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Cognitive Functioning, Physical Health and Early Non-response in Schizophrenia
monitoring of individual risk factors in patients with schizophrenia lies Figure 8: Incidence of Metabolic Syndrome in
in the fact that the prevalence of the metabolic syndrome in patients
enrolled in the CATIE studies was nearly twice that of age-matched
ATP IIIA over time
controls, with increased prevalence of all individual criteria of metabolic 3x
A retrospective review has also shown that the use of the 35 35
more efficacious second-generation antipsychotics comes at a cost to 30 30
the schizophrenia patient, as some second-generation antipsychotics 25 25
can induce a significantly greater impact on the incidence of
the metabolic syndrome in first-episode patients compared with the
first-generation antipsychotics (see Figure 8).
The differential effect of
antipsychotics on the prevalence of the metabolic syndrome is also
apparent in recent data from the Sertindole Cohort Prospective (SCoP)
study, where patients receiving risperidone exhibited a greater
Baseline Incidence 3-year follow-up Baseline Incidence 3-year follow-up
(n=122) cases (n=122) (n=122) cases (n=122)
likelihood of developing the metabolic syndrome than patients on 1984–1995 2000–2006
sertindole (see Figure 9).
As patients with schizophrenia are less likely
First-generation antipsychotics Second-generation antipsychotics
to receive and seek medical care for concomitant medical conditions,
The presence of metabolic syndrome was defined using the criteria set by the
Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program (NCEP).
the choice of an antipsychotic drug regimen that does not
Source: De Hert M et al., 2008.
exacerbate the risk factors for CVD and CHD is a major clinical and
public health challenge. Clinicians are advised to take into
Figure 9: Prevalence of Metabolic Syndrome up to
consideration the patient’s current medical illness risk factors and One Year
potential drug effects on the above-mentioned risk factors when
selecting an appropriate antipsychotic treatment.
Weight Gain with Antipsychotics
Any increase in adiposity can increase the risk of dyslipidaemia,
hypertension and hyperglycaemia, all of which are contributing risk
factors for CVD. All available antipsychotics induce weight gain to some
degree, but certain agents have been associated with greater weight
gain than others – an important consideration since antipsychotics are
Prevalence of metabolic
not used as short-term solutions, but rather as chronic therapies.
Pooled data from clinical trials and registration databases for individual
Baseline Week 12 Week 36 Last assessment
compounds demonstrate differential effects on bodyweight depending
Ser 988948 106
Ris 105 105 59 112
on the antipsychotic medication over the course of a year, ranging from
modest mean increases of <2kg/year with amisulpride, ziprasidone and
Data from the Sertindole Cohort Prospective (SCoP) study. Number of assessable patients
aripiprazole, to mean increases of 2–3kg/year with quetiapine and
differed at each time-point because only data from the fasting blood samples were used for
risperidone, to larger mean increases of 5.3–6.3kg/year with clozapine
the metabolic evaluation. Source: De Hert et al, 2009.
and increases of 6–12kg/year with olanzapine (lower estimates come
from analyses that include doses as low as 2.5mg/day, while higher Table 2: Atypical Antipsychotics and Associated
estimates are based on analyses using standard antipsychotic doses in
the range of 12.5–17.5mg/day).
A consensus statement jointly
issued by the Americans With Disabilities Act (ADA), the American
Drug Weight Gain Risk of Diabetes Worsening Lipid
Psychiatric Association (APA), the American Association of Clinical Profile
Endocrinologists (AACE) and the North American Association for the
Clozapine +++ + +
Study of Obesity concluded that olanzapine and clozapine were
Olanzapine +++ + +
associated with the greatest potential for weight gain among evaluated
Risperidone ++ D D
Quetiapine ++ D D
second-generation agents (see Table 2).
Recently available data from
Ziprasidone +/– – –
randomised clinical trials show that sertindole induces weight gain of
Aripiprazole +/– – –
2–3kg over a span of eight to 52 weeks, which is similar to the more
+ = increased effect; – = no effect; D = discrepant results.
modest increases observed with some other compounds.
Switching from a drug with a high risk of weight gain to one with a respectively, after one year of treatment.
In another study where
lower risk can have beneficial effects. In phase I of the CATIE trial, overweight patients currently taking olanzapine were randomly
where olanzapine was the most common antipsychotic taken at assigned to continue on olanzapine or switch to aripiprazole, those
baseline, the randomisation of patients to olanzapine, quetiapine or who switched experienced a significant weight improvement after 16
risperidone led to varying degrees of mean increases in weight, while weeks (-1.8kg versus +1.41kg; p<0.001).
A recent post hoc analysis
assignment to perphenazine or ziprasidone led to mean weight loss of the phase I CATIE results confirmed the weight loss described
(see Figure 10).
Weight change after switching to a low-weight-gain by previous studies upon switching from olanzapine to antipsychotics
agent from a higher-risk agent has been demonstrated in a number of with a lower risk of weight gain, whereas continued treatment with
studies; switching from risperidone or olanzapine to ziprasidone led olanzapine led to sustained weight gain (see Figure 11).
to a mean weight loss of 6.8kg (p<0.005) and 10.0kg (p<0.001), drug-induced weight gain can be effectively attenuated and at least
EUROPEAN PSYCHIATRIC REVIEW 31