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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 21  |  Issue : 1  |  Page : 4-11

A comparative study on metabolic syndrome in patients with schizophrenia treated using first-generation and second-generation antipsychotics


1 Assistant Professor, Department of Psychiatry, Apollo Medical College, Chittoor, Andhra Pradesh, India
2 Professor, Department of Psychiatry, Apollo Medical College, Chittoor, Andhra Pradesh, India
3 Junior Resident, Department of Anaesthesia, Apollo Medical College, Chittoor, Andhra Pradesh, India
4 Assistant Professor, Department of Pharmacology, Apollo Medical College, Chittoor, Andhra Pradesh, India

Date of Submission20-Jan-2020
Date of Decision10-Feb-2020
Date of Acceptance29-Mar-2020
Date of Web Publication03-Jul-2020

Correspondence Address:
Dr. Dinesh Panati
14-296, New Kayinikattu Street, Opposite Vegetable Market, Chittoor - 517 001, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AMH.AMH_4_20

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  Abstract 

Introduction: The prevalence of metabolic syndrome is more in patients with schizophrenia receiving first- and second-generation antipsychotics.
Aim and Objectives: The aim is to study the prevalence of metabolic syndrome in patients with schizophrenia treated with first-generation and second-generation antipsychotics and to compare the prevalence between two generations.
Materials and Methods: The study sample was obtained from the patients attending the outpatient clinic or admitted to the inpatient unit of the department of psychiatry at tertiary care unit. Patients with schizophrenia, 50 each on treatment with first- and second-generation antipsychotics for a minimum of 4 months were measured for fasting blood glucose, blood triglycerides, high-density lipoprotein, blood pressure, and waist circumference. Adult treatment panel diagnostic guidelines were used to diagnose metabolic syndrome.
Results: The prevalence of metabolic syndrome in first-generation group was (18%) and second-generation group was (40%). Comparison of the prevalence between the two groups showed Mann–Whitney value of −2.412*, which was statistically significant at P < 0.05. There was significant difference found in the chlorpromazine equivalent dosage of antipsychotics at P < 0.001. It signifies that though the second-generation group had received lesser amount of antipsychotic dose when compared to first-generation group, the prevalence of metabolic syndrome was more in the second-generation antipsychotic group.
Conclusion: Metabolic syndrome is seen in both the group of patients taking antipsychotics. In line with previous studies, our study also found that the prevalence of metabolic syndrome is more in patients taking second-generation antipsychotics.

Keywords: Antipsychotics, metabolic syndrome, schizophrenia


How to cite this article:
Panati D, Sudhakar T P, Swetha P, Sayeli VK. A comparative study on metabolic syndrome in patients with schizophrenia treated using first-generation and second-generation antipsychotics. Arch Ment Health 2020;21:4-11

How to cite this URL:
Panati D, Sudhakar T P, Swetha P, Sayeli VK. A comparative study on metabolic syndrome in patients with schizophrenia treated using first-generation and second-generation antipsychotics. Arch Ment Health [serial online] 2020 [cited 2020 Sep 20];21:4-11. Available from: http://www.amhonline.org/text.asp?2020/21/1/4/288919


  Introduction Top


Persons with schizophrenia have excess mortality in comparison with the general population. Approximately, their life expectancy is reduced to 20%.[1],[2] This excess mortality is due to physical illness; in particular, cardiovascular illness plays an important role.

In comparison with the general population, people with schizophrenia have two times more chances of death due to cardiovascular illness.[3],[4] In this context, the development of metabolic syndrome is a serious concern in patients with schizophrenia, which includes impaired glucose tolerance, obesity, hypertriglyceridemia, and hypertension. Patients with metabolic syndrome have high chances of myocardial infarction, coronary artery disease, and stroke.[5],[6] As of now, it is not clear regarding the cause of the metabolic syndrome, and it appears to be precipitated by multiple risk factors. Abdominal obesity and insulin resistance are the most critical factors contributing to metabolic syndrome.[7],[8] Studies say that varying degree of insulin resistance may be the common causative factor for the development of metabolic syndrome.[9],[10],[11] Some studies attribute metabolic syndrome in patients with schizophrenia may be due to a sedentary lifestyle, lack of exercise, abnormality of the hypothalamic–pituitary–adrenal axis, chronic stress, and smoking.

No study has conclusively indicated the etiology of metabolic syndrome in patients with schizophrenia, but it is believed that the disease itself, along with dietary habits, lifestyle, and antipsychotic medications, might play a role in the development of the metabolic syndrome.[12],[13],[14],[15]

Hence, the present study was focused on assessing the prevalence of metabolic syndrome in patients with schizophrenia who were being treated with both the classes of antipsychotic drugs.

Aim and objectives

The present study was aimed:

  1. To study the prevalence of metabolic syndrome in patients with schizophrenia treated with first-generation antipsychotic medication (FGAM) and second-generation antipsychotic medications (SGAMs)
  2. To compare the prevalence of metabolic syndrome, sociodemographic, and clinical profile of patients with schizophrenia treated with FGAM and SGAMs.



  Materials and Methods Top


The study was conducted in the department of psychiatry in our tertiary care institute.

Design

The study design used is a cross-sectional study design; all the assessments in this study were carried out only once.

Samples

The sample of patients were obtained from those attending the outpatient clinic or admitted to the inpatient unit of the department of psychiatry in our tertiary care institute. The sample comprises of 50 patients with schizophrenia on treatment with first-generation antipsychotics and 50 patients of schizophrenia on treatment with second-generation antipsychotics.

Sampling method

The random method of sampling was used to derive the sample.

Selection criteria

Inclusion criteria

  • Patients with Diagnostic and Statistical Manual of Mental Disorders-4th edition (DSM IV) diagnosis of schizophrenia as per the Structured Clinical Interview for DSM-IV Axis I Disorders-Clinical version
  • Males/females of age between 18 and 60 years
  • Patients should be prescribed antipsychotics for a minimum of 4 months.


Exclusion criteria

  • Patients having comorbid chronic medical illness
  • Patients with a history of comorbid substance abuse
  • Patients who were diagnosed as pregnant
  • Patients receiving medications other than antipsychotics and benzodiazepines
  • Patients who did not give consent to participate in the study.


Materials

Sociodemographic profile sheet

It has been developed for the purpose of the study. It consists of a semi-structured pro forma to record certain variables regarding the patient, such as age, sex, marital status, education, occupation, income, and place of residence.

Clinical profile sheet

This was used to collect data regarding duration of illness, duration of treatment, type of antipsychotic medication, and dosage of antipsychotic medication.

Structured Clinical Interview for Axis-1 Diagnostic and Statistical Manual of Mental Disorders-4th edition Disorders – Clinical Version [16]

This multi-modular scale was developed to obtain information, using a structured interview, for making the major axis-1 diagnoses according to the 4th edition of the DSM. Before covering the different modules (mania, psychosis, anxiety disorders, posttraumatic stress disorder, somatic disorder, eating disorder, and adjustment disorder), the clinician focuses on the main problem affecting the patient to get enough information to decide which module to use. This instrument is one of the most commonly utilized diagnostic instruments in psychiatric research. The format of the instrument is useful for clinicians as it allows for a comprehensive review of criteria utilized for making the major DSM-IV psychiatric diagnoses.

Adult Treatment Panel diagnostic guidelines for metabolic syndrome [17]

It is one of the most commonly used guidelines for the diagnosis of metabolic syndrome. It consists of the following five items with defining levels.

  1. Waist circumference (cm) - men >102 cm (>40 in)

    Women >88 cm (>35 in)
  2. High density lipoprotein (HDL) cholesterol (mg/dl) - men <40 mg/dl

    Women <50 mg/dl
  3. Triglycerides (mg/dl) - ≥150 mg/dl (≥1.7 mmol/L)
  4. Blood pressure (mmHg) - ≥130/85 mmHg
  5. Fasting glucose (mg/dl) - ≥110 mg/dl.


Patients having 3 or more of these items were considered to be having metabolic syndrome. The reliability and validity of these guidelines are well established.

Methodology

After getting the approval of the institutional ethics committee, the study was commenced. All patients fulfilling the selection criteria were approached and explained the purpose of the study. Written informed consent was obtained from all potential participants.

Patients who were receiving the FGAMs was inducted using computer-generated random numbers and assigned to Group I, and patients who were receiving the SGAMs was inducted by using computer-generated random numbers and assigned to Group II.

The sociodemographic and clinical profile of the samples from both the groups were obtained. The patients from both the groups were measured for their blood pressure, fasting blood glucose, fasting blood triglycerides, fasting HDL, and waist circumference (measured midway between the lowest rib and the iliac crest with the subjects standing). Then, the Adult Treatment Panel (ATP III) diagnostic guidelines were used to diagnose metabolic syndrome.

After assessing the prevalence of metabolic syndrome in each group, a comparison is made between two groups in the prevalence of metabolic syndrome and their sociodemographic and clinical profile.

Statistical analysis

The data were analyzed using “descriptive” and “inferential” statistics.

Descriptive statistics

Frequency counts were obtained for all discrete variables such as gender, marital status, education, occupation, socioeconomic class, and locality. Mean and standard deviation was computed for all continuous variables, for example, age, income, duration of illness, duration of treatment, dosage of antipsychotics, and for the items in ATPIII diagnostic guidelines.

Inferential statistics

  • The unpaired Student's t-test was used to compare the continuous variable in both the groups
  • The Chi-square test was used to compare the discrete variables in both the groups.



  Results Top


As shown in [Table 1], the majority of patients in the FGAM group were adult females, around the age of (32 ± 7) years who were educated till school, unmarried, unemployed, and came from urban background with lower socioeconomic class. Patients in the SGAM group were middle aged males, around the age of (34 ± 11) years who were educated till school, unmarried, unemployed and came from urban background with middle socioeconomic class.
Table 1: Sociodemographic variables of first-generation antipsychotic medications and second-generation antipsychotic medications groups

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As shown in [Table 2], patients in the FGAM group had 4.80 years of mean duration of illness, 3.48 years of mean duration of treatment, and the mean chlorpromazine equivalent dose of antipsychotics received in FGAM group was 499.24 mg/day. Patients in the SGAM group had 5.46 years of mean duration of illness, 4.14 years of mean duration of treatment, and the mean chlorpromazine equivalent dosage of antipsychotics received in SGAM group was 292.68 mg/day.
Table 2: Clinical profile of the patients in first-generation antipsychotic medications and second-generation antipsychotic medications groups

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As shown in [Table 3], patients in FGAM group had a waist circumference of 85 ± 14 cm, HDL cholesterol 40 ± 7 mg/dL, triglycerides 133 ± 67 mg/dL, systolic blood pressure 119 ± 12 mmHg, diastolic blood pressure 79 ± 9 mmHg, and fasting glucose 94 ± 18 mg/dL. Patients in SGAM group had waist circumference 89 ± 15 cm, HDL cholesterol 38 ± 6 mg/dL, triglycerides 133 ± 67 mg/dL, systolic blood pressure 119 ± 12 mmHg, diastolic blood pressure 79 ± 9 mmHg, and fasting glucose 96 ± 22 mg/dL.
Table 3: Metabolic syndrome criteria of the patient's in first-generation antipsychotic medications and second-generation antipsychotic medications groups

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As shown in [Table 4], the prevalence of metabolic syndrome in the FGAM group was (18%, shown in [Figure 1]) and in the SGAM group was (40%, shown in [Figure 2]). When compared to the FGAM group, the prevalence of metabolic syndrome was more in patients with the SGAM group.
Table 4: Prevalence of metabolic syndrome in first-generation antipsychotic medications and second-generation antipsychotic medications groups

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Figure 1: The prevalence of metabolic syndrome in first-generation antipsychotic medication group

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Figure 2: The prevalence of metabolic syndrome in second-generation antipsychotic medication group

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[Table 5] shows the comparison of statistical significance among the differences in sociodemographic variables between FGAM and SGAM groups [Table 1], although there were few differences in age, gender, socio-economic class, occupation, and income between two groups, the results were not statistically significant.
Table 5: Comparison of sociodemographic profile of patients in first-generation antipsychotic medications and second-generation antipsychotic medications groups

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[Table 6] compares the statistical significance among the differences in clinical profile between FGAM and SGAM groups [Table 2]. These results indicate that there was no statistically significant difference in the duration of illness and the duration of treatment between FGAM and SGAM groups. Mean chlorpromazine equivalent dose used by patients in FGAM group was 499.24, and in SGAM group was 292.68, this difference was found to be statistically significant.
Table 6: Comparison of clinical profile of patients in first-generation antipsychotic medications and second-generation antipsychotic medications groups

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As shown in [Table 7], there was a statistically significant difference seen in diastolic blood pressure between two groups as P < 0.005 level, and none of the other metabolic parameters were statistically significant between the two groups.
Table 7: Comparison of metabolic syndrome criteria of patients in first-generation antipsychotic medications and second-generation antipsychotic medications groups

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As shown in [Table 8], the difference in the prevalence of metabolic syndrome between the two groups [Table 4] was statistically significant as P < 0.05 level.
Table 8: Comparison of prevalence of metabolic syndrome in first-generation antipsychotic medications and second-generation antipsychotic medications groups

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  Discussion Top


The patient sample, though selected randomly, had much in common with earlier studies from India. Although the studies in the past have shown the prevalence of metabolic syndrome increases with age, especially above 40 years would be a significant risk factor in the general population.[18],[19] The risk of higher prevalence of metabolic syndrome with increasing age is more in patients with schizophrenia as compared to the general population,[18],[20] and this explains the mean age of patients of the current study is comparable to previous studies in studying the prevalence of metabolic syndrome in patients with schizophrenia. In our study, patients from both the groups were educated till school. Few studies associated with metabolic syndrome with higher education.[21],[22],[23] The prevalence of metabolic syndrome is more seen in married and also more among employed-as reported in previous studies,[21],[24] but patients from both the groups in our study were unmarried, unemployed. Majority of patients in both the groups were from urban background. A study reported the risk for developing metabolic syndrome is more with urban background, as reported by previous studies.[24] On comparison of sociodemographic profile between two groups no statistically significant results were obtained for sociodemographic parameters. A review from India has also found these sociodemographic variables were not consistently predicting the occurrence of metabolic syndrome, and results would vary across studies.[25] Hence, the sociodemographic factors that are observed in this study cannot be attributed to the development of metabolic syndrome, as there is no statistically significant difference between groups (FGAM and SGAM) in baseline.

Regarding clinical profile, the SGAM group has slightly more mean duration of illness and mean duration of the treatment than FGAM group. However, statistically there was no significant difference in duration of illness and duration of treatment between both the groups. However, statistically significant difference was found in the chlorpromazine equivalent dosage between the two groups (P < 0.001 level). Further, it was evident that patients who were in FGAM group received 70% higher chlorpromazine equivalent dosage, as compared to patients in SGAM group, but the occurrence of metabolic syndrome was twice as more in SGAM group. The similar clinical profile of samples has been reported from studies in the past, but only notable difference is most of our patients have received more chlorpromazine in FGAM group and more olanzapine in SGAM group.[26] Similar results have been found in CATIE study that patients on FGAM would have a lesser risk of developing the metabolic syndrome than SGAM.[27] It was further evident in a study from France with much larger samples of about 2270 patients.[28] Among the SGAM group virtually all patients who received clozapine has developed metabolic syndrome, about 60% of the patients who were on olanzapine has developed metabolic syndrome, and only 20% of the patients who received risperidone has developed metabolic syndrome. It shows the similar pattern which was documented by studies in the past that clozapine has high propensity to develop metabolic syndrome than other atypical antipsychotic medications, and olanzapine comes next then risperidone and then other atypical antipsychotic medications.[17],[27]

Regarding metabolic syndrome criteria, patients in FGAM group have more waist circumference, and it shows more weight gain which was probably due to the effect of chlorpromazine. The serum triglycerides and fasting blood glucose was marginally high. The HDL cholesterol level was marginally low, and both systolic and diastolic blood pressure was at a normal range. Studies in the past have found that 80% of patients treated with Chlorpromazine and thiothixene have been associated with significant weight gain.[28],[29] Another study has found nearly 25% of the patients who were treated for 1 year with chlorpromazine and other phenothiazines developed hyperglycemia and glycosuria.[30] The majority of the samples in the SGAM group have received olanzapine and clozapine which accounts for about 70%–80% and it explains significant weight gain in the SGAM group. In our study, clozapine was found to be associated with maximum hypertriglyceridemia followed by olanzapine and least with risperidone. Similar to our results, a study by Newcomer et al.[31] also found that fasting triglyceride levels is highest in the clozapine group, followed by the olanzapine group, while it was minimum in the risperidone group. The serum triglycerides and fasting blood glucose was also significantly increased, and HDL level was significantly lower than the normal in our sample. Olanzapine induced weight gain has also been associated with both elevated triglycerides and total cholesterol,[32],[33] and new-onset diabetes in patients treated with olanzapine.[34] This indicates that the risk of developing dyslipidemia was more in the SGAM group since HDL value is on lesser side which in turn is a risk factor for cardiac problems. The blood pressure was marginally elevated mainly on diastolic blood pressure. A study reported a prevalence of 29% for hypertension among 208 patients treated with antipsychotic medication.[35] Nevertheless, hypertension is one component of the metabolic syndrome which was not commonly associated with treatment with atypical antipsychotics. On comparison of metabolic syndrome criteria between two groups, a statistically significant difference was not found except for diastolic blood pressure. An Indian study compared typical and atypical antipsychotics on metabolic syndrome have reported raised blood pressure with risperidone.[36] However, we could not make any conclusion considering the limitation of our study in small sample size, and individual drugs have not compared.

The present study found the prevalence of metabolic syndrome of about 40% in the SGAM group and 20% in the FGAM group. Studies reported the prevalence of metabolic syndrome in patients with schizophrenia using drugs ranged from 14.7% to 68% across various studies.[16],[21] Similarly, studies have found a three-fold greater risk of developing metabolic syndrome in antipsychotic treated patients than the general population both at the community samples [27] and clinic samples.[37] From these results, it is evident that the prevalence of metabolic syndrome in our study is comparable to several previous studies. However, our sample size is limited with 50 patients in each group and hospital-based samples which may be a limitation. On comparison, a statistically significant difference was found in prevalence between two groups at the P < 0.05. It clearly showed that the prevalence of metabolic syndrome was high in the SGAM group than in the FGAM group. The multi-centric CATIE study reported no change of prevalence in the FGAM group over 3 months of follow-up, but a significant increase in the prevalence of metabolic syndrome in patients receiving the SGAM olanzapine.[38] Another study has reported three times higher prevalence of metabolic syndrome in patients treated with SGAs as compared with those on FGAs.[16] An Indian study has reported 11.6% prevalence in patients treated with SGAs, but none of the patients treated with FGAs developed metabolic syndrome.[36]

Even though atypical antipsychotics play an important role in the management of mental illness due to their efficacy; however, their use needs to be tempered with the knowledge that these medications can cause significant metabolic abnormalities such as metabolic syndrome in patients treated with these second-generation antipsychotics.[39],[40] The different atypical antipsychotic agents differ in their propensity to be associated with or even cause weight gain, diabetes mellitus or dyslipidemia when compared to conventional antipsychotics.[9] However, the risk of metabolic disorders in patients receiving FGAs could not be excluded as our study found 18% prevalence of metabolic syndrome in patients with FGAM.

This study used cross-sectional study design, which is inferior in establishing the cause-effect relationship compared to prospective cohort study design. Information about the activity of patients can act as important confounding factor while studying the prevalence of metabolic syndrome; this study has not captured information about physical activity. The mentioned factors are limitations of this study. Hence, in future, we recommend researchers to use prospective cohort study design and to capture information about physical activity while planning research to study the prevalence of metabolic syndrome with different types of antipsychotic drugs.


  Conclusion Top


This study found a higher prevalence of metabolic syndrome in both the groups, but the SGAM group has a greater prevalence of metabolic syndrome than the FGAM group, and the difference was statistically significant. In addition, it was also found that even lower dosage of SGAMs can cause a higher prevalence of metabolic syndrome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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