The Maudsley Deprescribing Guidelines. Antidepressants, Benzodiazepines, Gabapentinoids and Z-Drugs

Preface 

Acknowledgements

Notes on Using the Maudsley® Deprescribing Guidelines 

Abbreviations List 

Chapter 1 Introduction to Deprescribing Psychiatric Medications 1

• Deprescribing as an Intervention 1
• The context for deprescribing 2
• Why deprescribe? 7
• Barriers and facilitators to deprescribing 11
• Withdrawal Effects from Psychiatric Medications 13
• Mis-diagnosis of withdrawal effects as relapse 13
• Pathophysiology of psychiatric drug withdrawal symptoms 16
• Clinical aspects of psychiatric drug withdrawal 19
• Specific issues in psychiatric drug withdrawal 23
• How to Deprescribe Psychiatric Medications Safely 27
• The neurobiology of tapering 28
• Practical options for prescribing gradually tapering doses 36
• Psychological aspects of tapering 43
• Tapering psychiatric drugs in practice 45
• Further topics 52

Chapter 2 Safe Deprescribing of Antidepressants 57

• When and Why to Stop Antidepressants 57
• Adverse effects of antidepressants 66
• Discussing deprescribing antidepressants with patients 72
• Withdrawal Effects from Antidepressants 76
• Recent developments in the understanding of antidepressant withdrawal 76
• Pathophysiology of antidepressant withdrawal symptoms 80
• Clinical aspects of antidepressant withdrawal 87
• How common, severe and long‐ lasting are withdrawal symptoms from antidepressants? 92
• Protracted antidepressant withdrawal syndrome 96
• Post‐ SSRI sexual dysfunction 98
• Factors influencing development of withdrawal effects 99
• Stratfiying risk of antidepressant withdrawal 105
• Distinguishing antidepressant withdrawal symptoms from relapse 107
• Distinguishing antidepressant withdrawal symptoms from new onset of a physical or mental health condition 111
• Withdrawal symptoms during antidepressant maintenance treatment or switching medication 113
• How to Deprescribe Antidepressants Safely 115
• Tapering antidepressants gradually 119
• Hyperbolic tapering of antidepressants 125
• Practical options in prescribing gradually tapering doses of antidepressants 131
• Psychological aspects of antidepressant tapering 140
• Tapering antidepressants in practice 143
• Managing complications of antidepressant discontinuation 153
• Tapering Guidance for Specific Antidepressants 158
• Agomelatine 159
• Amitriptyline 163
• Bupropion 168
• Citalopram 174
• Clomipramine 183
• Desvenlafaxine 188
• Dosulepin 193
• Doxepin 198
• Duloxetine 203
• Escitalopram 209
• Fluoxetine 216
• Fluvoxamine 223
• Imipramine 228
• Lofepramine 233
• Mirtazapine 238
• Moclobemide 243
• Nortriptyline 248
• Paroxetine 253
• Phenelzine 259
• Sertraline 264
• Tranylcypromine 270
• Trazodone 275
• Venlafaxine 280
• Vilazodone 288
• Vortioxetine 292

Chapter 3 Safe Deprescribing of Benzodiazepines and Z-drugs 297

• When and Why to Stop Benzodiazepines and Z-drugs 297
• Discussing deprescribing benzodiazepines and z-drugs 304
• Withdrawal Symptoms from Benzodiazepines and Z-drugs 309
• Physical dependence vs addiction in use of benzodiazepines and z-drugs 311
• Pathophysiology of benzodiazepine withdrawal syndrome 313
• Variety of withdrawal symptoms from benzodiazepines and z-drugs 316
• Protracted benzodiazepine withdrawal syndrome 320
• Distinguishing benzodiazepine withdrawal symptoms from return of an underlying condition 323
• Withdrawal symptoms during benzodiazepine maintenance treatment 326
• How to Deprescribe Benzodiazepines and Z-drugs Safely 327
• Tapering benzodiazepines and z-drugs gradually 330
• Hyperbolic tapering of benzodiazepines and z-drugs 332
• Switching to longer-acting benzodiazepines to taper 335
• Making up smaller doses of benzodiazepines and z-drugs practically 338
• Other considerations in tapering benzodiazepines and z-drugs 342
• Psychological aspects of tapering benzodiazepines and z-drugs 345
• Tapering benzodiazepines and z-drugs in practice 348
• Management of complications of benzodiazepine and z-drug discontinuation 358
• Tapering Guidance for Specific Benzodiazepines and Z-drugs 362
• Alprazolam 364
• Buspirone 375
• Chlordiazepoxide 380
• Clonazepam 388
• Clorazepate 396
• Diazepam 404
• Estazolam 412
• Eszopiclone 418
• Flurazepam 423
• Lorazepam 429
• Lormetazepam 440
• Nitrazepam 446
• Oxazepam 452
• Quazepam 461
• Temazepam 467
• Triazolam 474
• Zaleplon 480
• Zolpidem 485
• Zopiclone 490

Chapter 4 Safe Deprescribing of Gabapentinoids 495

• When and Why to Stop Gabapentinoids 495
• Discussing deprescribing gabapentinoids 504
• Overview of Gabapentinoid Withdrawal Effects 507
• Physical dependence vs addiction in use of gabapentinoids 510
• How to Deprescribe Gabapentinoids Safely 512
• Principles for tapering gabapentinoids 512
• Making up smaller doses of gabapentinoids practically 516
• Other considerations in tapering gabapentinoids 520
• Psychological aspects of tapering gabapentinoids 523
• Tapering gabapentinoids in practice 525
• Management of complications of gabapentinoid discontinuation 532
• Tapering Guidance for Specific Gabapentinoids 537
• Gabapentin 538
• Pregabalin 546

Index 553

The Maudsley^® Deprescribing Guidelines

Comprehensive resource describing guidelines for safely reducing or stopping (deprescribing) antidepressants, benzodiazepines, gabapentinoids and z-drugs for patients, including step-by-step guidance for all commonly used medications, covering common pitfalls, troubleshooting, supportive strategies, and more.

Most formal guidance on psychiatric medication relates to starting or switching medications with minimal guidance on deprescribing medication. In 2023, the World Health Organisation and the United Nations called for patients, as a human right, to be informed of their right to discontinue treatment and to receive support to do so.

The Maudsley Deprescribing Guidelines fills a significant gap in guidance for clinicians by providing comprehensive and authoritative information on this important aspect of treatment.

This evidence-based handbook provides an overview of principles to be used in deprescribing. This is derived from fundamental scientific principles and the latest research on this topic, combined with emerging insights from clinical practice (including from patient experts).

Building on the recognised brand of The Maudsley Prescribing Guidelines, and the prominence of the authors’ work, including in The Lancet Psychiatry on tapering antidepressants (the most read article across all Lancet titles when it was released). The Maudsley Deprescribing Guidelines covers topics such as:

• Why and when to deprescribe antidepressants, benzodiazepines, gabapentinoids and z-drugs
• Barriers and enablers to deprescribing including physical dependence, social circumstances, and knowledge about the discontinuation process
• Distinguishing withdrawal symptoms, such as poor mood, anxiety, insomnia, and a variety of physical symptoms from symptoms of the underlying disorder that medication was intended to treat
• The difference between physical dependence and addiction/substance use disorder
• Explanation of why and how to implement hyperbolic tapering in clinical practice
• Specific guidance on formulations of medication and techniques for making gradual reductions, including using liquid forms of medication, and other approaches
• Step-by-step guidance for safely stopping all commonly used antidepressants, benzodiazepines, gabapentinoids and z-drugs, including fast, moderate and slow tapering regimens or schedules for each drug, and guidance on how to tailor these to an individual
• Troubleshooting issues which can arise on stopping these medications, including akathisia, withdrawal symptoms, acute or protracted, and relapse.

Written for anyone interested in safe deprescribing of psychiatric medications including psychiatrists, GPs, pharmacists, nurses, medical trainees, and interested members of the public. The Maudsley Deprescribing Guidelines is an essential resource on the subject that provides practical guidance on how to improve patient outcomes in this field of medicine.

Mark Horowitz, BA, BSc(Med), MBBS(Hons), MSc, GDipPsych, PhD, is a trainee psychiatrist and Clinical Research Fellow at North East London NHS Trust, where he runs a psychiatric drug deprescribing clinic. He is an Honorary Research Fellow at University College London and he co-authored the Royal College of Psychiatrists guide on ‘Stopping antidepressants’. He has authored multiple academic papers on how to safely stop psychiatric drugs in high impact journals, and lectured on this topic around the world to doctors, pharmacists and the public. He was commissioned by Health Education England to prepare a module on safe deprescribing of antidepressants for prescribers in the National Health Service (NHS). He has lived experience of stopping psychiatric drugs which informs most of his work.

David Taylor, PhD, FFRPS, FRPharmS, FRCPEdin, FRCPsych(Hon), is Director of Pharmacy and Pathology at the South London and Maudsley NHS Trust and Professor of Psychopharmacology at King’s College, London. He is the lead author of the Maudsley Prescribing Guidelines in Psychiatry and Editor-in-Chief of Therapeutic Advances in Psychopharmacology. He co-authored the Royal College of Psychiatrists guide on ‘Stopping antidepressants’. His pharmacy department ran a medication help-line for a decade which fielded queries largely related to withdrawal from psychiatric drugs. He has personal experience of stopping psychiatric drugs.