East Asian Arch Psychiatry 2010;20:57-61

ORIGINAL ARTICLE

Extent of Weight Gain in Patients with First- episode Psychotic Disorders after One Year of Antipsychotic Treatment in Hong Kong
香港首发精神病患者服用抗精神病药物一年后的增重程度
MMC Wong
黃美彰

Dr Mimi MC Wong, MB BS, MRCPsych, Castle Peak Hospital, Tuen Mun, Hong Kong SAR, China.

Address for correspondence: Dr Mimi MC Wong, Castle Peak Hospital, 15 Tsing Chung Koon Road, Tuen Mun, Hong Kong SAR, China.
Tel: (852) 2456 7111; Email: wmc009@ha.org.hk

Submitted: 16 February 2010; Accepted: 17 March 2010


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Abstract

Objectives: This study aimed to examine the extent of weight gain in a group of patients with first-episode psychotic disorders after receiving antipsychotic treatment for 1 year, and to examine any relationship with the type of antipsychotics prescribed.

Participants and Methods: A total of 160 consecutive participants with 1-year history of first-episode psychotic disorders were recruited, and their body mass index values before and 1 year after antipsychotic treatment were calculated.

Results: About half of the participants gained more than 7% of their baseline body weight. In general, the participants gained a median weight of 4.8 kg (interquartile range, 0.7-9.0 kg) after 1 year of treatment. Forty percent of the female and 47% of the male participants were overweight after treatment. Patients taking second-generation antipsychotics had more severe weight gain than those taking first-generation agents. Olanzapine treatment was associated with the greatest weight gain.

Conclusions: Weight gain is a significant problem even in the early stages of psychotic disorders. Health care professionals need to be aware of this issue and address it early in the course of management, so as to prevent harmful consequences of weight gain in the future.

Key words: Antipsychotic agents; Overweight; Psychotic disorders; Weight gain

摘要

目的: 检视首发精神病患者接受药物治疗1年后增重的程度,以及此副作用与该处方药物的关系。

参与者与方法: 共160名有1年首发精神病史的患者参与研究,比较药物治疗前及治疗后1年的 BMI值。

结果: 约一半参与者的基线体重上升超过7%。 在接受治疗后1年的增重中位数为4.8公斤(四分位数间距,0.7-9.0公斤),而40%女患者和47%男患者于药物治疗后出现超重情况。 服用第二代药物的患者,其增重程度较接受第一代药物治疗的患者为大。 服用奥氮平造成的增重程度是最大的。

结论: 即使治疗早期精神病,增重都是患者须面对的重大问题。 保健专家须对此提高警觉,亦应于治疗初期对以上问题多加留意,以免患者日后承受因增重造成的负面影响。

关键词:抗精神病药物、超重、精神病、增重

Introduction

Obesity has a high prevalence in patients with schizophrenia, regardless of age. Most studies on this topic involved patients with chronic schizophrenia and only a few deal with first-episode psychotic disorders. One study found that more young individuals with psychotic disorders were obese compared with those in the general population (56% vs 33%).1 Lifestyle and illness-related factors, such as lack of motivation and poverty, may contribute to the problem as well as unhealthy eating habits common to those with psychotic disorders.2 However, an important factor is the use of antipsychotics.3 Both first- and second-generation agents are associated with weight gain. The second- generation agents possess broad pharmacological profiles with activity at a number of receptor sites at therapeutic doses. As they are implicated in the regulation of food intake and energy homeostasis, they are likely to play a role in the weight gain associated with antipsychotic use.4 Clinically significant weight gain induced by antipsychotics has been noted in drug-naïve patients with first-episode schizophrenia in a population in India, particularly among those taking olanzapine.5 Weight gain is arguably a greater problem in young individuals experiencing first-episode psychosis. More of these patients, especially those who are younger, are in receipt of newer agents that are more likely to cause weight gain. This group is associated with high sensitivity towards issues of body image6 and teenagers often display lower self-esteem if they are overweight.7 Therefore, they are exposed to health risks associated with obesity, which include premature death2 whilst their adherence to antipsychotics may also be affected as a result of the weight gain.8 In those diagnosed to have first-episode psychotic disorders in the local population, it is therefore worth investigating the extent of weight gain in the initial stage of treatment.

This study aimed to examine the extent of weight gain in a group of patients with first-episode psychotic disorders after receiving antipsychotic treatment for 1 year, and to examine especially any relationship with the type of antipsychotics prescribed.

Methods

Participants

The participants were recruited from the inpatient unit and outpatient clinics of the Castle Peak Hospital, which serves the population of the Hong Kong Hospital Authority’s New Territories West Cluster. At the time of the study, this psychiatric centre had a catchment area of approximately 1,000,000 inhabitants. Those who had a primary diagnosis under F20-29 (schizophrenia, schizotypal and delusional disorder) according to the 10th revision of the International Classification of Diseases (ICD-10)9 were identified. Their case notes were assessed manually to confirm the diagnoses and to ensure this was the first presentation of psychotic symptoms to a psychiatric service. All eligible patients presenting with first-episode psychotic disorder between March and December 2007 were approached 10 to 12 months after their diagnosis, with a view to recruitment into the study. Patients were included if: (1) they were able to give informed consent, ethnically Chinese, and had adequate command and understanding of Chinese; (2) they had a primary diagnosis under F20-29 according to the ICD-10 criteria; and (3) they had taken antipsychotics since their first presentation with acute psychotic symptoms to a psychiatric service 10 to 12 months before the day of interview. They were excluded if they: (1) were older than 65 years; (2) had a past ICD-10 diagnosis of any psychotic disorder; (3) had abused or had been dependent on any psychoactive substance (including alcohol) in the past year; (4) had a current or past ICD-10 diagnosis of anorexia nervosa or bulimia nervosa, organic brain disorder, mental retardation, or mood disorder; (5) had prior treatment with antipsychotics for over 2 weeks in any 1 period before March 2007; (6) had discontinued antipsychotics due to remission of their psychotic disorder in response to formal instructions by a doctor; and (7) were pregnant at the time of interview. Approval of the New Territories West Cluster Clinical and Research Ethics Committee was obtained before the study commenced. Informed written consent was obtained from each participant. Their weight and height before starting antipsychotics were retrieved from the respective patient case notes, together with demographic data (age, gender, marital status), living conditions, education level, and physical health status.

Measurements

For all participants, nurses measured weight (in light clothing) and height rounded up to the nearest 0.1 kg and 0.001 m, respectively. The body mass index (BMI) was calculated and classified into 3 categories10: (1) less than 18.5 kg/m2 as underweight; (2) 18.5 to 22.9 kg/m2 as normal weight; and (3) equal to or greater than 23 kg/m2 as overweight, with a generally accepted view that BMI cut-off points defining overweight should be lower for Asians.11 The proposed cut-off point to define overweight for Hong Kong Chinese is 23 kg/m2.10 For those younger than 18 years, local growth charts with BMI and age were used to define underweight, normal weight, and overweight as BMI changed with age.12 Those with BMIs below the 10th percentile for age- adjusted BMI were defined as underweight. Those with a BMI above the 90th percentile were defined as overweight.7 Those in between were defined as normal.

Data analysis

Data were analysed using the Statistical Package for the Social Sciences (SPSS, Windows version 16.0). For continuous data, variables were presented as means and standard deviations (SDs) for normally distributed data or as medians and interquartile ranges (IQRs) for skewed data. The Kolmogorov-Smirnov test was used to test for normality. For categorical data, variables were presented as numbers and percentages. The Mann-Whitney U test was used for comparison of continuous variables with a skewed distribution if there were only 2 groups. For comparison of categorical data, Pearson’s Chi-square or Fisher’s exact tests were used. Spearman’s rank correlation coefficients were used to test for the correlation between continuous variables with skewed distribution.

Results

Participants

From March to December 2007, 173 patients with psychotic symptoms presenting for the first time and having diagnoses under F20-29 according to ICD-10 criteria were identified. Five of them were excluded: 1 had mental retardation, 2 had depression, and 2 had histories of substance abuse. Of the remaining 168 patients, 5 more were excluded (4 because their diagnoses were changed to organic brain syndrome [n = 1], drug-induced psychotic disorder [n = 1] and bipolar affective disorder [n = 2]; and 1 because of discontinuation antipsychotics by his / her doctor). Two other patients could not be contacted as they left Hong Kong immediately after discharge from hospital and were followed up overseas. One patient refused to be interviewed. There was no statistically significant difference in gender (p = 0.87), age (p = 0.35), and baseline BMI (p = 0.45) between the patients who participated (n = 160) and those who did not (n = 13).

The final sample consisted of 160 participants (90 female and 70 male) with a mean (SD, range) age of 30 (11, 14-59) years, and median (IQR) age being 28 (20-36) years. In all, 86% of the participants had achieved a secondary school education level or higher, 91% were living with their family, and 79% were unmarried (never married, separated, divorced and widowed). Their diagnoses at the time of the interview included schizophrenia, delusional disorder, unspecified psychosis, acute and transient psychotic disorder, and schizoaffective disorder. None of them had any medical problem or took non-psychiatric medications known to affect weight (eg steroids or other hormones).

Pattern of Antipsychotic Use

In all, 85 (53%) of the participants were taking second- generation antipsychotics at the time of interview. Initially, only 31 (19%) were on second-generation antipsychotics. The remaining 54 participants were initially started on first-generation antipsychotics and changed to second- generation antipsychotics within 6 months. Haloperidol, trifluoperazine, and flupenthixol accounted for 92% of the first-generation antipsychotics used at the time of interview by these participants, while risperidone, olanzapine, and quetiapine accounted for 74% of second-generation agents theytook. Besides, 98 participants were prescribed additional concomitant medications including anticholinergics, benzodiazepines, mood stabilisers, hypnotics, beta-blockers, and antidepressants for the management of their psychotic disorders.

Extent of Weight Gain of Participants after One Year

After the antipsychotic treatment, the participants had a mean (SD) BMI of 23 (4) kg/m2; 40% of the females and 47% of the males were overweight (Table 1). Before starting the treatment 1 year earlier, they had a mean (SD) BMI of 21 (4) kg/m2, at which time only 20% of the females and 33% of the males were overweight. In all, 123 participants had gained weight and the median gain being 4.8 (IQR, 0.7-9.0) kg after treatment with antipsychotics for 10 to 12 months. Twenty-two participants who were underweight before treatment had become normal in weight, while 30 who were either underweight or normal in weight before treatment had become overweight. In the remaining 71 participants, though they gained weight, their BMI classification remained unchanged. Besides, 62% of the females and 51% of the males experienced a more than 7% increase of their baseline body weight during the study period.

Relationship between Weight Gain and Antipsychotic Use

The difference in weight gain between genders was not statistically significant. The weight of the participants before starting antipsychotics was not related to the extent of weight gain after 10 to 12 months (Spearman’s correlation coefficient = 0.07, p = 0.36). A significantly higher magnitude of weight gain was associated with those taking second- generation antipsychotics (Table 2). There was no significant difference between the extent of weight gain experienced by those on second-generation antipsychotics from the start and those who had switched from first-generation to second-generation antipsychotics (p = 0.84). The extent of weight gain associated with individual antipsychotics is shown in Table 3. Although taking concomitant medications (including mood stabilisers) might also result in weight gain, a separate analysis yielded no such association with weight gain or being overweight.

Discussion

Being overweight is common in first-episode psychotic patients who have taken antipsychotics for about 1 year. In our study, a significant number of patients (of both genders) gained a significant amount of weight after such treatment. Rather than a percentage, we used the absolute magnitude of weight gain in the analysis of individual antipsychotics, so as to reduce the effect of the baseline body weight of the participants on weight gain, as the same amount of weight gain will appear less obvious in someone who is heavy at baseline.

Whilst the baseline BMI was calculated using body weight measured during the acute stage of the psychotic disorder, it is possible that it was lower than the usual weight of that individual due to the mental illness.4 Nevertheless, about half of our participants gained more than 7% in weight, which was compatible with results from an earlier study.3 Some of the participants in the current study even became overweight after their first year of treatment, in which case they were likely heavier than their usual weight.

According to existing research findings, both first- and second-generation antipsychotics are associated with weight gain.3 In this study, participants taking second-generation antipsychotics endured more severe weight gain. The difference in the extent of weight gain in patients receiving 1-year treatment with second-generation antipsychotics and those who were switched from first- to second-generation antipsychotics was not statistically significant. This may be because a large proportion of the participants who started the medication switched quite early so that most received second-generation antipsychotics in excess of 6 months before their body weight was measured. Risperidone, olanzapine, and quetiapine were the most frequently used second-generation agents, all of which were associated with moderate-to-severe weight gain.13 Among these, olanzapine treatment was associated with the greatest extent of weight gain.

From this study, it is evident that locally, first- generation antipsychotics were more commonly used to treat first-episode psychotic disorders. However, within 1 year, about one-third of the patients had switched to second- generation antipsychotics, resulting in similar numbers taking these 2 types of antipsychotics eventually.

Notably, weight gain ensued rather early in the course of treating psychotic disorders. Health care professionals managing first-episode psychotic patients should intervene early to address gain in weight. Baseline and regular monitoring of body weight and BMI should be determined at baseline and regularly monitored during follow-up, and performed together with other forms of metabolic screening (fasting glucose, lipid profiles). It may be difficult to avoid weight gain by choosing a specific antipsychotic, as most of them have similar effects on body weight. All patients should therefore be advised on appropriate measures to limit weight gain early in the course of their mental illness. Early behavioural interventions teaching strategies to enhance control over factors associated with antipsychotic-induced weight gain were reported to be effective in reducing antipsychotic treatment–induced weight gain in a first-episode psychosis cohort.14 The aim should be to prevent weight gain, and implementation of such a programme in this locality would definitely benefit patients. Moreover, it is likely to be more effective if patients can be advised on prevention before they gain weight, as opposed to offering curative advice after the event.

One limitation of this study was that factors known to result in weight gain (diet and exercise level) were not controlled for, and it may be unreasonable to conclude that antipsychotics were the only cause of weight gain. Second, not all antipsychotics were analysed for their liability to give rise to weight gain, and the dosages used were not taken into account. Lastly, only BMI data were used, whereas other anthropometric measurements (eg waist circumference, waist-hip ratio) were not available as they were not routinely collected at baseline. Nevertheless, this study is one of the few that provides local data on this issue in a relatively homogenous group of patients during the early stages of their psychotic disorder based on a reasonable sample size. The propensity of individual antipsychotics to induce weight gain in the local population is worthy of further study, and should be coupled with the study of interventions to overcome this problem. By such means it may be possible to reduce the metabolic side-effects associated with antipsychotics used in the treatment of mental illness.

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