Hong Kong J Psychiatry 2008;18:23-7

ORIGINAL ARTICLE

Relationships between Antipsychotic Medication and Anthropometric Measurements in Patients with Schizophrenia Attending a Psychiatric Clinic in Malaysia

透過一間馬來西亞精神科診所的精神分裂症患者，檢視抗精神病療程與人體測量數據的關係

O Ainsah, R Salmi, CB Osman, AS Shamsul

Dr O Ainsah, MD, MMed (Psy), PhD, Department of Psychiatry, Faculty of Medicine, Hospital Universiti Kebangsaan Malaysia, Jalan Tenteram, 5600, Ceras, Kuala Lumpur, Malaysia.
Dr R Salmi, MD, MMed (Psy), Unit of Psychiatry, Universiti of Technology Mara, Shah Alam, Selangor, Malaysia.
Dr CB Osman, MD, MMed (Psy), Department of Psychiatry, Faculty of Medicine, Hospital Universiti Kebangsaan Malaysia, Jalan Tenteram, 5600, Ceras, Kuala Lumpur, Malaysia.
Dr AS Shamsul, MD, McommHealth (Epidemiology and Statistics), Department of Community Health, Faculty of Medicine, Hospital Universiti Kebangsaan Malaysia, Jalan Tenteram, 5600, Ceras, Kuala Lumpur, Malaysia.

Address for correspondence: Dr Omar Ainsah, Department of Psychiatry, Faculty of Medicine, Hospital Universiti Kebangsaan Malaysia, Jalan Tenteram, 5600, Ceras, Kuala Lumpur, Malaysia.
Tel: 03 9170578; Fax: 03 91737841; E-mail: ainsah@mail.hukm.ukm.my

Submitted: 30 July 2007; Accepted: 23 October 2007

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Introduction

Antipsychotic medications, particularly new generation atypical antipsychotic medications, are reportedly associated with higher risks of developing obesity.¹ New generation antipsychotic medications cause weight gain, adversely affecting glucose and lipid metabolism and putting patients at greater risk of developing obesity-related diseases.^1,2

It has been reported that weight gain affects compliance and causes relapses.^3-5 A review suggests that 40 to 80% of patients taking antipsychotic medications experience weight gain exceeding their ideal body weight by 20% or greater.⁶ Patients with schizophrenia taking conventional antipsychotics have been found to have more than 3 times as much intra-abdominal fat as controls matched for age, gender, and lifestyle.⁷ Among conventional antipsychotics, the weight gain associated with chlorpromazine and thioridazine has been well described, whereas the high- potency typical antipsychotic medications, such as haloperidol and fluphenazine, have had fewer weight- inducing effects reported.^8,9

This study aimed to examine the relationship between obesity and antipsychotic prescription patterns, including the types of antipsychotics prescribed, concomitant use of depot conventional antipsychotics, antidepressants and the duration of the current antipsychotic treatments being used by patients with schizophrenia.

Methods

Subjects

This study was conducted at the Psychiatric Outpatient Clinic, Hospital Universiti Kebangsaan Malaysia (HUKM). Participants’ diagnoses were reviewed by researchers (postgraduate psychiatric trainees and consultant psychiatrists) using the Structured Clinical Interview for DSM-IV Axis I Disorder.¹⁰ Inclusion criteria required that patients were able to give informed consent, were aged between 18 and 60 years, had been on antipsychotics for at least 1 month and had adequate command and understanding of either Malay or English and were literate in one or other language. Patients who were intellectually subnormal or had marked cognitive deficits, dementia, substance dependence, medical conditions such as Cushing’s disease, polycystic ovarian syndrome, hypothyroidism, severe oedema, pregnancy, or were receiving other medication that could contribute significantly to weight change, e.g. steroids, insulin, orlistat, sibutramine, duromine, oestrogen and had a body mass index (BMI) of < 18.5 kg/m² were excluded.

Those who were able to give consent, fulfilled the study selection criteria, and met the diagnostic criteria for schizophrenia were enrolled in this study. Demographic data and drug factors i.e. types of antipsychotic medication, concomitant depot medication, antidepressants, and duration of current treatment, were obtained using a clinical interview, medical record / case notes and the HUKM E- prescribing system (an electronic system with information on drugs prescription, appointments, and doctors in-charge). Patients’ body weights, heights, and waist circumferences were also measured.

Measurements

The BMI and waist circumference (WC) were classified according to the Malaysian Practice Guideline in Management of Obesity (BMI classification for Asian populations proposed by the World Health Organization, 2004¹¹—BMI: 18.5-22.9 kg/m² as normal weight, 23- 27.4 kg/m² as overweight, > 27.5 kg/m² as obese; WC: > 90 cm in males as high, > 80 cm in females as high). This classification was adopted because Asian populations are at higher risk of developing health problems at a lower BMI and have a higher body fat percentage than non-Asians.^11,12 These BMI classifications are based on measurements proposed by analysing measurements of Asian populations as Asians are at higher risk of developing obesity-related problems.^12,13

Informed consent was obtained after the research procedures were fully explained to the subjects. Ethics approval was obtained from the Ethics Committee, HUKM.

Statistical Analysis

Antipsychotic medication prescribing patterns, social demographic profiles, and anthropometric measurements were analysed. The Chi-square test was used to compare the difference between groups of categorical data, while the parametric data were analysed using the t test (for normally distributed data) and Mann Whitney U test (for non-normally distributed data) to calculate the difference between two groups. Analysis of variance test was used to examine the difference among 3 groups of variables with normally distributed continuous data. Pearson correlation and Spearman correlation were used to examine the correlation between two continuous variables which were normally and non-normally distributed. Statistical significance was set at the p value of ≤ 0.05.

Results

Of 174 potential subjects identified, 97 (73.3%) fulfilled the inclusion criteria and participated in this study. Their socio- demographic data are shown in Table 1.

 Antipsychotic Medication Patterns

Sixty three (64.9%) patients received atypical antipsychotics and 34 (35.1%) received conventional antipsychotics (Table 2). Twenty (20.6%) patients received concomitant conventional depot antipsychotics while 23 (23.7%) received concomitant antidepressants. None had concomitant mood-stabilising treatments and none received more than 1 antipsychotic medication. Other medications prescribed concomitantly included anti-cholinergics (n = 30, 30.9%), benzodiazepines or zolpidem (n = 21, 21.6%). Twenty four (24.7%) male patients and 39 (40.2%) female patients received atypical antipsychotics, whilst 20 (20.6%) male patients and 14 (14.4%) female patients received conventional antipsychotics (Table 2). There was no significance gender difference (Chi-square = 3.83, p = 0.50) in the types of antipsychotic medications prescribed. The median age for subjects treated with typical antipsychotics (n = 34) was 34.29 (SD, 9.3) years while that for patients treated with atypical antipsychotics (n = 63) was 32.95 (SD, 8.99) years but this difference was not significant (t = 0.69, p = 0.49).

Antipsychotic Medication and Anthropometric Measurements

Of the 63 patients taking atypical antipsychotic medication, 45 (71.4%) were either overweight or obese, and 38 (60.3%) had high WC. Similar results were found in those receiving conventional antipsychotics; 27 (79.4%) respondents were either overweight or obese, and 24 (70.6%) had high WC. The mean BMI for patients taking atypical and conventional antipsychotics were 25.7 (SD, 0.3) kg/m² and 27.2 (SD, 0.2) kg/m² respectively, however the difference was not significant (t = 1.34, p = 0.18). The mean WC for patients taking atypical and conventional antipsychotic medication were 88.2 (SD, 11.9) cm and 93.4 (SD, 11.9) cm respectively. There was a significant difference between these two means (t = 2.04, p = 0.04) [Table 3]. Twenty three (23.7%) respondents were receiving concomitant antidepressants. There was no significant difference between the WC and BMI of those receiving concomitant antidepressants and those not receiving concomitant antidepressants (WC: χ² = 0.00, p = 0.97, BMI: χ² = 1.31, p = 0.25).

Post-hoc analysis of the duration of use of each type of antipsychotic and its correlation with WC showed that the WC of patients receiving olanzapine (n = 23, r^s = 0.45, p = 0.03) was positively related to the duration of use, while the duration of use of clozapine (n = 10, r^s = –0.66, p = 0.04) was inversely related to WC (Table 4). There were 20 (20.6%) patients being treated with combinations of depot antipsychotics. Seventeen (85%) had high WC. There was a significant difference between the WC of those being treated with a combination of depot antipsychotics and those not receiving this treatment (χ² = 4.86, p = 0.03) but this effect was not dose-related. The dosage of depot flupenthixol decanoate prescribed did not correlate with BMI (p = 0.48, r^s= 0.18) and WC (p = 0.51, r^s = 0.17). Only two respondents received depot fluphenazine decanoate.

Discussion

Obesity is highly prevalent among patients with schizophrenia. This issue needs to be addressed seriously. The different types of antipsychotic medication being prescribed appear to have different effects on WC. Patients treated with atypical antipsychotics, clozapine and olanzapine, had high WC. This may increase their risk of developing obesity and obesity-related physical illnesses.^13,14 Different drugs may cause different degrees of weight gain. Atypical antipsychotic medications, such as olanzapine and clozaril, are associated with a high risk of acquiring metabolic syndrome.¹⁵ It would be better to avoid drugs which induce marked weight gain unless there is no other choice or to only use them to treat patients with low body weights as this side-effect may be helpful.

Patients being given concomitant depot antipsychotics had significantly higher WC, suggesting that conventional depot antipsychotics are associated with obesity. A survey of 226 patients attending depot neuroleptic clinics found the prevalence of obesity in this group was 4 times higher than

that of the general population.¹⁶ The duration of the index drug treatment correlated with WC positively for olanzapine and inversely with clozapine, suggesting that patients being treated with clozapine may gain weight initially but that their weight will be reduced with time. Olanzapine induced weight gain but due to the short duration of olanzapine treatment in the patients in this study, it is difficult to comment on its long-term effects.

In this study, BMI and WC were classified according to Malaysian Practice Guideline in Management of Obesity (BMI classification for Asian populations proposed by the World Health Organization, 2004).¹¹ This classification is adopted as Asian populations are at higher risk of developing health problems at lower BMI and have higher body fat percentage than non-Asians.^17,18 This classification is very helpful clinically for detecting obesity at an early stage, enabling maximisation of health outcomes for schizophrenic patients.

Obesity is highly prevalent among patients with schizophrenia, increasing their risk of developing obesity- related physical illnesses. As different antipsychotic medications may affect body weight differently, the choice of antipsychotics should be tailored according to the needs of individual patients. Baseline and regular monitoring of body weight, BMI, WC, and metabolic measures, i.e. fasting blood sugar, lipid profile, should be considered routine investigations especially among patients being treated with atypical drugs like olanzapine and clozapine. Psycho-education, emphasising a healthy lifestyle including an exercise programme, should be given to every patient. Weight reduction programmes should be included as part of the treatment for schizophrenic patients with obesity. A case-controlled prospective study over a longer period of treatment would be helpful for examining the impact of antipsychotic treatments on patients’ anthropometric measurements and for controlling other variables.

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