Effects of herbal medicines containing Paeoniae Radix on patients with restless legs syndrome: A retrospective chart review study

Table 1 Demographic and clinical profile of participants

	General characteristics	Number of patients (%)
Sex	Male	3 (20.0)
	Female	12 (80.0)
Age	20s	1 (6.6)
	30s	0 (0)
	40s	3 (20.0)
	50s	0 (0)
	60s	7 (46.6)
	70s	4 (26.6)
Duration of symptom	Less than 1 year	3 (20.0)
	1-3 years	2 (13.2)
	3-5 years	1 (6.6)
	5-10 years	5 (33.3)
	More than 10 years	3 (20.0)
	Undetermined	1 (6.6)
Symptom site	Sole	3 (20.0)
	Thigh	5 (33.3)
	Calves	8 (53.3)
	Ankle	6 (40.0)
	Knee	1 (6.6)
	Feet	1 (6.6)
History	Hypertension	6 (40.0)
	Parkinson’s disease	1 (6.6)
	Dyslipidemia	4 (26.6)
	Iron deficiency anemia	1 (6.6)
	Cardiovascular disease	3 (20.0)
	Spinal stenosis	2 (13.2)
	Lung disease	1 (6.6)
	HIVD of L-Spine	2 (19.8)
	Gynecological disease	2 (13.2)
	Chronic kidney disease	1 (6.6)
HCP administrating duration	2-4 weeks	4 (26.7)
	4-6 weeks	5 (33.3)
	More than 6 weeks	6 (40.0)

HCP: Herbal medicines containing Paeoniae Radix; HIVD: Hernia of intervertebral discs.

Table 2 Summary of the clinical information and outcomes of each patient with restless legs syndrome taking herbal medicine containing Paeoniae Radix

Case	Age/Sex	Intervention/HCP use period	History	RLS duration/site	Other treatment	K-IRLS before and after treatment/Patient’s complaint after treatment	Adverse events
P1	68/F	Gyejibokryeonghwan/2P#2 51 days, 1P#1 85 days	Atherosclerosis, HTN, spinal stenosis	2 weeks/sole	None	K-IRLS: Total: Before 12 after 6; Urge to move: before 2 after 0; Duration; before 3 after 1; 0% of symptoms compared to pre-treatment, only noticeable when aware of symptoms	None
P2	48/F	Gamisoyosan/3P#3 140 days	Uterine myoma	2 years/calves, ankle	None	K-IRLS: Total: Before 19 after 13; Urge to move: before 3 after 1; Severity: Before 3 after 1; 40% of symptoms compared to pre-treatment; Frequency decreased to once a week	None
P3	23/F	Dangguijakyaksan/2P#2 84 days	Nonspecific	6 years/thigh	None	K-IRLS: Total: Before 22 after 9; Discomfort: Before 3 after 2; Frequency: Before 3 after 1; 20% of symptoms compared to pre-treatment; Declined symptoms severity and occurrence from 4-5 times a week to once a week after treatment	None
P4	73/F	Gyejibokryeonghwan Gamisoyosan/both 2P#2 28 days	HTN, dyslipidemia, HIVD of L-Spine	12 years/sole	Dopamine agonist (Pramipexole)	K-IRLS: Total: Before 35 after 21; Discomfort: Before 4 after 2; Urge to move: Before 4 after 2; Severity: Before 4 after 2; Relief from movement: Before 4 after 2; 70% of symptoms compared to pre-treatment, especially sleep disorder	None
P5	62/M	Jakyakgamchotang Gyejibokryeonghwan/both 1P#1 15 days	Nonspecific	8 years/calves, thigh, knee	None	K-IRLS: Total: Before 24 after 10; Discomfort: Before 3 after 1; Urge to move: Before 3 after 1; Frequency: Before 4 after 1; 30% of symptoms compared to pre-treatment, especially daytime tiredness	None
P6	68/F	Gyejibokryeonghwan/3P#3 14 days 2P#2 28 days, 1P#1 42 days; Dangguijakyaksan 1P#1/1P#1 30 days	HTN, dyslipidemia	4 years/sole	Dopamine agonists (Levodopa, Ropinirole hydrochloride)	K-IRLS: Total: Before 18 after 0; Discomfort: Before 2 after 0; Urge to move: Before 2 after 0; Frequency: Before 3 after 0; 0% of symptoms compared to pre-treatment	None
P7	60/F	Jakyakgamchotang 2P#2; Gyejibokryeonghwan 1P#1/113 days	HTN, dyslipidemia, asthma, HIVD of L-Spine	6 months/calves, ankle	Iron supplements (Iron acetyltransferrin)	K-IRLS: Total: Before 40 after 0; 0% of symptoms compared to pre-treatment	None
P8	70/F	Jakyakgamchotang 2P#2/35 days; Gyejibokryeonghwan 3P#3/35 days; Sihogyejitang 3P#3/28 days	Meningioma, angina pectoris	Unknown/calves, ankle, sole	None	K-IRLS: Total: Before 30 after 9; Discomfort: Before 4 after 1; Urge to move: before 4 after 1; Severity: Before 4 after 1; 50% of symptoms compared to pre-treatment, especially sleep disorder	None
P9	44/M	Gamisoyosan/2P#2 28 days	Nonspecific	8 years/calves	None	K-IRLS: Total: Before 16 after 14; Discomfort: Before 2 after 1; Urge to move: Before 2 after 1; 20% of symptoms compared to pre-treatment; especially sleep disorder	None
P10	43/F	Dangguijakyaksan Sihogyejitang/both 2P#2 30 days	CKD	7 years/calves, thigh, feet	GABA (Pregabalin); Iron supplements (Iron acetyltransferrin) Benzodiazepines (Clonazepam)	K-IRLS: Total: Before 37 after 36; 80% of symptoms compared to pre-treatment; even after the Pregabalin administration was stopped. Symptom frequency and duration were prolonged	None
P11	71/F	Sihogyejitang Danggwisayeokgaohsuyusaenggangtang Gyejibokryeonghwan/all 2P#2 14 days	HTN, dyslipidemia, spinal stenosis, iron deficiency anemia	10 years / ankle	Iron supplements (Dried ferrous sulfate); Benzodiazepines (Clonazepam); Dopamine agonist (Pramipexole)	K-IRLS: Total: Before 23 after 24; Discomfort: Before 4 after 3; Urge to move: before 4 after 2; 70% of symptoms compared to pre-treatment	None
P12	69/M	Jakyakgamchotang/1P#1 84 days	HTN, BPH	1 month/thigh	None	K-IRLS: Total: Before 9 after 5; Discomfort: Before 2 after 1; Sleep disorder: Before 2 after 0; 60% of symptoms compared to pre-treatment, the frequency of symptoms occurrence decreased to once a week after treatment; Increased quality of sleep time	None
P13	68/F	Dangguijakyaksan/2P#2 14 days	Nonspecific	50 years/calves, thigh, ankle	None	K-IRLS: Total: Before 32 after 34; Urge to move: before 4 after 3; Sleep disorder: Before 4 after 3; No change of symptoms	None
P14	74/F	Danggwisayeokgaohsuyusaenggangtang /2P#2 14 days	Nonspecific	10 years/calves	None	K-IRLS: Total: Before 15 after 19; 90% of symptoms compared to pre-treatment	None
P15	60/F	Jakyakgamchotang/1P#1 14 days	Parkinson’s disease	1 year/ankle	Dopamine agonists (Pramipexole, Rasagiline); NSAIDs (Naproxen, Celecoxib)	K-IRLS: Total: Before 13 after 9; Severity: Before 2 after 0; Frequency before 2 after 0; 90% of symptoms compared to pre-treatment; Reduced RLS symptom duration from 1 hour to less than 1 minute	None

RLS: Restless legs syndrome; HCP: Herbal medicines containing Paeoniae Radix; K-IRLS: Korean version of the international restless legs scale; HTN: Hypertension; HIVD: Hernia of intervertebral discs; CKD: Chronic kidney disease; GABA: Gamma-aminobutyric acid; BPH: Benign prostatic hyperplasia; NSAIDs: Nonsteroidal anti-inflammatory drugs.

Table 3 Comparisons of differences in the Korean version of the international restless legs scale scores before and after the administration of herbal medicine containing Paeoniae Radix

K-IRLS	Baseline	After treatment	P value
Total score	23.0 ± 9.7	13.9 ± 10.9	0.0051
Discomfort	2.6 ± 1.2	1.6 ± 1.1	0.0331
Urge to move	2.8 ± 1.1	1.3 ± 1.1	0.0021
Relief from movement	2.2 ± 1.3	1.6 ± 1.2	0.168
Sleep disorder	2.2 ± 1.3	1.6 ± 1.4	0.071
Day time tiredness	1.3 ± 1.4	1.0 ± 1.2	0.632
Severity	2.8 ± 1.0	1.2 ± 1.3	0.0031
Frequency	3.0 ± 0.9	1.6 ± 1.4	0.0071
Duration	2.4 ± 1.1	1.6 ± 1.4	0.0331
Effect on daily affairs	1.8 ± 1.5	0.8 ± 1.1	0.0351
Mood disturbance	1.4 ± 1.4	1.0 ± 1.2	0.305

¹Statistically significant at P < 0.05 by Wilcoxon signed rank test. mean ± SD values are displayed. The Wilcoxon signed-rank test was employed for comparing the values before and after treatment. K-IRLS: The Korean version of the international restless legs scale.

Table 4 Comparisons of the Korean version of the International Restless Legs Scale scores according to the herbal medicine containing Paeoniae Radix type

HCP	Administration group
	Baseline	After treatment	P value
Gyejibokryeonghwan (n = 7)	26.0 ± 9.7	10.0 ± 9.4	0.0281
Jakyakgamchotang (n = 5)	23.2 ± 12.6	6.6 ± 4.2	0.0421
Sihogyejitang (n = 3)	30.0 ± 7.0	23.0 ± 13.5	0.414
Dangguijakyaksan (n = 4)	27.3 ± 8.8	19.8 ± 18.0	0.273
Danggwisayeokgaohsuyusaenggangtang (n = 2)	19.0 ± 5.7	21.5 ± 3.5	0.180
Gamisoyosan (n = 3)	23.3 ± 10.2	16.0 ± 4.4	0.109

¹Statistically significant at P < 0.05 by Wilcoxon signed-rank test. mean ± SD values are displayed. The Wilcoxon signed-rank test was employed for comparing the values before and after treatment. HCP: Herbal medicine containing Paeoniae Radix.