assessment and diagnosis will drive physician prescribing - page 196
- Numerous drugs with differing mechanisms of action are in development because the cause of CIS remains unknown - page 197
- Psychiatrists are relatively unaware of the key drugs in development which show the greatest propensity to treat CIS - page 198
- Top five drugs listed by interviewed psychiatrists in development with potential for the treatment of CIS - page 199
- Other pipeline drugs with the potential for treatment of CIS - page 201
- Psychiatrists are relatively unaware of the key drugs in development which show the greatest propensity to treat CIS - page 198
- The future of CIS therapy - page 213
- Adjunctive therapy offers the greatest potential - page 213
- Approved drugs will be prescribed for CIS, newly diagnosed schizophrenia and off-label in other psychiatric disorders - page 214
- It is unlikely that a drug will be approved for CIS within the next five years - page 217
- APPENDIX A - page 219
- Bibliography - page 219
- Websites - page 230
- APPENDIX B - page 233
- Physician sample breakdown - page 233
- Physician research methodology - page 235
- APPENDIX C - page 236
- Physician questionnaire - page 236
- SECTION 1 Epidemiology and diagnosis of CIS - page 237
- Section 2 Treatment - page 243
- Section 3 Drug profiles - page 249
- Report methodology - page 255
- Date of research completion - page 255
- About Datamonitor - page 255
- About Datamonitor Healthcare - page 255
- Datamonitor Healthcare's research and analysis methodologies - page 256
- Datamonitor Healthcare's therapy area capabilities - page 256
- About the CNS analysis team - page 257
- Key therapy team members - page 258
- Lynda Lynch, Director CNS - page 258
- David Abramson, Therapeutic Lead Consultant - page 258
- Disclaimer - page 259
- List of Tables
- Table 1: Prevalence (%) of CIS across the seven major markets - page 43
- Table 2: CIS severity categorization - page 46
- Table 3: Severity of cognitive impairment in CIS patients (%) - page 46
- Table 4: Proportion (%) of males versus female patients with CIS across the seven major markets - page 49
- Table 5: Prevalence (%) of patients with CIS exhibiting comorbid psychiatric disorders across the seven major markets - page 51
- Table 6: Proportion (%) of patients with schizophrenia who suffer from CIS, across the seven major markets - page 62
- Table 7: Proportion of CIS patients developing dementia in later life (%) - page 68
- Table 8: Age (years) of onset of dementia in CIS patients versus the general population, across the seven major markets - page 69
- Table 9: Diagnostic criteria for schizophrenia and its subtypes - page 75
- Table 10: Physician usage of tools for the assessment of cognitive impairment (%) - page 80
- Table 11: MATRICS CCB for clinical trials - page 83
- Table 12: MATRICS community functioning measures - page 84
- Table 13: Proportion of patients with CIS diagnosed across the seven major markets (%) - page 93
- Table 14: Time period from schizophrenia diagnosis when CIS is diagnosed in schizophrenia patients across the seven major markets (% patients with CIS diagnosed at time points) - page 93
- Table 15: Treatment priority for the primary domains of schizophrenia - rated by dividing 100 points across five domains, with increasing importance recognized by increased number of points - page 99
- Table 16: Treatment priority for the primary domains of cognitive impairment in schizophrenia - rated by dividing 100 points across five domains, with increasing importance recognized by increased number of points - page 101
- Table 17: Selecting antipsychotics for patients with complicating problems - page 106
- Table 18: Drugs prescribed for the treatment of CIS - page 107
- Table 19: Drug classes prescribed for schizophrenia maintenance therapy - page 126
- Table 20: Drug classes prescribed for schizophrenia, 2004 - page 126
- Table 21: Proportion of patients receiving drugs for schizophrenia maintenance therapy (%) - page 128
- Table 22: Top five drugs prescribed for schizophrenia maintenance therapy across the seven major markets - page 130
- Table 23: Proportion of patients with schizophrenia specifically treated to improve cognitive functioning (%) - page 132
- Table 24: Proportion of patients receiving each therapy type used in the treatment of CIS across the seven major markets (%) - page 133
- Table 25: Non-pharmacological therapies used in the treatment of CIS (% of patients receiving psychosocial therapy that receive each intervention) - page 136
- Table 26: Treatment strategies employed to improve cognitive functioning, across the seven major markets (%) - page 142
- Table 27: Antipsychotic switch strategies for the treatment of CIS across the seven major markets (% of patients switched) - page 143
- Table 28: Antipsychotics switched-to for the treatment of CIS across the seven major markets (% of patients switched to therapy) - page 146
- Table 29: Top antipsychotic switching strategies for CIS across the seven major markets (% of patient switches) - page 148
- Table 30: Top six antipsychotics switched-to for the treatment of CIS across the seven major markets (% of patients switched to therapy) - page 149
- Table 31: Top antipsychotic switching strategies for CIS across the seven major markets (%) - page 154
- Table 32: Add-on strategies for the treatment of CIS across the seven major markets (% of patients that receive non-antipsychotic adjunctive therapy) - page 155
- Table 33: Non-antipsychotic drugs added-on for the treatment of CIS across the seven major markets (% of non-antipsychotic add-on strategies) - page 158
- Table 34: Top non-antipsychotic add-on strategies for CIS across the seven major markets (% of antipsychotic plus non-antipsychotic strategies) - page 161
- Table 35: Top six non-antipsychotic drugs added-on for the treatment of CIS across the seven major markets (% of patients receiving non-antipsychotic add-on therapy) - page 162
- Table 36: Top non-antipsychotic add-on strategies for CIS across the seven major markets (% of antipsychotic plus non-antipsychotic strategies) - page 167
- Table 37: Antipsychotic add-on strategies for the treatment of CIS across the seven major markets (% of patients who receive an additional antipsychotic) - page 168
- Table 38: Antipsychotics added-on for the treatment of CIS across the seven major markets (% of antipsychotic add-on strategies) - page 170
- Table 39: Top antipsychotic add-on strategies for CIS across the seven major markets (% of patients who receive an additional antipsychotic) - page 172
- Table 40: Top six adjunctive antipsychotics for the treatment of CIS across the seven major markets (% of patients receiving antipsychotic add-on therapy) - page 173
- Table 41: Top antipsychotic add-on strategies for CIS across the seven major markets (% of patients receiving antipsychotic add-on therapy) - page 177
- Table 42: Duration of time before patients progress to second-line therapy, across the seven major markets (weeks) - page 178
- Table 43: Second line therapeutic strategies in the treatment of CIS (% of patients that have progressed to second line therapy) - page 180
- Table 44: Key drug attributes most likely to influence physician drug choice (%) - page 183
- Table 45: Top five drugs in each country as rated by interviewed psychiatrists for the treatment of positive and negative, cognitive and global symptoms of schizophrenia - page 185
- Table 46: Pipeline drugs reported (unprompted) by interviewed psychiatrists - page 211
- Table 47: Other pipeline drugs with potential for the treatment CIS, not reported by interview psychiatrists - page 212
- Table 48: US physician sample breakdown, 2005 - page 233
- Table 49: Japanese physician sample breakdown, 2005 - page 233
- Table 50: French physician sample breakdown, 2005 - page 234
- Table 51: German physician sample breakdown, 2005 - page 234
- Table 52: Italian physician sample breakdown, 2005 - page 234
- Table 53: Spanish physician sample breakdown, 2005 - page 235
- Table 54: UK physician sample breakdown, 2005 - page 235
- List of Figures
- Figure 1: Prevalence, diagnosis and drug treatment rates of CIS across the seven major markets. - page 7
- Figure 2: Prevalence and diagnosis rates of CIS in the US - page 20
- Figure 3: Drug treatment patterns of schizophrenia and CIS in the US - page 21
- Figure 4: Prevalence and diagnosis rates of CIS in Japan - page 22
- Figure 5: Drug treatment patterns of schizophrenia and CIS in Japan - page 23
- Figure 6: Prevalence and diagnosis rates of CIS in France - page 24
- Figure 7: Drug treatment patterns of schizophrenia and CIS in France - page 25
- Figure 8: Prevalence and diagnosis rates of CIS in Germany - page 26
- Figure 9: Drug treatment patterns of schizophrenia and CIS in Germany - page 27
- Figure 10: Prevalence and diagnosis rates of CIS in Italy - page 28
- Figure 11: Drug treatment patterns of schizophrenia and CIS in Italy - page 29
- Figure 12: Prevalence and diagnosis rates of CIS in Spain - page 30
- Figure 13: Drug treatment patterns of schizophrenia and CIS in Spain - page 31
- Figure 14: Prevalence and diagnosis rates of CIS in the UK - page 32
- Figure 15: Drug treatment patterns of schizophrenia and CIS in the UK - page 33
- Figure 16: Prevalence of CIS across the seven major markets (%) - page 43
- Figure 17: Severity of cognitive impairment in CIS patients - page 48
- Figure 18: Proportion of males versus female patients with CIS across the seven major markets (%) - page 50
- Figure 19: Prevalence of anxiety disorders in CIS across the seven major markets (%) - page 52
- Figure 20: Prevalence of substance and alcohol abuse in CIS across the seven major markets (%) - page 54
- Figure 21: Prevalence of depression in CIS across the seven major markets (%) - page 56
- Figure 22: Prevalence of oppositional defiant disorder and conduct disorder in CIS across the seven major markets - page 57
- Figure 23: Prevalence of speech and language disorders in CIS across the seven major markets (%) - page 58
- Figure 24: Prevalence of autism and Asperger's disorders in CIS across the seven major markets (%) - page 59
- Figure 25: Prevalence of tic disorder/Tourette's syndrome disorders in CIS across the seven major markets (%) - page 61
- Figure 26: Proportion (%) of patients with schizophrenia who suffer from CIS, across the seven major markets - page 62
- Figure 27: Spectrum of CIS - page 65
- Figure 28: Cognitive impairment in schizophrenia over time - page 66
- Figure 29: Proportion of CIS patients developing dementia in later life (%) - page 67
- Figure 30: Age of onset of dementia in CIS patients versus the general population, across the seven major markets - page 69
- Figure 31: Atypical antipsychotic black-box warning against usage in elderly patients with dementia related psychosis. - page 72
- Figure 32: Proportion of patients with CIS diagnosed across the seven major markets - page 92
- Figure 33: Time period from schizophrenia diagnosis when CIS is diagnosed in schizophrenia patients across the seven major markets - page 94
- Figure 34: Correlation of perceived prevalence and early diagnosis of CIS - page 96
- Figure 35: Treatment priority for the primary domains of schizophrenia - rated by dividing 100 points across five domains, with increasing importance recognized by increased number of points - page 99
- Figure 36: Treatment priority for the primary domains of cognitive impairment in schizophrenia - rated by dividing 100 points across five domains, with increasing importance recognized by increased number of points - page 100
- Figure 37: Drug classes prescribed for schizophrenia maintenance therapy - page 125
- Figure 38: Proportion of patients receiving drugs for schizophrenia maintenance therapy (%) - page 128
- Figure 39: Proportion of patients with schizophrenia specifically treated to improve cognitive functioning - page 132
- Figure 40: Therapy types used in the treatment of CIS across the seven major markets - page 133
- Figure 41: Non-pharmacological therapies used in the treatment of CIS - page 137
- Figure 42: Treatment strategies employed to improve cognitive functioning, across the seven major markets - page 141
- Figure 43: Antipsychotic switch strategies for the treatment of CIS across the seven major markets (% of patients switched) - page 143
- Figure 44: Antipsychotics switched-to for the treatment of CIS across the seven major markets (%) - page 147
- Figure 45: Add-on strategies for the treatment of CIS across the seven major markets (%) - page 156
- Figure 46: Correlation of frequency of non-antipsychotic adjunctive usage and response of "other/not stated" - page 157
- Figure 47: Non-antipsychotic drugs added-on for the treatment of CIS across the seven major markets (%) - page 159
- Figure 48: Antipsychotic add-on strategies for the treatment of CIS across the seven major markets (%) - page 169
- Figure 49: Antipsychotics added-on for the treatment of CIS across the seven major markets (%) - page 171
- Figure 50: Duration of time before patients progress to second-line CIS therapy, across the seven major markets - page 178
- Figure 51: Second line therapeutic strategies - page 181
- Figure 52: Key drug attributes most likely to influence physician drug choice for the treatment of CIS - page 182
- Figure 53: Psychiatrist rating of drugs used for the treatment of CIS - page 184
- Figure 54: Unmet needs in the treatment of CIS - page 193
- Figure 55: Physician awareness of pipeline drugs - page 199
- Figure 56: Use of cognitive enhancing drugs in schizophrenia and other psychiatric disorders - page 216
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