The Maudsley Prescribing Guidelines in Psychiatry E-Book

David M. Taylor

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Serie: The Maudsley Prescribing Guidelines Series
• Sprache: Englisch

Seitenzahl: 2518

Veröffentlichungsjahr: 2025

Beschreibung

The most up-to-date edition of the gold-standard handbook on the safe and effective prescribing of psychotropic agents

Prescribing medications that treat mental illness is a challenging but essential component of clinical practice. Successful treatment outcomes require careful drug choice and dosage, and other considerations can also have an important impact on patient experiences and long-term care.

In the newly revised fifteenth edition of The Maudsley Prescribing Guidelines in Psychiatry, you will find up-to-date and authoritative guidance on prescribing psychotropic medications to patients. It is an indispensable evidence-based handbook that will continue to serve a new generation of clinicians and trainees.

The book includes analyses of all psychotropic drugs currently used in the United States, the United Kingdom, Canada, Australia, New Zealand, and Japan. It also contains detailed discussions of common and uncommon adverse effects, the ramifications of switching medications, special patient groups, and other clinically relevant subjects. A fully updated reference list closes out each section, as well.

The Maudsley Prescribing Guidelines in Psychiatry is perfect for trainees seeking essential and accurate information on the rational, safe, and effective use of medications for patients with mental illness. Practising clinicians will also benefit from the included guidance on complex issues that might arise less frequently.

Leseprobe

Table of Contents

Cover

Table of Contents

Series Page

Title Page

Copyright Page

Preface

Acknowledgements

Contributors’ conflict of interest

List of abbreviations

Chapter 1: Schizophrenia and related psychoses

ANTIPSYCHOTIC DRUGS

General introduction

General principles of prescribing

Antipsychotics – minimum effective doses

Quick reference for licensed maximum doses

Equivalent doses

High‐dose antipsychotic medication: prescribing and monitoring

Combined antipsychotics (antipsychotic polypharmacy)

Antipsychotic prophylaxis

Negative symptoms

Monitoring

Relative adverse effects – a rough guide

Treatment algorithms for schizophrenia

First‐generation antipsychotics – place in therapy

NICE guidelines for the treatment of schizophrenia

1

Antipsychotic response – to increase the dose, to switch, to add or just wait – what is the right move?

Acutely disturbed or violent behaviour

Antipsychotic depots/long‐acting injections

Depot antipsychotics – summary of pharmacokinetics

Management of patients on long‐term treatment with long‐acting injectable antipsychotic medication

Aripiprazole long‐acting injection

Olanzapine long‐acting injection

Paliperidone palmitate long‐acting injection

Risperidone long‐acting injection

Penfluridol weekly

Electroconvulsive therapy and psychosis

Omega‐3 fatty acid (fish oils) in schizophrenia

Alternative routes of administration

Stopping antipsychotics

ANTIPSYCHOTIC ADVERSE EFFECTS

Extrapyramidal symptoms

Akathisia

Treatment of tardive dyskinesia

Antipsychotic‐induced weight gain

Treatment of antipsychotic‐induced weight gain

Neuroleptic malignant syndrome

ECG changes – QT prolongation

Effects of antipsychotic medications on plasma lipids

Diabetes and impaired glucose tolerance

Blood pressure changes with antipsychotics

Antipsychotic‐associated hyponatraemia

Hyperprolactinaemia

Sexual dysfunction and antipsychotics

Pneumonia

Switching antipsychotics

Venous thromboembolism

REFRACTORY SCHIZOPHRENIA AND CLOZAPINE

Clozapine initiation schedules

Intramuscular clozapine

Optimising clozapine treatment

Alternatives to clozapine

Restarting clozapine after a break in treatment

Initiation of clozapine in the community

CLOZAPINE ADVERSE EFFECTS

Clozapine: common adverse effects

Clozapine: uncommon or unusual adverse effects

Clozapine: serious haematological adverse effects

Clozapine: serious cardiovascular adverse effects

Clozapine‐induced hypersalivation

Clozapine‐induced gastrointestinal hypomotility

Clozapine, neutropenia and lithium

Clozapine and chemotherapy

Genetic testing for clozapine treatment

Chapter 2: Bipolar disorder

Lithium

Valproate

Carbamazepine

Antipsychotic drugs in bipolar disorder

Antipsychotic long‐acting injections in bipolar disorder

Physical monitoring for people with bipolar disorder

1

,

2

Treatment of acute mania or hypomania

Rapid‐cycling bipolar affective disorder

Bipolar depression

Prophylaxis in bipolar disorder

Stopping lithium and mood stabilisers

Chapter 3: Depression and anxiety disorders

Introduction to depression

Antidepressants – general overview

Recognised minimum effective doses of antidepressants

Drug treatment of depression

Management of treatment-resistant depression – commonly used treatments

Management of treatment-resistant depression – other wellsupported treatments

Treatment-resistant depression – other reported treatments

Ketamine

Psychotic depression

Switching antidepressants

Antidepressant withdrawal symptoms

Stopping antidepressants

Electroconvulsive therapy and psychotropic drugs

Psychostimulants in depression

Post-stroke depression

Antidepressant prophylaxis

Drug interactions with antidepressants

Cardiac effects of antidepressants – summary

Antidepressant-induced arrhythmia

Antidepressant-induced hyponatraemia

Antidepressants and hyperprolactinaemia

Antidepressants and diabetes mellitus

Antidepressants and sexual dysfunction

SSRIs and bleeding

St John’s wort

Antidepressants: relative adverse effects – a rough guide

Anxiety spectrum disorders

Benzodiazepines in the treatment of psychiatric disorders

Benzodiazepines, z-drugs and gabapentinoids: dependence, withdrawal effects and discontinuation

Benzodiazepines and disinhibition

Premenstrual syndrome

Chapter 4: Addictions and substance misuse

Introduction

Alcohol dependence

Opioid dependence

Nicotine and smoking cessation

Stimulant use disorder (SUD)

GHB and GBL dependence

Benzodiazepine misuse

Drug‐induced excited state

Interactions between illicit drugs and prescribed psychotropic drugs

Drugs of misuse – a summary

Substance misuse in pregnancy

Gambling disorder

Chapter 5: Prescribing in children and adolescents

Principles of prescribing practice in childhood and adolescence

Depression in children and adolescents

Bipolar disorder in children and adolescents

Psychosis in children and adolescents

Anxiety disorders in children and adolescents

Obsessive compulsive disorder (OCD) and body dysmorphic disorder (BDD) in children and adolescents

Post‐traumatic stress disorder (PTSD) in children and adolescents

Attention deficit hyperactivity disorder (ADHD) in children and adolescents

Autism spectrum disorder (ASD) in children and adolescents

Tics and Tourette’s syndrome in children and adolescents

Melatonin in the treatment of insomnia in children and adolescents

Rapid tranquillisation (RT) in children and adolescents

Doses of commonly used psychotropic drugs in children and adolescents

Chapter 6: Prescribing in older people

General principles in prescribing in older adults

Dementia

Safer prescribing for physical conditions in dementia

Management of behavioural and psychological symptoms of dementia (BPSD)

Management of inappropriate sexual behaviour in older adults

Depression in older adults

Covert administration of medicines within food and drink

A guide to medication doses of commonly used psychotropics in older adults, [1] / National Institute for Health and Care Excellence (NICE).

7 Prescribing in pregnancy and breastfeeding

Drug choice in pregnancy

Drug choice in breastfeeding

Chapter 8: Prescribing in hepatic and renal impairment

Hepatic impairment

Renal impairment

Chapter 9: Drug treatment of other psychiatric conditions

Borderline personality disorder (BPD)

Eating disorders

Attention deficit hyperactivity disorder (ADHD) in adults

Chapter 10: Drug treatment of psychiatric symptoms occurring in the context of other conditions

Prescribing in human immunodeficiency virus (HIV)

Epilepsy

22q11.2 deletion syndrome

Learning disabilities

Huntington’s disease

Multiple sclerosis

Parkinson’s disease

Atrial fibrillation

Bariatric surgery

Menopause

Chapter 11: Pharmacokinetics

Plasma level monitoring of psychotropic drugs

Interpreting postmortem blood concentrations

Acting on clozapine plasma concentration results

Psychotropic drugs and cytochrome (CYP) function

Smoking and psychotropic drugs

Drug interactions with alcohol

Chapter 12: Other substances

Caffeine

Nicotine

Chapter 13: Psychotropic drugs in special conditions

Psychotropics in overdose

Driving and psychotropic medicines

Chapter 14: Prescribing psychotropics

Working towards adherence

Restarting psychotropic medications after a period of non‐compliance

Relational aspects of prescribing practice

Prescribing drugs outside their licensed indications (‘off‐label’ prescribing)

The Mental Health Act in England and Wales

Site of administration of intramuscular injections

Chapter 15: Miscellany

Biochemical and haematological effects of psychotropics

Summary of psychiatric adverse effects of non‐psychotropics

Index

End User License Agreement

List of Tables

Chapter 1

Table 1.1 Minimum effective dose/day – antipsychotics

Table 1.2 Maximum doses of antipsychotics according to European Medicines Ag...

Table 1.3 Licensed maximum doses of antipsychotics, according to US Food and...

Table 1.4 Equivalent doses of first‐generation antipsychotic medications.

Table 1.5 Second‐generation antipsychotics – approximate equivalent doses.

3–

...

Table 1.6 Suggested monitoring for people receiving antipsychotic medication...

Table 1.7 Approximate estimates of relative incidence and severity of advers...

Table 1.8 Long‐acting injectable antipsychotic medications – doses and frequ...

Table 1.9 Depot antipsychotics – summary of pharmacokinetics.

Table 1.10 Delayed doses of aripiprazole long‐acting injection.

4

Table 1.11 Switching to 1‐monthly aripiprazole long‐acting injection.

Table 1.12 Aripiprazole 2‐month ready‐to‐use initiation regimen.

8

Table 1.13 Recommendations for delayed maintenance dose of Ari 2MRTU.

Table 1.14 Starting treatment with Aristada.

17

Table 1.15 Equivalent doses and sites of administration for Aristada.

17

Table 1.16 Dosing regimen for olanzapine.

Table 1.17 Paliperidone dose and administration information.

3

Table 1.18 Approximate dose equivalence for paliperidone and risperidone.

3,6

Table 1.19 Switching to paliperidone palmitate 1‐monthly.

3

Table 1.20 Dosing of paliperidone long‐acting injection 3‐monthly.

15

Table 1.21 Paliperidone long‐acting injection – equivalent doses.

Table 1.22 Switching to paliperidone 6‐monthly.

23

Table 1.23 Switching from risperidone long‐acting injections.

3,4

Table 1.24 Initiation of risperidone ISM.

Table 1.25 Equivalent doses – risperidone‐based long‐acting injections.

6,7,2

...

Table 1.26 Alternative formulations and routes of administration of antipsyc...

Table 1.27 Reductions of olanzapine dose by up to 5 percentage points of D

2

...

Table 1.28 Most common extrapyramidal side effects.

Table 1.29 First‐choice agents prescribed for tardive dyskinesia (alphabetic...

Table 1.30 Other options for the treatment of tardive dyskinesia (in alphabe...

Table 1.31 Risk/extent of antipsychotic‐induced weight gain (drugs in alphab...

Table 1.32 Drug treatment of antipsychotic‐induced weight gain (alphabetical...

Table 1.33 Neuroleptic malignant syndrome.

Table 1.34 Medications other than benzodiazepines reported as treatments for...

Table 1.35 Antipsychotics – effect on QTc.

12,22,24,34–5

9

Table 1.36 Physiological risk factors for QTc prolongation and arrhythmia.

Table 1.37 Non‐psychotropics associated with QT prolongation (see Credibleme...

Table 1.38 Management of QT prolongation in patients receiving antipsychotic...

Table 1.39 Recommended monitoring for diabetes in patients receiving antipsy...

Table 1.40 Risk factors for orthostatic hypotension.

2

Table 1.41 Management of antipsychotic‐induced orthostatic hypotension.

2,

4

Table 1.42 Treatment of hyponatraemia associated with antipsychotic treatmen...

Table 1.43 Effects of antipsychotic medication on prolactin concentration.

4–

...

Table 1.44 The human sexual response.

Table 1.45 Sexual adverse effects of antipsychotics.

Table 1.46 Remedial treatments for psychotropic‐induced sexual dysfunction....

Table 1.47 Factors associated with antipsychotic‐induced pneumonia.

Table 1.48 Switching antipsychotic medications because of poor tolerability ...

Table 1.49 Findings of meta‐analyses of the risk of pathological blood clott...

Table 1.50 Clozapine dose (in mg/day) with the highest likelihood of providi...

Table 1.51 General recommendations for prescribing intramuscular clozapine....

Table 1.52 Suggested options for augmenting clozapine.

Table 1.53 Alternatives to clozapine (treatments are listed in alphabetical ...

Table 1.54 Summary of alternatives to clozapine in refractory schizophrenia....

Table 1.55 Suggested titration regimens for initiation of clozapine in the c...

Table 1.56 Suggested monitoring for myocarditis.

22,49,71,72

Table 1.57 Clozapine‐related hypersalivation – summary.

Chapter 2

Table 2.1 Lithium: prescribing and monitoring.

Table 2.2 Lithium: clinically relevant drug interactions.

Table 2.3 Valproate: prescribing and monitoring.

Table 2.4 Carbamazepine: prescribing and monitoring.

Table 2.5 Randomised controlled trials (RCTs) of the use of long‐acting inje...

Table 2.6 Mania: suggested drug doses.

Table 2.7 Mania: other possible treatments.

*

Table 2.8 Recommended treatment strategy fo rapid‐cycling bipolar disorder....

Table 2.9 Established treatments (listed in alphabetical order).

Table 2.10 Alternative treatments (refer to primary literature before using)...

Table 2.11 Other possible treatments (seek specialist advice before using)....

Table 2.12 Summary of maintenance in bipolar disorder.

7,57

Table 2.13 Withdrawal effects of lithium.

3–5

Chapter 4

Table 4.1 Mild alcohol withdrawal.

Table 4.2 Severe alcohol withdrawal.

Table 4.3 Short Alcohol Withdrawal Scale (SAWS).

13

Table 4.4 Alcohol withdrawal treatment interventions – a summary.

Table 4.5 Moderate alcohol dependence: example of a fixed‐dose chlordiazepox...

Table 4.6 Severe alcohol dependence: example of a fixed‐dose chlordiazepoxid...

Table 4.7 Treatment of somatic symptoms.

Table 4.8 The alcohol–disulfiram reaction.

Table 4.9 Timing of withdrawal symptoms of different opioids.

Table 4.10 Clinical Opiate Withdrawal Scale (COWS).

Table 4.11 Choosing between buprenorphine and methadone.

Table 4.12 Methadone titration where extent of prior use is unknown or uncon...

Table 4.13 Recommended ECG monitoring for people taking methadone.

Table 4.14 Conversion from buprenorphine to Espranor.

Table 4.15 Conventional sublingual buprenorphine daily treatment doses and r...

Table 4.16 Transferring from methadone to oral buprenorphine.

Table 4.17 Example protocols for transition from low‐dose methadone to bupre...

Table 4.18 Treatment of withdrawal symptoms in people taking opioids. Adapte...

Table 4.19 A suggested reduction regimen for buprenorphine.

Table 4.20 Nicotine preparations and doses.

Table 4.21 Treatment algorithm for people making an attempt to stop smoking....

Table 4.22 Treatment algorithm for people not making an attempt to stop, i.e...

Table 4.23 Psychosocial and pharmacological interventions in benzodiazepine ...

Table 4.24 Typical diazepam withdrawal schedule for iatrogenic dependence.

Table 4.25 Interactions between illicit drugs and psychotropics.

Table 4.26 Summary of drugs of misuse.

Table 4.27 Risks and management of various drugs in pregnancy.

Chapter 5

Table 5.1 Psychotropic medications approved by the UK Medicines and Healthc...

Table 5.2 Summary of pharmacotherapy for depression in children and adolesc...

Table 5.3 Pharmacological treatments of mania in children and adolescents....

Table 5.4 Pharmacological treatments of bipolar depression in children and ...

Table 5.5 Recommended first‐line treatments for acute mania.

*

Table 5.6 Recommended first‐line treatments for bipolar depression.

*

Table 5.7 Typical dosage of medications for treatment of anxiety disorders ...

Table 5.8 Alternative and experimental treatment of OCD in children and you...

Table 5.10 Prescribing in attention deficit hyperactivity disorder (ADHD)....

Table 5.11 Recommended drugs for rapid tranquillisation if the oral route i...

Table 5.12 Starting doses of commonly used psychotropic drugs in children a...

Chapter 6

Table 6.1 Characteristics of cognitive enhancers.

7–14

Table 6.2 Drug–drug interactions.

8–12,73,74

Table 6.3 Summary of British Association for Psychopharmacology recommendat...

Table 6.4 Anticholinergic Effect on Cognition (AEC) scale scores (Adapted f...

Table 6.5 Recommended drugs and drugs to avoid in dementia. Adapted with pe...

Table 6.6 Reduction or discontinuation regimen for antipsychotic drugs in B...

Table 6.8 Antidepressants and older people.

Chapter 7

Table 7.1 Summary of recommendations.

Table 7.2 Antidepressants in breastfeeding.

Table 7.3 Antipsychotics in breastfeeding.

Table 7.4 Mood stabilisers in breastfeeding.

Table 7.5 Hypnotics in breastfeeding.

Table 7.6 Stimulants in breastfeeding.

Chapter 8

Table 8.1 Antipsychotics in hepatic impairment.

Table 8.2 Antidepressants in hepatic impairment.

Table 8.3 Mood stabilisers in hepatic impairment.

Table 8.4 Stimulants in hepatic impairment.

Table 8.5 Sedatives in hepatic impairment.

Table 8.6 Other psychotropics in hepatic impairment.

Table 8.7 Psychotropic drug groups in hepatic impairment.

Table 8.9 Antidepressants in renal impairment.

10

Table 8.14 Attention deficit hyperactivity disorder (ADHD) drugs in renal i...

Table 8.15 Recommended psychotropics in renal impairment.

Chapter 9

Table 9.1 The advantages and disadvantages of medications indicated for tre...

Chapter 10

Table 10.1 Potential pharmacodynamic interactions with antiretrovirals.

40,4

...

Table 10.2 Summary of psychiatric adverse drug reactions (ADRs) with antire...

Table 10.4 Adverse and beneficial psychiatric side effects of antiseizure m...

Table 10.5 Psychotropics in epilepsy.

Table 10.6 Selected clinical features and risks in people with 22q11.2 dele...

Table 10.7 Management of psychiatric disorders in people with 22q11.2 delet...

Table 10.8 Some notes on currently and historically used medications for be...

Table 10.9 Evidence and experience regarding the pharmacological treatment ...

Table 10.10 Pharmacological treatment of mental and behavioural symptoms in ...

Table 10.11 Summary of treatments for mental state and behavioural changes i...

Table 10.12 Recommendations for treatment for depression in multiple sclero...

Table 10.13 Recommendations for treatment of depression in Parkinson’s dise...

Table 10.14 Recommendations for treatment of psychosis in Parkinson’s disea...

Table 10.15 Recommendations for using psychotropics in atrial fibrillation (...

Table 10.16 Antidepressants in bariatric surgery.

Table 10.17 Antipsychotics in bariatric surgery.

Table 10.18 Mood stabilisers in bariatric surgery.

Table 10.19 Miscellaneous agents in bariatric surgery.

Table 10.20 Menopause symptoms.

Table 10.21 Summary of antipsychotic/oestrogen interactions.

5,8,11

Table 10.22 Summary of the risks of using hormone replacement therapy (HRT)...

Table 10.23 Hormone replacement therapy (HRT) products and regimens.

Table 10.24 Topical vaginal oestrogen or GSM treatment.

Table 10.25 Management of adverse effects of hormone replacement therapy (H...

Chapter 11

Table 11.1 Interpreting sample results for drugs with established target ra...

Table 11.2 Target ranges for other psychotropics.

32,98,130

Table 11.3 Factors affecting postmortem blood concentrations.

Table 11.4 Recommended actions in response to clozapine concentrations.

*

...

Table 11.5 Effects of psychotropics on CYP function.

Table 11.6 Estimated phenotype frequency by ancestry for CYP1A2, CYP2D6, CY...

Table 11.7 Effect of smoking on psychotropic drugs.

Table 11.8 Drugs that inhibit alcohol dehydrogenase and aldehyde dehydrogen...

Table 11.9 Co‐administration of alcohol and substrates for CYP2E1 and CYP3A...

Table 11.10 Pharmacodynamic interactions with alcohol.

Table 11.11 Psychotropic drugs: choice in patients who continue to drink.

Chapter 12

Table 12.1 Typical caffeine content of drinks.

Table 12.2 Dose and psychotropic effects of caffeine.

Table 12.3 Interactions with caffeine.

Chapter 13

Table 13.1 Psychotropic drugs in overdose.

Table 13.2 Psychotropics and driving.

Table 13.3 Benzodiazepines concentration in normal dosing and the UK legal ...

Chapter 14

Table 14.1 Factors affecting adherence.

Table 14.2 Assessing adherence.

Table 14.3 Interventions for non‐adherence.

44

Table 14.4 Restarting medication up to 2 weeks after stopping oral treatmen...

Table 14.5 Examples of common unlicensed uses of drugs in psychiatric pract...

Table 14.6 Sites of administration of intramuscular injections.

Chapter 15

Table 15.1 Summary of biochemical changes associated with psychotropics.

Table 15.2 Summary of haematological changes associated with psychotropics....

Table 15.3 Summary of psychiatric adverse drug reactions (ADRs) with non‐ps...

Table 15.4 Adapted Naranjo adverse drug reaction (ADR) probability scale cr...

List of Illustrations

Chapter 1

Figure 1.1 Blood levels following discontinuation of treatment with 25mg eve...

Figure 1.2 Antipsychotic withdrawal symptoms.

Figure 1.3 (a) Linear dose reductions of olanzapine cause increasingly large...

Figure 1.4 Algorithm for treating catatonic stupor.

91

Figure 1.5 Management of antipsychotic‐induced hyperprolactinaemia.

38

Figure 1.6 The use of lithium with clozapine.

Chapter 2

Figure 2.1 Treatment of acute mania or hypomania.

6–21

Chapter 3

Figure 3.1 Drug treatment for depression.

Figure 3.2 Common withdrawal symptoms with SSRIs and similar drugs.

Figure 3.3 (a) Linear reductions of dose cause increasingly large reductions i...

Figure 3.4 The risk of recurrence in patients who have several episodes of dep...

Figure 3.5 (a) Linear reductions of dose cause increasingly large reductions i...

Figure 3.6 The pharmacological management of premenstrual dysphoric disorder.

Chapter 4

Figure 4.1 Clinical Institute Withdrawal Assessment of Alcohol Scale, Revise...

Figure 4.2 Flowchart for naloxone administration.

Chapter 5

Figure 5.1 Treatment options for children and young people with obsessive co...

Figure 5.2 Summary of recommendations for the treatment of tics and Tourette...

Figure 5.3 Summary of recommendations in the treatment of insomnia.

Chapter 6

Figure 6.1 Suggested guidelines for managing cardiovascular risk prior to an...

Figure 6.2 Flow chart for the use of covert medication.

Chapter 8

Figure 8.1 Classification of renal impairment. ACR, albumin : creatinine rat...

Chapter 11

Figure 11.1 Metabolism of alcohol.

Guide

Cover Page

Table of Contents

Series Page

Title Page

Copyright Page

Preface

Acknowledgements

Contributors’ conflict of interest

List of abbreviations

Begin Reading

Index

Wiley End User License Agreement

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The Maudsley Guidelines

Other books in the Maudsley Prescribing Guidelines series include:

The Maudsley Practice Guidelines for Physical Health Conditions in PsychiatryDavid Taylor, Fiona Gaughran, Toby Pillinger

The Maudsley Guidelines on Advanced Prescribing in PsychosisPaul Morrison, David Taylor, Phillip McGuire

The Maudsley Prescribing Guidelines for Mental Health Conditions in Physical IllnessSiobhan Gee, David M. Taylor

The Maudsley Deprescribing Guidelines: Antidepressants, Benzodiazepines, Gabapentinoids and Z‐drugsMark Horowitz, David M. Taylor

The Maudsley® Prescribing Guidelines in Psychiatry

15th Edition

David M. Taylor, BSc, MSc, PhD, FFRPS, FRPharmS, FRCPEdin, FRCPsychHon

Director of Pharmacy and Pathology, Maudsley Hospital andProfessor of Psychopharmacology, King’s College, London, UK

Thomas R. E. Barnes, MBBS, MD, FRCPsych, DSc

Emeritus Professor of Clinical Psychiatry at Imperial College London and joint head of the PrescribingObservatory for Mental Health at the Royal College of Psychiatrists’ Centre for Quality Improvement, London, UK

Allan H. Young, MB, ChB, MPhil, PhD, FRCP, FRCPsych

Chair of Mood Disorders and Director of the Centre for Affective Disorders in the Department of Psychological Medicine in the Institute of Psychiatry, Psychology and Neuroscience at King’s College, London, UK

This edition first published 2025© 2025 David M. Taylor

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.

The right of David M. Taylor, Thomas R. E. Barnes and Allan H. Young to be identified as the authors of this has been asserted in accordance with law.

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Preface

The Maudsley® Prescribing Guidelines in Psychiatry is now just one of several books in the Maudsley®Guidelines series. Since the publication of the 14th edition of the ‘big' MPG, it has been joined by the Maudsley® Deprescribing Guidelines: Antidepressants, Benzodiazepines, Gabapentinoids and Z‐drugs and by the Maudsley® Prescribing Guidelines for Mental Health Conditions in Physical Illness. These books cover some of the ground usually tackled in the main MPG but in much greater detail. In an effort to reduce repetition we have, in this 15th edition, left out (or let out) sections on such subjects as delirium, psychotropics in surgery and alternative routes of antidepressant administration and considerably reduced the size of sections on stopping psychotropics. What space has been made available by these changes has been filled by new sections on, for example, premenstrual syndrome, menopause, gambling disorder, ADHD in adults and relational aspects of prescribing practice.

This 15th edition of the MPG appears at a time when there is a growing antipathy towards the use of psychotropic drugs in mental illness. The prescribing advice given here assumes a decision to prescribe has already been made and so, to a large extent, we skirt the issue of whether or not prescribing is necessarily the right thing to do. Nonetheless, we do acknowledge that drug treatment is not always the best treatment for everyone in every situation. There are of course a range of effective non‐drug treatments for mental health problems. The advice and guidance given in this and previous editions is aimed at optimising prescribing practice rather than promoting prescribing per se.

As ever, I and my fellow authors are indebted to a large number of expert contributors who have enabled us to provide information and guidance on such a wide range of topics; a feature that is possibly unique to the Maudsley® Prescribing Guidelines in Psychiatry. Sincere thanks are also due to Ivana Clark, the managing editor of this edition.

Even though some sections have been transplanted to other books in The Guidelines series, the scope of this edition is greater than the last and, as a consequence, it is a weightier book. It is probably worth pointing out that a special effort has been made to be economic with words and references although I suspect this is of little consolation to those lugging the book from ward to ward or home to hospital. It is the ‘big’ MPG, after all.

David M. TaylorJanuary 2025

Acknowledgements

The following have contributed to the 15th edition of The Maudsley®Prescribing Guidelines in Psychiatry.

Aditya Sharma

Alys Cawson

Andrea Danese

Anna Walder

Bruce Clark

Daniel Harwood

Daniel Hayes

David Rogalski

Debbie Robson

Delia Bishara

Derek Tracy

Dimitrios Chartonas

Ebenezer Oloyede

Emily Finch

Emmert Roberts

Eromona Whiskey

Ewa Zadeh

Faiza Hoda

Frankie Anderson

Haroula Konstantinidou

Ian Osborne

Ilaria Bonoldi

Ivana Clark

Jacob Kranowski

Justin Sauer

Kalliopi Vallianatou

Kate Organ

Livia Martucci

Mariam Mustapha

Marinos Kyriakopoulos

Mark Horowitz

Marta Di Forti

Martina Carboni

Mary Thornton

Michael Craig

Michael Newson

Michele Sie

Mike Kelleher

Nicola Funnell

Nicola Kalk

Nicoletta Adamo

Oliver Howes

Paul Gringras

Paul Moran

Petrina Douglas‐Hall

Phillip Timms

Ray McGrath

Shubhra Mace

Siobhan Gee

Stephanie Lewis

Tennyson Lee

Thomas Reilly

Yuya Mizuno

Contributors’ conflict of interest

Many of the contributors to The Guidelines have received funding from pharmaceutical manufacturers for research, consultancy or lectures. Readers should be aware that these relationships inevitably colour opinions on such matters as drug selection or preference.

We cannot therefore guarantee that guidance provided here is free of indirect influence of the pharmaceutical industry but hope to have mitigated this risk by providing copious literature support for statements made. As regards direct influence, no pharmaceutical company has been allowed to view or comment on any drafts or proofs of The Guidelines and none has made any request for the inclusion or omission of any topic, advice or guidance. To this extent, The Guidelines have been written independent of the pharmaceutical industry.

List of abbreviations

5HT3

5‐hydroxytryptamine 3

22q11.2DS

22q11.2 deletion syndrome

%w/v

percentage weight per volume

AACAP

American Academy of Child and Adolescent Psychiatry

ACE

angiotensin‐converting enzyme

Ach

acetylcholine

AChE

acetylcholinesterase

AChE‐I

acetylcholinesterase inhibitors

ACOG

American College of Obstetricians and Gynecologists

AD

Alzheimer’s disease

ADAPT

Adolescent Depression Antidepressants and Psychotherapy Trial

ADAS‐cog

Alzheimer’s Disease Assessment Scale – cognitive subscale

ADH

alcohol dehydrogenase

ADHD

attention deficit hyperactivity disorder

ADIS

Anxiety Disorders Interview Schedule

ADL

activities of daily living

ADR

adverse drug reactions

AEC

Anticholinergic Effect on Cognition Scale

AF

atrial fibrillation

AIDS

acquired immune deficiency syndrome

ALAI

aripiprazole long‐acting injection

ALP

alkaline phosphate

ALT

alanine aminotransferase

AMPA

alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid

AN

anorexia nervosa

ANC

absolute neutrophil count

ANI

asymptomatic neurocognitive impairment

APP

amyloid precursor protein

ARIA

amyloid‐related imaging abnormality

ART

antiretroviral therapy

ASD

autism spectrum disorder

AST

aspartate aminotransferase

ATPase

adenosine triphosphatase

AUD

alcohol use disorder

AUDIT

Alcohol Use Disorders Identification Test

Aβ

beta amyloid

BAC

blood alcohol concentration

BAP

British Association for Psychopharmacology

BBB

blood–brain barrier

bd

twice a day

BDD

body dysmorphic disorder

BDNF

brain‐derived neurotrophic factor

BED

binge eating disorder

BEN

benign ethnic neutropenia

BMI

body mass index

BN

bulimia nervosa

BNF

British National Formulary

BP

blood pressure

BPD

Borderline personality disorder

BPSD

behavioural and psychological symptoms of dementia

BuChE

butyrylcholinesterase

CAMS

Childhood Anxiety Multimodal Study

CATIE

Clinical Antipsychosis Trials of Intervention Effectiveness

CBT

cognitive behavioural therapy

CDRS

Children’s Depression Rating Scale

CDR‐SB

Clinical Dementia Rating Scale – Sums of Boxes

CDRS‐R

Children’s Depression Rating Scale‐Revised

CGAS

Children’s Global Assessment Scale

CGI

Clinical Global Impression

CI

confidence interval

CIBIC‐plus

Clinician’s Interview‐Based Impression of Change plus caregiver input

CIGH

clozapine‐induced GI hypomotility

CIWA‐Ar

Clinical Institute Withdrawal Assessment of Alcohol Scale Revised

CK

creatine kinase

CKD

chronic kidney disease

CKD‐EPI

Chronic Kidney Disease Epidemiology Collaboration

CNS

central nervous system

COCP

combined oral contraceptive pill

COMT

catechol‐O‐methyltransferase

COPD

chronic obstructive pulmonary disease

COWS

Clinical Opiate Withdrawal Scale

CQC

Care Quality Commission

CrCl

creatinine clearance

CRLTA

clozapine‐related life‐threatening agranulocytosis

CRP

C‐reactive protein

CTO

Community Treatment Order

CUtLASS

Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study

CVD

cardiovascular disease

CY‐BOCS

Children’s Yale‐Brown Obsessive Compulsive Scale

CYP

cytochrome P450

DAI

Drug Attitude Inventory

DBM

dibenzoylmethane

DBT

dialectical behaviour therapy

DEXA

dual‐energy x‐ray absorptiometry

DHA

docosahexaenoic acid

DHEA

dehydroepiandrosterone

DIVA‐5

Diagnostic Interview for ADHD in Adults

DLB

dementia with Lewy bodies

DMDD

disruptive mood dysregulation disorder

DMq

dextromethorphan and low‐dose quinidine

DOACs

direct‐acting oral anticoagulants

DoLS

Deprivation of Liberty Safeguards

DSM‐5

Diagnostic and Statistical Manual of Mental Disorders

, 5th edition

DVLA

Driver and Vehicle Licensing Agency

ECG

electrocardiogram

ECT

electroconvulsive therapy

EEG

electroencephalogram

eGFR

estimated glomerular filtration rate

EMDR

eye movement desensitisation and reprocessing

EOSS

early‐onset schizophrenia spectrum

EPA

eicosapentaenoic acid

EPS

extrapyramidal symptoms

EPSE

extrapyramidal side effect

ER

extended release

ERK

extracellular signal‐regulated kinase

ES

effect size

EU

European Union

FBC

full blood count

FDA

Food and Drug Administration

FGA

first‐generation antipsychotic

FPG

fasting plasma glucose

FRAMES

feedback, responsibility,

principles

advice, menu, empathy, self‐efficacy

FSH

follicle‐stimulating hormone

FTI

Fatal Toxicity Index

GABA

gamma‐aminobutyric acid

GAD

generalised anxiety disorder

GASS

Glasgow Antipsychotic Side‐effect Scale

GBL

gamma‐butyrolactone

G‐CSF

granulocyte colony‐stimulating factor

GERD

gastro‐esophageal reflux disease

GFR

glomerular filtration rate

GGT

gamma‐glutamyl transferase

GHB

gamma‐hydroxybutyrate

GHB/GBL

gamma‐hydroxybutyrate/gamma‐butyrolactone

GI

gastrointestinal

GLP‐1

glucagon‐like peptide‐1

GP

general practitioner

GRDS

gastric reduction duodenal switch

GSM

genitourinary symptoms of menopause

HAD

HIV‐associated dementia

HAM‐D

Hamilton Depression Rating Scale

HAND

HIV‐assocated neurocognitive disorders

HbA

1c

glycated haemoglobin

HCl

hydrogen chloride

HD

Huntington’s disease

HDL

high‐density lipoprotein

hERG

human ether‐a‐go‐go‐related gene

HIV

human immunodeficiency virus

HLA

human lymphocyte antigen

HPA

hypothalamic–pituitary–adrenal

HR

hazard ratio

HRT

hormone replacement therapy

IADL

instrumental activities of daily living

ICD‐10

International Classification of Diseases 10

ICH

intracranial/intracerebral haemorrhage

IGSLI

International Study Group on Lithium

IHD

ischaemic heart disease

IM

intramuscular

INR

international normalised ratio

IR

immediate release

ISBD

International Society for Bipolar Disorders

ISTSS

International Society for Traumatic Stress Studies

IV

intravenous

Kiddie‐SADS

Kiddie‐Schedule for Affective Disorders and Schizophrenia

LAI

long‐acting injection

LC‐MS

liquid chromatography and mass spectrometry

LD

learning disabilities

LDL

low‐density lipoprotein

LFT

liver function test

LGIB

lower gastrointestinal bleeding

LMP

last menstrual period

MADRS

Montgomery–Asberg Depression Rating Scale

MAO

monoamine oxidase

MAOI

monoamine oxidase inhibitor

MARS

Medication Adherence Rating Scale

MASC

Multidimensional Anxiety Scale for Children

MCA

Mental Capacity Act

MCI

mild cognitive impairment

MDD

major depressive disorder

MDMA

3,4‐methylenedioxymethamphetamine

MDRD

Modification of Diet in Renal Disease

MDT

multidisciplinary team

MFQ

Mood and Feelings Questionnaire

MHA

Mental Health Act

MHRA

Medicines and Healthcare products Regulatory Authority

MI

myocardial infarction

MMSE

Mini Mental State Examination

MND

mild neurocognitive disorder

MoCA

Montreal Cognitive Assessment

MR

modified release

MS

mood stabilisers/multiple sclerosis

MSM

men who have sex with men

NAPLS

North American Prodromal Longitudinal Studies

NaSSA

noradrenergic and specific serotonergic antidepressant

NbN

neuroscience‐based nomenclature

NEET

not in education, employment or education

NICE

National Institute for Health and Care Excellence

NIMH

National Institute of Mental Health

NMDA

N‐methyl‐D‐aspartate

NMDAR

N‐methyl‐D‐aspartate receptor

NMS

neuroleptic malignant syndrome

NNH

number needed to harm

NNT

number needed to treat

NPIS

National Poisons Information Service

NPS

new psychoactive substances

NPV

negative predictive value

NRT

nicotine replacement therapy

NSAID

non‐steroidal anti‐inflammatory drug

OCD

obsessive compulsive disorder

od

once daily

OGTT

oral glucose tolerance test

on

at night

OOWS

Objective Opiate Withdrawal Scale

OR

odds ratio

OST

opioid substitution treatment

PAIN

Peri‐operative Pain and Addiction Interdisciplinary Network

PANDAS

paediatric autoimmune neuropsychiatric disorder associated with

Streptococcus

PANS

paediatric acute‐onset neuropsychiatric syndrome

PANSS

Positive and Negative Syndrome Scale

PAWS

post‐acute withdrawal syndrome

PBA

pseudobulbar affect

PD

Parkinson’s disease

PDSS

post‐injection delirium sedation syndrome

PE

pulmonary embolism

PET

positron emission tomography

PG

propylene glycol

P‐gp

P‐glycoprotein

PHQ‐9

Patient Health Questionnaire‐9

PLWH

people living with HIV

PMDD

premenstrual dysphoric disorder

PMR

postmortem redistribution

PMS

premenstrual syndrome

po

by mouth

POI

premature ovarian insufficiency

PORT

Program of Rehabilitation and Therapy

PP1M

paliperidone long‐acting injection 1‐monthly

PP3M

paliperidone long‐acting injection 3‐monthly

PPH

postpartum haemorrhage

PPI

proton pump inhibitor

PPV

positive predictive value

prn

as required

PSSD

post‐SSRI sexual dysfunction

PT

prothrombin time

PTSD

post‐traumatic stress disorder

PUFA

polyunsaturated fatty acid

PWE

people with epilepsy

RANZCP

Royal Australian and New Zealand College of Psychiatrists

RC

Responsible Clinician

RCADS

Revised Children’s Anxiety and Depression Scale

RCT

randomised controlled trial

REM

rapid eye movement

RID

relative infant dose

RIMA

reversible inhibitor of monoamine oxidase A

RLAI

risperidone long‐acting injection

ROMI

Rating of Medication Influences

RR

respiratory rate/risk ratio

RRBI

restricted repetitive behaviours and interests

RT

rapid tranquillisation

RTA

road traffic accident

rTMS

repetitive transcranial magnetic stimulation

RUPP

Research Units on Paediatric Psychopharmacology

RYGB

Roux‐en‐Y gastric bypass

SADQ

Severity of Alcohol Dependence Questionnaire

SAWS

Short Alcohol Withdrawal Scale

SC

subcutaneous

SCARED

Screen for Child Anxiety and Related Emotional Disorders

SCRA

synthetic cannabinoid receptor agonist

SD

sexual dysfunction

SERM

selective oestrogen receptor modulators

SERT

serotonin receptor

SGA

second‐generation antipsychotic

SIADH

syndrome of inappropriate secretion of antidiuretic hormone

SIB

Severe Impairment Battery

SJW

St John’s wort

SNRI

serotonin–noradrenaline reuptake inhibitor

SOAD

Second Opinion Appointed Doctor

SPC

Summary of Product Characteristics

SROM

slow‐release oral morphine

SSRI

selective serotonin reuptake inhibitor

STAR*D

Sequenced Treatment Alternatives to Relieve Depression

STOP‐PD II

Study of the Pharmacotherapy of Psychotic Depression II

SUD

stimulant use disorder

TADS

Treatment of Adolescents with Depression Study

TCA

tricyclic antidepressant

TD

tardive dyskinesia

tDCS

transcranial direct current stimulation

TDM

therapeutic drug monitoring

TdP

torsades de pointes

tds

three times a day

TF‐CBT

trauma‐focused cognitive behavioural therapy

TFT

thyroid function test

TIA

transient ischaemic attack

tMS

transcranial magnetic stimulation

TORDIA

Treatment of Resistant Depression in Adolescents

TRBD

treatment‐resistant bipolar disorder

TRD

treatment‐resistant depression

TREC

Tranquilização Rápida‐Ensaio Clínico [Rapid Tranquillisation Clinical Trial]

TRS

treatment‐resistant schizophrenia

TS

Tourette syndrome

U&Es

urea and electrolytes

UDP

uridine diphosphate

UGT

UDP‐glucuronosyltransferase

UGIB

upper gastrointestinal bleeding

UGT

UDP‐glucuronosyltransferase

UKTIS

UK Teratology Information Service

VaD

vascular dementia

VG

vegetable glycerine

VHR

Vienna High Risk

VMAT‐2

vesicular monoamine transporter 2

VNS

vagal nerve stimulation

VTE

venous thromboembolism

WBC

white blood cell

WCC

white cell count

WHO

World Health Organization

YMRS

Young Mania Rating Scale

ZA

zuclopenthixol acetate

Chapter 1Schizophrenia and related psychoses

ANTIPSYCHOTIC DRUGS

General introduction

Classification of antipsychotics

Before the 1990s, antipsychotics (or major tranquillisers as they were then known) were classified according to their chemistry. The first antipsychotic, chlorpromazine, was a phenothiazine compound – a tricyclic structure incorporating a nitrogen and a sulphur atom. Further phenothiazines were generated and marketed, as were chemically similar thioxanthenes such as flupentixol. Later, entirely different chemical structures were developed according to pharmacological paradigms. These included butyrophenones (haloperidol), diphenylbutylpiperidines (pimozide) and substituted benzamides (sulpiride, amisulpride).

Chemical classification remains useful but is rendered somewhat redundant by the broad range of chemical entities now available and by the absence of any clear structure–activity relationships for newer drugs. The chemistry of some older drugs does relate to their propensity to cause movement disorders. Piperazine phenothiazines (e.g. fluphenazine, trifluoperazine), butyrophenones and thioxanthenes are most likely to cause extrapyramidal effects, while piperidine phenothiazines (e.g. pipotiazine) and benzamides are the least likely. Aliphatic phenothiazines (e.g. chlorpromazine) and diphenylbutylpiperidines (pimozide) are perhaps somewhere in between.

Relative liability for inducing extrapyramidal side effects (EPSEs) was originally the primary factor behind the typical/atypical classification. Clozapine had long been known as an atypical antipsychotic on the basis of its low liability to cause EPSEs and its failure in animal‐based antipsychotic screening tests. Its remarketing in 1990 signalled the beginning of a series of new medications, all of which were introduced with claims (to varying degrees of accuracy) of ‘atypicality’. Of these medications, perhaps only clozapine, and possibly quetiapine, is completely atypical, seemingly having a very low or zero liability for extrapyramidal symptoms (EPS). Others show dose‐related effects, although, unlike with typical drugs, therapeutic activity can usually be achieved without EPSEs. This is possibly the real distinction between typical and atypical drugs: the ease with which a dose can be chosen within the licensed dosage range that is effective but does not cause EPSEs (for example, compare haloperidol with olanzapine).

The typical/atypical dichotomy does not lend itself well to classification of antipsychotics in the middle ground of EPSE liability. Thioridazine was widely described as atypical in the 1980s but is a ‘conventional’ phenothiazine. Sulpiride was marketed as an atypical but is often classified as typical. Risperidone, at its maximum dose of 16mg/day, is just about as ‘typical’ as a drug can be. Alongside these difficulties is the fact that there is nothing either pharmacologically or chemically which clearly binds these so‐called atypicals together as a group, save perhaps a general but not universal finding of preference for D2 receptors outside the striatum. Nor are atypicals characterised by improved efficacy over older drugs (clozapine and one or two others excepted) or the absence of hyperprolactinaemia (which is usually worse with risperidone, paliperidone and amisulpride than with typical drugs). Lastly, some more recently introduced agents (e.g. pimavanserin, xanomeline) have antipsychotic activity and do not cause EPS but have almost nothing in common with other atypicals in respect to chemistry, pharmacology or adverse‐effect profile.

In an attempt to get round some of these problems, typicals and atypicals were reclassified as first‐ or second‐generation antipsychotics (FGA/SGA). All drugs introduced since 1990 are classified as SGAs (i.e. all atypicals) but the new nomenclature dispenses with any connotations regarding atypicality, whatever that may mean. However, the FGA/SGA classification remains problematic because neither group is defined by anything other than time of introduction – hardly the most sophisticated pharmacological classification system. Perhaps more importantly, date of introduction is often wildly distant from date of first synthesis. Clozapine is one of the oldest antipsychotics (synthesised in 1959) while olanzapine is hardly in its first flush of youth, having first been patented in 1971. These two drugs are of course SGAs, apparently the most modern of antipsychotics.

In this edition of the Maudsley Prescribing Guidelines, we conserve the FGA/SGA distinction more because of convention than some scientific basis. Also, we feel that most people know which drugs belong to each group – it thus serves as a useful shorthand. However, it is clearly more sensible to consider the properties of individual antipsychotics when choosing drugs to prescribe or in discussions with patients and carers. With this in mind, the use of Neuroscience‐based Nomenclature (NbN)1 – a naming system that reflects pharmacological activity – is strongly recommended.

Choosing an antipsychotic

In the UK, the National Institute for Health and Care Excellence (NICE) guideline for medicines adherence2 recommends that patients should be as involved as possible in decisions about the choice of medicines that are prescribed for them, and that clinicians should be aware that illness beliefs and beliefs about medicines influence adherence. Consistent with this general advice that covers all healthcare, the NICE guideline for schizophrenia emphasises the importance of patient choice rather than specifically recommending a class or individual antipsychotic as first‐line treatment.3

Antipsychotics are effective in both the acute and maintenance treatment of schizophrenia and other psychotic disorders. They differ in their pharmacology, pharmacokinetics, overall efficacy/effectiveness and tolerability, and, perhaps more importantly, response and tolerability differ between patients. This variability of individual response means that there is no clear first‐line antipsychotic medication that is preferable for all.

Relative efficacy

After the publication of the independent CATIE4 and CUtLASS5 studies, the World Psychiatric Association reviewed the evidence relating to the relative efficacy of 51 FGAs and 11 SGAs and concluded that, if differences in EPS could be minimised (by careful dosing) and anticholinergic use avoided, there was no convincing evidence to support any advantage for SGAs over FGAs.6 As a class, SGAs may have a lower propensity for EPS and tardive dyskinesia (TD),7 but this was somewhat offset by a higher propensity to cause metabolic adverse effects. A meta‐analysis of antipsychotic medications for first‐episode psychosis8 found few differences between FGAs and SGAs as groups of drugs but minor advantages for olanzapine and amisulpride individually. A later network meta‐analysis of first‐episode studies found small efficacy advantages for olanzapine and amisulpride and overall poor performance for haloperidol.9

When individual non‐clozapine SGAs are compared, summary data suggest that olanzapine is marginally more effective than aripiprazole, risperidone, quetiapine and ziprasidone, and that risperidone has a minor advantage over quetiapine and ziprasidone.10 FGA‐controlled trials also suggest an advantage for olanzapine, risperidone and amisulpride over older drugs.11,12 A network meta‐analysis13 broadly confirmed these findings, ranking amisulpride second behind clozapine and olanzapine third. These three drugs were the only ones to show clear efficacy advantages over haloperidol. The magnitude of differences was again small (but potentially substantial enough to be clinically important)13 and must be weighed against the very different adverse effect profiles associated with individual antipsychotics. A 2019 network meta‐analysis of 32 antipsychotics14 ranked amisulpride as the most effective drug for positive symptoms and clozapine as the best for both negative symptoms and overall symptom improvement. Olanzapine and risperidone were also highly ranked for positive symptom response. The greatest (beneficial) effect on depressive symptoms was seen with sulpiride, clozapine, amisulpride, olanzapine and the dopamine partial agonists, perhaps reflecting the relative absence of neuroleptic‐induced dysphoria common to most FGAs.15 In the longer term, olanzapine may have advantages over some other antipsychotics.16 There was a tendency for more recently introduced drugs to have a lower estimated efficacy – a phenomenon that derives from the substantial increase in placebo response since 1970.17

Clozapine is clearly the drug of choice in refractory schizophrenia,18 although bizarrely, this is not a universal finding,19 probably because of the biased nature and quality of many active–comparator trials.20,21

Both FGAs and SGAs are associated with a number of adverse effects. These include weight gain, dyslipidaemia, increases in plasma glucose/diabetes,22,23 hyperprolactinaemia, hip fracture,24 sexual dysfunction, EPS including neuroleptic malignant syndrome,25 anticholinergic effects, venous thromboembolism (VTE),26 sedation and postural hypotension. The exact profile is drug specific (see individual sections on specific adverse effects), although comparative data are not robust27 (see large‐scale meta‐analyses13,28 for rankings of some adverse‐effect risks).

Adverse effects are a common reason for treatment discontinuation,29 particularly when efficacy is poor.13 Patients do not always spontaneously report adverse effects, however,30 and psychiatrists’ views of the prevalence and importance of adverse effects differ markedly from patient experience.31 Systematic enquiry, together with a physical examination and appropriate biochemical tests, is the only way accurately to assess their presence and severity or perceived severity. Patient‐completed checklists such as the Glasgow Antipsychotic Side‐effect Scale (GASS)32 can be a useful first step in this process. The clinician‐completed Antipsychotic Non‐Neurological Side‐Effects Rating Scale facilitates more detailed and comprehensive assessment.33

Non‐adherence to antipsychotic treatment is common and here the guaranteed medication delivery associated with depot/long‐acting injectable antipsychotic preparations (LAIs) is unequivocally advantageous. In comparison with oral antipsychotics, there is strong evidence that depots are associated with a reduced risk of relapse and rehospitalisation,34–36 although randomised controlled trials (RCTs) do not always reflect this difference.37 Any logical assessment of the benefits of LAIs and the damage caused by relapse would conclude that LAIs should be first‐line treatments, rather than reserved for those who have already relapsed on oral medication. Moreover, the wider use of SGA LAIs has to some extent changed the image of depots, which were sometimes perceived as punishments for miscreant patients. Their tolerability advantage probably relates partly to the better definition of their therapeutic dose range, meaning that the optimal dose is more likely to be prescribed (compare aripiprazole, with a licensed dose 300mg or 400mg/month, with flupentixol, which has a licensed dose in the UK of 50mg every 4 weeks to 400mg/week). The optimal dose of flupentixol is around 40mg every 2 weeks28 – just 5% of the maximum allowed.

As already mentioned, for patients whose symptoms have not responded sufficiently to adequate, sequential trials of two or more antipsychotic drugs, clozapine is the most effective treatment.38–40 Its use in these circumstances is recommended by NICE3 and probably every schizophrenia guideline besides. The biological basis for the superior efficacy of clozapine is uncertain.41 Olanzapine should probably be one of the two drugs used before clozapine.10,42 A case might also be made for a trial of amisulpride: it has a uniformly high ranking in meta‐analyses and one trial found continuation with amisulpride to be as effective as switching to olanzapine.43 This same trial also suggested clozapine might be best placed as the second drug used, given that switching provided no benefit over continuing with the first prescribed drug.

This chapter covers the treatment of schizophrenia with antipsychotic drugs, the relative adverse effect profile of these drugs and how adverse effects can be managed.

References

1. Zohar J, et al. Neuroscience‐based Nomenclature (NbN): a call for action.

World J Biol Psychiatry

2016;

17

:318–320.

2. National Institute for Health and Care Excellence. Medicines adherence: involving patients in decisions about prescribed medicines and supporting adherence. Clinical guideline [CG76]. 2009 (last updated March 2019, last checked December 2024);

https://www.nice.org.uk/Guidance/CG76

.