Adjunctive treatment for cognitive impairment in patients with chronic schizophrenia: a double-blind, placebo-controlled study

Figures & data

Figure 1 Flow chart of participation in the study.

Table 1 Demographic and clinical characteristics of patients who received donepezil or placebo

Characteristics	Donepezil (n=31)	Placebo (n=30)	F/χ^2	P-value
Age (years)	24.71 (5.91)	25.90 (4.42)	0.790	0.378
Sex, n (%)			0.455	0.500
Male	14 (45.16)	11 (36.67)
Female	17 (54.84)	19 (63.33)
Education (years)	11.65 (1.91)	10.23 (2.65)	0.488	0.487
Duration of illness (years)	4.83 (2.48)	5.12 (2.49)	0.212	0.647
Dose of antipsychotic agents (mg/day)/patients (total number)
Risperidone	4.07 (1.21)/15	4.03 (1.20)/15	0.006	0.940
Olanzapine	16.25 (6.45)/16	17.33 (6.51)/15	0.216	0.645
Positive psychiatric family history, n (%)	8 (25.81)	7 (23.33)	0.500	0.823
PANSS total score	54.94 (8.92)	52.37 (9.16)	1.231	0.272
CGI severity score	3.87 (0.81)	3.53 (0.68)	3.112	0.083
CDSS total score	3.55 (1.96)	3.00 (1.75)	1.487	0.227

Notes: χ² for categorical variables and analysis of variance for continuous variables; mean (standard deviation) unless otherwise indicated.

Abbreviations: PANSS, Positive and Negative Syndrome Scale; CDSS, Calgary Depression Scale for Schizophrenia; CGI, Clinical Global Impressions scale.

Table 2 Neuropsychological test scores of patients with schizophrenia who received donepezil or placebo

	Time	Donepezil group (n=26)	Placebo group (n=26)	Between-group comparison
				F	P-value
CPT-IP	Baseline	2.15 (0.51)	2.10 (0.58)	0.092	0.763
	12 weeks	2.25 (0.72)	2.30 (0.63)	0.016	0.901
WMS-III SST	Baseline	15.00 (3.26)	14.92 (3.38)	0.042	0.838
	12 weeks	16.92 (1.53)**	14.96 (2.35)	16.694	<0.001
WCST
Perseverative errors	Baseline	15.88 (5.94)	13.27 (5.84)	3.521	0.067
	12 weeks	15.19 (8.72)	12.88 (8.58)	1.604	0.212
Categories completed	Baseline	2.88 (1.56)	3.23 (1.31)	0.463	0.499
	12 weeks	3.04 (1.46)	3.35 (1.47)	3.063	0.086
TMT-A	Baseline	45.56 (15.02)	45.15 (13.00)	0.011	0.918
	12 weeks	38.63 (11.28)**	45.01 (12.34)	11.446	0.001
BACS SC	Baseline	44.12 (11.54)	43.62 (9.98)	0.028	0.868
	12 weeks	46.58 (9.92)	43.31 (7.76)	2.683	0.108
CFT animal naming	Baseline	15.23 (4.01)	15.54 (4.13)	0.074	0.786
	12 weeks	17.35 (3.78)**	14.81 (3.20)	11.644	0.001
BVMT-R
Total recall	Baseline	21.65 (8.05)	19.88 (8.51)	0.593	0.445
	12 weeks	25.54 (6.90) **	17.92 (6.04)	33.898	<0.001
Delayed recall	Baseline	8.73 (3.21)	8.04 (3.38)	1.098	0.300
	12 weeks	10.58 (2.18) *	7.69 (3.12)	22.148	<0.001
HVLT-R
Total recall	Baseline	21.50 (6.29)	20.62 (6.40)	0.253	0.617
	12 weeks	21.88 (5.40)	19.38 (4.89)	3.045	0.088
Delayed recall	Baseline	7.58 (2.56)	6.62 (2.89)	1.613	0.210
	12 weeks	8.04 (2.79)	6.31 (2.36)	2.406	0.128
Stroop Task
Word	Baseline	104.04 (19.49)	107.19 (23.94)	0.073	0.788
	12 weeks	106.69 (14.24)	109.38 (18.70)	0.316	0.577
Color	Baseline	66.08 (15.75)	69.46 (18.34)	0.063	0.803
	12 weeks	68.12 (15.51)	68.58 (14.52)	0.012	0.912
Color-Word	Baseline	43.46 (12.07)	41.5 (10.73)	1.106	0.298
	12 weeks	47.77 (14.62)	45.35 (12.60)	1.063	0.308

Notes: Within-group differences were analyzed using the paired-samples t-test.

* P<0.05,

** P<0.01; between-group comparisons were analyzed using analysis of covariance controlling for baseline, age, and education.

Abbreviations: CPT-IP, Continuous Performance Test-Identical Pairs; WMS-III SST, Wechsler Memory Scale-Third Edition Spatial Span; WCST, Wisconsin Card Sorting Test; TMT-A, Trail-Making Test Part A; BACS SC, Brief Assessment of Cognition in Schizophrenia Symbol Coding test; CFT, Category Fluency test; BVMT-R, Brief Visuospatial Memory Test-Revised; HVLT-R, Hopkins Verbal Learning Test-Revised.

Figure 2 Effect size of change in domain scores after 12 weeks of treatment with donepezil or placebo in patients with schizophrenia.

Notes: Between-group comparisons were analyzed using analysis of covariance controlling for baseline, age, and education. *P<0.008.

Table 3 Safety measures of patients with schizophrenia who received donepezil or placebo

Adverse events, n (%)	Donepezil (n=31)	Placebo (n=30)	χ^2/Fisher’s exact test	P-value
Extrapyramidal symptoms	10 (32.29)	9 (30.00)	0.036	0.849
Dry mouth	2 (6.45)	1 (3.33)	–	1.000
Insomnia and agitation	2 (6.45)	2 (6.67)	–	1.000
Dizziness	1 (3.23)	0 (0)	–	0.492
Nauseaa	1 (3.23)	1 (3.33)	–	1.000
Menstrual irregularities	1 (5.88)	2 (10.53)	–	0.612
Weight gain >7% (from baseline to last observation)	5 (16.12)	4 (13.33)	0.095	0.758

Note:

a Percentages are based on the number of female patients.