Background
Methods
Samples
Detection of serum clozapine concentration
C/D ratio and medical record information
Statistical analysis
Results
Demographic characteristics
Classification of psychiatric disorders | Number | Percentage (%) |
---|---|---|
Schizophrenia (n = 2835) | ||
Paranoid schizophrenia | 1425 | 38.16 |
Undifferentiated schizophrenia, | 1403 | 37.57 |
Residual schizophrenia | 7 | 0.19 |
Affective (mood) disorder(n = 831) | ||
Bipolar Disorder | 779 | 20.86 |
Recurrent depressive disorder | 24 | 0.64 |
Manic | 19 | 0.51 |
Major depressive episode | 9 | 0.24 |
Others (n = 68) | ||
Organic, including symptomatic, mental disorders | 30 | 0.80 |
Dissociation [conversion] disorder | 26 | 0.70 |
Behavioural and emotional disorders that usually begin in childhood and adolescence | 4 | 0.11 |
Mental retardation | 4 | 0.11 |
Generalized Anxiety Disorder | 2 | 0.05 |
Obsessive compulsive disorder | 1 | 0.03 |
Specific personality disorder | 1 | 0.03 |
Results of daily dose, serum concentration and C/D ratio
Variables | Mean ± SD | Median (interquartile range) | r |
---|---|---|---|
Daily dose (mg/day) | 191.02 ± 113.47 | 175.00(100.00–250.00) | 0.594**a |
Serum concentration (ng/mL) | 326.15 ± 235.66 | 272.36(148.09–445.98) | |
C/D ratio | 1.94 ± 1.25 | 1.67(1.10–2.47) |
Daily dose (mg/day) | Serum concentration (ng/mL) | C/D Ratio | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Groups | n | Mean ± SD | Median (interquartile range) | p | Mean ± SD | Median (interquartile range) | p | Mean ± SD | Median (interquartile range) | p |
Daily dose (mg/day) | ||||||||||
< 100 | 663 | 53.28 ± 18.12 | 50.00(50.00–75.00) | 131.38 ± 90.74 | 104.72(70.83–161.15) | 2.57 ± 1.64 | 2.08(1.54–3.07) | |||
100–200 | 1666 | 145.37 ± 35.01 | 150.00(100.00–175.00) | 0.000 | 289.09 ± 175.81 | 252.99(155.09–379.81) | 0.000 | 2.03 ± 1.21 | 1.75(1.13–2.69) | 0.000 |
201–400 | 1244 | 287.30 ± 52.27 | 300.00(250.00–300.00) | 448.54 ± 250.42 | 406.93(270.53–567.25) | 1.60 ± 0.91 | 1.39(0.97–2.03) | |||
> 400 | 161 | 486.65 ± 68.58 | 450.00(450.00–500.00) | 566.00 ± 326.99 | 501.03(283.86–805.97) | 1.19 ± 0.70 | 1.07(0.59–1.66) | |||
Serum concentration (ug/L) | ||||||||||
< 350 | 2344 | 153.91 ± 101.16 | 150.00(75.00–200.00) | 183.33 ± 86.97 | 174.10(110.25–255.72) | 1.56 ± 1.02 | 1.34(0.87–1.95) | |||
350–600 | 1048 | 239.59 ± 99.17 | 225.00(150.00–300.00) | 0.000 | 471.79 ± 82.37 | 462.06(400.09–535.34) | 0.000 | 2.37 ± 1.25 | 2.05(1.52–2.89) | 0.000 |
> 600 | 342 | 296.53 ± 112.01 | 300.00(225.00–375.00) | 858.70 ± 212.87 | 796.19(702.64–920.71) | 3.28 ± 1.36 | 3.04(2.23–3.96) |
Comparison of clozapine daily dose, serum concentration and C/D ratios among different groups
Variables | n | Percentage (%) |
---|---|---|
Sex | ||
Female | 1310 | 35.08 |
Male | 2424 | 64.92 |
Age group(year) | ||
10–17 | 116 | 3.11 |
18–44 | 2418 | 64.76 |
45–59 | 1089 | 29.16 |
60–75 | 111 | 2.97 |
Duration (month) | ||
< 180 | 1924 | 51.53 |
≥ 180 | 1810 | 48.47 |
Ethnicity | ||
Han | 3692 | 98.88 |
Hui | 42 | 1.12 |
Marital status | ||
Single | 1435 | 38.43 |
Married | 1992 | 53.35 |
Divorced | 307 | 8.22 |
Occupation | ||
unemployed | 1718 | 46.01 |
Farmer | 1091 | 29.22 |
Worker | 468 | 12.53 |
Others | 457 | 12.24 |
Comorbidity or not | ||
psychiatric disorders | 3424 | 91.70 |
Comorbidities | 310 | 8.30 |
Psychotic type | ||
Schizophrenia | 2835 | 75.92 |
Bipolar disorder | 779 | 20.86 |
Other types | 120 | 3.21 |
Inpatients/outpatients | ||
Inpatients | 3209 | 85.94 |
Outpatients | 525 | 14.06 |
Province | ||
Shandong | 3674 | 98.39 |
Others | 60 | 1.61 |
Daily dose (mg) | Serum concentration (ng/mL) | C/D Ratios | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Variables | n | Mean ± SD | Median (interquartile range) | P | Mean ± SD | Median (interquartile range) | P | Mean ± SD | Median (interquartile range) | P |
Gender | ||||||||||
Female | 1310 | 194.77 ± 107.31 | 175.00 (100.00–250.00) | 0.009a | 373.37 ± 248.72 | 320.66 (179.30–508.36) | 0.000a | 2.17 ± 1.34 | 1.88 (1.25–2.72) | 0.000a |
Male | 2424 | 188.99 ± 116.63 | 150.00 (100.00–250.00) | 300.63 ± 224.24 | 249.30 (131.06–403.78) | 1.83 ± 1.19 | 1.55 (1.02–2.32) | |||
Age group (year) | ||||||||||
10–17 | 116 | 216.27 ± 125.77 | 200.00 (100.00–300.00) | 0.000b | 338.65 ± 265.38 | 308.03 (113.66–490.33) | 0.000b | 1.61 ± 0.92 | 1.36 (0.86–1.98) | 0.000b |
18–44 | 2418 | 193.00 ± 115.91 | 175.00 (100.00–275.00) | 307.94 ± 233.20 | 249.40 (137.74–410.38) | 1.81 ± 1.14 | 1.56 (1.02–2.29) | |||
45–59 | 1089 | 188.65 ± 108.78 | 150.00 (100.00–250.00) | 361.99 ± 236.25 | 329.30 (174.70–489.60) | 2.20 ± 1.42 | 1.90 (1.27–2.73) | |||
60–75 | 111 | 144.59 ± 71.78 | 125.00 (100.00–200.00) | 358.25 ± 207.07 | 343.13 (185.77–472.19) | 2.67 ± 1.56 | 2.27 (1.55–3.38) | |||
Duration (month) | ||||||||||
≤ 180 | 1924 | 204.29 ± 116.87 | 200.00 (100.00–300.00) | 0.000a | 318.31 ± 239.00 | 259.64 (142.60–427.60) | 0.003a | 1.75 ± 1.11 | 1.47 (1.01–2.18) | 0.000a |
> 180 | 1810 | 176.91 ± 107.99 | 150.00 (100.00–225.00) | 334.48 ± 231.82 | 285.00 (152.64–458.75) | 2.15 ± 1.36 | 1.87 (1.24–2.73) | |||
Inpatients/outpatients | ||||||||||
Inpatients | 3209 | 188.85 ± 110.24 | 150.00 (100.00–250.00) | 0.097a | 343.72 ± 239.35 | 294.66 (161.98–465.91) | 0.000a | 2.06 ± 1.27 | 1.78 (1.19–2.59) | 0.000a |
Outpatients | 525 | 204.29 ± 130.79 | 200.00 (100.00–300.00) | 218.75 ± 177.34 | 172.72 (95.02–279.92) | 1.25 ± 0.83 | 1.05 (0.65–1.62) | |||
Psychiatric classification | ||||||||||
Schizophrenia | 2835 | 196.23 ± 116.14 | 175.00 (100.00–275.00) | 0.000b | 339.02 ± 241.59 | 284.83 (157.56–459.65) | 0.000b | 1.98 ± 1.29 | 1.70 (1.11–2.51) | 0.034b |
Bipolar disorder | 779 | 176.29 ± 105.53 | 150.00 (100.00–225.00) | 288.80 ± 209.00 | 234.49 (129.68–388.50) | 1.82 ± 1.10 | 1.59 (1.08–2.29) | |||
Other types | 120 | 163.54 ± 111.34 | 150.00 (50.00–225.00) | 264.62 ± 222.83 | 199.87 (109.82–331.52) | 1.94 ± 1.31 | 1.71 (0.99–2.37) | |||
Comorbidity or not | ||||||||||
Psychiatric disorders | 3424 | 193.16 ± 112.57 | 175.00 (100.00–250.00) | 0.000a | 325.84 ± 239.20 | 267.06 (145.14–447.17) | 0.044a | 1.89 ± 1.19 | 1.63 (1.07–2.40) | 0.000a |
Comorbidities | 310 | 167.34 ± 120.58 | 150.00 (100.00–200.00) | 329.60 ± 192.58 | 316.44 (179.28–434.09) | 2.51 ± 1.69 | 2.16 (1.44–3.28) | |||
Marital status | ||||||||||
Single | 1435 | 199.61 ± 119.93 | 175.00 (100.00–300.00) | 311.30 ± 222.63 | 258.11 (138.40–429.40) | 1.82 ± 1.23 | 1.54 (1.01–2.29) | |||
married | 1992 | 186.31 ± 109.68 | 150.00 (100.00–250.00) | 0.015b | 335.07 ± 239.53 | 281.97 (152.88–450.50) | 0.027b | 2.00 ± 1.19 | 1.77 (1.15–2.57) | 0.000b |
divorced | 307 | 181.39 ± 103.90 | 150.00 (100.00–225.00) | 337.68 ± 265.36 | 275.50 (150.02–465.99) | 2.17 ± 1.64 | 1.78 (1.12–2.70) | |||
Occupation | ||||||||||
unemployed | 1718 | 189.26 ± 106.65 | 175.00 (100.00–250.00) | 0.426b | 336.94 ± 228.71 | 291.61 (161.67–462.02) | 0.000b | 2.02 ± 1.25 | 1.74 (1.17–2.58) | 0.000b |
Farmer | 1091 | 188.10 ± 106.42 | 175.00 (100.00–250.00) | 321.17 ± 244.27 | 252.07 (140.51–432.51) | 1.88 ± 1.20 | 1.62 (1.05–2.39) | |||
Worker | 468 | 191.53 ± 131.32 | 150.00 (100.00–250.00) | 278.84 ± 184.37 | 253.39 (129.83–390.40) | 1.88 ± 1.43 | 1.53 (1.00–2.41) | |||
Others | 457 | 204.05 ± 132.79 | 175.00 (100.00–300.00) | 345.94 ± 277.56 | 268.62 (128.74–483.43) | 1.87 ± 1.17 | 1.63 (1.04–2.31) |
Trend tests of dose, concentration, and C/D ratio between age groups
Regression model and identifying factors
Variables | Univariate model | Multivariate model | |||
---|---|---|---|---|---|
B (95%CI) | p | B (95%CI) | p | ||
Daily dose (mg/day) | 1.065 (1.007;1.122) | 0.000 | 1.091 (1.036;1.146) | 0.000 | |
Sex | Male | -72.738 (-88.411;-57.065) | 0.00 | -71.282 (-84.858;-57.706) | 0.000 |
Age (year) | 1.716 (1.075;2.357) | 0.000 | 2.250 (1.488; 3.011) | 0.000 | |
Inpatients/outpatients | Outpatients | -124.971 (-146.352;-103.589) | 0.000 | -129.023 (-147.713;-110.333) | 0.000 |
Duration (month) | ≥ 180 | 16.170 (1.048;31.292) | 0.036 | -8.611 (-24.952; 7.730) | 0.302 |
Comorbidity or not | Comorbidity | 3.760 (-23.647;31.167) | 0.788 | 22.976 (-0.838; 46.790) | 0.059 |
Occupation | Unemployed | -9.003 (-33.245; 15.245) | 0.457 | 5.475(-14.465; 25.416) | 0.590 |
Farmer | -24.773 (-50.437; 0.892) | 0.059 | 12.585 (-8.773;33.943) | 0.248 | |
Worker | -67.096 (-97.387; -36.806) | 0.000 | -65.020 (-90.202; -39.838) | 0.000 | |
Others | 1 | 1 | |||
Psychiatric classification | Schizophrenia | 74.396 (31.533; 117.259) | 0.001 | 31.930 (-3.548; 67.408) | 0.078 |
Bipolar disorder | 24.177 (-20.925; 69.278) | 0.293 | 19.101 (-17.901; 56.103) | 0.312 | |
Other types | 1 | 1 | |||
Marital status | Single | -26.387 (-55.412; 2.638) | 0.075 | -4.381 (-29.126; 20.363) | 0.729 |
Married | -2.616 (-30.917; 25.685) | 0.856 | -8.678 (-31.990; 14.634) | 0.466 | |
Divorced | 1 | 1 |