The Effects on Metabolic Syndrome Parameters of Atypical Antipsychotic Agents in Schizophrenics Patients : 3 Years Retrospective Follow Up

Ha Hyun Bae; Hai Joo Yoon; Eun Kyung Park; Jong Il Lee

doi:10.16946/kjsr.2017.20.1.5

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Bae, Yoon, Park, and Lee: The Effects on Metabolic Syndrome Parameters of Atypical Antipsychotic Agents in Schizophrenics Patients : 3 Years Retrospective Follow Up

Original Article

Korean J Schizophr Res 2017;20(1):5-16.

Published online: 17 January 2017

DOI: https://doi.org/10.16946/kjsr.2017.20.1.5

The Effects on Metabolic Syndrome Parameters of Atypical Antipsychotic Agents in Schizophrenics Patients : 3 Years Retrospective Follow Up

Ha Hyun Bae, MD¹, Hai Joo Yoon, MA², Eun Kyung Park, RN³, Jong Il Lee, MD, PhD¹

¹Department of Psychiatry, National Center for Mental Health, Seoul, Korea

²Department of Clinical Psychology, National Center for Mental Health, Seoul, Korea

³Department of Clinical Trial Center, Samsung Medical Center, Seoul, Korea

Address for correspondence: Jong Il Lee, Department of Social Psych try and Rehabilitation, National Center for Mental Health, 127 Youngmas ro, Gwangjin-gu, Seoul 04933, Korea Tel: 02-2204-0120, Fax: 02-2204-0385 E-mail: lji7542@naver.com

Revised 2 January 20176 April 2017 Accepted 22 May 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objectives

Pharmacological treatment is critical on relapse prevention in patients with schizophrenia. However, atypical anti-psychotic agents are known to cause weight gain more than typical agents despite their various effects. In addition, they are known to affect blood sugar, blood pressure, cholesterol, cardiac function, and sexual function. This study was designed to ex-amine the effects on metabolic parameters when schizophrenic patients have been taken atypical antipsychotic agents.

Methods

This was a trial in 137 patients with DSM-IV-TR schizophrenia who were admitted or treated in mental hospital. An-thropometric measurement and blood testing were conducted at baseline, 12 month, 36 month, and sociodemographic and treatment history were collected from medical records. We conducted height, weight, waist circumference, blood pressure, FBS, total cholesterol, HDL, triglyceride, and QTc interval. Metabolic syndrome was diagnosed by ATPIIIa criteria.

Results

Aripiprazole showed the significant difference in the impact on weight, blood pressure, waist circumference, total cholesterol, HDL, triglyceride than paliperidone and olanzapine at 1-year and 3-year period. Olanzapine showed the significant increase of weight and triglyceride than paliperidone at 3-year period. The prevalence of metabolic syndrome increased in paliperidone at 1-year and in olanzapine at 3-year period compared to aripiprazole significantly.

Conclusion

We concluded that aripiprazole has less impact on the abdominal obesity, FBS, blood pressure, and cholesterol than paliperidone and olanzapine. Olanzapine showed the increase of longterm metabolic risk than other agents. There was needed the routine screening and multidisciplinary management of medical problems in schizophrenic patients for the prevention of metabolic syndrome.

Keywords: Schizophrenia, Atypical antipsychotics, Metabolic syndrome

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Table 1.

Characteristics of demographic and biochemical parametric markers of total subjects

Subjects	Paliperidone group	Olanzapine group	Aripiprazole group	p value
Variables	(Mean± SD)	(Mean± SD)	(Mean± SD)	p value
Total subject (N)	49	20	68
Male (%)	35(71.4%)	17(85.0%)	44(64.7%)
Female (%)	14(28.6%)	3(15.0%)	24(35.3%)
Age (year)	40.7±8.7	37.1±9.7	36.2±9.6	.342^a .036^b .927^c
Education (year)	12.5±2.7	12.4±2.4	12.6±2.7	.968^a .993^b .940^c
Duration of illness (year)	15.9±7.4	14.3±6.1	14.6±7.8	.625^a .673^b .986^c
CGI-S	4.96±0.82	5.35±0.75	4.19±0.76	.170^a .000^b .000^c
Weight (kg)	70.9±15.5	71.2±14.0	68.0±15.4	.996^a .609^b .713^c
BMI (kg/m²)	25.3±5.2	24.4±4.2	24.4±4.0	.745^a .559^b 1.000^c
Systolic pressure (mm Hg)	117.2±10.5	118.5±11.3	121.4±13.7	.920^a .190^b .653^c
Diastolic pressure mm Hg)	75.8±8.7	76.3±6.5	78.6±10.5	.982^a .271^b .609^c
Waist (cm)	88.0±12.2	87.4±11.7	86.8±11.6	.980^a .860^b .981^c
FBS (mg/dL)	88.6±17.1	91.6±26.6	90.7±23.5	.882^a .887^b .987^c
Total cholesterol (mg/dL)	175.1±35.8	187.5±45.1	188.1±38.8	.486^a .205^b .998^c
HDL (mg/dL)	46.6±11.8	46.1±10.5	45.1±11.7	.985^a .967^b 1.000^c
Triglyceride (mg/dL)	109.8±60.0	129.5±97.8	136.4±86.5	.652^a .210^b .943^c
QTc interval (ms)	417.3±23.7	409.2±23.2	415.7±21.4	.465^a .945^b .581^c

^a : comparison between PAL & OLA group,

^b : comparison between PAL & ARI groups,

^c : comparison between OLA & ARI group. CGI-S : Clinical Global Impression-Severity, BMI : Body Mass Index, FBS : Fasting Blood Sugar, HDL : High-Density Lipoprotein

Table 2.

The change of biochemical metabolic parameters for 36 months

Variables	Subjects	PAL group	OLA group	ARI group	P1	P2
Variables		(Mean± SD)	(Mean± SD)	(Mean± SD)	P1	P2
Weight (kg)	Baseline	70.9±15.5	71.2±14.0	68.0±15.4	1.000^a	.031^a
	12 montd	76.1±16.1	75.9±13.5	69.1±13.5	.007^b	.122^b
	36 montd	76.1±18.2	82.6±16.0	70.2±13.3	.047^c	.000^c
BMI (kg/m²)	Baseline	25.3±5.2	24.4±4.2	24.4±4.0	1.000^a	.039^a
	12 montd	27.2±5.5	25.8±3.6	24.5±4.1	.000^b	.014^b
	36 montd	27.1±6.1	28.2±4.5	24.7±4.2	.020^c	.000^c
Systolic pressure (mm Hg)	Baseline	117.2±10.5	118.5±11.3	121.4±13.7	.353^a	.153^a
	12 montd	119.7±10.8	124.2±9.7	117.6±11.5	.243^b	.081^b
	36 montd	122.2±14.2	129.2±13.0	119.1±12.9	.010^c	.001^c
Diastolic pressure (mm Hg)	Baseline	75.8±8.7	76.3±6.5	78.6±10.5	.893^a	.368^a
	12 montd	76.8±8.8	79.4±5.6	74.0±9.3	.037^b	.024^b
	36 montd	76.2±11.4	80.4±9.5	72.5±9.3	.009^c	.001^c
Waist (cm)	Baseline	88.0±12.2	87.4±11.7	86.8±11.6	1.000^a	.356^a
	12 montd	93.6±11.5	91.2±8.7	86.5±11.4	.000^b	.000^b
	36 montd	94.6±14.3	97.5±10.2	87.6±11.0	.013^c	.000^c
FBS (mg/dL)	Baseline	88.6±17.1	91.6±26.6	90.7±23.5	1.000^a	1.000^a
	12 montd	94.2±16.8	92.6±10.1	92.1±25.8	1.000^b	.320^b
	36 montd	100.6±31.6	97.4±10.9	93.5±26.3	.771^c	1.000^c
Total cholesterol (mg/dL)	Baseline	175.1±35.8	187.5±45.1	188.1±38.8	.178^a	.065^a
	12 montd	186.0±35.2	210.6±53.0	185.5±34.3	.783^b	.774^b
	36 montd	183.4±38.0	210.1±49.8	182.2±34.3	.013^c	.004^c
HDL (mg/dL)	Baseline	46.6±11.8	46.1±10.5	45.1±11.7	1.000^a	.360^a
	12 montd	43.2±9.9	41.6±10.2	49.6±12.2	.001^b	.017^b
	36 montd	44.8±12.8	40.8±8.2	49.0±11.3	.004^c	.001^c
Triglyceride (mg/dL)	Baseline	109.8±60.0	129.5±97.8	136.4±86.5	.067^a	.002^a
	12 montd	151.0±75.6	181.0±92.4	112.3±62.3	.069^b	.015^b
	36 montd	142.0±69.8	240.8±118.6	121.3±77.6	.000^c	.000^c
QTc interval (ms)	Baseline	417.3±23.7	409.2±23.2	415.7±21.4	1.000^a	1.000^a
	12 montd	417.3±29.6	403.5±19.7	404.2±23.2	.178^b	.015^b
	36 montd	416.5±24.7	411.7±16.1	403.7±19.2	1.000^c	.371^c

P1 : p value at 12 montd, P2 : p value at 36 montd,

^a : comparison between PAL & OLA group,

^b : comparison between PAL & ARI group,

^c : comparison between OLA & ARI group. BMI : Body Mass Index, FBS : Fasting Blood Sugar, HDL : High-Density Lipoprotein

Table 3.

The change of pre evalence of m etabolic synd drome and m markers in sc hizophreni ic patient ts for 36 m montds

Variables	Subjects	PAL group	OLA group	ARI group	χ²0	χ²1	χ²2	P0	P1	P2
Abdominal obesity (Waist circumference)	Baseline	44.9%	40.0%	51.5%	0.139^a	0.949^a	0.120^a	.793^a	.498^a	1.000^a
	12 montd	78.9%	60.0%	51.5%	0.492^b	1.991^b	0.282^b	.575^b	.198^b	.760^b
	36 montd	75.5%	85.0%	60.3%	0.814^c	0.046^c	1.042^c	.449^c	1.000^c	.398^c
Fasting blood sugar (FBS)	Baseline	20.4%	10.0%	19.1%	1.071^a	2.257^a	1.421^a	.486^a	.212^a	.270^a
	12 montd	31.6%	25.0%	13.6%	0.030^b	1.315^b	5.169^b	1.000^b	.321^b	.034^b
	36 montd	40.8%	30.0%	14.7%	0.909^c	0.743^c	0.426^c	.504^c	.528^c	.499^c
Blood pressure(BP)	Baseline	24.5%	20.0%	35.3%	0.161^a	2.451^a	3.254^a	.764^a	.185^a	.130^a
	12 montd	31.6%	40.0%	18.2%	1.561^b	0.764^b	0.193^b	.230^b	.360^b	.704^b
	36 montd	32.7%	55.0%	17.6%	1.666^c	11.148^c	10.539^c	.277^c	.002^c	.003^c
High-density lipoprotein (HDL)	Baseline	30.6%	30.0%	42.6%	0.003^a	0.703^a	1.883^a	1.000^a	.515^a	.264^a
	12 montd	44.7%	65.0%	31.8%	1.758^b	3.716^b	0.033^b	.246^b	.065^b	1.000^b
	36 montd	49.0%	65.0%	30.9%	1.132^c	0.795^c	2.983^c	8.437^c	.453^c	.097^c
Triglyceride(TG)	Baseline	20.4%	20.0%	36.8%	0.001^a	0.187^a	7.535^a	1.000^a	.746^a	.010^a
	12 montd	42.1%	70.0%	25.8%	3.634^b	2.142^b	0.008^b	.067^b	.182^b	1.000^b
	36 montd	44.9%	85.0%	26.5%	1.966^c	4.678^c	13.344^c	.187^c	.046^c	.000^c
Metabolic syndrome	Baseline	16.3%	10.0%	32.4%	0.459^a	0.620^a	3.910^a	.712^a	.517^a	.064^a
by ATPIIIa	12 montd	47.4%	45.0%	16.7%	3.836^b	7.638^b	2.297^b	.056^b	.014^b	.183^b
	36 montd	55.1%	85.0%	20.6%	3.893^c	3.110^c	18.021^c	.084^c	.094^c	.000^c

χ²0 : χ² at baseline, χ²1 : χ² at 12 montd, χ²2 : χ² at 36 montd. P0 : p value at baseline, P1 : p value at 12 montd, P2 : p value at 36 montd,

^a : comparison between PAL & OLA group,

^b : comparison between PAL & ARI group,

^c : comparison between OLA & ARI group. ATPIIIa : Adult Treatment Panel III, PAL : Paliperidone, OLA : Olanzapine, ARI : Aripiprazole

Table 4.

Reported and observed sid e effects in schizophrenic pati ents

Subjects	Paliperidone group	Olanzapine group	Aripiprazole group
Side effects	N (%)	N (%)	N (%)
Insomnia	19 (38.8%)	6 (30.0%)	47 (38.2%)
Weight gain	19 (38.8%)	13 (65.0%)	29 (23.6%)
Headache	13 (26.5%)	7 (35.0%)	29 (23.6%)
Anxiety	16 (32.7%)	10 (50.0%)	29 (23.6%)
Somnolence	16 (32.7%)	10 (50.0%)	19 (15.4%)
Akatdisia	3 (6.1%)	1 (5.0%)	14 (11.4%)
EPS	18 (36.7%)	7 (35.0%)	13 (10.6%)
Increased sleep	6 (12.2%)	7 (35.0%)	11 (8.9%)
Fatigue	3 (6.1%)	4 (20.0%)	9 (7.3%)
Constipation	11 (22.4%)	5 (25.0%)	7 (5.7%)
Agitation	2 (4.1%)	1 (5.0%)	7 (5.7%)
Dizziness	6 (12.2%)	3 (15.0%)	7 (5.7%)
Aggravation of psychosis	2 (4.1%)	2 (10.0%)	6 (4.9%)
Sexual dysfunction	14 (28.6%)	2 (10.0%)	5 (5.7%)
Dry moutd	6 (12.2%)	5 (25.0%)	1 (0.8%)

Total subjects : 200 (Aripiprazole group 123, Otder antipsychotic group 77)

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