|Year : 2019 | Volume
| Issue : 1 | Page : 80-87
Comparison between typical and atypical antipsychotics according their effects on metabolism in schizophrenia patients
Wafeek M El Sheikh1, Afaf Z Rajab1, Amr S Shalaby1, Ahmed G Shaheen2
1 Department of Neurology and Psychiatry, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Neurology Medicine, Ministry of Health, Abbasia, Cairo Governorate, Egypt
|Date of Submission||20-Sep-2017|
|Date of Acceptance||11-Nov-2017|
|Date of Web Publication||17-Apr-2019|
Ahmed G Shaheen
Abbasia, Cairo Governorate
Source of Support: None, Conflict of Interest: None
This study aimed at assessing the risk factors causing metabolic dysregulations in schizophrenia patients on antipsychotics treatment.
Schizophrenia is a devastating mental illness with wide prevalence of high mortality and morbidity rates associated with high prevalence of metabolic syndrome that is characterized by hyperglycemia, obesity, dyslipidemia, and hypertension.
Patients and methods
This is a cross-sectional study conducted on 40 patients suffering from schizophrenia taking typical and atypical antipsychotics only (groups I and II, respectively). Detailed general medical, neurological history, examination, and psychiatric history were taken from patients.
Results revealed insignificant difference among groups regarding gender, age of onset ( first episode, last episode), duration of last period of treatment and total illness, blunted effect, poor rapport, emotional withdrawal, lack of spontaneity of conversation, and difficulty in abstract and stereotyping thinking; in contrast, the number of relapses were increased significantly in groups. However, insignificant differences were detected between baseline and after 6 months regarding blood elements, triglyceride, 2 h postprandial, and liver and kidney function.
Schizophrenia as a syndrome can by itself produce metabolic abnormalities. It is usually treated with first-generation and/or second-generation antipsychotics, which also can produce metabolic adverse events, but the second-generation antipsychotics can produce more frequently and severely. There were some dysregulations obvious only with typical antipsychotics. The lipid and glucose metabolism were significantly dysregulated after 6 months, but it did not reach the threshold of diagnosis of diabetes mellitus or pathological dyslipidemia. In addition, healthier lifestyle, low carbohydrate and fatty meal consumption, good premorbid metabolic parameters, and good choice of antipsychotic help in prognosis of metabolic status of schizophrenic patients.
Keywords: antipsychotic treatments, life quality, metabolism, neurological history, schizophrenia
|How to cite this article:|
El Sheikh WM, Rajab AZ, Shalaby AS, Shaheen AG. Comparison between typical and atypical antipsychotics according their effects on metabolism in schizophrenia patients. Menoufia Med J 2019;32:80-7
|How to cite this URL:|
El Sheikh WM, Rajab AZ, Shalaby AS, Shaheen AG. Comparison between typical and atypical antipsychotics according their effects on metabolism in schizophrenia patients. Menoufia Med J [serial online] 2019 [cited 2019 May 21];32:80-7. Available from: http://www.mmj.eg.net/text.asp?2019/32/1/80/256135
| Introduction|| |
Schizophrenia is an acute mental disease characterized by delusions, hallucinations, negative symptoms, and cognitive dysfunction . Schizophrenia is a complex syndrome of developmental defects caused by environmental and genetic factors , but the underlying pathological mechanisms are still largely unknown. Schizophrenia patients have a higher mortality rate than the rest of the population, with standardized mortality rates of about 2.0 . This leads to reduction in life span, estimated to ∼20 years, which is mainly caused by cardiovascular disease . An important cardiovascular disease risk factor is the metabolic syndrome (MS), which has an increased prevalence in schizophrenia .
Although a typical antipsychotic differs in the MS prevalence, the subtending effects of molecular mechanisms are not well understood, and the prospects of designing the propensity for MS with antipsychotics remain uncertain in the immediate future .
Atypical antipsychotics are the major advancements in the management of schizophrenia. The reevaluation risk/benefit assessments of the different atypical antipsychotics supplies a chance to improve the medication pattern. The best clinical trial evidence revealed that efficacy in a typical antipsychotic is very similar, but safety and tolerability differ significantly .
Atypical antipsychotics differ in their potential to cause metabolic disturbances including dyslipidemia, obesity, diabetes, and the MS; clozapine and olanzapine carry the highest risks, and atypical antipsychotics such as risperidone and quetiapine have lowest risks. If their independent mechanism of metabolic dysregulation, then parameters put in place to prevent metabolic disease in those taking antipsychotics will only be partially effective . Therefore, the aim of this study was to assess the risk factors causing metabolic dysregulations in schizophrenia patients on antipsychotic treatment.
| Patients and Methods|| |
A clinical comparative nonrandomized cross-sectional investigation was carried out on 40 patients divided into two groups: group I comprised 20 patients suffering from schizophrenia and taking typical antipsychotics only, and group II comprised 20 patients suffering from schizophrenia and taking a typical antipsychotic only.
All patients were from the inpatient wards of Abbassia Mental Health Hospital during the period from 1 July 2014 to 31 December 2014 (period of 6 months).
Written informed consent was recorded from participants. The consent form was developed based on the standard in Quality Improvement System in Ministry of Health and Population in Egypt. It was modified according the ethics committee in Faculty of Medicine, Menoufia University.
The site of the study was Abbassia Mental Hospital inpatient wards; there were many barriers that filtered the patient to meet all the inclusion criteria and the most effector on the sample size was to choose patients. These patients were divided into two groups, one of them receiving only one medication, which is first-generation antipsychotic haloperidol, and the other group of patients receiving only one medication, which is second-generation antipsychotic (resperidole).
Inclusion criteria were male and female patients aged 18–60 years old, duration of illness for at least 1 year, and compliant on antipsychotic treatment for at least 1 month.
Exclusion criteria were the presence of any comorbid neurological or medical debilitating diseases such as severe kidney or liver disease, morbid obesity with BMI more than 30 before initialization of treatment, the presence of comorbid psychiatric/substance abuse disorders, history of hormonal abnormality – for example, thyroid dysfunction, lipid dysregulation, or inborn error of metabolism before initial treatment – patient who is refusing (or guardian) to give consent, noncompliance, and so on.
Detailed general medical, neurological history and examination, psychiatric history was taking from all patients, and assessed by semistructured interview sheet of Abbassia Hospital which contains descriptive variables: sociodemographic data, history of present illness, family history, school record and level of education, work records, marital history, and psychiatric examination, and diagnosis was done according to Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM 5) , full laboratory tests, for example, complete blood count, lipid profile, glucose, liver function, renal function, and BMI .
Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM 5) diagnostic criteria for schizophrenia
- Two (or more) of the following, each present for a significant proportion of time during a 1-month period (or less if successfully treated). At least one of these must be (1), (2), or (3): delusions, hallucinations, disorganized speech (e.g., frequent derailment or incoherence), grossly disorganized or catatonic behavior, and negative symptoms (i.e., diminished emotional expression or avolition)
- For a significant proportion of the time since the onset of the disturbance, level of functioning in one or more major areas, such as work, interpersonal relationships, or self-care, is markedly below the level achieved before the onset (or when the onset is in childhood or adolescence, there is failure to achieve expected level of interpersonal, academic, or occupational functioning)
- Continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least 1 month of symptoms (or less, if successfully treated) that meet Criterion A (i.e., active-phase symptoms) and may include periods of prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbances may be manifested by only negative symptoms or by two or more symptoms listed in Criterion A present in an attenuated form (e.g., odd beliefs, unusual perceptual experiences)
- Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out because either (i) no major depressive or manic episodes have occurred concurrently with the active-phase symptoms or (ii) if mood episodes have occurred during active-phase symptoms they have been present for a minority of the total duration of the active and residual periods of the illness
- The disturbance is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition
- If there is a history of autism spectrum disorder or a communication disorder of childhood onset, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations, in addition to the other required symptoms of schizophrenia, are also present for at least 1 month (or less if successfully treated).
Routine laboratory investigations include the following:
- Complete blood count: using Sysmex KX-21 automatized hematology analyzer (Sysmex Corporation, Kobe, Japan)
- Kidney functions: using the open system autoanalyzer synchron CX5 (Beckman Coulter Inc., Fullerton, California, USA)
- Liver function test: measured using a bio chromatic (405–510 nm) rate technique (Life Technologies Corporation, USA)
- Lipid profile: using the open system autoanalyzer synchron CX5 (Beckman Coulter Inc.)
- Random blood sugar: using Sysmex KX-21 automatized hematology analyzer (Sysmex Corporation).
The positive scale consists of seven items measuring symptoms that are super-added to Normal Mental Status, which include delusions, conceptual disorganization, grandiosity, hallucinations, hyperactivity, suspiciousness/persecution, and hostility. The negative scale measures include blunted affect, poor rapport, emotional withdrawal passive/apathetic social withdrawal, lack of spontaneity, flow of conversation, and stereotyped thinking .
The General Psychopathology Scale includes summation of the remaining 16 items: somatic concern, anxiety, guilt feelings, tension, mannerisms, posturing, depression, motor retardation, uncooperativeness, disorientation, poor attention, lack of insight and judgment, poor impulse control, disturbance of volition preoccupation, and active social avoidance. Positive and Negative Syndrome Scale is a reliable tool with an inter-rater reliability ranging from 0.83 to 0.87 (P < 0.001) .
Results were tabulated and statistically analyzed by using personal computer using Microsoft Excel 2016 and SPSS, version 21 (SPSS Inc., Chicago, Illinois, USA), percentage, mean, and SD. Analytical tests include χ2-test, Student's t-test, Mann–Whitney test, and correlation coefficient test. A value of P less than 0.05 was indicated to be statistically significant.
| Results|| |
In this study, there was insignificant difference among groups regarding demographic data (age, sex), age of onset ( first episode), age of last episode, and duration of last period of treatment and of total illness. However, a significant increase between them regarding the number of relapses was found. In comparison between baseline and after 6 months, there was a significant difference between groups regarding BMI at baseline and after 6 months. The mean at baseline (23.44 ± 2.42) in initial visit increased to 26.26 ± 2.41 after 6 months in group I and the mean of 27.70 ± 2.08 in the initial visit increased to 30.87 ± 2.08 after 6 months in group II [Table 1].
Results showed that insignificant differences were detected between baseline and after 6 months regarding blood elements in the studied groups. However, there was an insignificant difference between groups regarding hemoglobin, white blood cells (WBCs), and platelet, whereas there was a significant increase between groups regarding WBCs at baseline and after 6 months.
Regarding lipid profile, there was insignificant difference between baseline and after 6 months regarding triglycerides (TGs) but a significant increase in high-density lipoprotein (HDL) and cholesterol in groups. Both groups showed changes in the blood concentration of plasma TGs. The mean at baseline (159.55 ± 34.97) in the first visit increased to 163.88 ± 34.55 after 6 months in group I and the mean of 159.93 ± 35.09 in the first visit increased to 185.65 ± 34.0 after 6 months in group II. Both groups showed changes in the blood concentration of HDL and blood concentration of total cholesterol. The mean HDL at baseline of 58.43 ± 7.61 in the first visit dropped to 51.52 ± 7.70 after 6 months in group I, and 56.58 ± 7.37 in the first visit dropped to 49.58 ± 7.47 after 6 months in group II. The mean total cholesterol at baseline of 180.35 ± 13.86 in the first visit increased to 196.60 ± 14.24 after 6 months in group I, and 188.13 ± 18.5 in the first visit increased to 191.75 ± 33.21 after 6 months in group II. Comparison between groups shows nonsignificant difference regarding HDL, TGs, and cholesterol at baseline but significant increase of TGs after 6 months [Table 2].
|Table 2: Comparison between groups regarding blood elements and lipid profile|
Click here to view
Regarding blood sugar, there was a significant increase between baseline and after 6 months regarding fasting blood glucose (FBG) in two groups, but insignificant difference regarding 2 h postprandial in two groups. Both groups showed changes in fasting blood sugar and 2-h postprandial blood sugar. Mean fasting blood sugar at baseline was 84.68 ± 6.58 in the first visit, which increased to 92.45 ± 7.20 after 6 months in group I, and was 86.01 ± 9.09 in the first visit, which increased to 95.92 ± 12.37 after 6 months in group II. The mean 2-h postprandial blood sugar at baseline of 148.14 ± 22.48 in the first visit increased to 150.58 ± 13.45 after 6 months in group I, and 142.0 ± 24.58 in the first visit increased to 160.46 ± 17.78 after 6 months in group II. Comparison between groups shows nonsignificant difference among groups regarding FBG and 2 h postprandial at baseline but a significant increase after 6 months [Table 3].
|Table 3: Comparison between groups regarding blood sugar, liver, and kidney functions|
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Regarding liver function, there was no significant difference among baseline and after 6 months in the two groups. The mean serum glutamic pyruvic transaminase (SGPT) at baseline was 20.43 ± 11.43 in the first visit, which increased to 21.04 ± 11.88 after 6 months in group I, and 29.0 ± 12.49 in the first visit increased to 32.77 ± 14.11 after 6 months in group II. The mean serum glutamic oxaloacetic transaminase (SGOT) at baseline of 19.14 ± 4.53 in the first visit dropped to 17.61 ± 4.17 after 6 months in group I, and 16.67 ± 14.17 in the first visit dropped to 14.17 ± 5.18 after 6 months in group II [Table 3]. In addition, the mean albumin at baseline of 4.04 ± 1.42 in the first visit dropped to 3.72 ± 1.31 after 6 months in group I, and 4.27 ± 0.81 in the first visit dropped to 3.89 ± 0.74 after 6 months in group II. Moreover, the mean bilirubin at baseline of 0.47 ± 0.18 in the first visit dropped to 0.43 ± 0.17 after 6 months in group I, and 0.53 ± 0.12 in the first visit dropped to 0.48 ± 0.11 after 6 months in group II. There was insignificant difference between groups regarding albumin, bilirubin, SGPT, and SGOT after 6 months, but there was a significant increase in SGOT at baseline and a decrease in SGOT at baseline [Table 3].
Concerning renal function, there was an insignificant difference between baseline and after 6 months in the two groups. Both groups showed changes in renal function. The mean blood urea at baseline of 27.14 ± 10.11 in the first visit increased to 29.85 ± 11.12 after 6 months in group I and 24.67 ± 2.52 in the first visit increased to 26.04 ± 2.77 after 6 months in group II. However, regarding serum creatinine, the mean at baseline of 0.73 ± 0.08 in the first visit increased to 0.80 ± 0.09 after 6 months in group I and the mean of 0.67 ± 0.12 in the first visit increased to 0.74 ± 0.13 after 6 months in group II [Table 3].
| Discussion|| |
In this study, an insignificant difference was found between typical and atypical antipsychotic groups regarding demographic data (age, sex), age of onset ( first episode), age of last episode, duration of last period of treatment, illness, red blood cells, hemoglobin, and platelet. In contrast, there was a significant difference between groups regarding the number of relapses and WBCs at baseline and after 6 months. These results agreed with those of Kaneda et al. , who found insignificant differences between typical and atypical antipsychotics regarding age, duration of illness, and dose of typical antipsychotic medication; Brief Psychiatric Rating Scale and Energy Performance Score (EPS) were revealed by analysis of variance followed by post-hoc comparisons. In addition, Solia et al.  found insignificant differences among studied groups regarding sex (P = 0.45), age (0.192), schizophrenia spectrum (P = 0.583), age of onset (P = 0.804), current typical antipsychotic treatment (P = 0.110), current treatment with anxiolytics (P = 1.00), physical activity (P = 0.069), and hospitalization duration (P = 0.866). Moreover, Kang and Lee  found insignificant differences among groups regarding age, BMI, use of antidepressants, or severity of psychiatric symptoms as determined by the Clinical Global Impression – Severity scale. In addition, Gupta et al.  found a significant weight gain in patients taking atypical antipsychotics such as quetiapine, olanzapine, clozapine, and risperidone.
In this study, insignificant differences were found between baseline and after 6 months regarding blood elements, TGs, 2 h postprandial, liver function, and renal function in two groups. In contrast, there was a significant increase in HDL, cholesterol, FBG, and BMI in groups and a significant increase in lipid profile in group II. This was confirmed by Wei et al. , who found that BMI was associated with the presence of MS. About 11% of normal-weight patients met the criteria of MS, whereas over one half of overweight/obese patients met the criteria. A strong relation between MS and obesity was also found in the general population survey. Although BMI serves as a useful marker of obesity, waist circumference is a better anthropometric predictor of metabolic dysregulations than BMI . Solberg et al.  found that TGs were significantly higher among patients with schizophrenia than in the healthy group (P < 0.001). HDL cholesterol was significantly lower among patients than in the healthy group (P < 0.001). Cholesterol did not differ significantly among groups (P = 0.21). There was an insignificant difference in serum lipid levels between participants taking and not taking fatty acid supplements, as well as among patients with schizophrenia. Serum TG level was lower among the 11 patients with schizoaffective disorder than patients with schizophrenia (1.17 vs. 2.00, P = 0.006). On the other hand, our results disagree with those of Al-Thanoon and Mahmood , who found that chlorpromazine and olanzapine produce no effects on body weight, BMI, and waist circumference, whereas they found that olanzapine produces a significant increase in serum glucose concentration and chlorpromazine produces a decreased effect. Both drugs raise characters of lipid profile.
In this study, both groups showed changes in the blood concentration of plasma TGs, total cholesterol, fasting blood sugar, 2-h postprandial blood sugar, HDL, SGPT, serum urea and creatinine, and BMI. Their means at baseline in the first visit increased after 6 months in groups I and II compared with concentration of HDL, SGOT, albumin, and bilirubin, whose means at baseline in the first visit dropped after 6 months in groups I and II. Perez-Iglesias et al.  showed similar results regarding low-density lipoprotein (LDL), total cholesterol, body weight, and BMI, but not matching our results regarding FBS and significant changes with TG only with olanzapine group. In addition, Wysokinskia et al.  found that mean of TGA, TC, HDL, LDL, and FPG levels in schizophrenia were 139.9, 188.5, 45.3, 115.4, and 95.9 mg/dl, respectively, and there were significant differences (P < 0.001) between schizophrenia groups regarding previous characters, except FPG levels, which was not significantly different (P = 0.08) in schizophrenia groups. Monir  showed a significant change in metabolic profile as early as 6 weeks from the baseline assessment, and was still positive after 12 weeks. Changes were significantly constantly in LDL, HDL, total cholesterol, TG, FBS, body weight, and BMI, which was evident in both groups typical and atypical, whereas van Proeyen et al.  found that fasting glucose levels did not change significantly, but there was no significant change in HDL and LDLs, or total cholesterol. The difference in lipid profile in this study and our study can be explained by the limited number of patients and use of single drug (olanzapine), despite that findings of increased insulin and increased TG are predictors of insulin resistance and the increased possibility of hyperglycemia.
| Conclusion|| |
Schizophrenia as a syndrome can by itself produce metabolic abnormalities. It is usually treated with first-generation and/or second-generation antipsychotics, which also can produce metabolic adverse events, but the second-generation antipsychotics can produce more frequently and severely. There were some dysregulations obvious only with typical antipsychotics. The lipid and glucose metabolism were significantly dysregulated after 6 months, but it did not reach the threshold of diagnosis of diabetes mellitus or pathological dyslipidemia. In addition, the healthier lifestyle, low carbohydrate consumption, fatty meals, good premorbid metabolic parameters, and good choice of antipsychotics help in prognosis of metabolic status of schizophrenic patients.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]