. 2022 Apr-Jun;15(2):224–244. doi: 10.5935/1984-0063.20220045

Table 1.

Summary of studies on classic antiepileptic drugs (n=18).

	Study (date and reference)	Type of study (class of evidence)	N	Population	Type of therapy	Dose (per day)	Comparison	Significative PSG results (mean ± SD)
Carbamazepine	Yang et al. (1989)³²	Prospective, non- randomized, non- blind (class III)	7	Healthy male volunteers	Acute monotherapy	Mean plasma range 11.8+1.1 \|ig/ml 200-700mg/day	NA	•fSWS (%): in CBZ (35.3+10.8) vs. baseline (16.8+9.7)^ REM(%): in CBZ (19.5+4.3) vs. baseline (22.8+4.3)^
	Manni et al. (1990)³³	Observational, non- randomized, non- blind (class III)	14	Focal epilepsy	Chronic monotherapy	15-20mg/kg	Healthy controls (n=11)	Patients with poor seizure control (mean 2.7 seizures per month; n=6): REM(%): in CBZ (16.8+5.6) vs. controls (29.6+5)^* ^REM latency (min): in CBZ (140.4+32.5) vs. controls (75.1+16.2)^* •fWASO: in CBZ (42.5+17.4) vs. controls (13.4+10.8)^* No. of awakenings: in CBZ (10.3+4.0) vs. controls (2.6+1.7)^* No. of shifts to stage N1: in CBZ (13.0+6.8) vs. controls (3.7+1.6)^*No. of stage shifts: in CBZ (47.8+9.8) vs. controls (21.0+4.5)^*Patients with complete seizure control (n=8): REM latency (min): in CBZ (106.4+24.3) vs. controls (75.1+16.2)^*
								No. of awakenings: in CBZ (9.5+5.6) vs. controls (2.6+1.7)^* ‘TNo. of shifts to stage N1: in CBZ (10.0+4.1) vs. controls (3.7+1.6)^* No. of stage shifts: in CBZ (40.0+10.5) vs. controls (21.0+4.5)^* There were no significative differences between the groups.
	Riemman et al. (1993)³⁶	Prospective, non- randomized, non- blind (class III)	12	Healthy male volunteers	Acute monotherapy	400mg/day	NA	After 5-day course of CBZ: •fSE (%): in CBZ (95.2+1.6) vs. baseline (91.1+4.0)^** ^* N2 latency (min): in CBZ (9.9+6.3) vs. baseline (23.8+13.7)^ Wake time (%):** in CBZ (1.6+1.4) vs. baseline (3.5+2.9)^* •fSWS (%): in CBZ (13.2+7.0) vs. baseline (6.8+5.3)^ Total REM density (%):** in CBZ (16.6+5.6) vs. baseline (21.8+5.1)^*
	Gigli et al. (1997)³⁴	Prospective non- randomized, single- blinded (class III)	16 (n=7 patients)	Temporal lobe epilepsy	Acute or chronic monotherapy	Initial dose: 400mg Following: 800mg	Healthy subjects	Acute CBZ in controls: “TStage shifts: in acute CBZ (211.9+78.7) vs. baseline (176.9+56.4)^** ^* Acute CBZ in TLE: REM(%): in acute CBZ (14.1+3.9) vs. baseline (17.6+4.8)^ No. of entries in REM: in acute CBZ (44.9+12.3) vs. baseline (31.6+5.8)^ No significative changes in chronic CBZ
	Gann et al. (1994)³⁵	Prospective, nonrandomized, uncontrolled	12	Healthy volunteers	Acute monotherapy	400mg/day	NA	At night 5: •fSE(%): in CBZ (95.2+1.6) vs. baseline (91.1+4.0)^** ^* Stage N2 latency (min): in CBZ (9.9+6.3) vs. baseline (23.8+13.7)^ •fSWS(%): in CBZ (13.2+7.0) vs. baseline (6.8+5.3)^
		(class III)						Total REM-density (%): in CBZ (16.6+5.6) vs. baseline (21.8+5.1)^*
	De la Fuente et al. (2002)³¹	Randomized, single blinded (class II)	20	Borderline personality disorder	Acute monotherapy	400- 800mg/day	Placebo (n=10)	At baseline: Stage N1: in CBZ (5.67+2.07) vs. placebo (9.63+3.38)^ After treatment: •fStage N3(%): in CBZ (4.95+2.39) vs. baseline (2.38+2.63)^ •fSWS(%): in CBZ (11.81+10.63) vs. baseline (4.14+5.17)^**
	Nayak et al. (2016)³⁹	Cross-sectional case- control (class III)	40	Temporallobe epilepsy	Drug-naive (n=20) CBZ monotherapy (n=20)	NA	Healthy controls (n=40)	•fTST (h): in CBZ (8.50+0.58) vs. controls (7.48+0.55)^** ^* SE(%): in CBZ (76.38+12.23) vs. controls (84.64+9.51)^* Stage N1 (%): in CBZ (4.50+2.69) vs. controls (8.07+4.22)^* REM arousal index: in CBZ (9.30+7.39) vs. controls (4.84+6.35)^** ^* No significative differences in controls vs. drug-naive patients
Clobazam	Nicholson et al (1977)⁴¹	Prospective, Randomized, double-blind (class I)	6	Healthy adults	Single-dose (10mg or 20mg/day)	10mg, 20mg	Placebo and group with triflubazam	Clobazam 10mg: 4/Stage N1(%): in CLO (4.4+32) vs. placebo (6.6+32)^* 4/Sleep onset latency (min): in CLO (17.7+40) vs. placebo (27.1+40)^* Clobazam 20mg: 4/Stage N1(%): in CLO (4.3+32) vs. placebo (6.6+32)^* •fStage N2(%): in CLO (54.7±8) vs. placebo (49.2±8)^*Stage N3(%): in CLO (7.7±19) vs. placebo (11.2±19)^**SWS(%): in CLO (16.3+16) vs. placebo (19.7+16)^* Sleep onset latency (min): in CLO (16.0±40) vs. placebo (27.1±40)^*
Clonazepam	Saletu et al. (2010)⁴⁵	Single-blind, nonrandomized, crossover (class III)	21	Drug-free adults with bruxism	Single-dose (1mg/day)	1mg	Healthy controls and placebo	No. of awakenings: in CNZ (8.4±5.3) vs. placebo (13.0±6.2)^ Awakening index (no/h of sleep): in CNZ (1.2±0.8) vs. placebo (2.4±1.3)^ WASO (min): in CNZ (17.7±19.2) vs. placebo (54.0±61.0)^ •fTST (min): in CNZ (419.1±22.6) vs. placebo (372.0±71.3)^ •fSE (%): in CNZ (93.0±5.0) vs. placebo (83.3±15.9)^ Stage N1 (%): in CNZ (4.3±3.1) vs. placebo (7.5±3.6)^ •fStage N3(%): in CNZ (9.0±5.3) vs. placebo (7.1±3.8)^ Stage shift index (n/h of sleep): in CNZ (17.5±4.4) vs. placebo (21.0±5.1)^
	Ferri et al. (2013)⁴²	Observational (class III)	57	Idiopathic REM sleep behavior disorder (iREMSBD)	Chronic monotherapy	0.5-1.0mg	iREMSBD taking bedtime clonazepam (n=15) Control: iREMSBD	Comparison between the two groups at baseline: Stage shifts (n/hour): in in CNZ (12.8±4.7) vs. control (16.5±6.59)^* •fSE (%): in CNZ (83.6±6.99) vs. control (76.0±13.08)^* WASO (%): in CNZ (10.1±6.19) vs. control (17.9±9.84)^ Stage N1 (%):** in CNZ (6.6±3.06) vs. control (9.0±4.08)^* •fStage N2 (%): in CNZ (46.2±10.88) vs. control (38.7±8.81)^**
							drug-free (n=42)	There were no statistically significant differences in the first follow-up (2.6+1.08 years) of patients taking CNZ (n=13).
	Sakai et al. (2016)⁴³	Randomized, double blind, crossover (class I)	19	Primary sleep bruxism	Acute monotherapy, crossover with clonidine	1mg	Placebo	No significative differences in sleep parameters in CNZ vs. placebo.
	Ferri et al. (2017)⁴⁶	Observational (class III)	64	Idiopathic REM sleep behavior disorder (iREMSBD)	Chronic monotherapy or acute monotherapy	0.5-2mg	Drug-naive (n=29) Chronic CNZ therapy (n=14) Healthy controls (n=21)	In chronic treatment patients (n=14) vs. drug naïve patients (n=29) Stage N2: in chronic CNZ (44.6+9.14) vs. drug-naïve patients (38.5+8.53)^*In chronic treatment patients (n=14) vs. Controls (n=21) Awakenings (/hour): in chronic CNZ (4.0+2.32) vs. controls (7.2+2.9)^* SE (%): in chronic CNZ (83.5+7.85) vs. controls (68.3+12.55)^ SWS (%): in chronic CNZ (17.5+6.75) vs. controls (10.4+7.82)^ ^*
Phenobarbital	Prinz et al. (1981)⁵⁰	Prospective, non- randomized (class III)	5	Healthy volunteers	Acute and chronic monotherapy	100mg	Placebo	Acute: significative differences vs. placebo Chronic (1 month): 4/Sleep latency (min): in PB (3.40+0.87) vs. placebo (8.23+2.50) Stage N4 (%): in PB (2.95+0.89) vs. placebo (9.36+1.98)
	Karacan et al. (1981)⁴⁹	Double-blind, nonrandomized, crossover	24 (males only)	Healthy volunteers	Acute monotherapy	80, 140, 240mg	Placebo	Results presented in (mean). 80mg: 4/No. of stage shifts: in PB night 1 (34.5) vs. placebo (39.4)^*
		(class I)						Stage REM (%): in PB night 1 (21.9) vs. placebo (25.5)^ •fStage N2(%):** in PB night 1 (61.0) vs. placebo (56.1)^* No. of awakenings: in PB night 2 (0.9) vs. placebo (1.6)^*Latency to stage 0 (min): in PB night 2 (305) vs. placebo (205)^*Stage REM (%): in PB night 2 (21.2) vs. placebo (25.4)^** ^* •fStage N2(%): in PB night 2 (60.7) vs. placebo (56.6)^* 140mg: 4/Stage REM (%): in PB night 1 (18.9) vs. placebo (25.5)^** ^* “TStage N2(%): in PB night 1 (62.1) vs. placebo (56.1)^ 4/REM episode duration (min):** in PB night 1 (22.4) vs. placebo (26.3)^* cNo. of awakenings: in PB night 2 (0.7) vs. placebo (1.6)^**Latency to stage 0 (min): in PB night 2 (301) vs. placebo (205)^*4/Stage REM (%): in PB night 2 (19.6) vs. placebo (25.4)^ ^“TStage N2(%):* in PB night 2 (63.4) vs. placebo (56.6)^** ^* 4/REM episode duration (min): in PB night 2 (21.4) vs. placebo (27.9)^** ^* 240mg: 4/No. of stage shifts: in PB night 1 (32.9)^* vs. placebo (39.4)^**Latency to REM (min): in PB night 1 (148) vs. placebo (85)^ ^4/Stage REM (%):* in PB night 1 (16.1) vs. placebo (25.5)^ ^“TStage N2(%):* in PB night 1 (66.3) vs. placebo (56.1)^ ^4/No. of REM episodes:* in PB night 1 (3.5) vs. placebo (4.2)^ REM episode duration (min):** in PB night 1 (21.6) vs. placebo (26.3)^* 4/No. of awakenings: in PB night 2 (0.2) vs. placebo (1.6)^ ^4/No. of stage shifts:* in PB night 2 (27.5)^* vs. placebo (34.8)^**Latency to stage N1 (min): in PB night 2 (389) vs. placebo (205)^ ^Latency to REM (min):* in PB night 2 (171) vs. placebo (98)^ ^4/Stage REM (%):* in PB night 2 (15.8) vs. placebo (25.4)^ ^“TStage N2(%):* in PB night 2 (67.4) vs. placebo (56.6)^** ^* 4/No. of REM episodes: in PB night 2 (3.2) vs. placebo (4.2)^** ^* 4/REM episode duration (min): in PB night 2 (21.8) vs. placebo (27.9)^**
Phenytoin	Roder-Wanner et al. (1987)⁵³	Prospective longitudinal, non- blind (class III)	31	Patients with new-onset epilepsy	Acute monotherapy	100mg	Placebo	Acute 100mg PHE in whole group (n=31): “TStage N4 (%): in PHE (41.5+32.4) vs. placebo (29.1+27.3)^* Acute 100mg PHE in group with generalized epilepsy (n=9): “TStage N4 (%): in PHE (53.0+34.5) vs. placebo (36.8+29.5)^ Acute 100mg PHE in group with focal epilepsy (n=8): REM(%):** in PHE (17.1+ 8.4) vs. placebo (26.7+12.9)^* After 4-6 weeks of PHE (check figure in paper for values): xVSleep latency (min): in PHE vs. baseline^* Stage N1 (%): in PHE vs. baseline^* Stage N2 (%): in PHE vs. baseline^* •fSWS (%): in PHE vs. baseline^* REM(%): in PHE vs. baseline^*
Valproic acid	Harding et al. (1985)⁵⁶	Prospective, single- blind (class III)	10	Healthy adults	Acute monotherapy	2 days placebo, 2 days placebo + 500mg VPA, 14 days 1,000mg VPA	Placebo	Visual evocked potential (VEP) and EEG sleep recording: - No significative differences in VEP On sleep EEG: (no values presented) REM: in high dose VPA vs. placebo^ ^REM:* in high dose VPA vs. low dose^ ^REM:* in low dose VPA vs. withdrawal^** ^* *^TSWS:** in high dose VPA vs. placebo^* *^TSWS: in high dose VPA vs. low dose^
	Eisenser et al. (2004)⁵⁴	Randomized, placebo-controlled, double-blind, cross- over study (class I)	20	Idiopathic RLS	Acute monotherapy	300mg-SR In the first 2 days followed by 600mg-SR	Placebo and crossover with Levodopa	Latency to stage N2: In VPA-SR (40.6±28.8) vs. placebo (29.7±26.8);^*
	Nayak et al. (2016)⁵⁷	Case-control cross- sectional study (class III)	40	Juvenile myoclonic epilepsy	N=20 drug naïve N=20 on VPA		Healthy controls	REM in VPA (28.76 ± 12.23) vs. drug naïve patients (13.83±5.91) vs. controls (16.26±4.01)^** ^*

Abbreviations: CBZ = Carbamazepine; CLO = Clobazam; CNZ = Clonazepam; PB = Phenobarbital; VPA = Valproic acid;

p<0,05;

^**

p>0,01;

^***

p<0,001.