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The National Ribat University
Faculty of Graduate Studies
and Scientific Research
INVESTIGATION OF WEIGHT GAIN AMONG
PSYCHOTIC PATEINTS ON ANTI PSYCHOTIC
A Thesis Submitted in Fulfillment of Partial Requirement of master
Degree in Human Nutrition and Dietetics
SARA OMER MOHAMED
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. 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. 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 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. ﺔﺳارﺪﻟا ﺺﺨﻠﻣ ةدﺎﯾزو ﺾﯾﺮﻤﻟا نزو ةدﺎﯾز ﻰﻠﻋ ﻦﯿﺑاﺰﻧﻻوا ءاود ﺮﯿﺛﺄﺗ ﻦﻣ ﻖﻘﺤﺘﻟا ﻰﻟا ﮫﺳارﺪﻟا هﺰھ فﺪﮭﺗ ةدﺎﯾزو جﻼﻌ ﻟا ةﺮﺘﻓ لﻮﻃو ءاوﺪﻟا ﺔﻋﺮﺟ ﻦﯿﺑ ﺔﻗﻼﻌﻟا ﺔﺳارد ﻰﻟا فﺪﮭﺗ ﺎﻀﯾاو ﻞﻛﻼﻟ ﮫﺘﯿﮭﺷ ﺺﯿﺨﺸﺗ ﻢﺗ ﻦﯾﺰﻠﻟا ﻲﺣﺎﻤﻟا ﻲﻧﺎﺠﺘﻟا ﻲﻔﺸﺘﺴﻣ ﻦﻣ ﺾﯾﺮﻣ 49 رﺎﯿﺘﺧﺈﺑ ﮫﺳارﺪﻟا هﺰھ ﺖﻣﺎﻗ ن ءاوﺪﺑ جﻼﻌﻠﻟ نﻮﻌﻀﺨﯾ ﻦﯾﺰﻠﻟاو ﺔﯿﺒﻄﻘﻟا ﻰﺋﺎﻨﺛ بﺎﺌﺘﻛﻻا وا ﮫﯿﺼﺨﺸﻟا مﺎﺼﻔﻧﺈﺑ ﻢﮭﺿﺮﻣ .ﺔﻨﺴﻟا زوﺎﺠﺘﺗﻻ ﮫﯿﻨﻣز ةﺪﻣ لﻼﺧ ﻂﻘﻓ ﻦﯿﺑاﺰﻧﻻوا ﺔﺳارﺪﻟا ﮫﯾاﺪﺑ ﺪﻨﻋ لﻮﻄﻟاو نزﻮﻟا تﺎﺳﺎﯿﻗو ﻲﺿﺮﻤﻟا ﻊﻣ ﺮﺷﺎﺒﻣ نﺎﯿﺒﺘﺳا ماﺪﺨﺘﺳﺈﺑ ﺔﺳارﺪﻟا ﺖﻤﺗ 49 ﻞﺻا ﻦﻣ ﺎﻀﯾﺮﻣ 33 ﻰ : ﻟﺎﺘﻟﺎﻛ ﺔﺳارﺪﻟا ﺞﺋﺎﺘﻧ تءﺎﺟ ،ﻲﻟوﻻا ﺔﻨﯾﺎﻌﻤﻟا ﻦﻣ ﺮﮭﺷ ةﺮﺘﻓ ﺪﻌﺑ ﻢﺛو ﺔﯿﮭﺸﻟا ﻲﻓ ةدﺎﯾز ﻢھﺪﻨﻋ تﺮﮭﻇ ﺎﻀﯾﺮﻣ 47 ﺞ 2 نزﻮﻟا ةدﺎﯾز ﻂﺳﻮﺘﻣ نﺎﻛو ﻢﮭﻧازوا تداز ﺪﻗ ﻦﯿﺑ ﺔﻗﻼﻋ ﻚﻟﺎﻨھ ﺖﻧﺎﻛ ت . ﺎﯾﻮﻠﺤﻟا لوﺎﻨﺘﻟ ﻢﮭﺘﺒﻏر ﻰﻓ هدﺎﯾز ﻢھﺪﻨﻋ تﺮﮭﻇ ﺎﻀﯾﺮﻣ 22و ﻞﻛﻼﻟ نزﻮﻟا ةدﺎﯾزو ﻦﯿﺑازﻻوا ود ءا ﺔﻋﺮﺟ ﻦﯿﺑ ﺔﻗﻼﻌﻟا ﺖﺒﺜﺗ ﻢﻟ ﻦﻜﻟو جﻼﻌﻟا ةﺮﺘﻓ لﻮﻃو نزﻮﻟا ةدﺎﯾز ﻦﻤﻀﺘﺗ ﺔﯿﺠﯿﺗاﺮﺘﺳﻻا هﺰھ ،نزﻮﻟا ةدﺎﯾز ﻊﻨﻤﻟ ﺔﯿﺠﯿﺗاﺮﺘﺳإ ﻊﺿو ﻰھ ﺔﺳارﺪﻟا هﺰﮭﻟ ﮫﯿﺻﻮﺗ ﻢھا .ﺔﯿﺿﺎﯾﺮﻟا ﻦﯾرﺎﻤﺘﻟا ﻖﯾﺮﻃ ﻦﻋ ﺔﻜﻠﮭﺘﺴﻤﻟا تاﺮﻌﺴﻟا ةدﺎﯾزو ﺔﻟوﺎﻨﺘﻤﻟا ﺔﯾراﺮﺤﻟا تاﺮﻌﺴﻟا صﺎﻘﻧا Table of contents
ﺔﺳارﺪﻟا ﺺﺨﻠﻣ Table of contents 1-1 Introduction 1-2 Justification literature review 2-1 Mechanism of 2-2 Olanzapine and 2-3 Sedative effect of olanzapine on appetite 2-5 Olanzapine and 3-1 Study design 3-3 Study population 3-4 Study sample 3-5 Data collection 3-6 Data analysis results and discussion 4-1 Sociodemographic 4-2Drug related data 4-3 Eating behavior 4-4 Information about 4-5 Body weight data 4-6 Relation of dose and duration with conclusion and recommendation 5-2 Recommendation CHAPTER ONE
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, 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 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 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. 1-3 GENERAL OBJECTIVES
To determine weight gain among psychotic patients on atypical anti- psychotic 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. CHAPTER TWO
LITERATURE REVIEW
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 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) 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 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). 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 triglyceride and insulin levels because this type of weight gain is often coupled with insulin resistance(12). Patients who experienced antipsychotic-induced weight increases exhibit elevated rates of 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). 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 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 sleep. Olanzapine is safe and well tolerated at dosage between 5 to 10 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) 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 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 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 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) 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 14- week 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). 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). 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 lipoprotein- cholesterol 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 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). 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 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 other antipsychotic drug Exclude any patient taking olanzapine for more than one year. 3-5 DATA COLLECTION:
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. Books, journals and internet 3-6 DATA ANALYSIS:
Data were analyzed by using SPSS statistic package for social sciences. CHAPTER FOUR
RESUTS AND DISCUSSION
4-1 Sociodemographic data:
Age (years) Frequency 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. 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. Table 4-1-2 social status 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. 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. 4-2 drug related data:
Table 4-2-1 duration of olanzapine treatment
Duration Frequency 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 Table 4-2-2 dose of olanzapine
This table shows that the dose of 10 mg is most frequently prescribed, followed by 20 mg, 5 mg then 2.5 mg. Figure 4-2-1 frequency of olanzapine per day From The figure above shows that the majority of patients took olanzapine once per day. 4-3 Eating behavior data:
Table 4-3-1
Number of meals taken per day before start olanzapine
Number of meals Frequency Table 4-3-2
Number of meals taken per day after start olanzapine
Number of meals Frequency More than three 4 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) Table 4- 3
-3 the effect of olanzapine on appetite
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). Table 4- 3
esire to eat sweets and deserts
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). 4-4 information about sleep
Table 4-4-1 sleeping hours
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). 4-5 Body weight data
weight at the beginning of the study Table 4- 5-1
Weight(kg) Frequency Table 4- 5
eight after one mont
Weight(kg) Frequency 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 Table 4-5-3 increase in weight
Increase in weight 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, 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 There were statistical significant differences between weights at the beginning and at the end of study; P value was less than 0.05 (see Table 4-5-4
BMI at the beginning and end of study
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. 4-6 Relation of dose and duration of olanzapine with weight
Table 4- 6-
duration of olanzapine treatment * change in weight
Change in weight % of Total 10.1% 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, 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 . 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 5-2 RECOMMONDATIONS:
-Educating the patients about the chances of weight gain as a side effect
-Preventing weight gain in patients on olanzapine is the ideal strategy, involves caloric restriction and increased caloric expenditure through -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 -Studies in larger patient samples are required to confirm results of this RFERRENCES
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