Major depressive disorder (MDD) is one of the most common psychiatric diseases worldwide. The MDD market is a crowded and competitive market, with more than 30 marketed products available for the treatment of patients with MDD. The depression market is about to enter a dynamic phase with imminent patent expiries for top selling products, such as Eli Lilly’s Cymbalta, and Otsuka/BMS’s Abilify, along with the recent launch of the multimodal antidepressant, Lundbeck/Takeda’s Brintellix, in January 2014, and the potential introduction of seven promising late-stage pipeline products into the market during the forecast period, from 2013 to 2023.

Highlights

Key Questions Answered

• What will be the impact of imminent patent expiries for top selling products, such as Eli Lilly’s Cymbalta and Otsuka/BMS’s Abilify in the MDD market?
• What do physicians think about Lundbeck/Takeda’s Brintellix and what will be the impact of its 2014 launch in the MDD market?
• What is the significance of late-phase pipeline products and how will their launch shape the future treatment landscape in MDD?
• What are the significant unmet needs in the MDD market?
• What are the remaining opportunities in the MDD market?

Key Findings

• Minimal growth in the MDD market is expected from 2013 to 2023. The key drivers will be the increasing uptake for Lundbeck/Takeda’s Brintellix, the potential introduction of seven late-stage pipeline drugs into the MDD market, and the increasing number of prevalent cases of MDD.
• Key players develop products to broaden and strengthen their portfolios, enter into partnerships for the co-development and co-marketing of products in different regions, and develop products with a novel mechanism of action in order to compete effectively in the crowded depression market.
• The most pressing unmet need in the depression market is for the development of drugs with improved efficacy.
• Opportunities remain for products that will meet the significant unmet needs that exist in the MDD market. Products that demonstrate better efficacy, improved safety, and rapid antidepressant effects will move to the forefront of the treatment line.

Scope

• Overview of MDD, including epidemiology, etiology, pathophysiology, symptoms, diagnosis, and current treatment options.
• Annualized MDD therapeutics market revenue, annual cost of therapy and treatment usage pattern data from 2013 and forecast for ten years to 2023.
• Key topics covered include strategic competitor assessment, market characterization, unmet needs, and implications for the MDD therapeutics market.
• Pipeline analysis: comprehensive data split across different phases, emerging novel trends under development, and detailed analysis of mid-stage pipeline drugs.
• Analysis of the current and future market competition in the global MDD therapeutics market. Insightful review of the key industry drivers, restraints and challenges. Each trend is independently researched to provide qualitative analysis of its implications.

Reasons to buy

• Develop and design in-licensing and out-licensing strategies through a review of pipeline products and technologies, and by identifying the companies with the most robust pipeline. Additionally a list of acquisition targets included in the pipeline product company list.
• Develop business strategies by understanding the trends shaping and driving the global MDD therapeutics market.
• Drive revenues by understanding the key trends, innovative products and technologies, market segments, and companies likely to impact the global MDD therapeutics market in the future.
• Formulate effective sales and marketing strategies by understanding the competitive landscape and by analyzing the performance of various competitors.
• Identify emerging players with potentially strong product portfolios and create effective counter-strategies to gain a competitive advantage.
• Track drug sales in the global MDD therapeutics market from 2013-2023.
• Organize sales and marketing efforts by identifying the market categories and segments that present maximum opportunities for consolidations, investments and strategic partnerships.

Table of Contents

1 Table of Contents 8
1.1 List of Tables15
1.2 List of Figures 21

2 Introduction 23
2.1 Catalyst 23
2.2 Related Reports 23
2.3 Upcoming Related Reports 23

3 Disease Overview 24
3.1 Etiology and Pathophysiology 24
3.1.1 Etiology 24
3.1.2 Pathophysiology 24
3.2 Classification 26
3.3 Symptoms and Subtypes of Major Depressive Disorder 28
3.4 Prognosis 29
3.5 Quality of Life 29

4 Epidemiology 30
4.1 Risk Factors and Comorbidities 30
4.1.1 A Family History of MDD Increases the Risk for MDD by Almost 14 Times 30
4.1.2 Substance Abuse and Lifetime Anxiety Disorders are Highly Prevalent in MDD Patients 31
4.2 Global and Historical Trends 32
4.3 Forecast Methodology 35
4.3.1 Sources Used 37
4.3.2 Forecast Assumptions and Methods 41
4.3.3 Sources Not Used 43
4.4 Epidemiological Forecast for MDD (2013-2023) 45
4.4.1 Total Prevalent Cases of MDD 45
4.4.2 Age-Specific Total Prevalent Cases of MDD 47
4.4.3 Sex-Specific Total Prevalent Cases of MDD 48
4.4.4 Age-Standardized Total Prevalence of MDD 50
4.5 Discussion 51
4.5.1 Epidemiological Forecast Insight 51
4.5.2 Limitations of the Analysis 52
4.5.3 Strengths of the Analysis 53

5 Disease Management 54
5.1 Diagnosis and Treatment Overview 54
5.1.1 Diagnosis 54
5.1.2 Treatment Guidelines and Leading Prescribed Drugs 55
5.1.3 Clinical Practice 58
5.2 US 62
5.3 France 65
5.4 Germany 67
5.5 Italy 69
5.6 Spain 72
5.7 UK 74
5.8 Japan 76
5.9 Australia 78

6 Competitive Assessment 80
6.1 Overview 80
6.2 Product Profiles: Major Brands, Selective Serotonin Reuptake Inhibitors 82
6.2.1 Lexapro (Escitalopram) 82
6.2.2 Viibryd (Vilazodone) 86
6.2.3 Other Selective Serotonin Reuptake Inhibitors 91
6.3 Product Profiles: Major Brands, Serotonin-Norepinephrine Reuptake Inhibitors 95
6.3.1 Effexor (Venlafaxine) 95
6.3.2 Cymbalta (Duloxetine) 100
6.3.3 Pristiq (Desvenlafaxine) 104
6.3.4 Fetzima (Levomilnacipran) 109
6.3.5 Savella (Milnacipran) 114
6.4 Product Profiles: Major Brands, Other Antidepressants 117
6.4.1 Norepinephrine-Dopamine Reuptake Inhibitors 117
6.4.2 Noradrenaline and Specific Serotonergic Antidepressants 122
6.4.3 Monoamine Oxidase Inhibitors 127
6.4.4 Tricyclic Antidepressants 130
6.4.5 Brintellix (Vortioxetine) 133
6.5 Product Profiles: Major Brands, Antipsychotics 140
6.5.1 Abilify (Aripiprazole) 140
6.5.2 Seroquel XR (Quetiapine) 145
6.6 Other Therapeutic Classes 150

7 Unmet Needs and Opportunities 151
7.1 Overview 151
7.2 More Effective Pharmacotherapies 152
7.2.1 Unmet Needs 152
7.2.2 Gap Analysis 153
7.2.3 Opportunities 154
7.3 More Favorable Side Effect Profiles 154
7.3.1 Unmet Needs 154
7.3.2 Gap Analysis 155
7.3.3 Opportunities 155
7.4 Rapid Onset of Antidepressant Effects 156
7.4.1 Unmet Needs 156
7.4.2 Gap Analysis 156
7.4.3 Opportunities 156
7.5 Personalized Treatment Approach 157
7.5.1 Unmet Needs 157
7.5.2 Gap Analysis 158
7.5.3 Opportunities 158

8 Pipeline Assessment 159
8.1 Overview 159
8.2 Clinical Trial Mapping 159
8.2.1 Clinical Trials by Class of Therapy 159
8.3 Promising Drugs in Clinical Development 160
8.3.1 Brexpiprazole (OPC-34712) 163
8.3.2 Cariprazine (RGH-188) 170
8.3.3 ALKS-5461 176
8.3.4 Amitifadine (EB-1010) 183
8.3.5 GLYX-13 189
8.3.6 Tedatioxetine (Lu AA24530) 194
8.3.7 ETS6103 199
8.4 Other Drugs in Development 204

9 Current and Future Players 206
9.1 Overview 206
9.2 Trends in Corporate Strategy 209
9.3 Company Profiles 210
9.3.1 Lundbeck 210
9.3.2 Forest Laboratories (Actavis) 214
9.3.3 Eli Lilly 217
9.3.4 Pfizer 218
9.3.5 Otsuka Pharmaceutical 220
9.3.6 AstraZeneca 222
9.3.7 Takeda Pharmaceutical 224
9.3.8 Alkermes 226
9.3.9 Euthymics Bioscience 228
9.3.10 Naurex 230
9.3.11 e-Therapeutics 232

10 Market Outlook 235
10.1 Global 235
10.1.1 Forecast 235
10.1.2 Drivers and Barriers - Global Issues 239
10.2 US 241
10.2.1 Forecast 241
10.2.2 Key Events 245
10.2.3 Drivers and Barriers 245
10.3 France 248
10.3.1 Forecast 248
10.3.2 Key Events 251
10.3.3 Drivers and Barriers 251
10.4 Germany 253
10.4.1 Forecast 253
10.4.2 Key Events 257
10.4.3 Drivers and Barriers 257
10.5 Italy 259
10.5.1 Forecast 259
10.5.2 Key Events 263
10.5.3 Drivers and Barriers 263
10.6 Spain 265
10.6.1 Forecast 265
10.6.2 Key Events 269
10.6.3 Drivers and Barriers 269
10.7 UK 271
10.7.1 Forecast 271
10.7.2 Key Events 275
10.7.3 Drivers and Barriers 275
10.8 Japan 277
10.8.1 Forecast 277
10.8.2 Key Events 281
10.8.3 Drivers and Barriers 281
10.9 Australia 284
10.9.1 Forecast 284
10.9.2 Key Events 287
10.9.3 Drivers and Barriers 287

11 Appendix 290
11.1 Bibliography 290
11.2 Abbreviations 300
11.3 Methodology 305
11.4 Forecasting Methodology 305
11.4.1 Diagnosed MDD Patients 305
11.4.2 Percent of Drug-Treated Patients 305
11.4.3 Drugs Included in Each Therapeutic Class 306
11.4.4 Launch and Patent Expiry Dates 306
11.4.5 General Pricing Assumptions 307
11.4.6 Individual Drug Assumptions 308
11.4.7 Generic Erosion 314
11.4.8 Pricing of Pipeline Agents 314
11.5 Physicians and Specialists Included in this Study 316
11.6 About the Authors 318
11.6.1 Analyst 318
11.6.2 Therapy Area Directors 318
11.6.3 Epidemiologist 319
11.6.4 Global Head of Healthcare 320
11.7 About GlobalData 321
11.8 Disclaimer 321

List of Tables

Table 1: Classification and Criteria of Major Depressive Disorder (DSM-IV) and Major Depressive Episode (ICD-10) 27
Table 2: Subtypes of Major Depressive Disorder 28
Table 3: Risk Factors and Comorbidities for MDD 30
Table 4: Prevalence of the Most Frequent Psychiatric Comorbidities in Individuals with and without MDD 32
Table 5: Total Prevalence (%) of MDD According to the DSM-IV Criteria 34
Table 6: Total Prevalence* (%) of MDD According to the DSM-III Criteria 34
Table 7: Sources of the MDD Prevalence Data Used to Forecast the Total Prevalent Cases of MDD 36
Table 8: Sources Excluded from the Forecast for the Total Prevalent Cases of MDD 44
Table 9: Total Prevalent Cases of MDD, Ages ?20 Years, Both Sexes, N, 2013-2023 46
Table 10: Total Prevalent Cases of MDD, by Age, Both Sexes, N (Row %), 2013 47
Table 11: Total Prevalent Cases of MDD, by Sex, Ages ?20 Years, N (Row %), 2013 49
Table 12: Severity of Depressive Episodes according to ICD-10 and DSM-IV Diagnostic Criteria 54
Table 13: Treatment Guidelines for Major Depressive Disorder 56
Table 14: Most Prescribed Drugs for MDD by Class in the 7MM and Australia, 2013 58
Table 15: Country Profile - US 64
Table 16: Country Profile - France 66
Table 17: Country Profile - Germany 69
Table 18: Country Profile - Italy 71
Table 19: Country Profile - Spain 73
Table 20: Country Profile - UK 75
Table 21: Country Profile - Japan 77
Table 22: Country Profile - Australia 79
Table 23: Leading Treatments for MDD, 2013 81
Table 24: Product Profile - Lexapro 83
Table 25: Safety of Lexapro - Five Most Frequently Reported Adverse Events 85
Table 26: Lexapro SWOT Analysis, 2014 85
Table 27: Global MDD Sales Forecasts ($m) for Lexapro, 2013-2023 86
Table 28: Product Profile - Viibryd 88
Table 29: Summary of Efficacy Results for the Primary Endpoint in Viibryd Clinical Trials 88
Table 30: Safety of Viibryd - Five Most Frequently Reported Adverse Events 89
Table 31: Viibryd SWOT Analysis, 2023 90
Table 32: Global MDD Sales Forecasts ($m) for Viibryd, 2013-2023 91
Table 33: Relative Frequency of Common Adverse Effects for Different SSRIs 94
Table 34: Global MDD Sales Forecasts ($m) for Other SSRIs, 2013-2023 95
Table 35: Product Profile - Effexor 97
Table 36: Effexor SWOT Analysis, 2014 99
Table 37: Global MDD Sales Forecasts ($m) for Effexor XR, 2013-2023 100
Table 38: Product Profile - Cymbalta 101
Table 39: Cymbalta SWOT Analysis, 2023 103
Table 40: Global MDD Sales Forecasts ($m) for Cymbalta, 2013-2023 104
Table 41: Product Profile - Pristiq 105
Table 42: Efficacy of Pristiq in short-term studies 106
Table 43: Pristiq SWOT Analysis, 2014 108
Table 44: Global MDD Sales Forecasts ($m) for Pristiq, 2013-2023 109
Table 45: Product Profile - Fetzima 110
Table 46: Clinical Efficacy of Fetzima from its Three Pivotal Studies 111
Table 47: Safety of Fetzima - Five Most Frequently Reported Adverse Events in Clinical Studies 112
Table 48: Fetzima SWOT Analysis, 2014 112
Table 49: Global MDD Sales Forecasts ($m) for Fetzima, 2013-2023 113
Table 50: Product Profile - Savella 114
Table 51: Savella SWOT Analysis, 2014 116
Table 52: Global Sales Forecasts ($m) for Savella, 2013-2023 117
Table 53: Product Profile - Bupropion 119
Table 54: Safety of Bupropion - Five Most Frequently Reported Adverse Events 120
Table 55: Bupropion SWOT Analysis, 2014 121
Table 56: Global MDD Sales Forecasts ($m) for Bupropion 2013-2023 122
Table 57: Product Profile - Mirtazapine 124
Table 58: Safety of Mirtazapine - Four Most Frequently Reported Adverse Events 125
Table 59: Mirtazapine SWOT Analysis, 2014 126
Table 60: Global MDD Sales Forecasts ($m) for Mirtazapine, 2013-2023 127
Table 61: MAOI SWOT Analysis, 2014 129
Table 62: Global MDD Sales Forecasts ($m) for MAOIs, 2013-2023 130
Table 63: TCAs SWOT Analysis, 2014 132
Table 64: Global MDD Sales Forecasts ($m) for TCAs, 2013-2023 133
Table 65: Product Profile - Brintellix 135
Table 66: Efficacy of Brintellix in Six-Week to Eight-Week Clinical Trials 136
Table 67: Safety of Brintellix - Five Most Frequently Reported Adverse Events 138
Table 68: Brintellix SWOT Analysis, 2014 138
Table 69: Global MDD Sales Forecasts ($m) for Brintellix, 2013-2023 139
Table 70: Product Profile - Abilify 141
Table 71: Safety of Abilify - Five Most Frequently Reported Adverse Events 143
Table 72: Abilify SWOT Analysis, 2014 143
Table 73: Global MDD Sales Forecasts ($m) for Abilify, 2013-2023 144
Table 74: Product Profile - Seroquel XR 146
Table 75: Efficacy of Seroquel XR as an Adjunctive Therapy to Antidepressants 147
Table 76: Safety of Seroquel XR- Five Most Frequently Reported Adverse Events 148
Table 77: Seroquel XR SWOT Analysis, 2014 148
Table 78: Global MDD Sales Forecasts ($m) for Seroquel XR, 2013-2023 149
Table 79: Summary of Minor Therapeutic Classes in MDD, 2013 150
Table 80: Unmet Needs and Opportunities in MDD 152
Table 81: Comparison of Therapeutic Classes in Development for MDD, 2013 162
Table 82: Product Profile - Brexpiprazole 165
Table 83: Safety of Brexpiprazole - Most Frequently Reported Adverse Events 167
Table 84: Brexpiprazole SWOT Analysis, 2014 169
Table 85: Global MDD Sales Forecasts ($m) for Brexpiprazole, 2013-2023 170
Table 86: Product Profile - Cariprazine 172
Table 87: Cariprazine SWOT Analysis, 2014 175
Table 88: Global MDD Sales Forecasts ($m) for Cariprazine, 2013-2023 176
Table 89: Product Profile - ALKS-5461 178
Table 90: ALKS-5461 SWOT Analysis, 2014 182
Table 91: Global MDD Sales Forecasts ($m) for ALKS-5461, 2013-2023 183
Table 92: Product Profile - Amitifadine 184
Table 93: Amitifadine SWOT Analysis, 2014 188
Table 94: Global MDD Sales Forecasts ($m) for Amitifadine, 2013-2023 189
Table 95: Product Profile - GLYX-13 190
Table 96: GLYX-13 SWOT Analysis, 2014 193
Table 97: Global MDD Sales Forecasts ($m) for GLYX-13, 2013-2023 194
Table 98: Product Profile - Tedatioxetine 195
Table 99: Tedatioxetine SWOT Analysis, 2014 198
Table 100: Global MDD Sales Forecasts ($m) for Tedatioxetine, 2013-2023 199
Table 101: Product Profile - ETS6103 200
Table 102: ETS6103 SWOT Analysis, 2014 203
Table 103: Global MDD Sales Forecasts ($m) for ETS6103, 2013-2023 204
Table 104: Drugs in Development for MDD, 2014 205
Table 105: Key Companies in the MDD Market in the 7MM and Australia, 2013 208
Table 106: Lundbeck's MDD Portfolio Assessment, 2013 212
Table 107: Forest (Actavis)'s MDD Portfolio Assessment, 2013 215
Table 108: Eli Lilly's MDD Portfolio Assessment, 2013 217
Table 109: Pfizer's MDD Portfolio Assessment, 2013 219
Table 110: Otsuka's MDD Portfolio Assessment, 2013 221
Table 111: AstraZeneca's MDD Portfolio Assessment, 2013 223
Table 112: Takeda's MDD Portfolio Assessment, 2013 225
Table 113: Alkermes's MDD Portfolio Assessment, 2013 227
Table 114: Euthymics Bioscience's MDD Portfolio Assessment, 2013 229
Table 115: Naurex's MDD Portfolio Assessment, 2013 231
Table 116: e-Therapeutics's MDD Portfolio Assessment, 2013 233
Table 117: Global Sales Forecasts ($) for MDD, 2013-2023 237
Table 118: MDD Market - Drivers and Barriers, 2013-2023 239
Table 119: Sales Forecasts ($m) for MDD in the US, 2013-2023 243
Table 120: Key Events Impacting Sales for MDD in the US, 2013-2023 245
Table 121: MDD Market in the US - Drivers and Barriers, 2013-2023 245
Table 122: Sales Forecasts ($m) for MDD in France, 2013-2023 249
Table 123: Key Events Impacting Sales for MDD in France, 2013-2023 251
Table 124: MDD Market in France - Drivers and Barriers, 2013-2023 251
Table 125: Sales Forecasts ($m) for MDD in Germany, 2013-2023 255
Table 126: Key Events Impacting Sales for MDD in Germany, 2013-2023 257
Table 127: MDD Market in Germany - Drivers and Barriers, 2013-2023 257
Table 128: Sales Forecasts ($m) for MDD in Italy, 2013-2023 261
Table 129: Key Events Impacting Sales for MDD in Italy, 2013-2023 263
Table 130: MDD Market in Italy - Drivers and Barriers, 2013-2023 263
Table 131: Sales Forecasts ($m) for MDD in Spain, 2013-2023 267
Table 132: Key Events Impacting Sales for MDD in Spain, 2013-2023 269
Table 133: MDD Market in Spain - Drivers and Barriers, 2013-2023 269
Table 134: Sales Forecasts ($m) for MDD in the UK, 2013-2023 273
Table 135: Key Events Impacting Sales for MDD in the UK, 2013-2023 275
Table 136: MDD Market in the UK - Drivers and Barriers, 2013-2023 275
Table 137: Sales Forecasts ($m) for MDD in Japan, 2013-2023 279
Table 138: Key Events Impacting Sales for MDD in Japan, 2013-2023 281
Table 139: MDD Market in Japan - Drivers and Barriers, 2013-2013 281
Table 140: Sales Forecasts ($m) for MDD in Australia, 2013-2023 285
Table 141: Key Events Impacting Sales for MDD in Australia, 2013-2023 287
Table 142: MDD Market in Australia - Drivers and Barriers, 2013-2023 287
Table 143: Key Launch Dates 306
Table 144: Key Patent Expiries 307
Table 145: High-Prescribing Physicians (Non-KOLs) Surveyed, by Country 317

List of Figures

Figure 1: Overview of Targets of Antidepressant Action on Noradrenergic and Serotonergic Neurons 26
Figure 2: Total Prevalent Cases of MDD, Ages ?20 Years, Both Sexes, N, 2013-2023 46
Figure 3: Total Prevalent Cases of MDD, by Age, Both Sexes, N, 2013 48
Figure 4: Total Prevalent Cases of MDD, by Sex, Ages ?20 Years, N, 2013 49
Figure 5: Age-Standardized Total Prevalence (%) of MDD, by Sex, Ages ?20 Years, 2013 50
Figure 6: Disease Management Model for Major Depressive Disorder 60
Figure 7: Major Depressive Disorder Treatment Algorithm 62
Figure 8: Major Depressive Disorder Therapeutics - Class of Therapy, 2014 160
Figure 9: MDD - Phase IIb-III Pipeline, 2014 161
Figure 10: Competitive Assessment of Late-Stage Pipeline Agents in MDD, 2013-2023 162
Figure 11: Clinical and Commercial Positioning of Brexpiprazole 168
Figure 12: Clinical and Commercial Positioning of Cariprazine 174
Figure 13: Clinical and Commercial Positioning of ALKS-5461 181
Figure 14: Clinical and Commercial Positioning of Amitifadine 187
Figure 15: Clinical and Commercial Positioning of GLYX-13 192
Figure 16: Clinical and Commercial Positioning of Tedatioxetine 197
Figure 17: Clinical and Commercial Positioning of ETS6103 202
Figure 18: Company Portfolio Gap Analysis in MDD, 2013-2023 209
Figure 19: Lundbeck SWOT Analysis in MDD, 2013-2023 213
Figure 20: Forest (Actavis) SWOT Analysis in MDD, 2013-2023 216
Figure 21: Eli Lilly SWOT Analysis in MDD, 2013-2023 218
Figure 22: Pfizer SWOT Analysis in MDD, 2013-2023 220
Figure 23: Otsuka SWOT Analysis in MDD, 2013-2023 222
Figure 24: AstraZeneca SWOT Analysis in MDD, 2013-2023 224
Figure 25: Takeda SWOT Analysis in MDD, 2013-2023 226
Figure 26: Alkermes SWOT Analysis in MDD, 2013-2023 228
Figure 27: Euthymics Bioscience SWOT Analysis in MDD, 2013-2023 230
Figure 28: Naurex SWOT Analysis in MDD, 2013-2023 232
Figure 29: e-Therapeutics SWOT Analysis in MDD, 2013-2023 234
Figure 30: Global Sales for MDD by Region, 2013-2023 238
Figure 31: Sales for MDD in the US by Drug Class, 2013-2023 244
Figure 32: Sales for MDD in France by Drug Class, 2013-2023 250
Figure 33: Sales for MDD in Germany by Drug Class, 2013-2023 256
Figure 34: Sales for MDD in Italy by Drug Class, 2013-2023 262
Figure 35: Sales for MDD in Spain by Drug Class, 2013-2023 268
Figure 36: Sales for MDD in the UK by Drug Class, 2013-2023 274
Figure 37: Sales for MDD in Japan by Drug Class, 2013-2023 280
Figure 38: Sales for MDD in Australia by Drug Class, 2013-2023 286