Clozapine-induced seizures, electroencephalography abnormalities, and clinical responses in Japanese patients with schizophrenia

Figures & data

Table 1 Patient demographics

	Normal EEG	Abnormal EEG	P
Total number of patients	16	10
Sex (n)a	F: 9, M: 7	F: 9, M: 1	NS
Mean age (years)b	43.3±12.9	25.9±9.4	<0.01
Illness duration before clozapine treatment (years)b	15.4±10.4	6.9±5.3	<0.01
Mean dose of clozapine (mg)b	378.1±179.8	305.0±131.7	NS
Length of clozapine treatment (months)b	13.3±10.4	17.5±11.4	NS

Notes:

a Chi-square test

b Student’s t-test. Data are presented as mean ± standard deviation.

Abbreviations: EEG, electroencephalography; F, female; M, male; NS, not significant.

Table 2 Clinical courses of patients with EEG abnormalities and seizure

Case	Age (years)	Sex	Time (weeks)	Dose (mg)	Seizure	EEG	Response
1	23	F	23	600	Myoclonus	Spike and slow wave, theta	None
			52	600	Few myoclonic seizures	Spike, theta, delta	Start LTG 200 mg
			104	600		Slow wave	LTG 200 mg
			130	600	None Tonic–clonic	Theta	Increase to LTG 300 mg, decrease to clozapine 550 mg
			>130	550	None	None	LTG 300 mg
2	19	F	18	350	Myoclonus	Spike and slow wave, theta	None
			24	500	None	Spike and slow wave, theta	None
			36	500	Few myoclonic seizures		Start LTG 200 mg
			56	550	None	Spike and slow wave, theta	Decrease to LTG 150 mg
3	48	F	9	400	Myoclonus	Slow wave, spike and slow wave	None
			12	350	Myoclonus	Slow wave	Decrease to clozapine 300 mg
			26	300	None	Infrequent slow wave	None
4	24	F	8	300	Myoclonus	Spike and slow wave, delta	Start VPA 400 mg and increase to VPA 600 mg
			9	300	Myoclonus	Slow wave	VPA 600 mg
			12	300	Infrequent myoclonus None	Slow wave	VPA 600 mg, decrease to clozapine 200 mg
			15	200	None	Infrequent slow wave	Decrease to VPA 400 mg
			23	200		None	VPA 400 mg
5	22	F	8	300	Tonic–clonic	Spike and slow wave, theta	Start VPA 400 mg and increase to VPA 600 mg
			>8	300	None	Theta	Increase to clozapine 400 mg
			18	400	Partial seizure	Theta	Increase to VPA 800 mg
			>18	400	None	None	VPA 800 mg
6	25	F	4	250	None	Theta	None
			8	350	Myoclonus	Slow wave, spike and slow wave	Decrease to clozapine 275 mg
			14	275	Myoclonus	Spike and slow wave, delta	Start VPA 600 mg
			15	275	Few and frequent myoclonic seizures	Spike and slow wave, delta	Increase to VPA 800 mg
			>15	275	None	None	VPA 800 mg
7	22	F	8	200	None	Spike and slow wave	None
			52	300	None	Few frequent theta	None
8	37	F	52	325	None	Spike and slow wave, theta	None
			104	325	None	Spike and slow wave, theta, delta	None
9	22	F	8	200	None	Spike and slow wave	None
			34	300	None	Infrequent spike and slow wave	None
10	17	F	8	125	None	Many theta waves	None
			52	300	None	Spike and slow wave	None

Abbreviations: EEG, electroencephalography; F, female; LTG, lamotrigine; VPA, valproate.

Table 3 Comparison of clinical results between the normal and abnormal EEG groups

	Normal EEG	Abnormal EEG	P
Baseline PANSS (T)	99.4±27.8	87.9±15.2	NS
Last-observation PANSS (T)	59.1±12.1	46.7±11.3	0.02
Response rate (%)	37.4±16.9	46.6±9.9	NS

Note: Data are presented as mean ± standard deviation.

Abbreviations: EEG, electroencephalography; NS, not significant; PANSS (T), total Positive and Negative Syndrome Scale score.