Guía de Diabetes y Psicosis
Guía de Diabetes y Psicosis
Guía de Diabetes y Psicosis
544
ABSTRACT
Psychotic illness and its treatment are associated with an
increased rate of diabetes and worsening blood sugar
control.
The newer, second-generation antipsychotic agents are more
likely to produce this effect than the first-generation agents,
but both contribute to the problem.
The effect is usually related to insulin resistance through
weight gain, but other mechanisms may exist.
Diabetic ketoacidosis is rare.
Management of psychosis takes priority over concerns about
the potential metabolic sequelae of treatment, but the
prevalence of the latter requires that all patients taking
antipsychotic agents be actively screened and treated.
Patients treated with antipsychotic agents need baseline and
regular checks, including weight, blood glucose and lipid
levels and blood pressure.
Management of psychosis with its attendant medical
problems requires a multidisciplinary approach, with primary
health practitioners playing a central role.
Mortality and medical morbidity is higher in those with
psychosis than expected; preventive measures, combined
with early detection and treatment of hyperglycaemia and
other metabolic problems, is a key public health issue.
MJA 2004; 181: 544548
including diabetes and obesity. Consistent advice should be provided on diet, exercise and smoking, and the psychiatric team
should assume responsibility for ensuring appropriate screening is
undertaken, in close liaison with other healthcare providers.
Here, we outline the main findings of the consensus group. The
full consensus statements for professionals and for consumers and
carers are available at www.psychiatry.unimelb.edu.au/open/
diabetes_consensus/.
Antipsychotic therapy and diabetes
Many case reports and series and a few larger studies based on
administrative databases have described associations between antipsychotic treatment and the onset or exacerbation of diabetes.2-5
However, there are no long-term, randomised controlled trials to
guide clinical practice in this area. The existing evidence suggests
that the introduction of first-generation antipsychotic medications
(FGAs, see Box 1) was associated with a two- to threefold increase
in the prevalence of diabetes among treated patients6,7 (Level III
evidence [derived from pseudorandomised controlled trials, comparative studies, single-arm studies or interrupted time series
without a parallel control group8]). It also suggests that the obesity
rate (and, by inference, potential for diabetes) is much higher in
patients treated with depot FGAs than in the general population.9
P O S I TI O N S T A T E ME N T
1 Glossary
First-generation antipsychotic medications (FGAs): These are also
known as typical or conventional antipsychotic medications.
The prototypical agent, chlorpromazine, was first used in the mid1950s. Other medications in this class include fluphenazine,
thioridazine, haloperidol, droperidol, flupenthixol and
zuclopenthixol.
Second-generation antipsychotic medications (SGAs): These are
also known as atypical antipsychotic medications. The
prototypical agent, clozapine, was first used in Australia in the mid1990s. Other members of the class available in Australia are
amisulpride, aripiprazole, olanzapine, quetiapine and risperidone.
Impaired glucose metabolism: A general term encompassing
diabetes and the pre-diabetic disorders of impaired glucose
tolerance (IGT, characterised by normal fasting blood glucose level
but elevated 2-hour glucose level on the oral glucose tolerance test)
and impaired fasting glucose (IFG, elevated fasting glucose level but
normal 2-hour result on the oral glucose tolerance test).
Glycosylated haemoglobin (HbA1c): A marker of long-term
glycaemic control, expressed as a percentage. The average blood
glucose level in the past 60 days can be estimated with the formula
(HbA1c 2) 6.0 mmol/L.
Antipsychotic medication can be both life-enhancing and lifesaving for sufferers of psychosis. The Australian consensus group
recognised that successful treatment of the psychotic disorder has
priority over concerns about potential metabolic consequences.
The latter need to be dealt with in their own right after the total
risks and benefits of antipsychotic therapy have been estimated.14
Thus, selection of an antipsychotic medication for a particular
patient should be driven more by its capacity to reduce psychiatric
symptoms than its diabetic potential alone, particularly in the
absence of definitive information about causality and risk.15
The consensus group considered that pre-existing diabetes may
be a relative contraindication to the prescription of medications
which are known to have adverse short-term effects on weight and
metabolism. However, it is not an absolute contraindication, as
effective treatment of the psychosis should be the primary aim.
Because of the high prevalence of hyperglycaemia, informed
consent should be obtained from patients or their guardians, with
acknowledgement of the requirement to monitor for diabetes.
Mechanisms for links between psychosis and diabetes
The importance of weight gain to the development of type 2
diabetes is detailed in the recent American Diabetes Association
position statement.13 A hierarchy of potential short-term weight
gain exists among antipsychotic medications16 (Level II evidence
[obtained from at least one properly designed randomised controlled trial]8). The advent of new SGAs might lead to fewer adverse
metabolic consequences, but long-term real world data are
lacking.
In the longer term, obesity seems to be less related to specific
medications and more to behavioural factors, including diet and
exercise. These relationships have been described in the hare and
tortoise theory of antipsychotic-mediated weight gain.17 This
theory suggests that some medications have the propensity to drive
weight gain rapidly (the hares), while most others have a lesser
potential that nonetheless results in weight gain in the longer term
because of the interactions with the disease process itself and its
social consequences (the tortoises). However, non-controlled
descriptions of cross-sectional weight gain cannot be used to test
hypotheses, and a prospective study of a controlled cohort from
inception of antipsychotic treatment is required. People with
psychosis are undoubtedly at risk of diabetes, but factors other
than medication contribute to adverse metabolic outcomes. There
is no evidence that people with psychosis are less vulnerable to the
effects of obesity, and some evidence that they may be more
vulnerable.
Population rate
2.5%4.2% 6,7
Unknown
First-generation
antipsychotics (since 1952)
17% 6
3.4%
(Busselton, 1981)11
Second-generation
antipsychotics (since 1990)
19% 10
7.5%
(Australia, 2000) 12
Era
Pre-antipsychotic
medications
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P O S I TI O N S T A T E ME N T
Ethnic predisposition
(eg, Indigenous Australian, Pacific Islander,
Asian, African American)
Lack of exercise
Poor diet
Obesity
Measure body
mass index and
waist - hip ratio
every visit or
every 3 months
Normal
Measure
blood pressure
and lipid profile
every 6 months
Diagnosis of diabetes
HbA1c every 3-6 months to monitor glycaemic control* (HbA1c is not used to diagnose diabetes)
* Medicare covers up to four assessments per year.
P O S I TI O N S T A T E ME N T
547
P O S I TI O N S T A T E ME N T
the external consultants who provided so much of their time to the project.
Participants in the project were:
Consensus working group: Mr Simon Bell (pharmacist, Sydney), Dr Nicholas
Carr (general practitioner, Melbourne), Dr Leon Chapman (co-chair; diabetologist, Melbourne), Dr Michael DEmden (endocrinologist, Brisbane), Mr
Steven Elsom (mental health nurse, Melbourne), Dr Grace Groom (Mental
Health Council of Australia, Canberra), Professor Scott Henderson (psychiatrist, Canberra), Professor Ian Hickie (psychiatrist, Sydney), Associate Professor Linda Hoffman (endocrinologist, Hobart), Associate Professor Tim
Lambert (co-chair; psychiatrist, Melbourne), Dr Alan Rosen (psychiatrist,
Sydney), Professor Bruce Singh (psychiatrist, Melbourne), Professor Tim
Welborn (endocrinologist, Perth), Dr Peter Wynn Owen (psychiatrist, Perth).
Consultant review group: Mr John Bell (pharmacist, Sydney), Dr Elsa
Bernardi (psychiatrist, Sydney), Dr Grant Blashki (general practitioner, Melbourne), Professor Vaughan Carr (psychiatrist, Newcastle), Professor David
Castle (psychiatrist, Melbourne), Professor Stanley Catts (psychiatrist, Brisbane), Professor Donald Chisholm (endocrinologist, Sydney), Professor
Michael Clinton (clinical nurse, Perth), Professor David Copolov (psychiatrist,
Melbourne), Ms Linda Fellows (pharmacist, Perth), Mr Tony Fowke (National
Consumer and Carer Forum, Perth), Associate Professor Tim Greenaway
(endocrinologist, Hobart), Professor Mark Harris (general practitioner, Sydney), Ms Brenda Happell (clinical nurse, Melbourne), Dr Dan Haupt (Washington State University, USA), Ms Barbara Hocking (SANE Australia,
Melbourne), Professor Assen Jablensky (psychiatrist, Perth), Professor
Jayashri Kulkarni (psychiatrist, Melbourne), Dr Johanna Lammersma (psychiatrist, Adelaide), Ms Janet Meagher (National Consumer and Carer Forum,
Sydney), Dr John Newcomer (Washington State University, USA), Professor
Saxby Pridmore (psychiatrist, Hobart), Mr Rob Ramjan (Schizophrenia Fellowship of NSW, Sydney), Associate Professor Geoff Riley (psychiatrist, Fremantle), Ms Liz Stewart (National Consumer and Carer Forum, Sydney), Dr Julie
Thompson (general practitioner, Moe), Mr Keith Wilson (Mental Health
Council of Australia, Fremantle).
Carer and consumer groups: Association of Relatives and Friends of the
Mentally Ill (ARAFMI), GROW Self Help/Mutual Help Groups, Australian
Mental Health Consumer Network (AMHCN), Carers Australia, Consumers
Health Forum, beyondblue: the national depression initiative, state representatives (carer and consumer) from the Australian Capital Territory, New
South Wales, Northern Territory, Queensland, South Australia, Western
Australia and Tasmania.
Competing interests
T J R L was paid an honorarium to attend the initial consensus meeting. He
has served on advisory boards for Janssen-Cilag, Eli Lilly, Pfizer, Lundbeck,
Sanofi, Novartis and Faulding; has received funding for unrestricted research
from Eli Lilly, Novartis, Janssen-Cilag, Bristol-Myers Squibb, Pfizer and
AstraZeneca; and has received travel assistance to attend meetings from Eli
Lilly, Novartis, Janssen-Cilag, AstraZeneca and Bristol-Myers Squibb.
L H C was paid an honorarium for 3 days work initiating the consensus
meetings and associated work relating to the project. Eli Lilly sponsored him
to attend the 2002 Annual Meeting of the American Diabetes Association.
References
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2 Newcomer J, Haupt D, Fucetola R, et al. Abnormalities in glucose
regulation during antipsychotic treatment of schizophrenia. Arch Gen
Psychiatry 2002; 59: 337-345.
3 Gianfrancesco F, Grogg A, Mahmoud R, et al. Differential effects of
risperidone, olanzapine, clozapine, and conventional antipsychotics on
type 2 diabetes: findings from a large health plan database. J Clin
Psychiatry 2002; 63: 920-930.
4 Henderson D, Ettinger E. Schizophrenia and diabetes. Int Rev Neurobiol
2002; 51: 481-501.
5 Livingstone C, Rampes H. Atypical antipsychotic drugs and diabetes.
Practical Diabetes Int 2003; 20: 327-331.
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