Preface 1 .................................................... XIII
Preface 2 ...................................................... XV
A view from Esteve ............................................ XIX
Dedication and Acknowledgements ............................... XXI
List of Contributors ........................................ XXIII
Glossary ..................................................... XXIX
VOLUME 1
1. Depressive Disorders ......................................... 1
1.1. Introductory and Basic Aspects .......................... 3
Neurobiology of Mood Disorders .......................... 3
Luz Romero, Ana Montero, Begoña Fernández and
José M. Vela
1.1.1. Definition of mood disorders, impact on a
global scale and unmet needs ..................... 3
1.1.2. Causes and associations in mood disorders:
genetics and pharmaco-genetics .................. 10
1.1.3. Pathogenesis of mood disorders .................. 14
1.1.4. Concluding remarks .............................. 33
References .................................................. 35
1.2. Clinics ................................................ 51
Clinical Aspects of Depressive Disorders
Rosario Peérez-Egea, Victor Pérez,
Dolors Puigdemont and Enric Alvarez
1.2.1. Introduction .................................... 51
1.2.2. Classification .................................. 52
1.2.3. Epidemiology .................................... 61
1.2.4. Physiopathology ................................. 63
1.2.5. Treatment of affective disorders ................ 68
References ................................................. 104
1.3. Pharmacology .......................................... 111
Pharmacotherapy of Depression
Begoña Fernández, Luz Romero and
Ana Montero
1.3.1. Introduction ................................... 111
1.3.2. Current antidepressant treatments .............. 112
1.3.3. New strategies for antidepressant treatments ... 116
1.3.4. Concluding remarks ............................. 131
References ................................................. 132
1.4. Experimental Research ................................. 141
Modeling Human Depression by Animal Models
Ana Montero, Begoña Fernández and
Luz Romero
1.4.1. Introduction ................................... 141
1.4.2. Types of validity .............................. 142
1.4.3. Animal models of depression .................... 145
1.4.4. Some concluding remarks ........................ 160
References ................................................. 162
1.5. Chemistry ............................................. 173
Marketed Drugs and Drugs in Development
Jörg Holenz, Josê Luis Díaz and Helmut Buschmann
1.5.1. Summary of drug classes ........................ 173
1.5.2. Tricyclic and tetracyclic antidepressants ...... 173
1.5.3. Serotonergic agents ............................ 193
1.5.4. Noradrenaline reuptake inhibitors .............. 231
1.5.5. Monoamine oxidase inhibitors ................... 233
1.5.6. Miscellaneous agents ........................... 239
1.5.7. Compounds launched in single countries ......... 248
1.5.8. New opportunities for marketed drugs ........... 249
1.5.9. Summary of antidepressants in development ...... 249
References ................................................. 261
2. Schizophrenia and Other Psychoses .......................... 297
2.1. Introductory and Basic Aspects ........................ 299
Current Status and Challenges in Schizophrenia
Research
Francesc Artigas
2.1.1. Introduction ................................... 299
2.1.2. Clinical diagnosis and assessment of
schizophrenia .................................. 300
2.1.3. Epidemiology ................................... 306
2.1.4. Course of schizophrenia ........................ 307
2.1.5. Brain pathology in schizophrenia ............... 308
2.1.6. Pathogenesis and pathophysiology of
schizophrenia .................................. 316
2.1.7. Concluding remarks ............................. 326
References 327
2.2. Clinics ............................................... 335
Schizophrenia: A Clinical Review
Salvador Ros and Francisco Javier Arranz
2.2.1. Introduction ................................... 335
2.2.2. Background ..................................... 336
2.2.3. Epidemiology ................................... 341
2.2.4. General semiology .............................. 341
2.2.5. Positive symptoms in schizophrenia ............. 342
2.2.6. Negative symptoms in schizophrenia.............. 345
2.2.7. Cognitive alterations in schizophrenia ......... 347
2.2.8. Characteristics of cognitive deterioration
in schizophrenia ............................... 350
2.2.9. Methods to evaluate cognitive deterioration
in schizophrenia ............................... 356
2.2.10.Affective symptoms in schizophrenia ............ 358
2.2.11.Schizophrenia and suicide ...................... 360
2.2.12.Onset and states ............................... 365
2.2.13.Etiopathogeny .................................. 367
2.2.14.Prognosis ...................................... 373
2.2.15.Schizophrenia therapy .......................... 375
References ................................................. 378
2.3. Pharmacology .......................................... 389
Pharmacotherapy of Schizophrenia
Analía Bortolozzi, Llorenc Díaz-Mataix and
Francesc Artigas
2.3.1. Antipsychotic drugs: introduction .............. 389
2.3.2. Atypical Antipsychotics: introduction .......... 401
2.3.3. Other major investigational approaches ......... 425
2.3.4. Concluding remarks: challenges in drug
discovery ...................................... 429
References 432
2.4. Experimental Research ................................. 449
Modeling schizophrenia in experimental animals
Pau Celada, Anna Castañé, Albert Adell and
Francesc Artigas
2.4.1. Introduction ................................... 449
2.4.2. Neurophysiology of schizophrenia ............... 450
2.4.3. Pharmacological models of schizophrenia ........ 453
2.4.4. Neurodevelopmental models ...................... 464
2.4.5. Genetic models ................................. 468
2.4.6. Other animal models ............................ 473
2.4.7. Concluding remarks ............................. 474
References ................................................. 475
2.5. Chemistry ............................................. 491
Marketed Drugs and Drugs in Development
Antonio Párraga, Jörg Holenz and Helmut Buschmann
2.5.1. Summary of drug classes ........................ 491
2.5.2. Typical antipsychotics ......................... 494
2.5.3. Atypical antipsychotics ........................ 549
2.5.4. Drugs in development ........................... 579
References ................................................. 586
VOLUME 2
3. Anxiety .................................................... 617
3.1. Introductory and Basic Aspects
3.1.1. Definition and classification of anxiety
disorders ...................................... 619
Francisca López-Ríos, Serafin Gómez-Martin
and Antonio Molina-Moreno
References ............................................ 643
3.1.2. Epidemiology of anxiety disorders .............. 645
Flor Zaldívar-Basurto and José M. Garcia-Montes
References ............................................ 662
3.1.3. Etiology of Anxiety ............................ 667
Margarita Moreno, Ginesa López-Crespo and
Pilar Flores
References ............................................ 678
3.1.4. Anxiety disorders and drug abuse ............... 685
Diana Cardona-Mena, Margarita Moreno and
Pilar Flores
References ............................................ 701
3.1.5. Neurobiology of anxiety (I): Panic disorder,
posttraumatic stress disorder, social phobia
and obsessive-compulsive disorder .............. 709
Lola Roldán-Tapia, Ginesa López-Crespo, Francisco
Antonio Nieto-Escámez and Diana Cardona-Mena
References ............................................ 743
3.1.6. Neurobiology of anxiety (II): Childhood
anxiety, generalized anxiety disorder and
mixed anxiety-depressive disorder .............. 761
Francisco Antonio Nieto-Escámez, Ginesa
López-Crespo, Lola Roldán-Tapia and
Fernando Cañadas-Pérez
References............................................. 785
3.1.7. Consequences of anxiety on memory
processes (I): Introductory and clinical
aspects ........................................ 803
Fernando Cañadas-Pérez, Francisco Antonio Nieto-
Escámez, Lola Roldán-Tapia and Ginesa
Löpez-Crespo
References ............................................ 821
3.1.8. Consequences of anxiety on memory
processes (II): Neurobiologicai aspects ........ 831
Francisco Nieto-Escámez, Fernando Cañadas-Pérez,
Lola Roldán-Tapia and Fernando Sánchez-Santed
References ............................................ 864
3.2. Clinics ............................................... 881
Clinical Aspects of Anxiety
Blanca Gutiérrez and Jorge Cervilla
3.2.1. Conceptual introduction ........................ 881
3.2.2. Panic disorder ................................. 882
3.2.3. Generalized anxiety disorder ................... 885
3.2.4. Phobic anxiety disorders ....................... 888
3.2.5. Obsessive-compulsive disorder .................. 890
3.2.6. Conclusion ..................................... 892
References ................................................. 893
3.3. Pharmacology .......................................... 895
Pharmacology of Anxiety
José Manuel Baeyens
3.3.1. Introduction ................................... 895
3.3.2. Drugs used in treatment of anxiety disorders:
an overview .................................... 896
3.3.3. Generalized anxiety disorder (GAD) ............. 902
3.3.4. Social anxiety disorder (SAD) or social
phobia ......................................... 905
3.3.5. Simple or specific phobia ...................... 908
3.3.6. Panic disorder (PD) ............................ 908
3.3.7. Posttraumatic stress disorder (PTSD) ........... 911
3.3.8. Obsessive-compulsive disorder (OCD) ............ 914
References ................................................. 918
3.4. Experimental Research ................................. 923
Modeling Human Anxiety by Animal Models
Enrique Portillo and José Miguel Vela
3.4.1. General concepts on animal models .............. 923
3.4.2. General aspects of human anxiety ............... 925
3.4.3. Animal anxiety ................................. 926
3.4.4. Potential issues in animal models of anxiety ... 937
3.4.5. Conclusions: Implication for drug discovery .... 940
References ................................................. 942
3.5. Chemistry ............................................. 951
Marketed Drugs and Drugs in Development
Mónica García-López, Susana Yenes, Helmut
Buschmann and Antoni Torrens
3.5.1. Summary of drug classes ........................ 951
3.5.2. Benzodiazepines ................................ 951
3.5.3. Serotonergic drugs ............................. 999
3.5.4. GABAergic agents .............................. 1006
3.5.5. Dopaminergic agents ........................... 1011
3.5.6. Serotonin reuptake stimulants ................. 1017
3.5.7. 5-HT2 receptor antagonists .................... 1019
3.5.8. β-adrenoceptor antagonists .................... 1021
3.5.9. Glucocorticoid receptor antagonists ........... 1026
3.5.10.GAT-1 inhibitors .............................. 1029
3.5.11.Calcium channel blockers ...................... 1032
3.5.12.No-described mechanism of action .............. 1039
3.5.13.Drugs in development .......................... 1051
References ................................................ 1069
4. Attention Deficit and Hyperactivity Disorders ............. 1089
4.1. Introductory and Basic Aspects ....................... 1091
Neurobiological aspects of Attention Deficit and
Hyperactivity Disorders
Javier Burgueño, Rafael Franco and
Francisco Ciruela
4.1.1. Definition and introductory clues ............. 1091
4.1.2. Etiology of ADHD .............................. 1095
References ................................................ 1100
4.2. Clinics .............................................. 1105
Attention Deficit Hyperactivity Disorder:
Clinical and Therapeutic Facts
Francisco Javier Arranz and Salvador Ros
4.2.1. Introduction .................................. 1105
4.2.2. Epidemiology .................................. 1108
4.2.3. Etiology ...................................... 1114
4.2.4. Pathophysiology ............................... 1118
4.2.5. Clinical features ............................. 1122
References ................................................ 1146
4.3. Pharmacology ......................................... 1155
Pharmacology: Targets of Drug Action
Francisco Ciruela, Rafael Franco and
Javier Burgueño
4.3.1. Neurobiological evidence for ADHD as an
organic phenomenon ............................ 1155
4.3.2. Neurochemistry of ADHD: Neurotransmitter
imbalance ..................................... 1156
References ................................................ 1177
4.4. Chemistry ............................................ 1183
Marketed Drugs and Drugs in Development
Jörg Holenz, Jose Luis Díaz and Helmut Buschmann
4.4.1. Summary of drug classes ....................... 1183
4.4.2. Drugs in development .......................... 1192
References ................................................ 1194
Index ........................................................ 1197
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