Pharmacotherapy of Bipolar Disorders Pharmacotherapy of Bipolar Disorders J-M. Aubry, F. Ferrero, N. Schaad Copyright © 2007 John Wiley and Sons Ltd. ISBN: 978-0-470-05823-7 Pharmacotherapy of Bipolar Disorders Jean-Michel Aubry Department of Psychiatry, Geneva University Hospitals, Switzerland François Ferrero Department of Psychiatry, Geneva University Hospitals, Switzerland Nicolas Schaad Pharmacie interhospitalière de la Côte, Morges and University of Geneva, Switzerland in collaboration with Mark S. Bauer Department of Psychiatry and Human Behavior, Brown University, USA First published in French as Pharmacothérapie des troubles bipolaires, © 2004, Copyright, Editions Médecine & Hygiène, Geneva, Switzerland Translated into English by Kirsten Harrison English language translation Copyright © 2007 John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England Telephone (+44) 1243 779777 Email (for orders and customer service enquiries): [email protected] Visit our Home Page on www.wileyeurope.com or www.wiley.com All Rights Reserved. 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Anniversary Logo Design: Richard J. Pacifi co Library of Congress Cataloging-in-Publication Data British Library Cataloguing in Publication Data (Applied for) A catalogue record for this book is available from the British Library ISBN 978-0-470-05823-7 Typeset in 10/12pt Times by SNP Best-set Typesetter Ltd., Hong Kong Printed and bound in Great Britain by Antony Rowe Ltd, Chippenham, Wiltshire This book is printed on acid-free paper responsibly manufactured from sustainable forestry in which at least two trees are planted for each one used for paper production. Cover image : Le Regard, Lucette Geissberger, 1995 (Private Collection) Contents About the authors xv Foreword by N. Sartorius xvi Preface xvii Dedication xviii 1 Epidemiology of bipolar disorders 1 1.1 Contribution of epidemiological studies to the diagnosis 1 1.2 The defi nition of bipolar disorder 2 1.3 Demographic and social variables 2 1.3.1 Gender 2 1.3.2 Age 2 1.3.3 Urban and rural 3 1.3.4 Social–economic factors 3 1.3.5 Marital status 3 1.3.6 Cultural factors 3 1.4 A few important historical epidemiological studies 4 1.4.1 Amish study 4 1.4.2 Epidemiologic Catchment Area (ECA) study 4 1.4.3 New Haven study 5 1.4.4 National Comorbidity Survey (NCS) 5 1.5 Other studies carried out within the general population 5 1.5.1 Studies extending the boundaries of bipolar disorder 6 1.6 Key points 7 References 7 2 Classifi cation of bipolar disorders 10 2.1 Mania 12 2.2 Hypomania 13 2.3 Cyclothymia 14 2.4 Hyperthymia and hyperthymic temperament 14 2.5 Bipolar depression 15 2.6 Depressive Mixed States (DMX) 15 2.7 Mixed mania 15 2.8 Bipolar I disorder 16 2.9 Bipolar II disorder 16 vi Contents 2.10 Bipolar III disorder (pharmacological hypomania) 17 2.11 Bipolar IV disorder 17 2.12 Rapid cycling 17 2.13 Minor bipolar disorders 18 2.14 Some open questions 18 2.15 Key points 18 References 19 3 How to defi ne a mood stabilizer 23 3.1 The defi nitions of a mood stabilizer 23 3.2 Key points 25 References 26 4 Lithium 27 4.1 History 27 4.2 Mode of action 27 4.3 Clinical studies 28 4.3.1 Lithium and the treatment of mania 28 4.3.2 Predictors of antimanic effi cacy 30 4.3.3 Predictors of a partial response or a non-response to lithium 30 4.3.4 Lithium and the treatment of depression 31 4.3.5 Lithium and relapse prevention 31 4.3.6 Lithium and suicide 33 4.3.7 Response to lithium after interrupting and resuming treatment 34 4.4 Principal indications 34 4.5 Pharmacokinetics 34 4.5.1 Plasma levels 34 4.6 Interactions 35 4.6.1 Calcium channel blockers 35 4.6.2 Angiotensin II receptor antagonists 35 4.6.3 Antibiotics 35 4.6.4 Nonsteroidal anti-infl ammatory drugs 35 4.6.5 Antipsychotics 36 4.6.6 Carbamazepine 36 4.6.7 Topiramate 36 4.6.8 Diuretics 36 4.6.9 Angiotensin converting enzyme (ACE) inhibitors 37 4.6.10 Laxatives 37 4.6.11 Theophylline 37 4.7 Medications that can be administered with lithium 37 4.7.1 Valproic acid 37 4.7.2 Antibiotics 37 4.7.3 Anticoagulants 38 4.7.4 Antidepressants 38 4.7.5 Aspirin 38 4.7.6 Beta-adrenoceptor antagonists 38 4.7.7 Digoxin 38 4.7.8 Lamotrigine 38 4.7.9 Paracetamol (Acetaminophen) 39 Contents vii 4.8 Side-effects 39 4.8.1 Central nervous system 39 4.8.2 Neurological 40 4.8.3 Cardiovascular 40 4.8.4 Kidneys and electrolytes 41 4.8.5 Endocrine 41 4.8.6 Gastrointestinal 43 4.8.7 Dermatological 43 4.8.8 Haematological 43 4.8.9 Other unwanted effects 44 4.9 Practical aspects 44 4.9.1 Before prescribing 44 4.9.2 Treatment introduction 44 4.9.3 Treatment follow-up 45 4.10 Key points 45 References 46 5 Carbamazepine 53 5.1 History 53 5.2 Mode of action 53 5.3 Clinical studies 53 5.3.1 Carbamazepine in the treatment of mania 53 5.3.2 Carbamazepine and the treatment of depression 54 5.3.3 Carbamazepine and relapse prevention 54 5.3.4 Predictors of response to carbamazepine 55 5.3.5 Predictors of poor response 56 5.4 Principal indications 56 5.5 Pharmacokinetics and metabolism 56 5.6 Interactions 57 5.7 Side-effects 57 5.7.1 Haematological 57 5.7.2 Cardiovascular 60 5.7.3 Hepatic 60 5.7.4 Central nervous system 60 5.7.5 Gastrointestinal 61 5.7.6 Dermatological 61 5.7.7 Immunological reactions 61 5.7.8 Metabolic 61 5.8 Practical aspects 62 5.8.1 Before prescribing 62 5.8.2 Treatment introduction 62 5.8.3 Treatment follow-up 62 5.9 Key points 63 References 63 6 Lamotrigine 69 6.1 History 69 6.2 Mode of action 69 viii Contents 6.3 Clinical studies 70 6.3.1 Lamotrigine and depression 70 6.3.2 Lamotrigine and rapid cycling 72 6.3.3 Lamotrigine and mania 73 6.3.4 Lamotrigine and relapse prevention 74 6.3.5 Lamotrigine and bipolar disorder with comorbid borderline personality disorder 75 6.3.6 Lamotrigine and bipolar disorder with comorbid cocaine or alcohol dependence 75 6.4 Principal indications 75 6.5 Pharmacokinetics and metabolism 75 6.6 Interactions 76 6.6.1 With other mood stabilizers 76 6.6.2 With other medications 78 6.7 Side-effects 79 6.7.1 Dermatological 79 6.7.2 Central nervous system 80 6.7.3 Gastrointestinal 81 6.7.4 Ocular 81 6.7.5 Weight gain 81 6.7.6 Taste 81 6.7.7 Haematological 81 6.8 Practical aspects 81 6.8.1 Before prescribing 81 6.8.2 Treatment introduction 82 6.8.3 Treatment follow-up 82 6.9 Key points 82 References 83 7 Topiramate 88 7.1 History 88 7.2 Mode of action 88 7.3 Clinical studies 88 7.4 Pharmacokinetics and metabolism 89 7.5 Interactions 89 7.6 Side-effects 90 7.6.1 Central nervous system 90 7.6.2 Metabolic 90 7.6.3 Gastrointestinal 91 7.6.4 Ocular 91 7.7 Practical aspects 91 7.7.1 Before prescribing 91 7.7.2 Treatment introduction 91 7.8 Key points 92 References 92 8 Valproic acid 95 8.1 History 95 8.2 Mode of action 95 Contents ix 8.3 Clinical studies 96 8.3.1 Valproic acid in the treatment of mania 96 8.3.2 Valproic acid in the treatment of depression 96 8.3.3 Valproic acid and relapse prevention 98 8.3.4 Predictors of response to valproic acid 99 8.4 Principal indications 99 8.5 Pharmacokinetics and metabolism 101 8.6 Interactions 101 8.6.1 Acetylsalicylic acid 101 8.6.2 Anticoagulants 101 8.6.3 Benzodiazepines 101 8.6.4 Erythromycin 101 8.6.5 Fluoxetine 102 8.6.6 H antagonists 102 2 8.6.7 Haloperidol 102 8.6.8 Oral contraceptives 102 8.6.9 Paracetamol (Acetaminophen) 102 8.6.10 Sertraline 102 8.7 Interactions with other bipolar disorder medications 102 8.7.1 Carbamazepine 102 8.7.2 Clozapine 103 8.7.3 Lamotrigine 103 8.7.4 Lithium 103 8.7.5 Quetiapine 103 8.7.6 Risperidone 103 8.7.7 Topiramate 103 8.7.8 Other medications 103 8.8 Side-effects 104 8.8.1 Haematological 104 8.8.2 Gastrointestinal 104 8.8.3 Neurological 105 8.8.4 Central nervous system 105 8.8.5 Endocrine 105 8.8.6 Others 106 8.9 Practical aspects 106 8.9.1 Divalproex versus valproate 106 8.9.2 Before prescribing 107 8.9.3 Treatment introduction 107 8.9.4 Treatment follow-up 108 8.10 Key points 108 References 108 9 The role of atypical or second generation antipsychotics 115 9.1 What is an atypical antipsychotic? 115 9.1.1 For the pharmacologist 115 9.1.2 For the clinician 117 9.2 Side-effects 117 9.2.1 Weight gain 117 x Contents 9.2.2 Diabetes 119 9.2.3 Effect on plasma lipids 120 9.2.4 Extrapyramidal symptoms 120 9.2.5 Sedation 121 9.2.6 Cardiovascular 121 9.2.7 Prolactin secretion 122 9.2.8 Liver 122 9.2.9 Haematological side-effects 122 9.2.10 Sexual dysfunction 122 9.2.11 Enuresia 122 9.2.12 Other side-effects 122 9.3 Effects on memorization processes 123 9.4 Interactions 123 9.5 Antipsychotics and bipolar disorder 123 9.6 Atypical or second generation antipsychotics and the treatment of mania 123 9.7 Atypical or second generation antipsychotics and the treatment of depression 126 9.8 Atypical or second generation antipsychotics and maintenance treatment 128 9.9 Key points 130 References 130 10 Other medications used for bipolar disorders 139 10.1 Gabapentin 139 10.2 Oxcarbazepine 140 10.3 Calcium channel blockers 140 10.4 Omega-3 fatty acids 141 10.5 Key points 143 References 143 11 Medications that may potentially induce a depressive state 147 References 149 12 Medications that may potentially induce a (hypo)manic syndrome 152 References 154 13 Maintenance treatment: when should a long-term treatment be introduced? 156 13.1 When should a mood stabilizer for maintenance treatment be introduced? 156 13.2 Initiating treatment during a manic or mixed episode 157 13.3 Initiating treatment during a depressive episode 157 13.4 Initiating treatment during a euthymic period 157 13.5 Choosing a maintenance treatment 158 13.6 Key points 160 References 160 14 Treatment of the depressive phase of bipolar disorders 162 14.1 Antidepressants 162 14.2 Risk of manic switch 165 Contents xi 14.3 Duration of antidepressant treatment 166 14.4 Antidepressant discontinuation syndromes 166 14.5 Mood stabilizers 167 14.6 Antipsychotics 168 14.7 Depression in the absence of a mood stabilizer 169 14.8 Depressive relapse despite a mood stabilizing treatment 170 14.9 Depressive relapse despite a combined treatment 171 14.10 Resistant depression 171 14.11 Key points 171 References 172 15 Treatment of bipolar II disorder 177 15.1 Treatment of bipolar II depression 177 15.2 Treatment of hypomania 178 15.3 Long-term treatment 179 15.4 Key points 180 References 180 16 Treatment of manic phases 183 16.1 Different subtypes of mania 183 16.2 Treatment of hypomania 183 16.3 Treatment of euphoric mania 184 16.4 Treatment of dysphoric mania 187 16.5 Treatment of mania with psychotic symptoms 187 16.6 Treatment of mania in patients with rapid cycling 187 16.7 Other psychotropic drugs evaluated for the treatment of mania 188 16.8 Other treatments 188 16.8.1 Nimodipine 188 16.8.2 Tamoxifen 188 16.8.3 Electroconvulsive therapy and transcranial magnetic stimulation 189 16.9 Key points 189 References 189 17 Treatment of rapid cycling 195 17.1 Lithium 195 17.2 Valproate 196 17.3 Carbamazepine and oxcarbazepine 196 17.4 Lamotrigine 197 17.5 Other anticonvulsants 197 17.6 Clozapine and other atypical antipsychotics 197 17.7 Thyroid hormones 198 17.8 Key points 199 References 199 18 Treatment of mixed states 203 18.1 Lithium 203 18.2 Valproate 204