Previous Hospital Admissions and Disease Severity Predict the Use of Antipsychotic Combination Treatment in Patients With Schizophrenia

Albert Bolstad; Ole A Andreassen; Jan I Røssberg; Ingrid Agartz; Ingrid Melle; Lars Tanum

BMC Psychiatry. 2011;11(126)

Methods

Sample

All the psychiatric hospitals in Oslo participate in the cross-sectional Thematically Organized Psychosis (TOP) Study, in which patients with psychotic disorders were recruited from outpatient as well as inpatient hospital units in a catchment area-based psychiatric service from 2003 to 2010. Up to 2008, we do not possess accurate data concerning out- or inpatient status at the time of inclusion in the study. A number of patients were recruited while being hospitalized, but actually included after discharge. The TOP study includes patients with a DSM-IV^[14] diagnosis of schizophrenia and schizoaffective disorders, bipolar disorders and psychosis NOS. Patients were excluded if there was a previous history of head trauma, serious somatic illness or they were unable to give written, informed consent. For further information about the inclusion procedures, see.^[15–17] A total of 329 patients, 213 (64.7%) men and 116 (35.3%) women, with schizophrenia fulfilled the inclusion criteria of the present study, including current use of antipsychotic medication and information on previous treatment history (For further patient characteristics, see Table 1).

The protocol was approved by The Norwegian Data Inspectorate and by the Regional Committee for Medical Research Ethics. All included patients received both written and oral information about the study and gave their written consent. The study was performed in full accordance with the Declaration of Helsinki (1965) and later revisions.

Assessment

All patients included in the study went through the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I)^[18] for diagnostic purposes. All raters were investigators in the study, with a background either as medical doctor or clinical psychologist. The raters were trained in clinical interviews and assessments including video and case report ratings. Tests for rating reliability were performed for the different diagnoses, PANSS and GAF scores. The diagnostic reliability was found to be satisfactory with an overall agreement for DSM-IV diagnostic categories of 82% with κ = 0.77 (95% CI: 0.60–0.94). The level of functioning was assessed by use of the split version of the Global Assessment of Functioning scale (GAF).^[18] The GAF rating was carried out by the investigators, with a satisfactory inter-rater reliability for GAF-F (ICC (1.1) = 0.86).

Relevant information on present and former drug treatment and previous hospitalisation were obtained from patient interviews and hospital records. If a patient used more than one antipsychotic drug at the time of the study, the drug prescribed in the highest dose, estimated from Defined Daily Doses (DDD), was defined as the primary therapeutic agent. If prescribed doses of two or more antipsychotics were equipotent, the medication with the longest duration was defined as the primary therapeutic agent. Secondary and tertiary therapeutic agents were established in line with this.

Statistical Analysis

Descriptive statistics was used for the initial analyses of frequencies, means and standard deviations (SD). Independent sample t-tests were used on between-group comparisons of means. Mann-Whitney test were used when skewed distribution of data were assumed. When dichotomous variables, we used Pearson Chi Square tests. Significant relationships were further explored by using a Backward Stepwise logistic regression model. Due to the low accuracy on the present inpatient versus outpatient treatment status, we did not include this factor in the logistic regression analyses. The effect sizes are presented as odds ratios. Nagelkerke's R-square was used to indicate goodness of fit. All analyses were performed using the Statistical Package for Social Sciences (SPSS), Version 14.

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Cite this: Previous Hospital Admissions and Disease Severity Predict the Use of Antipsychotic Combination Treatment in Patients With Schizophrenia - Medscape - Aug 03, 2011.

Table 1. Background variables of patients included in the study (n = 329#)
	Mean (S.D)	Median (min. - max.)
Age (years), (n = 329)	31.9 (9.6)	30 (17–60)
Age of psychosis onset (years) (n = 140)	23.8 (8.3)	22 (7–54)
Duration of untreated psychosis (weeks) (n = 142))	134 (182)	76 (0–1040)
GAF-Symptom (n = 329)	40.0 (10.5)	38 (8–81)
GAF-Function (n = 329)	41.0 (9.5)	40 (21–81)
PANSS-positive (n = 305)	16.3 (5.9)	16 (7–32)
PANSS-negative (n = 307)	17.0 (6.6)	16 (7–43)
PANSS-general(n = 304)	33.3 (8.7)	33 (16–69)
PANSS-total (n = 302)	66.7(7.0)	67 (30–144)
Previous hospital admissions (n = 329)	3.5(5.3)	2 (0–40)

S.D.; standard deviation, GAF; Global Assessment of Functioning PANSS, Positive and Negative Syndrome Scale, # A total of 329 patients, 213 (64.7%) men and 116 (35.3%) women, with schizophrenia were included. Among these 261 (79.3%) patients fulfilled the DSM-IV (16) criteria for the paranoid type of schizophrenia, 40 (12.2%) patients undifferentiated type, 16 (4.9%) disorganized type, 11(3.3%) residual type and 1 (0.3%) catatonic type.

Table 2. Received primary therapeutic agent (PTA) in the study population, n = 329
Drug or treatment regimen	No. of patients (%)	Mean daily dose mg*	CPZ equivalents mg**
Second generation antipsychotic (SGA)	305 (92.7%)
Olanzapine	104 (31.6%)	14.4	288
Risperidon or Risperdal Consta	41 (20.6%)	3.7	244
Quetiapine	58 (17.6%)	537,5	698
Aripiprazole	51 (15.5%)	14.2	189
Ziprasidon	20 (6.1%)	85.8	137
Amisulpride	11 (3.3%)	615.9	616
Clozapine	16 (4.8%)	390.6	391
Sertindole	4 (1.2%)	18.2	342
First generation antipsychotic (FGA)	24 (7.3%)
Perphenazine or Perphenazine decan.	12 (3.6%)	8.9	111
Zuclopenthixol or Zuclopenthixol decan.	6 (2.1%)	20.0	80
Chlorprothixen	3 (0.9%)	116.7	233
Levomepromazine	1 (0,3%)	120	120
Chlorpromazine	1 (0.3%)	30.0	120
Flupentixol	1 (0.3%)	1.0	50
Haloperidol	0 (0%)
No. of patients using only one antipsychotic drug	228 (69.3%)
No. of patients using more than one antipsychotic drug	101 (30.7%)

*Per oral medication only.
** CPZ equivalents; Chlorpromazine equivalents according to Kroken et al 2009: https://www.biomedcentral.com/1471–244X/9/24/table/T1

Table 3. Group wise comparing of means
	Patients with one antipsychotic	Patients with two or more antipsychotics
	Mean	Mean
Age (n = 329)	32.12	31.32
Age at onset of psychosis (n = 140)	24.11	23.06
Duration (weeks) of untreated psychosis (n = 142)	151	91
GAF-S (n = 329)	41.51	36.65
GAF-F (n = 329)	42.32	38.15
PANSS-positive (n = 305)	15.81	17.38
PANSS negative (n = 307)	16.16	18.82
PANSS general (n = 304)	32.75	34.82
PANSS total (n = 302)	64.65	71.29
Number of previous admissions(n = 329)	2.916	4.881

GAF-S; Global Assessment of Functioning,-Symptom, GAF-F Global Assessment of Functioning, -Functions, PANSS; Positive and Negative Syndrome Scale

Table 4. Independent sample t-test comparing group of patients with one antipsychotic versus patients with two or more antipsychotics
	T-test for equality of means
	t	Sig (2-tailed)	95% Confidence for the difference Lower -Upper
Age (n = 329)	0.689	0.486	−1.457 – 3.060
Age at onset of psychosis (n = 140)	0.795*	0.429	−1.583 – 3.692
Duration (weeks) of untreated psychosis (n = 142)	2.318*	0.022	8.757 – 110.567
GAF-S (n = 329)	3.971	0.000	2.452 – 7.267
GAF-F (n = 329)	3.734	0.000	1.972 – 3.363
PANSS-positive (n = 305)	−2.187	0.030	−2.997 – −0.158
PANSS negative (n = 307)	−3.297	0.001	−4.239 – −1.070
PANSS general (n = 304)	−1.916	0.056	−4.195 – −0.056
PANSS total (n = 302)	−3.133	0.002	−10.821 – −2.471
Number of previous admissions (n = 329)	−2.859*	0.005	−3.323 – −0.606
No. of previous admission dichotomized, (0 or 1 vs. 2 or more previous admissions)	−3.189*	0.002	−0.284 – −0.067

* Equal variances not assumed due to Levene's Test for Equality of Variances, p < 0.05

Table 5. Number of previous hospital admissions; comparison of patients with only one antipsychotic versus patients with two or more antipsychotics
		No. of previous admissions to psychiatric ward
		0	1	2	3	4	5	6	7	8+
	N = 329	49	79	63	39	29	14	13	13	30
One antipsychotic	228 (69.3%)	40 (81.6%)	61 (77.2%)	46 (73.0%)	28 (71,8%)	13 (44.8%)	8 (57.1%)	8 (44.8%)	8 (61.5%)	16 (53.3%)
Two or more antipsychotics	91 (30.7%)	9 (18.4%)	18 (22.8%)	17 (27.0%)	11 (28.2.%)	16 (55.2%)	6 (42.9%)	5 (38.5%)	5 (38.5%)	14 (46.7%)

Table 6. Logistic regression model; Backward Stepwise (Wald) Previous admissions dichotomized 0–1 versus 2 or more
Patient factor	Odds Ratio (Exp.(B))	95.0% C.I. for OR Lower -Upper	P-value	Wald
GAF-Symptom	0.953	0.924 – 0.983	0.002	9.239
PANSS-negative symptoms	1,048	1.007 – 1.090	0.022	5.242
Two or more hospital admissions	2.445	1.416 – 4.225	0.001	10.258

GAF; Global Assessment of Functioning, PANSS; Positive and Negative Syndrome Scale, OR; Odds Ratio
*Nagelkerke R Square = 0.135

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