A Study on Discontinuation Rate on Maintenance Treatment of Antipsychotic Agents in Schizophrenic Patients

Ha Hyun Bae; Eui Hyeon NA; Hai Joo Yoon; Eun Kyung Park; Jong-Il Lee

doi:10.16946/kjsr.2017.20.2.69

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Bae, NA, Yoon, Park, and Lee: A Study on Discontinuation Rate on Maintenance Treatment of Antipsychotic Agents in Schizophrenic Patients

Original Article

Korean J Schizophr Res 2017;20(2):69-76.

Published online: 20 January 2017

DOI: https://doi.org/10.16946/kjsr.2017.20.2.69

A Study on Discontinuation Rate on Maintenance Treatment of Antipsychotic Agents in Schizophrenic Patients

Ha Hyun Bae, MD¹, Eui Hyeon NA, MD², Hai Joo Yoon, MA³, Eun Kyung Park, RN⁴, Jong-Il Lee, M.D., PhD^1,

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

²Department of Psychiatry, The Catholic Of Korea Seoul ST, Mary's Hospital, Seoul, Korea

³Department of Clinical Psychology, National Center for Mental Health, Seoul, Korea

⁴Department of Clinical Trial Center, Samsung Medical Center, Seoul, Korea

Address for correspondence: Jong-Il Lee, Department of Psychiatry, National Center for Mental Health, 127 Youngmasan-ro Gwangjin-gu, Seoul 04933, Korea Tel: 02-2204-0120, Fax: 02-2204-0385 E-mail: lji7542@naver.com 본 연구는 Janssen Korea Ltd. 지원을 받아 수행된 연구임.

Received 27 March 2017 Revised 26 July 2017 Accepted 23 October 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

Relapse prevention is a major therapeutic goal in the treatment of schizophrenia. However, many patients experience multiple functional impairments and treatment resistance due to recurrence. This study was designed to investigate the follow-up of patients with using antipsychotic drugs and to compare the total treatment failure rate, withdrawal reasons, and duration period of antipsychotic drugs.

Methods

The subjects were 1963 patients who taking antipsychotic drugs under the diagnosis of schizophrenia. We selected 1836 patients using 10 antipsychotic drugs according to frequency of using. The rate of total treatment failure of them was divided into 6-month, 1-year, 2-year, 3-year, and 5-year according to the time of drug withdrawal. We compared the total treatment failure rate at 1 and 3-year between 10 antipsychotic drugs.

Results

The total treatment failure rate of clozapine was lowest compared with the other 9 antipsychotic drugs in all the surveyed periods. When evaluating actual number of subjects, olanzapine, sulpiride, risperidone, aripiprazole, amisulpride, and haloperidol were lower significantly compared with ziprasidone at 1-year in the total treatment failure rate, but there was no significant difference between them except clozapine at 3-year. The results of the analysis based on the number of prescriptions showed that the total treatment failure rate of the atypical antipsychotic drug was lower than that of the typical antipsychotic drug at 1-year, but the difference was decreased over time except quetiapine and ziprasidone.

Conclusion

In conclusion, although there is some controversy about which drug to prescribe to the patient, the clinician needs a proper prescription considering various factors such as efficacy, side effects, price, and formulations of each drug.

Keywords: Schizophrenia, Antipsychotic drugs, Total treatment failure

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Fig. 1.

The period of continuation in antipsychotic drugs (days). OLA: olanzapine, RSP: risperidone, QUE: quetiapine, ABI: aripiprazole, ZIP: ziprasidone, CLO: clozapine, HAL: haloperidol, CPZ: chlorpramazine, SUL: sulpiride.

Table 1.

Sociodemographic characteristics

Variable	N=1963
Age (years)	42.60±10.959
Sex
Male	990 (50.4%)
Female	973 (49.6%)
Education (years)	11.83±3.101
Occupation
Part-time	125 (6.4%)
Full-time	145 (7.4%)
Student	28 (1.4%)
Homemaker	175 (8.9%)
Unemployed	1490 (75.9%)
치료 여부
Antipsychotic naive	553 (28.2%)
Ex-affected Antipsychotic	1410 (71.8%)
첫 복용나이	30.07±11.098

Table 2.

Discontinuation rate according to period and reasons of discontinuation on 10 antipsychotics of trial 1 (N=1836)

Antipsychotic agent (N)	Discontinuation rate						Reasons of diiscontinuation
Antipsychotic agent (N)	Within 6 month	Within 1 year	Within 2 years	Within 3 years	Within 5 years	Lack of efficacy	Adverse event	Poor adherence	Others
OLA (180)	45.6%	64.0%	80.7%	87.4%	94.6%	29 (17.1%)	36 (21.2%)	58 (34.1%)	47 (27.6%)
RIS (732)	49.5%	63.7%	79.7%	85.6%	92.8%	156 (23.0%)	139 (20.5%)	183 (26.9%)	201 (29.6%)
QUE (55)	43.6%	65.4%	83.6%	92.7%	98.2%	22 (40.7%)	5 (9.3%)	13 (24.1%)	14 (25.9%)
ABI (51)	52.9%	60.7%	76.4%	84.2%	96.1%	17 (35.7%)	5 (10.2%)	12 (24.5%)	15 (30.6%)
AMI (48)	56.3%	62.6%	79.3%	89.7%	95.8%	19 (41.3%)	8 (17.4%)	8 (17.4%)	11 (23.9%)
ZIP (28)	78.6%	89.3%	92.9%	96.5%	100%	13 (45.9%)	5 (17.9%)	2 (5.6%)	8 (30.6%)
CLO (61)	11.5%	18.1%	29.6%	37.8%	52.5%	4 (12.5%)	15 (46.9%)	8 (25.0%)	5 (15.6%)
HAL (508)	51.6%	65.2%	76.2%	83.7%	90.0%	95 (20.8%)	127 (27.8%)	126 (27.6%)	109 (23.8%)
CPZ (54)	57.4%	66.7%	77.8%	83.4%	88.9%	16 (33.3%)	10 (20.9%)	12 (25.9%)	10 (20.9%)
SUL (119)	46.2%	60.5%	77.3%	83.2%	89.1%	30 (28.3%)	15 (14.2%)	40 (37.7%)	21 (19.8%)

OLA: olanzapine, RIS: risperidone, QUE: quetiapine, ABI: aripiprazole, AMI: amisupride, ZIP: ziprasidone, CLO: clozapine, HAL: haloperidol, CPZ: chlorpramazine, SUL: sulpiride

Table 3.

Discontinuation rate according to period and reasons of discontinuation on 10 antipsychotic of total trials (N=5057)

Antipsychotic agent(N)	Discontinuation rate						Reasons of discontinuation N(%)
Antipsychotic agent(N)	Within 6 month	Within 1 year	Within 2 years	Within 3 years	Within 5 years	Lack of efficacy	Adverse event	Poor adherence	Others
OLA(708)	41.3%	59.8%	77.3%	84.9%	93.7%	134 (20.2%)	115 (17.3%)	237 (35.7%)	177 (26.7%)
RIS(1842)	44.3%	60.5%	76.4%	83.4%	91.8%	348 (20.6%)	302 (17.9%)	557 (32.9%)	484 (28.6%)
QUE(227)	47.8%	68.6%	83.6%	92.9%	98.7%	79 (38.0%)	25 (12.0%)	46 (22.1%)	58 (27.9%)
ABI(250)	45.6%	59.2%	78.8%	88.8%	98.8%	76 (30.8%)	29 (11.7%)	67 (27.1%)	75 (30.4%)
AMI(181)	44.8%	60.8%	79.0%	86.2%	97.8%	50 (28.2%)	47 (26.6%)	33 (18.6%)	47 (26.6%)
ZIP(84)	65.5%	81.0%	89.3%	94.1%	100%	32 (38.1%)	11 (13.1%)	12 (14.3%)	29 (34.5%)
CLO(277)	21.6%	31.7%	45.0%	56.5%	74.8%	8 (3.9%)	41 (19.8%)	68 (32.9%)	90 (43.4%)
HAL(945)	52.3%	67.3%	78.8%	85.8%	92.1%	204 (23.5%)	196 (22.6%)	256 (29.3%)	214 (24.6%)
CPZ(121)	52.5%	70.5%	80.3%	86.9%	95.1%	43 (37.4%)	18 (15.7%)	31 (26.9%)	23 (20.0%)
SUL(422)	44.0%	60.5%	75.4%	83.9%	90.5%	98 (25.7%)	40 (10.5%)	156 (40.8%)	88 (17.0%)

OLA: olanzapine, RIS: risperidone, QUE: quetiapine, ABI: aripiprazole, AMI: amisupride, ZIP: ziprasidone, CLO: clozapine, HAL: haloperidol, CPZ: chlorpramazine, SUL: sulpiride

Table 4.

Comparison of discontinuation rate of 10 antipsychotic agents in first trials

OLA	χ²=0.501	χ²=0.595	χ²=1.762	χ²=0.818	χ²=0.751	χ²=64.082	χ²=0.008	χ²=0.009	χ²=0.009
OLA	p=.526	p=.432	p=.225	p=.403	p=.583	p=.000	p=1.000	p=1.000	p=1.000
χ²=0.134	RIS	χ²=0.169	χ²=1.060	χ²=0.325	χ²=1.352	χ²=86.437	χ²=0.801	χ²=0.265	χ²=0.235
p=.731	RIS	p=.725	p=.283	p=.575	p=.331	p=.000	p=.376	p=.722	p=.708
χ²=0.019	χ²=0.135	QUE	χ²=0.198	χ²=0.018	χ²=1.545	χ²=29.320	χ²=0.623	χ²=0.465	χ²=0.426
p=1.000	p=.773	QUE	p=.819	p=1.000	p=.247	p=.000	p=.459	p=.628	p=.537
χ²=0.540	χ²=0.352	χ²=0.495	ABI	χ²=0.089	χ²=2.443	χ²=24.178	χ²=1.974	χ²=1.233	χ²=1.373
p=.512	p=.553	p=.550	ABI	p=.818	p=.150	p=.000	p=.182	p=.339	p=.295
χ²=0.062	χ²=0.004	χ²=0.097	χ²=0.140	AMI	χ²=1.752	χ²=26.027	χ²=0.866	χ²=0.630	χ²=0.613
p=.866	p=1.000	p=.838	p=.837	AMI	p=.232	p=.000	p=.331	p=.463	p=.515
χ²=4.982	χ²=6.037	χ²=3.802	χ²=6.043	χ²=4.633	ZIP	χ²=29.047	χ²=0.864	χ²=0.523	χ²=0.797
p=.030	p=.015	p=.070	p=.022	p=.038	ZIP	p=.000	p=.448	p=.743	p=.570
χ²=39.370	χ²=47.210	χ²=26.987	χ²=19.916	χ²=22.635	χ²=36.843	CLO	χ²=90.685	χ²=35.464	χ²=51.889
p=.000	p=.000	p=.000	p=.000	p=.000	p=.000	CLO	p=.000	p=.000	p=.000
χ²=0.030	χ²=0.617	χ²=0.002	χ²=0.813	χ²=0.136	χ²=5.014	χ²=50.437	HAL	χ²=0.025	χ²=0.001
p=.856	p=.435	p=1.000	p=.362	p=.752	p=.024	p=.000	HAL	p=1.000	p=1.000
χ²=0.090 p=.871	χ²=0.294 p=.662	χ²=0.018 p=1.000	χ²=0.691 p=.426	χ²=0.193 p=.683	χ²=3.408 p=.073	χ²=28.034 p=.000	χ²=0.049 p=.881	CPZ	χ²=0.025 p=1.000
χ²=0.699 p=.464	χ²=0.480 p=.540	χ²=0.533 p=.506	χ²=0.010 p=1.000	χ²=0.115 p=.861	χ²=6.729 p=.009	χ²=28.180 p=.000	χ²=1.265 p=.289	χ2=0.772 p=.404	SUL

: comparison of discontinuation rate at 1-year,: comparison of discontinuation rate at 3-year. N: 1,836. OLA: olanzapine, RSP: risperidone, QUE: quetiapine, ABI: aripiprazole, AMI: amisupride, ZIP: ziprasidone, CLO: clozapine, HAL: haloperidol, CPZ: chlorpramazine, SUL: sulpiride

Table 5.

Comparison of discontinuation rate of 10 antipsychotic agents in total trials

OLA	χ²=0.713	χ²=9.863	χ²=2.447	χ²=0.222	χ²=5.275	χ²=89.946	χ²=0.356	χ²=0.361	χ²=0.151
OLA	p=.436	p=.001	p=.140	p=.726	p=.020	p=.000	p=.574	p=.680	p=.735
χ²=0.127	RIS	χ²=13.855	χ²=4.765	χ²=0.927	χ²=6.717	χ²=109.126	χ²=2.759	χ²=1.007	χ²=0.065
p=.752	RIS	p=.000	p=.027	p=.399	p=.006	p=.000	p=.100	p=.377	p=.828
χ²=5.711	χ²=5.567	QUE	χ²=2.402	χ²=5.029	χ²=0.123	χ²=83.654	χ²=8.205	χ²=3.456	χ²=10.579
p=.018	p=.020	QUE	p=.153	p=.031	p=1.000	p=.000	p=.004	p=.080	p=.001
χ²=0.021	χ²=0.153	χ²=4.518	ABI	χ²=0.664	χ²=1.945	χ²=67.901	χ²=1.484	χ²=0.288	χ²=3.054
p=.881	p=.731	p=.036	ABI	p=.459	p=.206	p=.000	p=.253	p=.610	p=.088
χ²=0.067	χ²=0.006	χ²=2.699	χ²=0.108	AMI	χ²=3.530	χ²=44.620	χ²=0.016	χ²=0.030	χ²=0.499
p=.865	p=1.000	p=.117	p=.766	AMI	p=.064	p=.000	p=1.000	p=1.000	p=.539
χ²=14.370	χ²=14.194	χ²=4.640	χ²=13.021	χ²=10.594	ZIP	χ²=40.133	χ²=4.457	χ²=2.788	χ²=5.827
p=.020	p=.000	p=.033	p=.000	p=.001	ZIP	p=.000	p=.031	p=.107	p=.016
χ²=63.019	χ²=81.815	χ²=68.090	χ²=40.404	χ²=37.895	χ²=63.928	CLO	χ²=112.298	χ²=34.820	χ²=64.186
p=.000	p=.000	p=.000	p=.000	p=.000	p=.000	CLO	p=.000	p=.000	p=.000
χ²=10.224	χ²=12.556	χ²=0.130	χ²=5.803	χ²=2.928	χ²=6.623	χ²=113.283	HAL	χ²=0.099	χ²=0.848
p=.002	p=.000	p=.752	p=.017	p=.103	p=.010	p=.000	HAL	p=.890	p=.365
χ²=5.094 p=.027	χ²=4.819 p=.028	χ²=0.135 p=.808	χ²=4.480 p=.040	χ²=3.013 p=.088	χ²=2.885 p=.104	χ²=52.036 p=.000	χ²=0.492 p=.538	CPZ	χ²=0.637 p=.479
χ²=0.071	χ²=0.000	χ²=4.125	χ²=0.114	χ²=0.003	χ²=12.684	χ²=55.928	χ²=5.987	χ²=4.028
p=.802	p=1.000	p=.049	p=.745	p=1.000	p=.000	p=.000	p=.017	p=.055	SUL

: comparison of discontinuation rate at 1-year,: comparison of discontinuation rate at 3-year. N: 5.057. OLA: olanzapine, RSP: risperidone, QUE: quetiapine, ABI: aripiprazole, AMI: amisupride, ZIP: ziprasidone, CLO: clozapine, HAL: haloperidol, CPZ: chlorpramazine, SUL: sulpiride

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