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South African Expert Group - Johannesburg, August 2005
Introduction
The therapeutic use and usefulness of the atypical (second generation)
antipsychotic medications has been debated for some time. To this effect
the atypical antipsychotics have become well recognised as part of the
treatment regimen for psychotic disorders. Due to the efficacy and
safety profile of the atypical antipsychotics they have been suggested
as the first line option for the treatment of psychosis 10,11. The
choice of antipsychotic drug should be made jointly by the clinician
responsible for treatment, and in consultation with the individual being
treated.
The treatment decision should be based on the relative
benefits of the drugs and their side effect profiles where possible
1,2,3. Further to the use of second generation antipsychotics, the South
African Medical Journal published a drug alert from the Medicines
Control Council regarding the increased risk of hyperglycaemia and
diabetes mellitus in patients being treated with the atypical
antipsychotic medications 18.
The worldwide prevalence of diabetes is increasing rapidly. The World
Health Organization has predicted that by 2030 the number of adults with
diabetes will have doubled worldwide, from 177 million in 2000 to 370
million 4. Historically it is well known, even from studies in the
pre-neuroleptic era that schizophrenia itself might predispose
individuals to diabetes 5,10. On the other hand, schizophrenics have
diabetogenic lifestyles 6. The estimated prevalence of diabetes in
persons with psychotic illnesses before the development of antipsychotic
medications was 2,5% to 4,2% 10.
Since the availability of the
first-generation (typical) antipsychotics (in clinical use from 1952)
the estimated prevalence of diabetes amongst persons with psychoses
increased from the previous level of 2,5 - 4,2% to 17% (general
population rate 3,4%) . A further increase in the prevalence of
diabetes, to 19%, has been observed in this group of patients since the
introduction of the second-generation (atypical) anti-psychotic agents
in 1990 (general population rate 7,5%) 10,11,12,13. Drugs regarded as
atypical anti-psychotic agents include: clozapine, risperidone,
olanzapine, quetiapine, ziprasidone and aripiprazole.
Atherosclerosis is a multifactorial process that can culminate in
clinical outcomes such coronary disease, cerebrovascular disease and
peripheral vascular disease. In most instances dyslipidaemia requires
additional risk factors, but severe monogenic disorders of lipid
metabolism can cause premature atherosclerosis in the absence of other
risk factors. In severe monogenic disorders of lipid metabolism, the
total cholesterol will exceed 7.5mmol/L and the prevalence may be as
high as 1 in 100 people in many communities. Occasionally lesser
heritable traits can be converted into significant derangements by an
additional factor such as diabetes, obesity, alcohol or renal and
thyroid disease. Dyslipidaemia can simply be classified into
hypercholesterolaemias, mixed hyperlipidaemias and
hypertriglyceridaemias.
Whereas atherosclerosis can develop in
all of these patterns, pancreatitis is a potentially very serious
complication of hypertriglyceridaemias of >15 mmol/L.
Hypercholesterolaemias of low density lipoprotein (LDL), where the total
cholesterol is between 5 and 7.5 mmol/L, can be assessed for their
impact on risk by a calculation utilising age, gender, total
cholesterol, HDL cholesterol, blood pressure and smoking so that the
decision on management is based on global risk. Generally a global risk
for heart disease of >20% in 10 years warrants treatment.
Hypercholesterolaemias of LDL that result in total cholesterol of >7.5
mmol/L can cause heart disease as early as the 4th decade of life and
require treatment from young adulthood 19.
From a pragmatic point of view all healthcare practitioners should be
aware of the above factors. Timely screening for diabetes and effective
risk management should be a priority in the clinical management and
follow-up of all schizophrenic patients. The management of the psychotic
state in the schizophrenic without or with diabetes should first be
optimized and then should the patient be referred to the diabetologist
or expert medical practitioner to manage the diabetes 7,11,13. The
choice of antipsychotic drug should be based on the capacity of the
specific drug to reduce psychotic/psychiatric symptoms (efficacy) as
well as the whole side-effect profile (safety) of the drug for a
specific individual patient. Management of the mental condition of the
patient should always be paramount for the psychiatrist. The
psychiatrist must, however, take account of physical and metabolic
parameters due to either the underlying disease or induced by therapy
and initiate effective management where required.
Purpose of this Consensus Statement and Guidelines
- The primary goal of this document is patient orientated. The guidelines
are designed to ensure that the physical and mental well-being of patients
with mental illness is safeguarded by sound clinical practice.
- To create awareness of the increased risk of diabetes in patients with
psychoses, amongst psychiatrists and other medical practitioners in South
Africa
- To provide practical guidelines that will ensure timeous detection and
appropriate management of diabetes in all mentally ill patients.
- To note that the strength of data as it relates to
schizophrenia/diabetes/antipsychotic medication remains inconsistent. .
- To affirm the integral relationship between psychiatry and medicine.
- To guide and solicit funding support for patients suffering from
schizophrenia.
- To define the roles of the psychiatrist and
endocrinologist/diabetologist, both for practical management purposes as
well as for medico-legal purposes
- To determine the relative risk between the typical and atypical
antipsychotics.
Proposed Guidelines:
Step 1: Identify subjects at increased risk for the development of
diabetes
Step 2: Screen all subjects with a new diagnosis of schizophrenia for the
presence of diabetes and hypertension before commencing drug therapy
Step 3: Management of risk factors related to the development of diabetes
and hypertension in subjects with schizophrenia
Step 4: Monitor all subjects being treated for schizophrenia for the new
development of diabetes, hypertension or dyslipidaemia
Step 5: Indications for referral and referral pathway for subjects in
whom metabolic abnormalities are identified
Methods:
Step 1: Identify subjects at increased risk for the development of
diabetes
The following are risk factors for the development of diabetes:
- Age > 40 years
- First-degree relative with diabetes (family history)
- Ethnic predisposition / member of high-risk population (Asian/Indian)
- History of gestational diabetes mellitus
- Polycystic ovary syndrome
- History of delivery of a macrosomic infant (birth weight > 4.0 kg)
- Hypertension (Blood pressure >130/80 mmHg, or on therapy for
hypertension)
- Dyslipidaemia (see Normal Values for definition)
- Overweight (Body Mass Index > 25 kg/m2)
- Abdominal obesity (see Normal Values for definition)
- Acanthosis nigricans
- Schizophrenia 8,10
Step 2: Screening for diabetes, dyslipidaemia and hypertension at
diagnosis of schizophrenia.
The psychiatrist diagnosing schizophrenia is required to perform the
following clinical and laboratory tests in order to identify subjects
affected with diabetes, dyslipidaemia and / or hypertension prior to the
initiation of drug therapy. This assessment does not replace the need
for the psychiatrist to consider other organic / physical disorders that
may account for the mental illness and to evaluate these conditions
appropriately:
- Measure the subject's standing height without shoes, preferably using a
wall-mounted stadiometer
- Measure the subjects body mass in light indoor clothing
- Calculate the body mass index as the weight in kilogram divided by the
height in meters squared.
- Measure the waist circumference with a tape measure. The waist is
defined as the point midway between the lower costal margin and the upper
border of the iliac crest
- Measure the blood pressure in the arm with the patient in a sitting
position after a 30 minute period of rest.
- Request the following laboratory tests:
- Fasting venous plasma glucose
- Serum thyrotrophin (TSH)
- Fasting total serum cholesterol
- If the total serum cholesterol exceeds 5.0 mmol/L, if the serum is
lipaemic, or if the patient has hypertension, a full fasting lipogram is
required (total cholesterol, high density lipoprotein (HDL) cholesterol, low
density lipoprotein (LDL) cholesterol and triglycerides).
Normal values and definitions:
Body mass index:
| < 20 kg/m2: | Underweight
| | 20 - 24.9 kg/m2: | Normal
| | 25 - 29.9 kg/m2: | Overweight
| | > 30 kg/m2: | Obese
| | 30 - 34.9 kg/m2: | Class 1 obesity
| | 35 - 40 kg/m2: | Class 2 obesity
| | > 40 kg/m2: | Morbid obesity
|
Waist circumference - central obesity is defined as follows:
| Male (non-Asian): | > 94 cm
| | Female (non-Asian) | > 80 cm
| | Asian male: | > 90 cm
| | Asian female: | > 80 cm
|
| Blood pressure: |
| Systolic | Diastolic | |
|
| Normal blood pressure: | < 120mmHg |
AND | < 80 mmHg |
| Pre-hypertension: | 120-139 mmHg |
OR | 80-89 mmHg |
| Hypertension stage 1: | 140-159 mmHg |
OR | 90-99 mmHg |
| Hypertension stage 2: | > 160 mmHg |
OR | > 100 mmHg
|
Fasting glucose levels:
Normal < 5.6 mmol/L
Diabetes > 7.0 mmol/L
Random glucose levels:
Normal < 7.8 mmol/L
Fasting lipid levels:
Cholesterol
Normal: < 5.0 mmol/L
Intermediate hypercholesterolaemia: 5.0 - 7.5 mmol/L
Severe hypercholesterolaemia: > 7.5 mmol/L
Triglycerides
Normal: < 1.5 mmol/L
Intermediate hypertriglyceridaemia: > 2.5 mmol/L
Severe hypertriglycerdiaemia: > 5.0 mmol/L
If triglycerides are > 15.0 mmol/L, emergency referral and management is
required.
Step 3: Management of risk factors related to the development of diabetes
and hypertension in subjects with schizophrenia.
If risk factors for the development of diabetes are identified and / or if there
are abnormalities identified in the screening process, the following management
advice must be given to the affected persons:
- Cessation of cigarette smoking
- Limit alcohol use to one unit per day
- Attainment of ideal body weight
- Exercise programme, taking account of any associated co-morbidities
- Dietary advice: reduction in saturated fat and cholesterol, reduction
in total calories if overweight or obese, reduction in salt intake if blood
pressure abnormal, increased consumption of fresh fruit and vegetables.
Referral to a professional dietician may be required, based on individual
judgement.
NB: Lifestyle management should be an integral part of the management of any
psychiatric patient
Step 4: Monitor all subjects being treated for schizophrenia for the new
development of diabetes, hypertension or dyslipidaemia
The following monitoring schedule is required after diagnosis:
- 6 weeks after commencing drug therapy: measure height, weight and blood
pressure. Note that > 7% gain in body weight at 6 weeks has been shown to be
a risk factor for the development of diabetes and these subjects need closer
follow up (every 8 weeks). If parameters are normal and < 7% weight gain has
occurred in 6 weeks, follow up at 4 months. If abnormal, refer as shown in
step 5.
- 4 months after commencing drug therapy or changing drug therapy:
measure height, weight, blood pressure, fasting plasma glucose, fasting
cholesterol and triglycerides. If parameters are normal, follow up at 12
months. If abnormal, refer as shown in step 5.
- 12 months after commencing drug therapy: measure height, weight, blood
pressure, fasting plasma glucose, fasting cholesterol and triglycerides. If
parameters are normal, follow up every 12 months. If abnormal, refer as
shown in step 5.
Step 5: Indications for referral and referral pathways for subjects in whom
metabolic abnormalities are identified:
| Body mass index: | 30 kg/m2; refer to dietician
| | Blood pressure: | Systolic blood pressure > 120-139 mmHg OR
diastolic blood pressure > 80-89 mmHg on 2 or more occasions; refer to
primary health care clinic for assessment and management of hypertension.
Consider alternatives before using potentially diabetogenic drugs for
managing hypertension
| | Fasting plasma glucose: | > 11.1 mmol/L; refer immediately to
primary health clinic, general practitioner or physician
> 5.5 mmol/L; refer to primary health clinic, general practitioner or
physician for glucose tolerance test
| | Random plasma glucose: | > 7.8 mmol/L: refer to primary health
clinic, general practitioner or physician for glucose tolerance test
| | Fasting Lipids: | |
| Cholesterol: | Total cholesterol > 7.5 mmol/L; refer to
secondary level hospital, general practitioner or physician for evaluation
and management
| | Triglycerides: | > 5.0 mmol/L; refer to secondary level
hospital or physician for evaluation and management
> 15 mmol/L: refer urgently to tertiary hospital or physician for evaluation
and urgent management
|
International Management Algorithms and Consensus Statements:
- Consensus Summary: ‘Schizophrenia and Diabetes 2003' UK Expert
Consensus Meeting, Dublin, 3-4 October 2003 9
- Diabetes, Psychotic Disorders and Antipsychotic Therapy: A Consensus
Statement, University of Melbourne, Australia 10,11
- Atypical Antipsychotics in Psychiatric Practice: Practical Implications
for Clinical Monitoring, Canadian Working Group 8,12 and Proposed Screening
and Monitoring of Patients Taking Antipsychotic Medications 12
- Consensus Development Conference on Antipsychotic Drugs and Obesity and
Diabetes, American Diabetes Association 13,14
- Consensus Summary: ‘Metabolic and Lifestyle Issues and Severe Mental
Illness – New Connections to Well-Being?' UK Expert Consensus Meeting,
Dublin, 14-15 April 2005 20
- South African Hypertension Guideline 2006, Joint National Hypertension
Guideline Working Group 2006 19
References
- Sartorius N, Fleischhacker WW, Gjerris et al. The Usefulness and Use of
Second-Generation Antipsychotic Medications. Curr Opinion in Psychiatry
2002;15(Suppl 1):S1-S51
- Sartorius N, Al-Habeeb T, Furedi J et al. The Role of Second Generation
Antipsychotics in the Management of Acute Psychotic Disorders & Ways to
Facilitate the Application of New Knowledge about Them. Update Europe
2002;7:1-35
- National Institute for Clinical Excellence (NICE): Guidance on the Use
of Newer (Atypical) Antipsychotic Drugs for the Treatment of Schizophrenia.
Technology Appraisal Guidance – No 43 ; May 2005 (Review)
- Holt RIG. Diagnosis, Epidemiology and Pathogenesis of Diabetes
Mellitus: An Update for Psychiatrists. Br J Psychiatry 2004;184(suppl
47):S55-S63
- Kohen D. Diabetes Mellitus and Schizophrenia: Historical Perspective.
Br J Psychiatry 2004;184(suppl 47):S64-S66
- Peet M. Diet, Diabetes and Schizophrenia: Review and Hypothesis. Br J
Psychiatry 2004;184(suppl 47):S102-S105
- Gough S and Peveler R. Diabetes and its Prevention: Pragmatic Solutions
for People with Schizophrenia. Br J Psychiatry 2004;184(suppl 47):S106-S111
- Canadian Diabetes Association. Clinical Practice Guidelines for the
Prevention and Management of Diabetes in Canada. Cdn J Diab 2003;27(suppl
2):S1-S140
- Dinan TG (Ed) Schizophrenia and Diabetes 2003: An Expert Consensus
MeetingBr Jnl Psychiatry 2004;vol 184(suppl 47)
- Lambert TJR & Chapman LH (Eds). Diabetes, Psychotic Disorders and
Antipsychotic Therapy: A Consensus Statement. Med J Australia
2004;181(10):544-548
- Lambert TJR & Chapman LH (Eds). Diabetes, Psychotic Disorders and
Antipsychotic Therapy: A Consensus Statement Full Report at:
http://www.psychiatry.unimelb.edu.au/open/diabetes_consensus/
- Poulin MJ, Cortses L, Williams R, Wine N, McIntyre RS. Atypical
Antipsychotics in Psychiatric Practice: Practical Implications for Clinical
Monitoring. Can J Psychiatry 2005;50:555-562
- American Diabetes Association: Consensus Development Conference on
Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care
2004;27(2):596-601
- Kane JM, Barrett EJ, Casey DE, Correll CU et al. Metabolic Effects of
Treatment With Atypical Antipsychotics. J Clin Psychiatry
2004;65(11):1447-1455
- Goff DC, Cather C, Eden Evins A, Henderson DC, Freudenreich O et al.
Medical Morbidity and Mortality in Schizophrenia: Guidelines for
Psychiatrists. J Clin Psychiatry 2005;66:183-194
- Canada's Food Guide to Healthy Living, Health Canada, Available:
http://www.hc-sc.gc.ca/fn-an/food-guide-aliment/fg_rainbow-arc_en_ciel_ga_e.html
- Gadsby R. Managing Type2 Diabetes. Update August 2005:8-12.
- Medicines Control Council: Hyperglycaemia and Diabetes Mellitus
Associated with Atypical Antipsychotics. SAMJ 2005; 95(4): 230.
- Joint National Hypertension Guideline Working Group 2006: South African
Hypertension Guideline 2006. SAMJ 2006; 96(4): 335-362
- Dursun S (Ed). Metabolic Issues, Lifestyle and Psychosis: New
Connections. Jnl Psychopharmacology 2005; 19(6) Supplement
Expert Group:
| Co-ordinator: | |
| Dr Frans A Korb | Psychiatrist & Senior Clinical Research
Physician Neuroscience, Eli Lilly (SA)(Pty)Ltd |
| Chairman: | |
| Dr Eugene Allers | Psychiatrist, Private Practice, Johannesburg |
| Discussants: | |
| Dr Wayne May | Specialist Endocrinologist and Diabetologist,
Claremont, Cape Town
| | Professor Ayesha Motala | Chief Specialist and Head, Diabetes and
Endocrine Unit, Inkosi Albert Luthuli Central Hospital, Durban
| | Dr Ray Moore | Specialist Endocrinologist and Diabetologist,
Umhlanga Hospital Durban
| | Dr Fraser Pirie | Principle Specialist, Diabetes and Endocrine
Unit, Inkosi Albert Luthuli Central Hospital, Durban and Chairperson of the
Society for Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA)
| | Professor Willie Mollentze | Chief Specialist and Head of
Medicine, University of Free State
| | Dr Ian Wesmore | Psychiatrist, Private Practice, Bloemfontein
| | Dr Hoepie Howell | Psychiatrist, Private Practice, Bloemfontein
| | International Consultants: |
| Dr Richard Holt | Senior Lecturer in Endocrinology and
Metabolism, University of Southampton, Southampton; UK Vice-Chair of the
Science and Research Group of the Professional Advisory Council, Diabetes UK
| | Dr Peter Haddad | Consultant Psychiatrist/Honorary Lecturer,
Salford, UK
| | Contributors: | |
| Professor David Marais | Head of Lipid Clinic, Groote Schuur
Hospital, University of Cape Town and Chairperson of the Lipid and
Atherosclerosis Society of South Africa (LASSA)
| | Professor Derick Raal | Professor and Head of Endocrine and Lipid
Unit, University of the Witwatersrand, Johannesburg
| | Editing of Final manuscript: | Dr Fraser Pirie
| | Correspondence to: | Dr FA Korb, c/o Eli Lilly (SA)(Pty)Ltd,
Private Bag X119, BRYANSTON, 2021. Fax: (011) 510 9335, Tel: (011) 510 9300,
e-mail: korb_frans@lilly.com
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