دليل الفصام واضطراب المزاج ثنائي القطب

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اطماره الجر
Ministry of Health
MOH Protocols for the Management of Patients with SCHIZOPHRENIA and BIPOLAR Affective Disorder
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Ministry of Health
ACKNOWLEDGEMENT
Since the establishment of AI Amal complex for mental health as a major and teaching hospital our vision is to provide the best services for our patients in mental health field.
We believe such vision to be fulfilled it requires great effort to currently improve and update the medical resources and knowledge of our medical staff.
This book is a humble effort of elite group of consultant psychiatrists in psychiatry department that serve as one of our efforts in the context of our vision.
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Ministry of Health
Table of Contents
• Introduction....6
A. Abbreviations Used....6
B. Purpose 8
C. Aim & Scope....8
D. PRESCRIBERS OF BIOLOGIC THERAPY 9
E. TREATMENT GOALS 9
F. Targeted Population 9
G. End Users 9
H. Setup 10
I. Setting 10
J. Methodology....10
K. Updating....11
L. Conflict of Interest 12
M. Funding....12
N. Targeted end users....12
O. DISCLAIMER....13
P. Preface 13
Q. Preface 14
• Chapter 1 (Schizophrenia)....15
A. Introduction 15
B. GENERAL PSYCHIATRIC MANAGEMENT 16
C. ACUTE TREATMENT FOR FIRST PSYCHOTIC EPISODE OF SCHIZOPHRENIA .....17
D. PSYCHOSOCIAL INTERVENTIONS 19
E. High – dose Antipsychotic: Prescribing and Monitoring 20
F. Strategies for Inadequate Response....22
G. Switching Antipsychotic Drugs because of Poor Tolerability 23
H. Equivalent Doses of Conventional Antipsychotic Drugs....25
I. Second Generation antipsychotics Equivalent Doses....26
J. Minimum effective Doses 27
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L. Antipsychotic Drugs: Licensed Maximum Dose....28
M. USE OF ECT IN SCHIZOPHRENIA 29
N. RECOMMENDATION FOR THE MANAGEMENT OF NEGATIVE SYMPTOMS OF SCHIZOPHRENIA....29
O. TREATMENT ALGORITHMS FOR SCHIZOPHRENIA 30
P. ADVICE ON PRESCRIBING LONG ACTING INJECTABLE ANTIPSYCHOTICS ....32
Q. RISPERIDONE LONG – ACTING INJECTION....35
R. Paliperidone Palmitate LAI....37
S. REFRACTORY SCHIZOPHRENIA....40
T. Extrapyramidal Side Effects of Antipsychotics Effects....44
U. CATATONIA 49
V. Cardiovascular effects of antipsychotic drugs treatment....51
W. ANTIPSYCHOTIC DRUGS ON HYPERPROLACTINEMIA 53
X. ANTIPSYCHOTIC INDUCED WEIGHT GAIN....55
Y. Substance Use Disorder and Schizophrenia (Dual Diagnosis) 57
Z. LONG TERM HOSPITALIZATION 57
References (Chapter 1)....59
• Chapter 2 (Bipolar Disorder)....60
A. Introduction 60
B. ACUTE MANAGEMENT OF BIPOLAR MANIA AS ADOPTED FROM CANMAT ......63
C. ACUTE MANAGEMENT OF BIPOLAR DEPRESSION....71
D. MAINTENANCE THERAPY FOR BIPOLAR DISORDER....79
E. BIPOLAR DISORDER IN SPECIAL PATIENT POPULATION 84
F. ACUTE AND MAINTENANCE MANAGEMENT OF BIPOLAR II DISORDER......97
G. BIPOLAR SPECTRUM DISORDERS....102
- Chapter 3 (GUIDELINES FOR THE USE AND MANAGEMENT OF LONG ACTING INJECTABLE ANTIPSYCHOTICS IN SERIOUS MENTAL ILLNESS)....113
A. Indications....113
B. Most appropriate introduction period during the illness....113
C. Schizophrenia....115
D. Bipolar disorder....116
E. In the acute phase....119
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اطماره الجر
Ministry of Health
F. Bipolar disorder....120
G. Procedures for follow-up and monitoring....123
H. Specific populations....124
• Chapter 4 (Appendix)....132
A. MANAGEMENT OF THE SUICIDAL PATIENT ....143
B. BLACK-BOX WARNING AND PSYCHIATRIC DRUGS....147
C. LABORATORY AND OTHER TESTING FOR PATIENTS TAKING PSYCHOTROPIC MEDICATIONS....148
D. CLOZAPINE MONITORING....155
E. LITHIUM MONITORING....158
F. MAX. DOSES OF PSYCHOTROPIC DRUG ....162
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Ministry of Health
- Introduction
Schizophrenia and BAD are two major psychiatric disorders, they contribute the great percentage of patients admitted at psychiatric hospitals in KSA & worldwide.
Their chronic disabling symptoms cause considerable burden not only to sufferers but also to their families, and contribute to poorer quality of life and considerable economic burden on society.
In many instances, there is a delay in seeking treatment and in some cases such delay may stretch up to nearly ten years.
This may result from ignorance of the condition, fear of taking medications, and the stigma of receiving a psychiatric diagnosis, and or having to accept psychiatric treatment
There are a lot of schools and guidelines dealing with the treatment of both disorders, in order to find more or less common protocols for treatment of these disorders and our need for national guidelines to deal with this disorder in proper practice way, and also to improve the outcome of such disorders, with an initiative of the Ministry of Health of the Kingdom of Saudi Arabia, a multidisciplinary expert panel of psychiatrists and pharmacists with practice experience in the clinical management of Schizophrenia and BAD disorders where invited to be part of work group to update the previous practical guidelines on biological treatment of these disorders.
Management of Schizophrenia and BAD in daily clinical practice is highly variable as there are many issues that are still debated and not definitely addressed by evidence-based medicine. Biologic therapy is now a well-established strategy for Schizophrenia and BAD.
The recommendations were developed after rigorous evaluation of existing international guidelines as well as the latest emerging evidence.
A. Abbreviations Used
ECG: Electrocardiogram.
SGAs: Second Generation antipsychotic.
FGAs: First Generation antipsychotic.
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Eps: Extrapyramidal symptoms.
LAI: Long acting injection.
I.M: Intramuscular.
CBC: Complete Blood Count.
WBC: White Blood Count.
ANC: Absolute Neutrophil Count.
CBT: Cognitive Behavioral Therapy.
NMS: Neuroleptic Malignant Syndrome.
BAD: Bipolar Affective Disorder.
NOS: Not elsewhere classified.
RCT: Randomized Control Trial.
TAU: Treatment as Usual.
IPSRT: Interpersonal and Social Rhythm Therapy.
Li: Lithium.
DVP: Divalproex.
ER, XR: Extended Release.
MAOI: Monoamine Oxidase Inhibitors.
TCA: Tricyclic Antidepressant.
SSRI: Selective Serotonin Reuptake Inhibitors.
STEP-SD: Systematic Treatment Enhancement.
FFT: Family Focus Therapy.
MADRS: Asberg Depression Rating Scale.
NAC: N-Acetyl Cysteine.
PT: Prothrombin Time.
CANMAT: Canadian Clinical Practice Guidelines.
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B. Purpose
Our purpose is to improve the outcome in the treatment practice for Schizophrenia and BAD by delivering an update guidelines to the hands of psychiatrists in KSA.
These protocols have been developed to guide medical practitioners for the use of the most effective available treatments for schizophrenia and bipolar disorders in the in-patient and out-patient settings and serve as a framework for clinical decisions and supporting best practices.
The overall aim of these protocols is to establish evidence based recommendations on the use and application of biological therapy for Schizophrenia and BAD, these protocols also address the use of biological therapy in special and problematic medical conditions.
These protocols are developed to provide practical, evidence-based recommendations to primary care physicians and specialists in psychiatry for the management of Schizophrenia and BAD disorders. We have omitted treatments that are currently not available in Saudi Arabia.
There is a clear need for national guidelines due to the extended role and high availability of literature on these agents.
C. Aim & Scope
These protocols are developed to facilitate the assessment of the disorders, and to ensure that their management is appropriate and effective.
These protocols will cover the management of disorders in adults and address the issues of medication use during pregnancy and breastfeeding.
The overall aim of these protocols is to deliver evidence-based recommendations on the use, screening, and monitoring of biologic therapy in patients with Schizophrenia and BAD. These protocols also aim to propose updated decision-making algorithms for practitioners involved in the treatment of these patients and consideration is given to special patient population.
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D. PRESCRIBERS OF BIOLOGIC THERAPY
Biologic therapies should be prescribed by psychiatrists with extensive clinical experience in the treatment of schizophrenia and BD with systemic agents, considering that use of these therapies requires appropriate patient selection and follow up.
E. TREATMENT GOALS
Before starting biologic therapy, it is preferable to define treatment goals for each patient. Psychometric assessment tools are recommended for use in daily practice in order to establish and monitor the achievement of treatment goals and guide therapy.
F. Targeted Population
The content of the protocols will be useful for all doctors treating patients with schizophrenia and BD disorders. Efforts have been made to ensure that the guidelines are particularly useful for primary care physicians and specialists in psychiatry, the doctor treating the patient is ultimately responsible for clinical decisions made after reviewing the individual patient's history, clinical presentation and treatment options available.
G. End Users
Psychiatry Consultants, Specialists and Residents, primary care physicians, Psychiatry clinical pharmacists, Pharmacists, Nurses.
Primary Care Physicians Role:
1- initially, primary care physician assess the case for mental health disorders, if he provisionally diagnoses the case with schizophrenia or bipolar disorder he should refer the case to specialized psychiatry clinic.
2- After the case of schizophrenia or bipolar disorder has been stabilized, and proper care was provided by the treating psychiatrist, who can refer back the case to primary care physician for regular follow up and continuing the psychiatric Management plan.
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3- During follow up of a Known case schizophrenic or bipolar disorders in the primary care clinic, once the case showed any signs or symptoms of disorder relapse or any safety issues (e.g. suicidality or homicidally), primary care physician should refer the case to specialized psychiatry clinic for stabilization and management.
4- primary care physician should commit to this guideline in regard to all steps of assessment, Management, prescription of psychotropic medications and required routine investigations.
H. Setup
The primary care units, in-patient and outpatient settings and serve as a framework for clinical decisions and supporting best practices.
I. Setting
— Eradah Complex / Hospital and Mental Health.
– Psychiatric clinics in MOH General Hospitals.
J. Methodology
These protocols have been produced by a committee of psychiatrists, a clinical psychologist, pharmacist, patient representative, and family practitioners appointed by the Ministry of Health. They were developed by revising the existing protocols, reviewing relevant literature, including overseas clinical practice guidelines and by expert clinical consensus of professionals with experience in treating patients in the local setting.
The following principles underlie the development of these protocols: Treatment recommendations are supported by scientific evidence whenever possible (randomized controlled clinical trials represent the highest level of evidence) and expert clinical consensus is used when such data are lacking. Treatment should maximize therapeutic benefits and minimize side effects.
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Ministry of Health
We agree on these reviews with more than 75% of the members' votes, In the event of a disagreement, the reviews should be worked on again until an agreement is reached that exceeds this percentage.
Team members reviewed this protocol in several sessions for editing, updating, improving, reviewing, taking expert opinions, and annual updating if any changes or updates released by international/national guidelines.
Policies-procedures and an agreement form should be developed by hospital according to hospital quality standers.
The multidisciplinary work group was made up of expert psychiatrists and pharmacists. Published protocols concerning the treatment of Schizophrenia and BAD were evaluated using the Appraisal of Guidelines, Research and Evaluation II (AGREE II) scale. The guidelines found to meet the criteria for use for our patients are: The NICE Guidelines, American psychiatric Association, The Maudsely Guidelines, the Canadian Guidelines plus a lot of evidence based scientific researches
Formal consensus methodology was adopted to reach consensus on specific items. The consensus statements are based on the best available evidence and their development followed a standardized process. A statement was regarded as consented when agreement was achieved by at least 75% of the voting experts. The strength of recommendation was not expressed.
K. Updating
This edition of the protocols contains updated recommendations based on latest evidence, as well as detailed discussions and recommendations on the management of schizophrenia and BD disorders in adult populations.
Review of protocols Evidence-based clinical practice protocols are only as current as the evidence that supports them. Users must keep in mind that new evidence could supersede recommendations in these protocols. The workgroup advises that these protocols be scheduled for review five years after publication, or when new evidence appears that requires substantive changes to the present recommendations.
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اشراه الجر
Ministry of Health
Updates of the present protocols will be provided as needed to incorporate new data or agents.
L. Conflict of Interest
This protocol developed based on valid scientific evidence, critical assessment of that evidence, and objective clinical judgment that relates the evidence to the needs of practitioners and patients. No financial relationships with pharmaceutical, medical device, and biotechnology companies.
M. Funding
No fund was provided.
N. Targeted end users
• Psychiatry and Addiction Medicine Consultants, Specialists and Residents
- Nurses
• Psychiatry clinical pharmacists
- Pharmacists
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O. DISCLAIMER
Clinical practice Protocols are evidence-based decision-making tools for managing health conditions. They are based on the best information available at the time of writing, and are to be updated regularly. The present guidelines are not meant to serve as strict treatment guidelines. They are also not intended to replace clinical judgement of practicing physicians but are only tools to help manage patients who require biologic treatment for Schizophrenia and BAD. Decisions concerning treatment must always be taken on a case-by-case basis and the prescribing physicians need to personalize care and tailor the treatment regimen to patients' personal circumstances and medical history.
Physicians should also consult the approved product monographs within their institution's formulary for each drug for dosage, special warnings and precautions for use, contraindications, and monitoring of side effects and potential harms. Institution formulary restrictions may also need to be considered when selecting treatment options. Prescribing physicians should refer to their institution's formularies during the decision-making process for choosing specific agents within a recommended specific class.
P. Preface
It is of my great pleasure and honor to present Eradah Psychiatric Complex's first booklet specialized in management protocols of Schizophrenia and Bipolar disorders. And it is of utmost importance to keep it updated with the latest medical treatment protocols for such mental disorders, which form burdens on not only patients but also their families. This booklet comprises comprehensive guidelines of most medical procedures and protocols, which have been collected from a variety of trusted international periodicals, for these conditions.
In addition, we will make sure that this publication gets updated with the latest globally available on the topic in the following copies. We have provided the handbook with the most famous rating scales of Schizophrenia and Bipolar disorders, which concern all of those specializing in Psychiatry in helping to determine the severity of the conditions and the effectiveness of treatment.
Not to forget our endless gratitude to Dr. Khaled Saad Sherra, Dr. Samia Abdulrahman, and Dr. Dalia Mokhtar for their great efforts in elaborating and piecing together this very influential work.
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السلام عليكم
Ministry of Health
Hoping that Allah may benefit with this work all those working in the Psychiatric field and that it may lay the groundwork for many publications and periodicals to follow from Eradah Complex for Mental Health at Riyadh.
Declaring that Allah's behind our intentions.
Dr. Mohamed M. Al Qahtani
Executive Director of Eradah Complex for Mental Health at Riyadh
Q. Preface
This protocol has been developed after a comprehensive review of the most updated international guidelines to provide the evidence-based recommendation for the most common Psychiatric Disorders for the purpose of improving the quality of services given to our patients.
It is not intended to serve as a Standard of Medical Care. Adherence to it will not ensure successful outcome for every individual, nor should it be interpreted as including all proper methods of care or excluding other acceptable methods of care aimed at the same results. It should not replace the best of the psychiatrist judgment.
The protocol is composed of 3 chapters (Schizophrenia Management, Bipolar Disorder Management and Assessment by Standardized Rating Scales) with the future plan to include more chapters of the most major psychiatric disorders that of clinical importance to the psychiatrist.
Acknowledging the rapid advancement of the scientific knowledge, this protocol will be updated every 2 years.
Committee Monist
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• Chapter 1 (Schizophrenia)
A. Introduction
Schizophrenia is a relatively common mental illness with a life time risk approaching one percent, it represents a major psychiatric disorder in which a person's perception, thought mood and behavior are significantly altered, and symptoms are usually divided into positive symptoms including hallucination and delusions and negative symptoms. Each person will have a unique combination of symptoms and experiences. The first symptoms tend to start in young adulthood, at the time when a person usually make a transition to independent living, but can occur at any age. The symptoms and behavior associated with psychosis can have a distressing impact on the individual, family and friends.
Clinical practice guidelines have been defined as systematically developed statements based on evidence based recommendations for patient management to assist practitioner and patient in decision about appropriate health care for specific situation. The aim of these guidelines is to improve the assessment and treatment of patient with schizophrenia at all stages of the illness.
This management protocol for schizophrenia was prepared after re-viewing the current standard guidelines being followed worldwide. The Algorithm for Pharmacological and Psychosocial treatment is formulated after cross – comparison across four different guidelines. Based on the current status of the evidence some of the recommendation have been combined to form a unified guidelines for management that specify 4 main topics, each of which a physician must consider when seeing a patient. Assessment, pharmacotherapy, psychosocial intervention and delivery of services. Within each of the first 3 topics, 3 phases of the illness are distinguished:
- The Acute Phase, where signs and symptoms worsen, usually bringing the patient to medical attention.
- The Stabilization Phase, where in the illness is subsiding after on a acute episode.
- The Stable or Chronic Phase, wherein acute symptoms may have subsided but functioning is often persistently impaired.
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The emphasis of this protocol is on practical issues rather than theoretical knowledge, and pertinent on most important clinical problems that face mental health practitioners who deal with adult schizophrenic patients.
B. GENERAL PSYCHIATRIC MANAGEMENT
Includes the following:
• Assessing symptoms and establishing diagnosis.
• Developing a plan of treatment.
• Developing a therapeutic alliance and promoting treatment adherence.
- Providing patient and family education and therapy.
• Treating comorbid condition.
- Attending to patient social circumstances and functioning.
• Integrating treatment from multiple clinicians.
• Documenting treatment.
Assessment before starting Antipsychotic Medication
• Undertake and record the following baseline investigation.
- Weight (plotted on chart)
- Waist circumference
- Pulse and blood pressure
- Fasting glucose, glycosylated haemoglobin (HBA1C), blood lipid profile and Prolactin level.
- Assessment of any movement disorder.
- Assessment of nutritional status, diet and level of physical activity
- Electrocardiogram (ECG) if there is history of cardiovascular disease or a physical examination has identified specific cardiovascular risk (Hypotension) or for an inpatient.
Monitoring Throughout Antipsychotic Treatment
- Response to treatment including change in symptoms and behaviour.
- Side effects of treatment.
• The Emergence of movement disorder.
- Weight, weekly for the first 6 weeks, then at 12 weeks, at 1 year and then Annually (Plotted on a chart)
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- Waist circumference annually (Plotted on a chart)
- Fasting blood glucose, HbA1c, blood lipid level at 12 weeks and one years and then annually.
- Pulse, blood pressure at 12 weeks at 1 year then Annually
- Adherence.
• Overall Physical Health.
C. ACUTE TREATMENT FOR FIRST PSYCHOTIC EPISODE OF SCHIZOPHRENIA
Treatment Goals
- To prevent harm, control disturbed behaviour, and reduce severity of psychosis associated symptoms (e.g. Agitation, Aggression, Affective Symptoms)
- To determine and address the factors that led to the occurrence of the acute episode
- Rapid return to the best level of functioning.
- To develop alliance with the patient and family.
- To formulate short and long term management plan.
- To connect the patient with appropriate after care in the community.
Acute Phase
- Treatment with Antipsychotic medication is indicated.
- Second Generation (SGAs) / First Generation (FGAs)
• Clinical observation during the first two weeks is vital for the following:
- Efficacy including change in symptoms and behaviour.
- Side effects of treatment, taking into account overlap be-
- Tween certain side effect and clinical features of Schizophrenia, for example the overlap between akathisia and agitation or anxiety.
- Physical Health
- Recognized rating scales should be used to monitor change.
- Titrate and adjust the dose according to response and tolerability
• Assess over 2 – 3 weeks.
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- Where there is no response at 2 – 3 weeks treatment should be changed (switch drug or increase the dose).
- Where there is some response, staying, switching and augmenting appear to be equal even though modestly effective.
- Carry on a trial of medication at optimum dosage for 4 -6 weeks.
- Offer Clozapine to people with Schizophrenia.
Whose illness has not responded adequately to treatment despite the sequential use of adequate doses at least two different Antipsychotic drugs. At least one of the drugs should be a non- clozapine second generation antipsychotic.
Stabilization Phase
- Antipsychotic should be continued for 1 – 2 years after the first Episode.
- Those who made functional recovery may be considered candidate for a trial of no medication.
- Withdrawal of Antipsychotic Medications should be done slowly over 6 – 12 months.
- Patient who were ill for an extended period before initial treatment and or have history of violent or suicidal behaviour may require more extended period.
- 80 % of first Episode are at high risk of a second episode within the first 2 – 5 years.
Stable Phase
- Duration of treatment is 2 years for the first episode.
• 5 – 10 years is for 2 or more episodes.
- Life time treatment for multiple episodes or more than two episodes in 5 years.
• A minimum of 5 years of stability without relapse should be
- Observed before slow withdrawal of antipsychotics over 6 – 24 months.
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Questions to consider before reducing the dose of maintenance Antipsychotic treatment
- Is the patient symptoms free, and if so for how long? Long standing, non-distressing symptoms which have not previously been responsive to medication maybe excluded.
- What is the severity of the side effects (EPS, Tardive Dyskinesia, obesity, etc.)?
- What is the previous pattern of illness? Consider the speed of
- Onset, duration and severity of episodes and any danger posed to self or others.
- Has dosage reduction been attempted before? If so what was the outcome?
- What are the patient current social circumstances? Is a period of relative stability or are stressful life events anticipated?
- What is the social cost of relapse (e.g. is the patient the sole bread winner for a family)?
- Is the patient able to monitor his/her own symptoms? If so, will he/she seek help?
D. PSYCHOSOCIAL INTERVENTIONS
In the Acute Phase
- Aimed at reducing over stimulating or stressful relationships, life events and promoting relaxation or reduce arousal through simple clear, coherent communication with structured and predictable environment with tolerant non – demanding supportive relationship with the psychiatrist and other member of the treatment team.
- Engagement of the patient and patient's family member in a collaborative treatment relationship.
• Educational meeting to the family members.
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In stabilization Phase
- Aimed at sustaining symptoms remission or control, minimize stress on the patient, provide support to minimize the likelihood of relapse, enhance the patient adaptation to live.
- In the community, facilitate the continued reduction in symptoms and consolidation of remission and promote the process of recovery.
- Psychotherapeutic intervention remains supportive but may be less structured and directive than in the acute phase.
In Stable Phase
- For most persons with schizophrenia in the stable phase, treatment program that combine medication with a range of psychosocial services are associated with improved outcomes.
- The selection of appropriate and effective psychosocial treatments needs to be driven by the circumstances of the individual patient's medication and his or her social context.
• Major goals of psychosocial treatment are:
1. Prevention of relapse and reduction of symptoms severity.
2. Reduction of negative symptoms.
3. Improving functional status and quality of life.
4. Patient and self-help treatment organization.
- A Number of Psychosocial Treatment have Demonstrated effectiveness. The treatment includes:
1. Family Interventions.
2. Supported Employment.
3. Assertive community treatment.
4. Social skill training.
5. Cognitive behaviourally oriented psychotherapy.
E. High – dose Antipsychotic: Prescribing and Monitoring
High dose can result from the prescribing of either:
- A single antipsychotic in a dose that is above the recommended maximum or two or more antipsychotics that when expressed as a percentage of
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their respective maximum recommended doses and added together result in a cumulative dose of
• More than 100%.
- Regarding efficacy, there is no firm evidence that high doses of antipsychotics are any more effective than standard doses.
- The majority of side-effects associated with antipsychotic treatment are dose related. These include, EPS, sedation, postural hypotension, anticholinergic effects, QTC prolongation and sudden death.
Before using high-dose antipsychotics, ensure that:
- Sufficient time has been allowed for response.
- At last two different antipsychotics have been tried sequentially (one first generation and if possible olanzapine)
- Clozapine has failed or not been tolerated due to agranulocytosis or other serious adverse effect, most other side effects can be managed, a very small proportion of patients may also refuse clozapine outright.
• Compliance is not in doubt.
- Adjunction medication such as antidepressants, or mood stabilizer are not indicated.
• Psychological approaches have failed or are not appropriate.
Process:
- Rule out contraindications (ECG abnormalities, hepatic impairment).
- Consider and minimize any risks by concomitant medication (e.g., potential to cause QTC prolongation, electrolyte disturbance or pharmacokinetic intervention via CYP inhibition).
- Document the decision to prescribe high doses in the clinical notes along with a description to the target symptoms. The use of appropriate scale is advised.
• Physical monitoring should be carried out.
- All patients on high doses should have regular ECGs (baseline, when steady-state serum levels have been reached after each dosage increment, and then every 6-12 months).
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- Target symptoms should be assessed after 6 weeks and 3 months if insufficient improvement in these symptoms has occurred, the dose should be decreased to the normal range.
Prescribing combined antipsychotics
- There is no good objective evidence that combined antipsychotics (That do not include clozapine) offer any efficacy advantage over a single antipsychotic.
- It has been shown that co-prescribed aripiprazole reduces weight in those given clozapine and normalizes proactive in those on haloperidol and risperidone long acting injection (although not amisulpride). But no regulatory trials demonstrating safety.
- There is substantial evidence to support the potential for harm. Therefore, the use of combined antipsychotic should be avoided.
- As minimum requirement, all patients who are on combined antipsychotics drugs should have their side-effects systematically assessed (including ECG monitoring) and any beneficial effect on symptoms carefully documented.
F. Strategies for Inadequate Response
- Review diagnosis.
- Explore adherence.
• Rule out substance abuse.
The 4 main Pharmacological Strategies
- Optimization
- Substitution
- Augmentation
- Combination
20 % of multiple Episodes have no response.
30 % Respond Partially.
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G. Switching Antipsychotic Drugs because of Poor Tolerability
General Recommendations for switching antipsychotic drugs
<table><tr><td>Adverse Effect</td><td>Suggested drugs</td><td>Alternative</td></tr><tr><td>Acute EPS</td><td>AripiprazoleOlanzapineQuetiapine</td><td>Clozapine</td></tr><tr><td>Dyslipidemia</td><td>AmisulprideAripiprazole</td><td></td></tr><tr><td>Impaired Glucose Tolerance</td><td>AmisulprideAripiprazole</td><td>Risperidone Haloperidol</td></tr><tr><td>Hyperprolactinemia</td><td>AripiprazoleQuetiapine</td><td>Clozapine Olanzapine</td></tr><tr><td>Postural hypotension</td><td>AmisulprideAripiprazole</td><td>Haloperidol Sulpiride Trifuphenazine</td></tr><tr><td>QT Prolongation</td><td>AripiprazolePaliperidone(with ECG monitoring)</td><td>Low dose Monotherapy of any drug not formally contra indicated (with ECG monitoring)</td></tr><tr><td>Sedation</td><td>AmisulprideAripiprazoleRisperidoneSulpiride</td><td>Haloperidol Trifluphenazine</td></tr><tr><td>Sexual Dysfunction</td><td>AripiprazoleQuetiapine</td><td>Clozapine</td></tr><tr><td>Tardive Dyskinesia</td><td>Clozapine</td><td>Aripiprazole Olanzapine Quetiapine</td></tr><tr><td>Weight Gain</td><td>AmisulprideAripiprazoleHaloperidol</td><td>Trifluphenazine</td></tr></table>
* There is evidence that both switching to and co-prescription of aripiprazole are effective in reducing weight, prolactin and dyslipidemia and in reversing impaired glucose tolerance.
ECG, electrocardiogram; EPS, extrapyramidal side-effects.
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H. Equivalent Doses of Conventional Antipsychotic Drugs
<table><tr><td>Antipsychotic</td><td>Equivalent Dose (Consensus)</td><td>Range of Values in Literature</td></tr><tr><td>Chlorpromazine</td><td>100 mg / day</td><td>-</td></tr><tr><td>Flupenthixol</td><td>3 mg / day</td><td>2 – 3 mg day</td></tr><tr><td>Flupenthixol Depot</td><td>10 mg / week</td><td>10 – 20 mg / week</td></tr><tr><td>Fluphenazine</td><td>2 mg / day</td><td>2 – 5 mg / week</td></tr><tr><td>Fluphenazine Depot</td><td>5 mg / week</td><td>1 – 12.5 mg / week</td></tr><tr><td>Haloperidol</td><td>2 mg / day</td><td>1.5 – 5 mg / day</td></tr><tr><td>Haloperidol Depot</td><td>15 mg / week</td><td>5 – 25 mg / week</td></tr><tr><td>Sulpride</td><td>200 mg / day</td><td>200 – 300 mg/day</td></tr><tr><td>Trifluperazine</td><td>5 mg / day</td><td>2.5 – 5 mg/ day</td></tr><tr><td>Zuclopenthixol</td><td>25 mg / day</td><td>25 – 60 mg/day</td></tr><tr><td>Zuclopenthixol Depot</td><td>100 mg / day</td><td>40 – 100 mg/week</td></tr></table>
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I. Second Generation Antipsychotics Equivalent Doses
<table><tr><td>Drug</td><td>Approximate equivalent dose (per day, unless stated)</td></tr><tr><td>Aripiprazole</td><td>10 mg</td></tr><tr><td>Olanzapine</td><td>7.5-10 mg</td></tr><tr><td>Paliperidone palmitate</td><td>75 mg/month</td></tr><tr><td>Quetiapine</td><td>300 mg</td></tr><tr><td>Risperidone oral</td><td>3 mg</td></tr><tr><td>Risperidone LAI</td><td>37.5 mg/2 weeks</td></tr></table>
Comparing potencies of FGAs with SGAs introduces yet more uncertainty in respect to dose equivalence. Very approximately, 100mg chlorpromazine is equivalent to 1.5mg risperidone.
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J. Minimum effective Doses
<table><tr><td>K. Drug</td><td>First episode</td><td>Multi-episode</td></tr><tr><td>FGAs</td><td></td><td></td></tr><tr><td>Chlorpromazine</td><td>200 mg*</td><td>300 mg</td></tr><tr><td>Haloperidol</td><td>2 mg</td><td>4 mg</td></tr><tr><td>Sulpride</td><td>400 mg*</td><td>800 mg</td></tr><tr><td>Trifluperazine</td><td>10 mg*</td><td>15 mg</td></tr><tr><td>SGAs</td><td></td><td></td></tr><tr><td>Amisulpride</td><td>400 mg*</td><td>unclear ?400 mg</td></tr><tr><td>Aripiprazole</td><td>10 mg</td><td>10 mg</td></tr><tr><td>Olanzapine</td><td>5 mg</td><td>7.5 mg</td></tr><tr><td>Quetiapine</td><td>150 mg*</td><td>300 mg</td></tr><tr><td>Risperidone</td><td>2 mg</td><td>3 mg</td></tr></table>
* Estimate - too few data available.
FGA, first-generation antipsychotic; SGA, second-generation antipsychotic.
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L. Antipsychotic Drugs: Licensed Maximum Dose
<table><tr><td>Antipsychotic Drugs</td><td>Maximum dose (mg)</td></tr><tr><td>First Generation – Oral</td><td>Daily</td></tr><tr><td>- Chlorpromazine</td><td>1000 mg</td></tr><tr><td>- Flupenthixol</td><td>18 mg</td></tr><tr><td>- Haloperidol</td><td>20 mg</td></tr><tr><td>- Perphenazine</td><td>24 mg</td></tr><tr><td>- Pimozide</td><td>20 mg</td></tr><tr><td>- Sulpride</td><td>2400 mg</td></tr><tr><td>Trifluperazine</td><td>None (suggest 30 mg / day)</td></tr><tr><td>- Zuclophentixol</td><td>150 mg / day</td></tr><tr><td>Second Generation – Oral</td><td>Daily</td></tr><tr><td>- Amisulpride</td><td>1200 mg</td></tr><tr><td>- Aripiprazole</td><td>30 mg</td></tr><tr><td>- Clozapine</td><td>900 mg</td></tr><tr><td>- Olanzapine</td><td>20 mg</td></tr><tr><td>- Paliperidone</td><td>12 mg</td></tr><tr><td>- Quetiapine</td><td>750 – 800 (see BNF)</td></tr><tr><td>- Risperidone</td><td>16 (see BNF)</td></tr><tr><td>Depots</td><td></td></tr><tr><td>- Flupenthixol depot</td><td>400 mg / month</td></tr><tr><td>- Fluphenazine depot</td><td>50 mg / week</td></tr><tr><td>- Haloperidol depot</td><td>300 mg every 4 weeks (see BNF)</td></tr><tr><td>- Risperidone</td><td>50 mg / 2 week</td></tr><tr><td>- Zuclopenthixol depot</td><td>600 mg / week</td></tr><tr><td>- Paliperidone depot</td><td>150 mg / month</td></tr></table>
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M. USE OF ECT IN SCHIZOPHRENIA
In Acute Phase
- ECT in combination with antipsychotic is considered in the following situations:
1. Severe psychotic symptoms that have not responded to treatment with antipsychotic agents, a trial of clozapine will generally be indicated before acute treatment with E.C.T.
2. E.C.T. should be considered for patient with prominent catatonic features that have not responded to an acute trial of Lorazepam.
3. For patient with schizophrenia and co-morbid depression.
4. ECT may be beneficial if depressive symptoms are resistant to treatment or if features such as suicidal ideation and behaviours or inanition which necessitate a rapid therapeutic response are present.
N. RECOMMENDATION FOR THE MANAGEMENT OF NEGATIVE SYMPTOMS OF SCHIZOPHRENIA
- Psychotic illness should be identified and treated as early as possible as this may offer some protection against the development of negative symptoms.
- For any given patients, the antipsychotic that gives the best balance between overall efficacy and side effects should be used.
- Where negative symptoms persist beyond the acute episode of psychosis.
- Ensure EPS (especially Bradykinesia) and depression are detected and treated if present and consider the contribution of the environment to negative symptoms (e.g. Institutionalization, lack of stimulation).
- Consider Augmentation of Antipsychotic treatment with an Antidepressant such as SSRI, ensuring that choice is based on minimizing the potential for compounding side effect through pharmacokinetic or pharmacodynamics drug
- Interactions.
- If clozapine is prescribed, consider augmentation with Lamotrigine or a suitable second antipsychotic.
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- There are insufficient data to make recommendation about other pharmacological strategies, but prednisolone, Minocycline, Selegiline, Ginkgo biloba, testosterone and ondansetron may have potential.
O. TREATMENT ALGORITHMS FOR SCHIZOPHRENIA
Treatment for first episode of Schizophrenia

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Treatment for Relapse or Acute Exacerbation of Schizophrenia (Full Adherence to Medication Confirmed)

Treatment for Relapse or Acute Exacerbation of Schizophrenia (Adherence Doubtful or Known to be Poor)

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P. ADVICE ON PRESCRIBING LONG ACTING INJECTABLE ANTIPSYCHOTICS
- For FGAs, give a test dose – because FGAs are long acting any adverse effect that result from injection are likely to be long – lived. A test dose consisting of a small dose of active drugs in a small volume of oil serves a dual purpose: It is a test of the patient sensitivity to EPS and will reveal any sensitivity to the base oil. For SGAs, test dose is not required.
- Begin with the lowest therapeutic dose.
- Administer at the longest possible licensed interval. All LAIs, can be safely administered at their licensed dosing intervals, bearing in mind the maximum recommended single dose. There is no evidence to suggest that shortening the dose intervals improves efficacy. Moreover, injection is painful, so less frequent administration is desirable. The observation that some patient deteriorate in the days before the next dose is not supported by facts. In trial, relapse seemed to occur 3 – 6 months after withdrawing therapy.
- Adjust doses only after adequate period of assessment
- Depot preparations are not recommended for those who are antipsychotic – naïve.
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Antipsychotic LAIs: Suggested doses and frequencies
<table><tr><td>Drug</td><td>Licensed injection site</td><td>Test dose (mg)</td><td>Dose range (mg/week)</td><td>Dose interval (weeks)</td><td>comments</td></tr><tr><td>Flupentixol decanoate</td><td>Buttock or thigh</td><td>20</td><td>50 mg every 4 weeks to 400mg a week</td><td>2-4</td><td>Maximum licensed dose is very high relative to other LAIs</td></tr><tr><td>Fluphenazine decanoate</td><td>Gluteal region</td><td>12.5</td><td>12.5mg every 2 weeks to 100 mg every 2 weeks</td><td>2-5</td><td>High EPS</td></tr><tr><td>Haloperidol decanoate</td><td>Gluteal region</td><td>25</td><td>50-300 mg every 4 weeks</td><td>4</td><td>High EPS</td></tr><tr><td>Paliperidone Palmitate</td><td>Deltoid or gluteal</td><td>Not Required</td><td>50-150 mg monthly</td><td>Monthly</td><td>Loading dose required at treatment initiation</td></tr><tr><td>Risperidone microspheres</td><td>Deltoid or gluteal</td><td>Not Required</td><td>25-50 mg every 2 weeks</td><td>2</td><td>Drug release delayed for 2-3 weeks</td></tr><tr><td>Zuclopenthixol</td><td>Buttock or thigh</td><td>100</td><td>200 mg every 3 weeks to 600mg a week</td><td>2-4</td><td>? Slightly better efficacy than some FGAs</td></tr></table>
Reducing dose of depots
Questions to consider before reducing the dose of maintenance of antipsychotic treatment:
- Are the patient symptoms free and if so, for how long? Long standing, non-distressing symptoms which have not previously been responsive to medication may be excluded.
- What is the severity of the side-effect (EPS – Tardive dyskinesia, obesity, etc...)?
- What is the previous pattern of illness (consider the speed of onset, duration and severity of episodes and any danger posed to self or others)?
- What are the patient’s current social circumstances? Is it period of relative stability or are stressful life event anticipated?
- What is the social cost of the relapse (e.g., is the patient the sole breadwinner for a family?)
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- Is the patient able to monitor his/her own symptoms? If so, will he/she seek help?
- After consideration of the above, the decision is taken to reduce medication dose, the patient's family should be involved.
- If it has not already been done. Oral antipsychotic medication should be discontinued first.
- The interval between injections should be increased up to 4 weeks before decreasing the dose each time {not with risperidone}.
- The dose should be reduced by no more than a third at any one time {special considerations apply to risperidone}.
- Decrements should, if possible, be made no more frequently than every 3 months preferably every 6 months.
- Discontinuation should be seen as the end point of the above process. Nice (2014) now suggested that intermittent treatment (symptoms triggered) is preferable than no treatment.
- If the patient becomes symptomatic this should be seen not as a failure but rather as an important step in determining the minimum effective dose that the patient requires.
- If the patient becomes symptomatic this should be seen not as a failure but rather as an important step in determining the minimum effective dose that the patient requires.
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Q. RISPERIDONE LONG – ACTING INJECTION
- Risperidone depot is not an esterified form of the parent drug; it contains Risperidone coated in Polymer to form microspheres. These microspheres have to be suspended in an aqueous base immediately before use.
- The Injection must be stored in a fridge (consider practicality for community Nurses)
- It is available as doses of 25 mg, 37.5 mg and 50 mg Injection.
- A Test dose is not required or sensible (testing tolerability with oral Risperidone is desirable but not always practical.
- It takes 3 – 4 weeks for the first injection to produce Therapeutic plasma level.
- Patients must be maintained on a full dose of their previous antipsychotic for at least 3 weeks after the administration of the first Risperidone injection.
- Oral antipsychotic cover is sometime required for longer (6 – 8 weeks). If the patient is not already receiving and oral antipsychotic, Oral Risperidone should be prescribed.
- Patients who refuse oral treatment and are acutely ill should not be given Risperidone L.A.I because of the long delay in drug release.
- Risperidone Depot must be administered every 2 weeks, the product License does not allow long interval between doses.
- The most effective way of predicting response to Risperidone L.A.I is to establish dose and response with oral Risperidone.
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Switching to Risperidone Long Acting Injection (R.L.A.I)
<table><tr><td>Switching From</td><td>Recommended Method of Switching</td><td>Comments</td></tr><tr><td>No treatment (New patient or recently non-compliant)</td><td>Start Risperidone Oral at 2 mg tab/day and titrate to effective dose. If tolerated, prescribe equivalent dose of RLAI. Continue with oral Risperidone for at least 3 weeks then taper over 1 – 2 weeks.Be prepared to continue Oral Risperidone for longer.</td><td>Use oral Risperidone before giving the Injection to assure good tolerability. Those responded to 2 mg/day start on 25 mg injection every 2 weeks. Those on higher doses start on 37.5 mg injection every 2 weeks, 50 mg injection every 2 weeks maybe required.</td></tr><tr><td>Oral Antipsychotic (Not Risperidone)</td><td>Either:-a. Switch to oral Risperidone and titrate to effective dose,If tolerated, prescribe equivalent dose of RLAI – continue with the oral Risperidone as described above.Or,b. Give RLAI then slowly discontinue oral antipsychotics as described above.</td><td>Dose assessment is difficult in those switching from another antipsychotic. Broadly speaking those on low oral dose should be switched to 25 mg Injection every 2 weeks.Those of on higher oral dose should receive 37.5 mg Injection or 50 mg Injection every 2 weeks.</td></tr><tr><td>Depot Antipsychotics</td><td>Give RLAI one week before the last depot injection is given.</td><td>For those on low doses start 25 mg injection every 2 weeks and then adjust as necessary. Start 37.5 mg injection every 2 weeks in those previously on doses in the middle or upper range of licensed doses. 50 mg injection every 2 weeks maybe required.</td></tr><tr><td>Antipsychotics - Poly pharmacy with Depot</td><td>Give RLAI one week before the last depot injection is given, Slowly taper oral Antipsychotics3-4 weeks later, Be prepared to continue oral Antipsychotic longer.</td><td>Aim to treat patient with RLAI as the sole Antipsychotic.</td></tr></table>
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R. Paliperidone Palmitate LAI
It is the major active metabolite of risperidone:
- Following on intra muscular injection, active paliperidone plasma levels are seen within few days, there tone co-administration of oral paliperidone or risperidone during initiation is not required.
- Dosing consists of two initiation doses (deltoid) followed by monthly maintenance doses (deltoid or gluteal)
- Following administration of a single IM dose to the deltoid muscle, on average 28% higher peak concentration compared with IM injection to the gluteal muscle.
- The two muscle injections on day 1 an 8 help quickly to attain therapeutic drug concentrations.
- Paliperidone palmitate IM does not require cold storage.
- No oral supplementation is required on initiation for paliperidone palmitate.
- No test dose is required for paliperidone palmitate but patient should ideally be currently stablished on or have previously responded to oral paliperidone or risperidone.
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Paliperidone dose and administration information
<table><tr><td></td><td>Dose</td><td>Route</td></tr><tr><td>Initiation</td><td></td><td></td></tr><tr><td>Day 1</td><td>150 mg IM (234 mg)*</td><td>Deltoid only</td></tr><tr><td>Day 8 (+/-4 days)</td><td>100 mg IM (156 mg)*</td><td>Deltoid only</td></tr><tr><td>Maintenance</td><td></td><td></td></tr><tr><td>Every month (+/-7 days) thereafter</td><td>50-150 mg (78-234 mg)*</td><td>Deltoid or gluteal</td></tr></table>
* Paliperidone palmitate dose can be expressed in terms of active moiety (50-150mg) or weight of compound (78-234 mg).
The maintenance dose is perhaps best judged by consideration of what might be a suitable dose of oral risperidone and then giving paliperidone palmitate it an equivalent dose (see below).
IM, intramuscular
Approximate dose equivalent
<table><tr><td>Risperidone oral (mg/day) (bioavailability=70%)</td><td>Paliperidone oral (mg/day) (bioavailability=28%)</td><td>Risperidone LAI (Consta) (mg/2 weeks)</td><td>Paliperidone palmitate (mg/monthly)</td></tr><tr><td>2</td><td>4</td><td>25</td><td>50</td></tr><tr><td>3</td><td>6</td><td>37.5</td><td>75</td></tr><tr><td>4</td><td>9</td><td>50</td><td>100</td></tr><tr><td>6</td><td>12</td><td>-</td><td>150</td></tr></table>
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Switching to paliperidone palmitate
<table><tr><td>Switching From</td><td>Recommended Method of Switching</td><td>Comments</td></tr><tr><td>No treatment</td><td>Give the two initiation doses: 150 mg IM deltoid on day 1 and 100 mg IM deltoid on day 8 Maintenance dose starts 1 month later.</td><td>In general, the lowest most effective maintenance dose should be used the manufacturer recommends of 75 mg monthly for the general adults population. this is approximately equivalent to 3mg/day oral risperidone in practice the modal dose is 100 mg/monthMaintenance dose adjustments should be made monthly. however the full effect of the dose adjustment may not be apparent for several months</td></tr><tr><td>Oral paliperidone/ risperidone</td><td>Give the two initiation doses followed by the maintenance dose and prescribe equivalent dose.</td><td>Oral paliperidone/risperidone supplementation during initiation is not necessary.</td></tr><tr><td>Oral antipsychotics</td><td>Reduce the dose of the oral antipsychotic over 1-2 weeks following the first injection of paliperidone. Give the two initiation doses followed by the maintenance does.</td><td></td></tr><tr><td>Depot antipsychotic</td><td>For risperidone LAI, begin paliperdone 5-6 weeks after the last injectionNB. No initiation doses are required.</td><td>Doses of palipridone palmitate IM may be difficult to predict.The manufacturer recommends a dose of 75 mg monthly for general adult population. If switching from RLAI and prescribe equivalent dose maintenance dose adjustments should be made monthly. however the full effect of the dose adjustment may not be apparent for several months</td></tr><tr><td>Antipsychotic polypharmacy with depot</td><td>Start paliperidon (at the maintenance dose) when the next injection is dueNB. No initiation doses are required Reduce the dose of the oral antipsychotic over 1-2 weeks following the first injection of paliperidone</td><td>Aim to treat the patient with palipreidone palmitate IM as the sole antipsychoticThe maintenance dose should be governed as far as possible by the total dose of oral and injectable antipsychotic.</td></tr></table>
IM, intramuscular; RLAI, risperidone long-acting injection.
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S. REFRACTORY SCHIZOPHRENIA
- For a patient not responding to Antipsychotic therapy, if dose has been optimized, consider watchful waiting.
- Consider increasing Antipsychotic dose according to tolerability.
- If this fails, consider switching to Olanzapine or Risperidone (if not already used).
- If this fails, use Clozapine (Supporting evidence very strong)
- If clozapine fails, use time limited augmentation strategies (Supporting evidence variable)
Implementation of Treatment with Clozapine
- Before initiating treatment with Clozapine a complete blood count (CBC) with differential should be performed.
- The patient general and cardiovascular health status should be evaluated.
- The cardiovascular side effect of clozapine should be considered in planning treatment for patients with pre-existing heart disease.
- Treatment should be initiated at low dose (12.5 – 25 mg once or twice daily) and increased gradually (by no more than
- 25 – 50 mg /day). As tolerated until target dose is reached.
- Because of the risk of marked hypotension, sedation and seizures with rapid escalation, dose titration should not occur more rapidly.
- During dose titration, the patient's cardiovascular status including orthostatic, pulse, blood pressure and subjective complaints of dizziness should be monitored.
- Since side effect of clozapine in the initial and dose adjustment phases maybe severe in some patient, admission to hospital may- be justifiable (e.g., For unstable patients who require rapid dose increase to a therapeutic level. Patient with a limited support sys- tem or patient prone to orthostatic hypotension or seizures)
- The total dose of clozapine should be divided. The larger dose can be given at night.
- Adequate safety monitoring during treatment is important to minimize the risk of adverse events.
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- The clozapine package label stated that WBC and neutrophil counts should be evaluated before treatment is initiated, weekly during the first 6 months of treatment and at least every 2 weeks after 6 months of treatment. Then is usually done monthly.
- Clozapine treatment should not be initiated:
- If the initial WBC count is less than 3500/mm3.
- If the patient has a history of myeloproliferative disorder.
- If the patient has a history of clozapine – induced agranulocytosis or granulocytopenia.
- Advised to report any sign of infection immediately (e.g. Sore throat, fever, weakness, lethargy).
- A WBC count less than 2000 /mm3 or absolute neutrophil count (ANC) less than 1000 /mm3 indicating impending or actual agranulocytosis and the clinician should stop Clozapine treatment immediately.
- A WBC of 2000 – 3000 /mm3 or ANC of 1000 – 1500 /mm3 indicates high risk of or impending agranulocytosis, and clinician should stop Clozapine treatment immediately.
- Check the WBC and differential daily and monitor for signs of infection.
- Clozapine may be resumed if no infection is present, the WBC rises to more than 3000/mm3 and ANC is more than 1500/mm3 (resume checking WBC twice a week until it is 3500/mm3).
- If the WBC is 3000 – 3500/mm3, if it falls to 3000/mm3 over 1 – 3 weeks, or if immature WBC form are present, repeat the WBC count with differential count. If the subsequent WBC count is 3000 – 3500/mm3, and the ANC is more than 1500/mm3, repeat the WBC count with a differential count twice a week until the WBC count is more than 3500/mm3.
- A rechallenge with clozapine should not be undertaken in patient with confirmed cases of a agranulocytosis (ANC less than 500/mm3)
- Rechallenge should be considered only:
- For patient whose WBC count remained greater than 2000/mm3.
- For whom trials with multiple other antipsychotic had failed but a good clinical response to Clozapine was shown.
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- Myocarditis seems to occur within 6 -8 weeks of starting Clozapine (Median 3 weeks).
- Cardiomyopathy may occur later in treatment (median 9 months) but both may occur at any time.
- Patient should be closely monitored for signs of myocarditis especially in the first few months of treatment.
- Symptoms include: fever, flue-like symptoms, fatigue, and dyspnoea (increased respiratory rate) chest pain.
- Signs include: Tachycardia.
- On radiography / echo. (ECG Changes ST depression) enlarged heart.
• Laboratory investigation: eosinophilia.
- Suggested monitoring.
- Baseline pulse, temperature respiratory rate and C-reactive protein, Troponin, Echo cardiograph (if available).
• Daily if possible pulse, temperature, respiratory rate
• C-reactive protein and troponin on day 7 – 14 – 21 and 28.
- If C-reactive protein is less than 100 mg/L and troponin less than twice upper limit of normal, stop clozapine, and repeat echocardiogram.
- If fever + tachycardia + raised C-reactive protein or troponin (but not as above) do C-reactive protein and troponin daily.
Clozapine Augmentation Strategy
- Clozapine augmentation has become common practice because of inadequate response to Clozapine alone is a frequent clinical events.
- The evidence based on supporting augmentation strategies is growing but is not sufficient to allow the development of any algorithm or schedule of treatment options.
- It is recommended that all augmentation attempts are carefully monitored and, if no clear benefits is forthcoming, abandoned after 3 – 6 months.
- Depending on the type of residual symptoms (e.g. Positive symptoms, Negative, Mood symptoms, Cognitive or Aggressive behaviour).
- Strategies include:
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