Download INVESTIGATION OF WEIGHT GAIN AMONG PSYCHOTIC

The National Ribat University
Faculty of Graduate Studies
and Scientific Research
INVESTIGATION OF WEIGHT GAIN AMONG
PSYCHOTIC PATEINTS ON ANTI PSYCHOTIC
OLANZAPINE
A Thesis Submitted in Fulfillment of Partial Requirement of master
Degree in Human Nutrition and Dietetics
BY:
SARA OMER MOHAMED
supervisor
PROFESSOR YOUSIF BABIKER YOUSIF
December 2014
DEDICATION
I dedicate this study to my mother, my father, and my husband
who gave me all the encouragement and support to finish this study.
I
AKNOWLEDGMENT
Thanks first and foremost to God, who gave me the ability to complete
this work and my sincere thanks to my teacher Professor YOUSIF
BABIKER YOUSIF for his help, support and guidance. My thanks also go to
my teachers in Alribat University, to the staff of Altigani Almahi hospital
and to the patients who agreed to participate in the study.
II
ABSTRACT
The aim of this study is to investigate the effect of olanzapine on weight
gain and appetite and to study the relation between the dose, duration
of olanzapine and weight gain.
The study involved 49 pa ents from Altegani Almahi hospital in
Omdurman, they diagnosed as schizophrenic or bipolar depression, who
use olanzapine only for less than one year. The study was carried out by
using direct questionnaire and anthropometric measurements such as
weight height and BMI. Weight was remeasured after one month.
Results revealed that 67.3% of pa ents experienced weight gain, the
mean weight gain was 2kg. Olanzapine induced increase in appetite on
47 pa ents out of 49. And increase in desire to eat sweets on22 pa ents
out of 49.
There was significant relationship between duration of treatment and
weight gain, but not related to dose of olanzapine.
Recommendation from this study is that, putting strategy to prevent
weight gain in patients on olanzapine, this strategy involves caloric
restriction and increased caloric expenditure through exercises.
III
‫ﻣﻠﺨﺺ اﻟﺪراﺳﺔ‬
‫ﺗﮭﺪف ھﺰه اﻟﺪراﺳﮫ اﻟﻰ اﻟﺘﺤﻘﻖ ﻣﻦ ﺗﺄﺛﯿﺮ دواء اوﻻﻧﺰاﺑﯿﻦ ﻋﻠﻰ زﯾﺎدة وزن اﻟﻤﺮﯾﺾ وزﯾﺎدة‬
‫ﺷﮭﯿﺘﮫ ﻟﻼﻛﻞ واﯾﻀﺎ ﺗﮭﺪف اﻟﻰ دراﺳﺔ اﻟﻌﻼﻗﺔ ﺑﯿﻦ ﺟﺮﻋﺔ اﻟﺪواء وﻃﻮل ﻓﺘﺮة اﻟﻌﻼج وزﯾﺎدة‬
‫اﻟﻮزن‪ .‬ﻗﺎﻣﺖ ھﺰه اﻟﺪراﺳﮫ ﺑﺈﺧﺘﯿﺎر ‪ 49‬ﻣﺮﯾﺾ ﻣﻦ ﻣﺴﺘﺸﻔﻲ اﻟﺘﺠﺎﻧﻲ اﻟﻤﺎﺣﻲ اﻟﻠﺰﯾﻦ ﺗﻢ ﺗﺸﺨﯿﺺ‬
‫ﻣﺮﺿﮭﻢ ﺑﺈﻧﻔﺼﺎم اﻟﺸﺨﺼﯿﮫ او اﻻﻛﺘﺌﺎب ﺛﻨﺎﺋﻰ اﻟﻘﻄﺒﯿﺔ واﻟﻠﺰﯾﻦ ﯾﺨﻀﻌﻮن ﻟﻠﻌﻼج ﺑﺪواء‬
‫اوﻻﻧﺰاﺑﯿﻦ ﻓﻘﻂ ﺧﻼل ﻣﺪة زﻣﻨﯿﮫ ﻻﺗﺘﺠﺎوز اﻟﺴﻨﺔ‪.‬‬
‫ﺗﻤﺖ اﻟﺪراﺳﺔ ﺑﺈﺳﺘﺨﺪام اﺳﺘﺒﯿﺎن ﻣﺒﺎﺷﺮ ﻣﻊ اﻟﻤﺮﺿﻲ وﻗﯿﺎﺳﺎت اﻟﻮزن واﻟﻄﻮل ﻋﻨﺪ ﺑﺪاﯾﮫ اﻟﺪراﺳﺔ‬
‫وﺛﻢ ﺑﻌﺪ ﻓﺘﺮة ﺷﮭﺮ ﻣﻦ اﻟﻤﻌﺎﯾﻨﺔ اﻻوﻟﻲ‪ ،‬ﺟﺎءت ﻧﺘﺎﺋﺞ اﻟﺪراﺳﺔ ﻛﺎﻟﺘﺎﻟﻰ‪ 33:‬ﻣﺮﯾﻀﺎ ﻣﻦ اﺻﻞ ‪49‬‬
‫ﻗﺪ زادت اوزاﻧﮭﻢ وﻛﺎن ﻣﺘﻮﺳﻂ زﯾﺎدة اﻟﻮزن ‪2‬ﻛﺞ‪ 47 .‬ﻣﺮﯾﻀﺎ ﻇﮭﺮت ﻋﻨﺪھﻢ زﯾﺎدة ﻓﻲ اﻟﺸﮭﯿﺔ‬
‫ﻟﻼﻛﻞ و‪ 22‬ﻣﺮﯾﻀﺎ ﻇﮭﺮت ﻋﻨﺪھﻢ زﯾﺎده ﻓﻰ رﻏﺒﺘﮭﻢ ﻟﺘﻨﺎول اﻟﺤﻠﻮﯾﺎت‪ .‬ﻛﺎﻧﺖ ھﻨﺎﻟﻚ ﻋﻼﻗﺔ ﺑﯿﻦ‬
‫زﯾﺎدة اﻟﻮزن وﻃﻮل ﻓﺘﺮة اﻟﻌﻼج وﻟﻜﻦ ﻟﻢ ﺗﺜﺒﺖ اﻟﻌﻼﻗﺔ ﺑﯿﻦ ﺟﺮﻋﺔ دواء اوﻻزاﺑﯿﻦ وزﯾﺎدة اﻟﻮزن‬
‫اھﻢ ﺗﻮﺻﯿﮫ ﻟﮭﺰه اﻟﺪراﺳﺔ ھﻰ وﺿﻊ إﺳﺘﺮاﺗﯿﺠﯿﺔ ﻟﻤﻨﻊ زﯾﺎدة اﻟﻮزن‪ ،‬ھﺰه اﻻﺳﺘﺮاﺗﯿﺠﯿﺔ ﺗﺘﻀﻤﻦ‬
‫اﻧﻘﺎص اﻟﺴﻌﺮات اﻟﺤﺮارﯾﺔ اﻟﻤﺘﻨﺎوﻟﺔ وزﯾﺎدة اﻟﺴﻌﺮات اﻟﻤﺴﺘﮭﻠﻜﺔ ﻋﻦ ﻃﺮﯾﻖ اﻟﺘﻤﺎرﯾﻦ اﻟﺮﯾﺎﺿﯿﺔ‪.‬‬
‫‪IV‬‬
Table of contents
Content
page
Dedication
Acknowledgment
Abstract
‫ﻣﻠﺨﺺ اﻟﺪراﺳﺔ‬
Table of contents
Chapter one
introduction
1-1 Introduction
1
1-2 Justification
2
1-3 Objectives
3
Chapter two
literature review
2-1 Mechanism of
4
action
2-2 Olanzapine and
5
weight gain
2-3 Sedative effect of
7
olanzapine
2-4 Effect of
8
olanzapine on appetite
2-5 Olanzapine and
11
obesity
V
Chapter three
methodology
3-1 Study design
15
3-2 Study area
15
3-3 Study population
15
3-4 Study sample
15
3-5 Data collection
16
3-6 Data analysis
16
Chapter four
results and discussion
4-1 Sociodemographic
17
data
4-2Drug related data
21
4-3 Eating behavior
24
data
4-4 Information about
27
sleep
4-5 Body weight data
28
4-6 Relation of dose
32
and duration with
weight gain
Chapter five
conclusion and recommendation
5-1 Conclusion
34
5-2 Recommendation
35
References
36
VI
CHAPTER ONE
INTRODUCTION
1-1 INTRODUCTION
Olanzapine is an atypical anti-psychotic approved by the food and drug
administration (FDA) for the treatment of schizophrenia and bipolar
depression , classified as athienobenzodiazepine(1) and is the one of the
second generation antipsychotics .(2)
Atypical antipsychotics are currently the most frequently prescribed class
of drugs for schizophrenia , this indicates that these agents provide
antipsychotic efficacy with lower risk of extra pyramidal symptoms than
typical antipsychotics .(3)
Second generation antipsychotics (SGAs) are associated with weight gain
and
metabolic
alteration
including
hyperglycemia,
dyslipidemia,
hypertension and metabolic syndrome. These metabolic side effects
increase cardiovascular risk and are related to medication noncompliance
.The mechanisms behind weight gain can be an increase in food intake
and/or a decrease in energy expenditure .(2)
Weight gain is a common feature of antipsychotic drug treatment. Most
atypical antipsychotics are associated with greater weight gain liability
than their typical counterparts .The molecular mechanisms responsible for
antipsychotic induced weight gain are not fully known. There is ample
evidence, however, that binding to certain neurotransmitter receptors may
explain antipsychotic associated weight gain. (3)
Knowing which drugs are more likely to cause weight gain in the short
term and long term is essential to any discussion with the patient about
the risks versus the benefits of the therapy.(4)
There are direct associations between obesity and several diseases
including high blood pressure , infertility , type 1 diabetes, many types of
-1-
cancer, heart disease, stroke, asthma, osteoarthritis, back pain ,
depression, liver diseases kidney disease, sleep apnoea a condition that
cause interrupted breathing during sleep , gastro-oesophageal reflux
disease and pregnancy complications such as gestational diabetes or
preeclampsia. Avery high degree of obesity (BMI 35 kg /m2) seems to be
linked to higher mortality rates. (5)
1-2 JUSTIFICATION
Olanzapine is widely spread in the prescriptions for patients with
schizophrenia or bipolar disorder.
Some drugs affect the nutrition status of patients. olanzapine causes
sedation and changes in appetite, so it may affect the nutrition status of
the patients.
To my knowledge no such studies have been done before in Sudan, so we
need to confirm the effect of olanzapine on patient's weight. If results of
the study confirm that olanzapine causes weight gain, we will put
recommendations for patients to prevent obesity and it's complications.
-2-
1-3 GENERAL OBJECTIVES
To determine weight gain among psychotic patients on atypical antipsychotic olanzapine .
1-4 SPICIFIC OBJECTIVES
- To study the effect of olanzapine treatment on appetite.
- To find out relations between the dose of drug and duration of treatment
with the weight gain.
-3-
CHAPTER TWO
LITERATURE REVIEW
2-1
MECHANISM OF ACTION:
Although the use of atypical antipsychotics offers many benefits , these
drugs appear to be associated with varying degrees of metabolic adverse
effects, such as weight gain, impaired glucose metabolism , dyslipidemia
and in some cases more serious morbidity such as cardiovascular
disease.(3)
The specific binding profiles of atypical antipsychotics vary greatly, each
drug has unique pharmacological properties, including activity at multiple
receptors. This complex pharmacology leads to interactions of varying
intensity with numerous serotonergic, dopaminergic, histaminergic,
adrenergic and muscarinic acetylcholine receptors. The specific binding
profile of different antipsychotic agents may help explain the occurrence
of particular side effects associated with each drug, for example drug
affinity at the histamine H1 receptor is linked to weight gain, whereas
affinity at muscarinic receptors is linked to dry mouth and constipation
.Atypical antipsychotics are antagonist for both serotonin and dopamine
receptors. Olanzapine has relatively high serotonin receptor blocking
activity but relatively lower affinity for the dopamine receptor, it has
affinity also to bind with histamine and muscarinic receptors.(3)
Olanzapine
act
by
blocking
the
transmission
of
serotonin,
noreepinephrine and dopamine. It is also a potent anticolinergic, which
helps to prevent antipsychotic-induced movement disorders like extra
pyramidal symptoms. And it is also a potent antihistamine which causes
sedation and weight gain (6).
Recently it has been proposed that there is an interesting mechanism to
explain why olanzapine might cause metabolic side effects leading to
obesity and diabetes based on an animal model in male Sprague–Dawley
-4-
rats. They found a tendency for increased 14C-1-deoxyglucose uptake
into fat depots of fed rats and a free fatty acid uptake into fat depots
elevation, in parallel with increased adipose tissue lipogenesis. These
results, consistent with the olanzapine-induced hyperglycemia hypothesis,
suggest that this drug exerts direct metabolic effects that together favor
increased accumulation of fuel into adipose tissue (7).
2-2
OLANZAPINE AND WEIGHT GAIN:
The more common side effects of olanzapine are, blurred vision, change
in walking and balance, difficulty with speaking, mask-like face, rapid
weight gain and restlessness(8).
Meta-analysis by Allison etal. determined that patients receiving standard
doses of most antipsychotic drugs experienced weight gain versus
placebo after 10 weeks and that the amount of weight gain varied by
agent, most likely reflecting differing degrees of action on serotonergic,
dopaminergic, cholinergic, histaminergic and other neurotransmitter
systems. In this analysis, patients given clozapine and olanzapine
treatment had the greatest weight gain (9). Study of one year weight gain
in patients treated with atypical antipsychotic olanzapine : at standard
doses of olanzapine, mean weight gain ranged from 6.8 to 11.8 Kg (15.1
to 16.1 lb) during the first year of treatment, with many patients gaining
more than10% of their initial body weight, while 15mg/day dose of
olanzapine resulted in mean weight gain of 11kg(16.4lb) over 11 months
(10). Similarly, data from studies on weight change due to antipsychotics
revealed that 14
37% of olanzapine-treated patients experienced
weight gain of 7% of their body weight (11). A recent report noted that
olanzapine therapy in patients with first episode schizophrenia causes an
increase in central body fat deposition that is associated with raised
-5-
triglyceride and insulin levels because this type of weight gain is often
coupled
with
insulin
antipsychotic-induced
morbidity
and
resistance(12).
weight
reduced
increases
treatment
Patients
exhibit
who
experienced
elevated
compliance,
even
rates
of
if
the
psychopharmacological treatment is effective(13),(14).Weight gain in
older patients (>60 years)treated with atypical antipsychotics is lower
than that seen in younger adults. Olanzapine is reported to be associated
with the weight gain on short and long term use, weight gain can be a
disincentive to comply with treatment and complicates comorbid medical
conditions such as obesity and heart disease(15).
Body weight, body composition, resting energy expenditure, and
substrate oxidation as well as leptin, insulin, glucose and lipid levels were
examined in a group of patient volunteers with first episode psychosis.
Results: after 11 weeks of olanzapine therapy, the median increase in
body weight was 4.7 kg, body fat, measured by dual-energy x-ray
absorptiometry , increased significantly, lean body mass and bone
mineral content did not change. Resting energy expenditure, measured by
indirect calorimetry, did not change. Fasting insulin and triglyceride
levels significantly increased, but there were no changes in
glucose
levels, total, high density lipoprotein, or low density lipoprotein
cholesterol levels, or leptin levels (12).
A recent study suggested that 40-80% of patients treated with
antipsychotics medications experienced weight gain that exceeds ideal
body weight by 10% or greater (16).
Weight gain is considered clinically significant if it exceeds 7% of the
initial weight after 10 weeks (17).
-6-
Long-term treatment with olanzapine in schizophrenic patients could lead
to significant weight gain and its associated health problems, such as
diabetes and heart disease. With the increased prevalence of metabolic
illness in schizophrenia, it is of great clinical importance to determine to
what extent the olanzapine induces changes that reflect state of eating
behaviors. The deleterious effects of olanzapine on serum lipids can be
independent of the body mass index or, in addition, to weight-related
effects (18).
2-3
SEDATIVE EFFECT OF OLANZAPINE:
Antipsychotics in general can contribute to decreased caloric dissipation
via diminished physical activity, due to their sedative effects (19).
Drugs with high H1 receptor affinity have sedative effects, leading some
investigators to speculate that sedation may induce weight gain because
of reduced mobility(20) .Sedation can impair a person's ability to function
normally over the long term use. Olanzapine has the highest affinity for
the histamine H1 receptors, this explains why olanzapine has relatively
large sedative effect even though it is a high potency medication.
Olanzapine can improve the quality of sleep in individuals with
schizophrenia (21).
Antagonism of histamine H1 receptors has been identified as a main
cause of second generation antipsychotics (SGA)-induced obesity.
Antagonism of H1 receptors by SGAs may time-dependently affect the
hypothalamus-brainstem circuits to cause weight gain by stimulating
appetite and fat accumulation but reducing energy expenditure (22).
Olanzapine is effective in improving overall psychopathology including
positive symptoms, negative and secondary depressive features. And the
common side effects are weight gain, sleepiness and increase duration of
-7-
sleep. Olanzapine is safe and well tolerated at dosage between 5 to 10
mg\day (23).
2-4 EFFECT OF OLANZAPINE ON APPETITE:
One of the ways olanzapine can lead to changes in the patterns of food
intake is by increasing appetite and preference of certain diets (24) (25)
(26).
Body weight data were collected from 2 trials over six weeks, study 1
comparing olanzapine and haloperidol and study 2 olanzapine and
risperidone they found that: increased appetite was more frequent during
olanzapine treatment than during haloperidol, but not significantly
different from risperidone(27). After 16 weeks of olanzapine treatment,
the patients gained weight, increased their waist circumference, had fewer
positive schizophrenia symptoms and increased in sensitivity to appetitive
stimuli was observed in insular cortices, amygdala and cerebellum
(28).Randomized study investigating the effect of clozapine and
olanzapineon abnormal eating behavior (food craving, binge eating), the
result was: the number of patients reporting food craving, binge eating or
both increased over time. The likelihood to experience food craving at
any time during drug treatment was higher in olanzapine group than
clozapine, the likelihood to experience binge eating at any time during
drug treatment was not statistically significantly higher in the olanzapine
group (29).
Weight gain may be related to changes in appetite and food intake,
however, it is unclear whether changes in appetite in response to
treatment with second generation antipsychotics are persistent in patients
treated
chronically with these medications and the extent to which
changes in appetite are related to any continuing weight gain associated
-8-
with long term treatment with these drugs. In a randomized 5 month
study of the effects of the olanzapine and risperidone on metabolic
changes in chronic schizophrenic patients ,appetite changes were assessed
using two scales and were correlated with weight gain and metabolic
changes .There is evidence that the hormone ghrelin is related to appetite
stimulation and falls during satiation after meals , therefore ghrelin was
measured before and after a fatty meal at baseline and after 1 months of
drug treatment, the results was as follows; neither olanzapine nor
risperidone increased appetite during the 5 months of study , and there
was a trend for a decrease in appetite over time. Weight only increased
slightly during treatment and changes in appetite scores were not
correlated with changes in weight or changes in glucose or lipids . Fasting
ghrelin did not increase in olanzapine or risperidone treated patients, and
there were no significant changes in gherlin responses to a fatty meal
between baseline and 1 months of drug treatment (30).
Study conducted by Zwaal etal resulted in that, acute injection of
olanzapine, selectively increases meal-related ghrelin secretion and this
may partially underlie the impairment in satiation that results in increase
food intake (31).
Current evidence indicates that antipsychotic-induced weight gain and
lipid disturbances may be explained by the antipsychotics' hyperphagic
effects, linked to lack of satiation as observed in patients and in animal
models(32)(33).
Recent investigations have also linked antipsychotic drug treatment to
alterations in hypothalamic lipid metabolism. In an acute study on mice,
it was proposed that H1 receptor-mediated activation of hypothalamic
AMP-activated
protein
kinase
(AMPK)
-9-
represents
an
important
mechanism of action for antipsychotic-induced hyperphagia (34). AMPK,
a sensor of energy homeostasis at the cellular level, integrates metabolic
signals and regulates energy balance via modulation of hypothalamic
fatty acid metabolism within the hypothalamus (35).
Body mass indices (BMI), caloric intake and energy expenditure were
measured in 10 olanzapine treated subjects, at 4 week follow up , patients
had increases in both caloric intake and body mass index, without any
change in their resting and daily energy expenditure(36).
Appetite and weight data were collected from 4 prospective, 11- to 14week clinical trials. Patients' appetites were assessed with Eating
Behavior Assessment (EBA, Study 1), Platypus Appetite Rating Scale
(PARS, Study 2), Eating Inventory (EI, Study 3), Food Craving Inventory
(FCI, Study 3), and Eating Attitude Scale (EAS, Study 4). The results
were: In Studies 1 (EBA) and 4 (EAS), patients who reported overall
score increases on appetite scales, indicating an increase in appetite,
experienced the greatest overall weight gains. However, in Studies 2
(PARS) and 3 (EI, FCI), patients who reported overall score increases on
appetite scales did not experience greater weight changes than patients
not reporting score increases. Early weight changes (1-4 weeks) were
more positively correlated with overall weight changes than early or
overall score changes on any utilized appetite assessment scale (37).
Psychotic patients are characterized by sedentary life style and poor
dietary intake. These patients are less likely to make healthy dietary
choices compared with the general population, including more fat and
sugar and less fiber in their diet. Most of the studies on food intake in
volunteers and patients treated with second generation anti psychotics
show an increase in food intake during treatment (38) (39).
- 10 -
2-5 OLANZAPINE AND OBESITY:
The presence of obesity and increase in body mass are important risk
factors for cardiovascular disease and diabetes.
In India there was a study which examined the effects of olanzapine,
risperidone, and haloperidol on weight and body mass index (BMI),
patients were followed for a period of 6 weeks. The results: the analysis
of 66 patients showed a prevalence of overweight at 11.7%, and obesity
at 31.8%. The prevalence of obesity in patients is over 30 times as high as
that of the matched healthy control group. Subjects in the olanzapine
group had the greatest weight gain at 5.1 kg, followed by risperidone at
4.1 kg and haloperidol at 1.8 kg (40).
Obesity and diabetes represent a growing problem in the general
population of the United States. These disorders are present at even
greater rates in individuals with schizophrenia (41).
weight gain of at least 1.0 kg at 3 weeks after initiation of olanzapine is a
robust predictor of substantial weight gain (defined as gaining at least 5
kg or 7% of baseline body weight) at 30 weeks in individuals with bipolar
disorder (42), and weight gain of at least 7% of baseline body weight
during the first 6 weeks of olanzapine treatment for schizophrenia has
been shown to be associated with greater weight gain after 1 year of
treatment (12). Substantial body weight gain occurs in up to 50% of
patients during long-term antipsychotic treatment (43).
Clozapine and olanzapine have been shown to increase serum levels of
leptin, a hormone exclusively expressed and secreted by differentiated
adipocytes . It acts as a feedback signal from the adipose tissue and may
play a role in the pathophysiology of obesity. Leptin levels increase
exponentially with body mass index or percentage of body fat (44).
- 11 -
olanzapine monotherapy is associated with significant weight gain and an
increase in body fat. Both weight gain and increase in body fat were
associated with a significant increase in serum leptin levels (24).
The successful use of antipsychotic drugs such as clozapine and
olanzapine in the treatment of schizophrenia is hampered by their
unwanted obesogenic effect and associated metabolic side effects (9).
After 11 weeks of a pilot study to compare between the effects of
olanzapine and ziprasidone on weight gain and body composition among
schizophrenic patients the results were: olanzapine-treated patients
showed significant weight gain, particularly fat gain, with increased low
density lipoprotein-cholesterol and decreased high density lipoproteincholesterol concentrations. In contrast, ziprasidone-treated patients
showed no significant weight gain with increased high density
lipoprotein-cholesterol concentration. (45).
Metabolic syndrome (MetS) has been recognized as a risk factor for
cardiovascular morbidity and mortality in general population and in
patients with severe mental illnesses like schizophrenia. Prevalence of
MetS in patients with schizophrenia was found to be ranging from 3.3%
to 68.0%. Prevalence in antipsychotic-naïve and antipsychotic-treated
patients ranged between 3.3-16.0% and 31.0-68.0% respectively, and was
higher in younger patients, female gender and Hispanics, and lower in
African-Americans and Orientals. Prevalence of metabolic abnormalities
was higher in patients receiving second generation antipsychotics
(SGAs), especially with clozapine, olanzapine, and risperidone, as
compared to first generation antipsychotics (46).
The weight gain induced by SGAs is usually centrally distributed, with an
increase in waist circumference (30) (47).This is associated with insulin
- 12 -
resistance and metabolic syndrome, which increase the risk of diabetes
and cardiovascular disease (48).
Obesity is highly prevalent among patients treated with atypical
antipsychotics for schizophrenia. Assessment and monitoring of obesity
along with preventive and curative measures should be part of the clinical
management of patients treated with antipsychotics (40).
- 13 -
CHAPTER THREE
SUBJECT AND METHOD
3-1 STUDY DESIGN:
It is a prospective hospital based study
3-2 STUDY AREA:
Altegani Almahi hospital in omdurman
It is a specialized psychiatry hospital .Patients from all states in Sudan
are referred to this hospital. It consists of emergency part, words and
refer clinics.
3-3 STUDY POPULATION:
Psychotic patients with schizophrenia or bipolar depression taking
olanzapine tablets who are attending the refer clinics.
3-4 STUDY SAMPLE:
Case finding during 1 months; data were collected from 49 adult
outpatients (22women and 27 men) between 17 and 60 years of age.
The sample selected randomly.
EXCLUSION CRITERIA:
Exclude
any
patient
taking
olanzapine
combined
with
antipsychotic drug
Exclude any patient taking olanzapine for more than one year.
3-5 DATA COLLECTION:
PRIMARY DATA:
- 14 -
other
-Questionnaire:
From which dose of drug, duration of treatment, appetite, sleeping
hours and patient's compliance data were collected.
-Anthropometric measurement:
Weights, heights and BMI
Weights and heights were measured at baseline study and then weights
were measured after one month.
BMI calculated at baseline and at the end of study
Dietary assessment data were not collected as the patients could not
give reliable information due to their disease condition.
SECONDARY DATA:
Books, journals and internet
3-6 DATA ANALYSIS:
Data were analyzed by using SPSS statistic package for social sciences.
- 15 -
CHAPTER FOUR
RESUTS AND DISCUSSION
4-1 Sociodemographic data:
Table 4-1-1 age
Age (years)
Valid
Frequency
Percent
15-25
17
34.7
26-35
16
31.7
36-45
10
0.41
46-55
5
10.1
56-65
1
.01
Total
49
100.0
From this table we can read that, ages of study sample range from 15 to
65 year and majority of study sample fall in the range 15 to 35. 23 of 33
patients (69.7%) who exhibit weight gain (table 4-12) fall in this range.
And 10 of them fall in range 36-55 .This finding oppose the results of Jain
et al (49), they found that, the increase in weight was significantly
related to age ≥ 40 years and female sex, indica ng that women ≥ 40 of
age are more prone to gain weight with olanzapine therapy in
comparison with women
40 and men of any age group.
- 16 -
Gender
60
55
50
45
40
30
Percent
20
10
0
Male
Female
Gender
Figure 4-1-1 gender
Figure 4-1 showed that 55% of study sample were males (27
pa ents) and 45% female (22patients). 22 pa ents of 33 who
experienced weight gains (table 4-12) were males and 11 of them were
females, this result also opposed the results of Jain et al above.
- 17 -
Table 4-1-2 social status
Frequency
Valid
Percent
Married
16
32.7
Single
29
59.2
Divorced
3
6.1
Widow
1
2.0
49
100.0
Total
This table explains that most of the patients under study were single
represent 59.1 % of study sample. This result correlated to results by
Tien et al (50): chance for never-married men to develop schizophrenia
is 50 mes higher, and for never-married women 14 mes higher than
married ones. Also Nyer et al (51) found that, in middle-aged and older
individuals with schizophrenia or schizoaffective disorder and depressive
symptoms, marriage appeared to enhance quality of life.
- 18 -
70
60
61
50
40
30
27
Percent
20
10
12
0
Continue
Stop
Non
Continuing of work
Figure 4-1-2 con nuing of work
We observe from this figure that 61% of sample con nued in their jobs,
and 27% of them left their jobs due to their disease condition. This may
participate in reducing energy expenditure and so weight gain.
This finding correlated to study of Briggs et al (52) which resulted in that
people with schizophrenia appear to have problems holding down
employment and have achieved a lower educational attainment.
- 19 -
4-2 drug related data:
Table 4-2-1 duration of olanzapine treatment
Duration
Frequency
Percent
1-2 months
15
30.6
3-4 months
14
28.6
5 -6months
8
16.3
7-8months
1
2
11-12
11
22.4
Total
49
100.0
Duration of olanzapine treatment for all patients under the study range
from 1 to 12 month.
Patients who used olanzapine for more than an year were excluded
because there was a study by Kinon et al (53) which stated the mean
weight gain during olanzapine treatment tended toward a plateau after
the ini al 39 weeks of treatment with no further significant gain out of
three years.
- 20 -
Table 4-2-2 dose of olanzapine
Dose
Frequency
Percent
2.5mg
4
8.1
5 mg
8
16.3
10 mg
27
55.1
20mg
10
22.5
Total
49
100.0
This table shows that the dose of 10 mg is most frequently prescribed,
followed by 20 mg, 5 mg then 2.5 mg.
- 21 -
120
100
96
80
60
Percent
40
20
0
OD
BD
Frequency
Figure 4-2-1 frequency of olanzapine per day
From The figure above shows that the majority of patients took
olanzapine once per day.
- 22 -
4-3 Eating behavior data:
Table 4-3-1
Number of meals taken per day before start olanzapine
Number of meals
Frequency
Percent
Two meals
38
77.6
Three meals
11
22.4
Total
49
100.0
Table 4-3-2
Number of meals taken per day after start olanzapine
Number of meals
Frequency
Percent
Two meals
11
4.51
Three meals
34
67.3
4
8.1
49
100.0
More than three
meals
Total
From the two tables above it is clear that, 38 patients took two meals
before they started olanzapine treatment, 23 of them converted to
three meals per day after start olanzapine treatment, three of them took
more than three meals, and twelve of them still took two meals.
11 pa ents took three meals before they started olanzapine treatment,
10 of them converted to more than three meals a er starting olanzapine
and one still took three meals.
These results support that olanzapine can induce hyper phagia (32) (33)
(54)
- 23 -
Table 4- 3-3 the effect of olanzapine on appetite
Frequency
Valid
Increase
Percent
38
77.6
Decease
2
4.1
No Change in
9
18.4
49
100.0
appetite
appetite
Total
38 of 49 patients (77.6%) experienced increase in appetite due to the
effect of olanzapine therapy; this finding is comparable to that of Bromel
etal (55) who found that 9 of 12 pa ents reported increased appe te
during olanzapine therapy. Also Previous studies have consistently
reported that increased appetite is a common adverse effect of
olanzapine treatment (17) (18).
- 24 -
Table 4- 3-4 desire to eat sweets and deserts
Frequency
Valid
Percent
Increase
22
44.9
Decease
3
6.1
No Change
24
49.0
Total
49
100.0
22 pa ents out of 49(44.9%) exhibited increased desire to eat sweets
and deserts this confirm the results of Kluge et al (food craving) (29).
- 25 -
4-4 information about sleep
Table 4-4-1 sleeping hours
Frequency
Valid
Increase
No Change
Percent
47
95.9
2
4.1
49
100.0
of weight
Total
95.9% of patients had an increase in their sleeping hours, this
indicates that olanzapine can induce sedation which leads to
decrease energy expenditure, this correlated to previous studies:
Antipsychotics in general can contribute to decreased caloric dissipation
via diminished physical activity, due to their sedative effects (19).
Olanzapine can improve the quality of sleep in individuals with
schizophrenia (21). The common side effects of olanzapine are weight
gain, sleepiness and increased duration of sleep (23).
- 26 -
4-5 Body weight data
weight at the beginning of the study Table 4- 5-1
Weight(kg)
Frequency
Percent
40-50
8
16.3
51-60
14
28.6
61-70
11
22.4
71-80
11
22.4
81-90
1
2.0
91-100
4
8.2
49
100.0
Total
Table 4- 5-2 Weight after one month
Weight(kg)
Frequency
Percent
40-50
5
10.2
51-60
10
20.4
61-70
16
32.7
71-80
13
26.5
81-90
2
4.1
91-100
3
6.1
49
100.0
Total
Tables 10 and 11 shows increase in the frequency of weight gain
in the ranges 61-70 kg 71-80 kg and 81-90 kg after one month of
treatment.
- 27 -
Table 4-5-3 increase in weight
Increase in weight
Frequency
Percent
0.5 kg
2
6.1
1 kg
10
30.3
1.5 kg
2
6.1
2 kg
8
24.2
2.5
3
9.1
3
5
15.2
4
1
3
5
1
3
6
1
3
Total
33
100
From tables 10, 11 and12 we can find that weights of 33 pa ents (67.3%)
increased, 5 pa ents had decrease in their weights and 11 patients
hadn't any changes.
The maximum weight gain was 6 kg and minimum weight gain was 0.5
kg and the mean weight gain was 2kg per month, this finding support
that of other studies, Allison et al (9) reported an es mated of 4.15 kg
during 10 weeks of olanzapine treatment, Kluge etal (29) observed a
mean increase of 3.9 kg during 4 weeks of treatment with olanzapine,
- 28 -
and Eder etal (24) found a mean weight gain of 3.3 kg during 8 weeks of
olanzapine treatment.
The weight gain observed in olanzapine-treated patients suggests that
these subjects maintained a positive energy balance and deposited this
energy in the form of triglycerides in adipose tissue. A positive energy
indicates increased caloric intake or decreased energy expenditure (54).
Although I did not directly measure the caloric intake of these patients, I
assessed their appetite, which was expected to be associated with
caloric intake.
There were statistical significant differences between weights at the
beginning and at the end of study; P value was less than 0.05 (see
appendix 2).
- 29 -
Table 4-5-4
BMI at the beginning and end of study
N
Minimum
Maximum
Mean
Std. Deviation
BMI1
49
17.2
32.9
24.727
4.0538
BMI2
49
17.6
33.3
25.151
4.0099
The median increase of BMI was 0.8 kg/m2.There were statistical
significant differences between BMI at beginning and at the end of
study, P value was less than 0.05 (see appendix 3). This can be correlated
to a study which confirmed by Park etal (45): BMI increased significantly
in olanzapine-treated patients, with a median increase of 2.10 kg/m2 or
10.93% of ini al BMI.
- 30 -
4-6 Relation of dose and duration of olanzapine with weight
gain:
Table 4- 6-1
duration of olanzapine treatment * change in weight
Change in weight
-ve
Duration of
1-2 months
olanzapine
treatment
Count
% of Total
3-4months
Count
% of Total
5-6months
Count
% of Total
7-8months
Count
% of Total
11-12
Count
% of Total
Total
Count
% of Total
Non
Total
0.5-3kg
4-6kg
0
5
8
2
15
0%
10.2%
16.3%
4.1%
29.8%
0
1
12
1
14
.0%
2%
24.5%
2%
28.5%
3
2
2
0
7
6.1%
4.1%
4.1%
0%
14.3%
1
0
1
0
2
2%
.0%
2%
.0%
4%
1
3
7
0
11
2%
6.1%
14.3%
.0%
22.4%
5
11
30
3
49
10.1%
22.4%
61.2%
6.1%
100.0%
This table showed that the number of patients having increase in their
weights and using olanzapine for 3-4 months was higher than that of
pa ents using olanzapine for 1-2 months.
There was positive association between duration of olanzapine
treatment and weight gain (see appendix 4). This results support the
study of Ujike etal (56), they found that, olanzapine-induced weight gain
correlated negatively with baseline BMI and positively with clinical global
improvement and the length of olanzapine treatment, but it did not
correlate with the daily dose of olanzapine, concomitant antipsychotics,
sex and age.
- 31 -
There was no significant relation between the dose of olanzapine and
weight gain (see appendix 4), this finding support that, the weight gain
was not related to dose of the drug Jain et al (49), Ujike et al(56), also
Kinon et al (53) found that the effect of olanzapine dose on weight was
not significant .
- 32 -
CHAPTER FIVE
CONCLUSION AND RECOMMENDATION
5-1 CONCLUSION:
This study showed that olanzapine causes weight gain due to it's sedative
effect which induce and prolong sleep, also due to it's effect on increasing
appetite and food craving to sweets and deserts. These effects resulted in
increase in energy intake and reduce in energy expenditure and so
accumulation of extra energy in form of fats in adipose tissues.
Olanzapine-induced weight gain related, positively to the duration of
treatment, but not related to dose of drug, age and gender.
Patient's compliance with treatment was not affected by increase in
weight.
- 33 -
5-2 RECOMMONDATIONS:
-Educating the patients about the chances of weight gain as a side effect
of treatment.
-Preventing weight gain in patients on olanzapine is the ideal strategy,
involves caloric restriction and increased caloric expenditure through
exercise.
-Refer patients to a nutritional consultation.
-Informing patients about complications of obesity.
-Recording weights weekly and thus both clinician and patients can be
alerted to small increase in weight before the problem become too
difficult.
-Studies in larger patient samples are required to confirm results of this
study.
- 34 -
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- 42 -