Obsessive Compulsive Disorder

Introduction xvii

SECTION 1 ASSESSMENT AND TREATMENT

1 Assessment 3
Jose M. Menchon

Introduction 3

Detecting OCD 5

Screening in clinical interview 7

Structured interviews 8

Clinical assessment of obsessive-compulsive symptoms 9

Yale-brown obsessive-compulsive scale 10

Dimensional yale-brown obsessive-compulsive scale (DY-BOCS) 11

Leyton obsessional inventory (LOI) 12

Maudsley obsessional-compulsive inventory (MOCI) 13

Padua inventory (PI) 13

Obsessive compulsive inventory (OCI) 14

Insight 14

Rating insight 15

Assessment of the risk of suicide 17

Differential diagnosis, comorbidities and related disorders 18

Organic brain disorders 19

Schizophrenia 20

Depression 20

Hypochondriasis 20

Phobias 21

Tourette disorder and tic disorders 21

Obsessive-compulsive personality disorder (OCPD) 21

Body dysmorphic disorder (BDD) 21

Hoarding 22

Other disorders 22

Conclusions 22

References 23

2 Pharmacotherapy of obsessive-compulsive disorder 31
Eric H. Decloedt and Dan J. Stein

Introduction 31

Placebo-controlled studies of clomipramine 32

Placebo-controlled studies of fluvoxamine 32

Placebo-controlled studies of fluoxetine 33

Placebo-controlled studies of paroxetine 34

Placebo-controlled studies of sertraline 34

Placebo-controlled studies of citalopram/escitalopram 34

Placebo-controlled studies of venlafaxine 35

Improving early response in OCD 35

Special populations: children 36

Clomipramine 36

Fluvoxamine 36

Fluoxetine 36

Paroxetine 37

Sertraline 37

Citalopram 38

Meta-analyses 38

Tolerability of clomipramine and serotonin reuptake inhibitors 40

Optimal dose of treatment 41

Duration of treatment 42

Refractory OCD 43

Increased dose of SSRI 43

Augmentation of SSRI treatment with antipsychotics 44

Other drugs 45

Alternative modes of administration of SSRIs 46

Combining SRIs 46

Switching SSRIs 46

Adding psychotherapy 47

Future therapeutic options 47

Conclusion 48

References 48

3 Cognitive behavioural therapy in obsessive-compulsive disorder: state of the art 58
Martin E. Franklin, Addie Goss and John S. March

Theoretical models 58

Treatment 60

Exposure plus response prevention (ERP) 60

Cognitive therapies 63

ERP plus medication 63

OCD protocols 64

Assessment 64

Adult ERP protocol 65

Paediatric ERP protocol 67

Dissemination 67

Future research 69

Summary 69

References 70

4 Electroconvulsive therapy, transcranial magnetic stimulation and deep brain stimulation in OCD 75
Rianne M. Blom, Martijn Figee, Nienke Vulink and Damiaan Denys

Introduction 75

Electroconvulsive therapy 75

Transcranial magnetic stimulation 76

Mechanism of action 77

Efficacy of rTMS in OCD 77

Side effects and safety 84

Conclusion and future directions 85

Lesioning 85

Deep brain stimulation 86

Efficacy of DBS in OCD 86

Mechanism of action of DBS in OCD 92

Side effects of DBS in OCD 92

Follow-up treatment 94

Conclusions: DBS 94

Conclusion 94

Acknowledgements 95

References 95

5 Approaches to treatment resistance 99
Stefano Pallanti, Giacomo Grassi and Andrea Cantisani

Terminological problems and operational definitions 100

Pharmacological strategies in resistant OCD 103

Switching 103

Infusion therapy 104

Cognitive behavioural therapy 105

Serotoninergic agents 106

Dopaminergic agents 108

Glutamatergic agents 113

Opioids 115

Physical therapies 115

Electroconvulsive therapy (ECT) 115

Repetitive transcranial magnetic stimulation (rTMS) 116

Deep brain stimulation (DBS) 116

Family intervention 117

Conclusions and future perspectives 117

References 118

SECTION 2 CLINICAL SPOTLIGHTS

6 Subtypes and spectrum issues 135
Eric Hollander, Steven Poskar and Adriel Gerard

The obsessive-compulsive spectrum 135

Introduction 135

Cluster approach 135

Compulsivity and impulsivity 137

Repetitive behaviour domain 138

Determining placement of proposed OCSDs using cross-cutting domains 139

Obsessive-compulsive spectrum nosology 144

OCD subtypes: understanding the heterogeneity of OCD 148

Dimensional approach 148

Associated symptom domains 150

Compulsive hoarding: OCPD, OCD subtype, dimension, OCSD or something else? 151

Conclusion 154

References 154

7 Paediatric OCD: developmental aspects and treatment considerations 160
Daniel A. Geller, Alyssa L. Faro, Ashley R. Brown and Hannah C. Levy

Introduction 160

Epidemiology 160

Aetiological considerations 161

Genetic factors 161

Non-genetic factors 164

Aetiology: summary 167

Clinical features 167

Gender and age at onset 168

Elaboration of phenotypic dimensions 168

Comorbid conditions 169

Neuropsychological endophenotypes 170

Clinical features: summary 170

Clinical assessment 171

Differential diagnosis 172

Normal development 172

Other psychiatric disorders 172

Treatment 173

Pharmacotherapy 174

Moderating effect of comorbid conditions 175

Multimodal treatment 176

Medication augmentation strategies in treatment resistance 177

Safety and tolerability 178

Treatment: summary 178

Course and prognosis 179

Conclusions and future research 179

Acknowledgements 180

References 180

SECTION 3 RESEARCH SPOTLIGHTS

8 Methodological issues for clinical treatment trials in obsessive-compulsive disorder 193
Samar Reghunandanan and Naomi A. Fineberg

Introduction 193

Randomized controlled trials 194

The rationale of placebo 196

Recruitment criteria 199

Diagnosis 199

OCD dimensions and subtypes 200

The problem of comorbidity 201

Rating scales for OCD trials 203

Evaluating anxiety and depression in OCD 204

Measuring response and remission 205

Relapse prevention 207

Treatment-resistant OCD 208

Psychological treatment trials 209

Integrated pharmacological and psychological treatments in OCD 210

Health-related quality of life 211

Summary 211

References 212

9 Serotonin and beyond: a neurotransmitter perspective of OCD 220
Anat Abudy, Alzbeta Juven-Wetzler, Rachel Sonnino and Joseph Zohar

Serotonin 221

Serotonin and metabolite concentrations in OCD - 30 years later 222

Pharmacological challenge tests 224

Pharmacotherapy 225

Animal models and the role of serotonin 226

Dopamine 227

Dopamine and metabolite concentrations in humans 227

Pharmacological challenge tests 228

Pharmacotherapy 229

Animal models and the role of dopamine 231

Glutamate 232

The glutamatergic influence 232

Glutamate and metabolite concentrations in humans 232

Animal models and the role of glutamate 233

Serotonin: is it the one to blame? 233

The puzzle of antipsychotics and OCD: Is dopamine the answer? 234

So, is it a question of location? (Or . . . location, location, location?) 234

References 235

10 Brain imaging 244
David R. Rosenberg, Phillip C. Easter and Georgia Michalopoulou

Neuroimaging modalities 244

Structural assessment 244

Functional neurochemical assessment 245

Structural assessment of OCD 246

Total brain volume/ventricles 246

Basal ganglia 246

Prefrontal cortex 248

Medial temporal-limbic cortex 252

Pituitary 253

Supramarginal gyrus 253

White matter 254

Functional neuroimaging studies of OCD 255

Neurochemistry 258

Serotonin 258

N-acetyl-aspartate 258

Choline 259

Creatine/phosphocreatine 262

Glutamate 262

Conclusion 266

Acknowledgements 267

References 268

11 The genetics of obsessive-compulsive disorder: current status 277
David L. Pauls

Introduction 277

Twin studies 277

Family studies 279

Family history studies 280

Family interview studies 280

Segregation analyses 284

Candidate gene studies 285

Genetic linkage studies 290

Future work 291

Acknowledgements 292

References 292

12 Neurocognitive angle: the search for endophenotypes 300
Samuel R. Chamberlain and Lara Menzies

Introduction 300

Heritability of OCD 301

The concept of an endophenotype 302

Applying the endophenotype construct to OCD 305

Domains of interest in hierarchical modelling of OCD 307

Cognition 307

Neuroimaging 308

Searching for endophenotypes of OCD 311

Cognition 311

Neuroimaging 313

Other potential endophenotypes 316

Summary 317

Acknowledgements and disclosures 319

References 320

13 Conclusion and future directions 327
Joseph Zohar

References 329

Index 331