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

CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into the CIS market 5
Key metrics 7
CHAPTER 2 INTRODUCTION AND SCOPE 17
Coverage of the Stakeholder Insight Survey 17
Epidemiology and diagnosis of CIS 17
Treatment of CIS 17
Drug profiles 18
CHAPTER 3 COUNTRY TREATMENT TREES 19
US 20
Japan 22
France 24
Germany 26
Italy 28
Spain 30
UK 32
CHAPTER 4 EPIDEMIOLOGY & PATIENT SEGMENTATION 34
Key findings 34
Cognitive impairment in schizophrenia: definition and classification 35
Diagnostic criteria of schizophrenia 35
A – Characteristic symptoms 36
B – Social/occupational dysfunction 38
C – Duration 38
D – Schizoaffective and mood disorder exclusion 38
E – Substance/general medical condition exclusion 38
F – Relationship to a pervasive developmental disorder 38
The seven domains of cognitive impairment in schizophrenia 38
CIS affects patient’s quality of life – improvement of which may prove to be a useful endpoint in clinical trials 40
Epidemiology of CIS 42
Prevalence of CIS 42
Schizophrenia affects 1% of the population 42
CIS is stated as affecting 60% of patients with schizophrenia, although the true rate is likely to be higher 42
Half of CIS patients suffer from mild cognitive impairment 46
CIS is almost equally prevalent in males and females 48
More than one-third of CIS patients suffer from one or more comorbidities 50
Anxiety is the most prevalent comorbidity CIS 51
Substance and alcohol abuse is frequently observed in CIS 53
Depression affects one-third of CIS patients 55
Oppositional defiant disorder and conduct disorder is reported in one in five CIS patients 57
Speech/language disorder is reported in 13% of CIS patients 58
Autism and Asperger’s disorder affects only 6% of CIS patients 59
Tic disorders and Tourette’s syndrome are not frequently seen in CIS patients 60
Psychiatrists reported that prevalence of CIS increase with age, although this is not supported by clinical data 61
One-third of patients with CIS develop dementia in later life 67
Data suggests that onset of dementia occurs 10 years earlier in patients with CIS 68
Black box warnings restrict off-label antipsychotic use in elderly patients with dementia 70
CHAPTER 5 DIAGNOSIS AND TREATMENT OPTIONS 74
Key findings 74
Schizophrenia diagnostic guidelines 75
Summary of the diagnostic criteria for schizophrenia 75
Numerous cognitive tests are used by psychiatrists to assess cognitive impairment in schizophrenia 76
MiniMental State Examination 76
Positive and Negative Syndrome Assessment 76
Wechsler Memory Scale 77
Wisconsin Card Sorting Test 77
Neuropsychological Assessment Battery 78
Alzheimer’s Disease Assessment Scale 78
There is insufficient physician awareness of CIS and the available assessment tools 79
MATRICS program provides consensus on clinical trial endpoints 82
Strategic trial design can support demonstration of drug efficacy in CIS 84
MATRICS recommendations for the clinical trial design for cognition enhancing drugs in schizophrenia 84
Treatment Units for Research on Neurocognition and Schizophrenia encourage scientific research into CIS 89
Less than 40% of patients with CIS are diagnosed 90
CIS is detected early during the course of schizophrenia in Japan, France and Germany 93
Positive symptoms remain the priority treatment domain of schizophrenia 97
Social cognition, attention and executive function are the most clinically important domains of CIS to treat 100
Guidelines for the treatment of schizophrenia provide little information on treating cognitive deficits 104
Pharmacological treatments for schizophrenia and CIS 107
Atypical antipsychotics 108
Olanzapine 108
Risperidone 109
Quetiapine 110
Aripiprazole 111
Ziprasidone 111
Amisulpride 112
Perospirone 112
Sertindole 112
Zotepine 113
Clozapine 113
Typical neuroleptics 114
Alzheimer’s and dementia drugs 114
Donepezil 115
Rivastigmine 116
Galantamine 117
Memantine 117
Other drugs 118
Buflomedil 118
Citicoline 118
Benzodiazepines 118
Non-pharmacological therapy 119
Psychosocial therapy 119
Acute phase 120
Stabilization phase 121
Stable phase 121
CIS increases the already high economic burden of schizophrenia 121
CHAPTER 6 PRESCRIBING TRENDS AND INFLUENCING FACTORS 124
Key findings 124
Prescribing trends 125
Atypical antipsychotics form more than 90% of schizophrenia maintenance treatment strategies 125
Zyprexa and Risperdal are the most frequently used antipsychotics in schizophrenia maintenance therapy 127
Only one-third of patients receive specific therapy for the treatment of cognitive impairment 130
Time restrictions, and limited finances and resources, curtail the use of psychosocial therapy in CIS 133
A variety of non-pharmacological therapeutic strategies are employed in the treatment of CIS 135
Four strategies predominate for improving cognitive functioning in schizophrenia 138
Switching from one atypical antipsychotic to another is the most frequently employed strategy to improve cognitive functioning 142
Switching atypical antipsychotics is employed in two-thirds of antipsychotic switching strategies 142
Risperdal and Zyprexa are the most frequent antipsychotics switched-to across the seven major markets 145
Abilify and Geodon are the most frequent antipsychotics switched-to in the US 149
Risperdal and Zyprexa are the most common antipsychotics switched-to in Europe and Japan 151
Addition of an adjunctive non-antipsychotic drug is the third most frequently implemented strategy to improve cognitive functioning 155
Addition of an anti-Alzheimer’s drug is the most frequent adjunctive non-antipsychotic therapy employed to improve cognitive functioning 155
Aricept is the most frequent non-antipsychotic drug added-on to schizophrenia maintenance therapy to improve cognitive functioning 158
Aricept is the most frequent non-antipsychotic drug added-on to schizophrenia maintenance therapy in the US 162
Aricept is the most frequent non-antipsychotic drug stated to be added-on to schizophrenia maintenance therapy in Europe and Japan 164
Addition of an adjunctive antipsychotic drug is the fourth most frequently implemented strategy to improve cognitive functioning 168
Addition of atypical antipsychotics is the most frequent antipsychotics adjunctive therapy employed to improve cognitive functioning 168
Seroquel and Abilify are the most frequent antipsychotics added-on to schizophrenia maintenance therapy in the US 173
Zyprexa and Risperdal are the most frequent antipsychotics added-on to schizophrenia maintenance therapy in Europe and Japan 174
Patients remain on CIS therapy for approximately four months before switching to a second-line strategy 178
Switching to an alternative antipsychotic is the most frequently employed second-line strategy to improve cognitive functioning 179
Factors influencing physician decision making 182
Efficacy in improving the cognitive functioning in patients with CIS is the most likely attribute to influence physician drug choice 182
Abilify rated most highly for the treatment of cognitive symptoms of schizophrenia 184
Abilify rated most highly for the treatment of cognitive symptoms of schizophrenia in the US 186
Zyprexa rated most highly for the treatment of global symptoms of schizophrenia in Japan 186
Abilify rated most highly for the treatment of global symptoms of schizophrenia in France 187
Abilify rated most highly for the treatment of global symptoms of schizophrenia in Germany 188
Clozapine rated most highly for the treatment of global symptoms of schizophrenia in Italy and Spain 189
Clozapine rated most highly for the treatment of global symptoms of schizophrenia in the UK 190
CHAPTER 7 IMPROVING TREATMENT OUTCOMES 192
Key findings 192
The primary unmet need is the availability of a drug for the treatment of CIS 193
Improved efficacy in multiple domains of cognitive impairment is desirable 193
Greater efficacy without compromising upon side-effect profiles 194
Increased public, patient and physician awareness and education 195
Improved cognitive assessment and diagnosis will drive physician prescribing 196
Numerous drugs with differing mechanisms of action are in development because the cause of CIS remains unknown 197
Psychiatrists are relatively unaware of the key drugs in development which show the greatest propensity to treat CIS 198
Top five drugs listed by interviewed psychiatrists in development with potential for the treatment of CIS 199
Other pipeline drugs with the potential for treatment of CIS 201
The future of CIS therapy 212
Adjunctive therapy offers the greatest potential 212
Approved drugs will be prescribed for CIS, newly diagnosed schizophrenia and off-label in other psychiatric disorders 213
It is unlikely that a drug will be approved for CIS within the next five years 216
APPENDIX A 218
Bibliography 218
Websites 229
APPENDIX B 232
Physician sample breakdown 232
Physician research methodology 234
APPENDIX C 235
Physician questionnaire 235
SECTION 1 Epidemiology and diagnosis of CIS 236
Section 2 Treatment 242
Section 3 Drug profiles 248
Report methodology 254
Date of research completion 254
About Datamonitor 254
About Datamonitor Healthcare 254
Datamonitor Healthcare’s research and analysis methodologies 255
Datamonitor Healthcare’s therapy area capabilities 255
About the CNS analysis team 256
Key therapy team members 257
Lynda Lynch, Director CNS 257
David Abramson, Therapeutic Lead Consultant 257
Disclaimer 258