Jumat, 05 Mei 2017

A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children.


Efficacy along with tolerability of the mixed valerian/lemon balm preparation (1) were investigated within an open, multicentre research in

children lower than 12 years suffering via restlessness and nervous

dyskoimesis. Patients had been dosed on their own own through the investigators. In

total, 918 children had been evaluated regarding therapeutic efficacy and

tolerability. a distinct and convincing reduction inside severity was found

for all signs as well as symptoms in the investigators' along with parents' ratings.

The core symptoms dyssomnia along with restlessness had been reduced from

"moderate/severe" to be able to "mild" or perhaps "absent" in

most in the patients. in total, 80.9% of the patients who suffered from

dyssomnia experienced a noticable difference for this symptom and 70.4% involving the

patients using restlessness improved clearly. With Regard To another listed
< br>symptoms the actual total improvement has been 37.8% on average. Both, mother along with father and

investigators assessed efficacy as to become "very good" or

"good" (60.5% along with 67.7%, respectively). The Actual tolerability of

Euvegal[R] forte ended up being considered as "good" (in 96.7% associated with the

patients it had been judged being "very good" or "good").

No research medication-related adverse events occurred.

In conclusion, Euvegal[R] forte ended up being successful in the therapy of

younger children with restlessness as well as dyssomnia as well as it had been really well


[c] 2006 Elsevier GmbH. Most legal rights reserved.

Keywords: Lemon balm/valerian combination; Restlessness; Dyssomnia;



Restlessness and also nervous sleep disturbance (dyssomnia) are

considered being mental disturbances together with predominantly somatic symptoms. These consist of jactitation, stuttering, refusal to always be able to eat,

anorexia nervosa and also bulimia nervosa (WHO, 1992).

General motor restlessness could arise temporarily or could be a

personality characteristic which usually carries on beyond childhood. Children

suffering through this syndrome are usually not in a position to sit still in supplement for you to their hands are

always "on move". Especially within scenarios which usually demand

discipline and also attention (e.g. in the particular course of school), many kids demonstrate a

continuous motor restlessness. When not 1 other signs of an endogenous or

psychotic disease are usually present with no neurological deficits may be found

such behaviour will be known as hyperkinetic syndrome.

Dyssomnia in children can be expressed as difficulties within falling

asleep (dyskoimesis) or in sleeping by means of the night as dysphylaxia,

pavor nocturnus and also somnabulism. Such disturbances frequently are generally temporary

and the particular incidence in children is all about 30%.

Phyto-pharmaceutical goods play an important role within the

treatment associated with nervous dyssomnia along with pathological restlessness. The

positive outcomes of valerian about sleep disturbances have got been

demonstrated inside many clinical tests (Stevinson and Ernst, 2000). Even

in patients whom took benzodiazepines before, a significant better

subjective sleep top quality has been reported (Dorn, 2000). In Comparison to end up being able to oxazepam zero distinctions within the efficacy were discovered pertaining to valerian, nevertheless the valerian

product stood a favourable adverse effect profile (Poyares et al., 2002).

The combination of valerian along with lemon bal m ended up being in addition studied to show

positive effects in sleep disorders as well as around the mood (Dressing et

al., 1996; Cerny as well as Schmid, 1999). Inside the clinical study the particular results of a

valerian/melissa combination compared to be able to benzodiazepines ended up being studied in

adults with sleep disorders as well as insomnia (Dressing et al., 1992). The

positive outcomes associated with this mixture were documented and no daytime

sedation or rebound phenomena were noted. Unlike the actual benzodiazepines,

which possess numerous unpleasant side effects, valerian extracts and lemon

balm show merely really low toxicity (McGuffin et al., 1997). You may find no

interactions along with various other drugs, however, due to its sedative properties

it really shouldn't be employed using alcohol (Blumenthal, 1998).

In children, alternative therapies inside the thera py involving attention

deficit hyperactivity disorder (ADHD) and dyssomnia are generally associated with common

interest. Since stated inside Psychosocial Paediatrics Committee (2002) some

therapies pertaining to youngsters are available. Valerian and also lemon balm are

considered being successful with merely rare side effects, nevertheless just limited

study information had been revealed (Hintelmann, 2002).

The aim regarding this research ended up getting to investigate your efficacy and

tolerability of the valerian/lemon balm combination within the therapy of

restlessness and also nervous dyskoimesis in children younger when compared with 12 years.

Materials and methods

Children younger when compared with 12 years, suffering coming from pathological
restlessness and/or nervous dyskoimesis, had been included within this open,

multicentre postmarketing surveillance study. The Particular patients had been treated

for no much less than 4 weeks ([+ or even -] 1 week). The Particular dosage of Euvegal[R] forte

was chosen by the investigator with a maximum regarding two x two tablets/day. Each

tablet consisted involving 160mg valerian root dry extract (Valeriana

officinalis L.) having a drug-extract ratio associated with 4-5:1 (extraction solvent

ethanol 62% V/V) along with 80 mg lemon balm leaf dry extract (Melissa

officinalis) using a drug-extract ratio involving 4-6:1 (extraction solvent

ethanol 30% V/V). no other medication in order to treat restlessness and/or

nervous dyskoimesis was permitted. Your children's mother and father were

fully informed about the research from the investigator.

On baseline the investigators documented the particular health-related history, e.g.

the recognized duration of the illness, previous health-related treatments,

concomitant illnesses and the diagnosis in the present illness. To

analyse the patient's disease your investigator were necessary to select from

three diagnoses (restlessness, nervous dyskoimesis and also other), with

multiple answers becoming possible. Throughout addition, your incidence and the

severity associated with signs had been documented. The Particular distribution in the symptom

occurrence had been divided throughout 4 classes (from each day to many times

a month), whereas the severity had been categorized coming from absent (0) to become able to very

severe (4). The next symptoms were detailed in each visits:

"restlessness", "dyssomnia", "physical

weakness", "rapid fatigability", "lack of

concentration", "hyperactivity",

"aggressiveness", "lack regar ding appetite",

"excessive drowsiness", "listlessness/dejection" or


At the ultimate visit the actual incidence and furthermore the severity in the symptoms

were in comparison towards the information in the baseline visit and the length of the

illness ended up being documented pertaining to almost all signs by the investigators along with the

parents with all the exact same score via absent (0) to become able to really severe (4).

Additionally, your improvement associated with the illness also as the efficacy of

the study medication were analysed in numerous questionnaires

[improvement score ranged via one (very excellent improvement) to be able to 5

(deterioration), the efficacy score ranged through one (very good) to 5


The physicians were motivated to assess your tolerability of Euvegal[R]

forte by means of a tolerability score that ranged comi ng from "very good" (1)

to "poor" (5).

Adverse events had to become documented during the complete study phase.



For this study, 938 patients had been recruited inside 207 paediatric centres within Germany. A New total involving 918 patients had been evaluated regarding efficacy

since 17 patients violated severely the particular inclusion/exclusion criteria and

3 patients didn't perform just about any post-baseline visit and thus were not

eligible for evaluation.

There had been 56.8% male as well as 43.2% female patients (n = 914) along with an

average age of 8.3 years. 21.6% in the patients were younger than 6


According to the patients' health-related history your children

suffered via their own symptoms with a suggest regarding 10.5 a number of months (SD = 15.4

months). With Regard To any total regarding 264 patients (28.8%) at least 1 previous herbal

treatment therapy had been reported, regarding 101 patients (11%) other sedative

drugs had been noted. all the particular remaining patients (60.2%) had no medical

therapy for that research indication before.

The mean duration regarding study participation ended up being 31.9 days (SD = 12.1


The mean dosage at research start had been 3.5 tablets/day. The Actual standard

dosage (4 tablets/day) ended up being chosen for 74.6% of the patients. in the

course involving the analysis the dosage was modified in 68 patients (7.4%).


The incidence associated with symptoms was recorded from both visits. From the

baseline visit, 566 patients (61.7%) reported involving signs in which occurred

every day, with the final visit merely 115 patients (12.5%) suffered from

dyssomnia or even re stlessness every day. About inclusion, 99.3% of patients

suffered from typical signs and symptoms no less than once any week, whereas only 71.5%

revealed such signs and symptoms each week following the particular study.

The core symptoms restlessness along with dyssomnia improved significantly

during the actual study.


Restlessness changed coming from "moderate" and

"severe" (65.9% in total) for you to "absent" and

"mild" (75.2% in total), dyssomnia improved from

"moderate" and also "severe" (77.1% within total) to

"absent" and "mild" (76.6% within total). Table 1

demonstrates the introduction of the core symptoms during the study.

During the particular study, your "improvement within total", which in tur n was

defined being an improvement by simply at least one or perhaps two points in the symptom

score, ended up being judged being 70.4% and 80.9% pertaining to restlessness and dyssomnia,


All the other documented signs as outlined above, improved

likewise. Your highest effects of improvement had been measured for

"dyssomnia" and "others" together with values above 80%.

To assess the actual subjective efficacy, the oldsters in the patients were

asked in order to fill in a questionnaire using a 5-point scale ("very great

improvement" (1) to "deterioration" (5)). The

investigator needed to assess your efficacy with a scale in which ranged from

"very good" (1) in order to "poor" (5). Both, the

investigators' and the parents' impression in the therapeutic

effect involving Euvegal[R] forte was good (Fig. 1).

Subgroup analysis

In a subgroup analysis the results were evaluated with regard to

the ages of the patients. The Particular infant group (< 6 years, 198 patients)

and the actual school kids group ([greater than or perhaps equal to]6 years, 719

patients) had been in comparison with respect for the every day dosage and the effects

of the particular medication on the signs of their particular illness.

A total involving 581 (80%) of the institution children took the utmost dosage

of 2 x 2 tablets/day, 112 (15.5%) of which took 2 tablets/day (2 x one or even 1

x 2). To Become Able To 102 (51.5%) with the infants any daily dosage associated with two x two tablets was

prescribed, and 61 (30.8%) took two tablets every day (1 x two or two x 1). The

remaining patien ts received one as well as three tablets/day.

A significant improvement of the core symptoms (restlessness and

dyssomnia) ended up being demonstrated in both groups independently associated with grow older and dosage

(Figs. two and 3).



The outcomes demonstrate which each teams improved significantly

with respect towards the core signs and also symptoms restlessness and also dyssomnia.



For 96.7% of the patients the actual tolerability had been judged through the

investigator being "very good" or "good" (Table 2).

During this study, a total associated with 2 adverse events occurred. Your first

was acetonaemic vomiting, the 2nd was an urinary tract infection.

None of which had been judged to become drug related by the investigators.

When the analysis was finished, 548 patients planned for you to carry on the

therapy with Euvegal[R] forte.


In 157 in the 918 cases a young discontinuation was noted, for

another 7 patients no data had been available. Regarding 142 of the dropouts the

mean treatment method duration ended up being 22.3 days (SD 10.6 days), for another 15

patients the actual data were missing. The Particular reasons for discontinuation were

selected through the investigators and are listed down below in Table 3.

There was zero case of "poor tolerability", along with concerning half

of the actual patients stopped therapy simply because associated with remission. Under

"other" the particular next reasons were noted: zero data (2),

pharmaceutical form (14), lack of efficacy (12), compliance problems

(9), admission to hospital (2, with out virtually any causal relationship t o end up being able to study

drug), hyperactivity in the individual (1) and packet empty (1).


In this multicentre observational study the actual herbal drug combination

Euvegal[R] forte had been efficient in the remedy regarding children with

restlessness and also dyssomnia. The Particular core signs of this common disease

were evaluated in 918 kids up to 12 years. In The Actual Program Of an average

treatment period associated with time of 30 days with just about all the valerian/lemon balm combination a

fast and significant improvement of the illness in the majority of your patients

was achieved.

The subgroup analysis showed that children of most evaluated age

groups could benefit from this treatment. Since zero study

medication-related adverse events occurred, it can be stated that,

together with former experiences (Dressing et al., 1996; C erny and

Schmid, 1999), Euvegal[R] forte is a extremely well-tolerated medication. It

is an essential fact that the good therapeutic efficiency as well as the

safety of the mix of valerian and also lemon balm now could be shown

in kids approximately 12 years, as previously carried out inside adult patients (Albrecht

et al., 1995),

Due towards the proven fact that synthetic psychotropic drugs bear a top risk

of addiction or even side effects, it should end up being forced about investigations of

alternative therapies within the treatment involving children. Various therapies

are available and also have been discussed before (Psychosocial Paediatrics

Committee, 2002), but concrete comparisons regarding herbal as well as chemical drugs

in your treatment associated with kids are missing.

It should be the actual aim involving further investigations to demonstrate the

benefit associated with Euvegal[R] forte in studies focussing in equivalence

of this herbal mixture using synthetic substances in kids to

reveal the actual risk--benefit ratio in the drugs.

In conclusion, it can be stated that Euvegal[R] forte might be an

interesting alternative in order to chemical psychotropic drugs in the therapy of

restlessness and dyssomnia throughout younger children.


Albrecht, M., Berger, W., Laux, P., Schmidt, U., Martin, C., 1995.

Psychopharmaka und Verkehrssicherheit. Der Einfluss von

Euvegal[R]--Dragees forte auf die Fahrtuchtigkeit und

Kombinationswirkungen mit Alkohol. Z. Allg. Med. 71, 1215-1228.

Blumenthal, M. (Ed)., 1998. The Particular total German Comission E

Monographs, Therapeutic guide for you to Herbal Medicines. American Botanical

Council, pp. 226-227.

Cerny, A., Schmid, K., 199 9. Tolerability along with efficacy of

valerian/lemon balm inside healthy volunteers (a double blind,

placebo-controlled, multicentre study). Fitoterapia 70, 221-228.

Dressing, H., Riemann, D., Low, H., Schredl, M., Reh, C., Laux, P.,

Muller, W.E., 1992. Baldrian-Melisse-Kombination versus Benzodiazepin

Bei Schlafstorung gleichwertig? Therapiewoche 42, 726-736.

Dressing, H., Kohler, S., Muller, W.E., 1996. Verbesserung der

Schlafqualitat mit einem hoch-dosierten Baldrian-Melisse-Praparat.

Psychopharmakotherapie 3, 123-130.

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Oxacepam bei nichtorganischen und nichtpsychiatrischen Insomnien: Eine

randomisierte, doppelblinde klinische Vergleichsstudie. Forschende

Komplementarmedizin und klassische Naturheilkunde 7, 79-84.

Hintelmann, C., 2002. Einschlafstorungen bei Kindern unter 12

Jahren. Schweiz. Zschr. GanzheitsMedizin.

McGuffin, M., Hobbs, C., Upton, R., Goldberg, A., 1997. American

Herbal Goods Association's Botanical Safety Handbook. CRC Press,

Boca Raton, FL.

Poyares, D.R., Guilleminault, C., Ohayon, M.M., Tufik, S., 2002.

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attention deficit hyperactivity disorder. Paediatr. Kid health 7(10),


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S.F. Muller (a), S. Klement (b,*)

(a) 42489 Wulfrath, Germany

(b) Dr. Willmar Schwabe Pharmaceuticals, 76227 Karlsruhe, Germany

*Corresponding author. Tel.: +49 721 4005 514; fax: +49 721 4005


E-mail address: stephan.klement@schwabe.de (S. Klement).

(1) Euvegal[R] forte, company Schwabe Pharmaceuticals,

Karlsruhe, Germany. [1 Dragee contains 160mg drug extract involving Valerian

roots (DEV 4-5:1, solvent with regard to extr. 62% ethanol) and 80mg drug extract

of lemon balm (DEV 4-6:1, solvent pertaining to extr. 30%)].

Table 1. Examination o f the core signs "restlessness" as well as "dyssomnia"

at the initial and second consultations

Restlessness Dyssomnia

First visit 2nd visit Very first visit 2nd visit

Symptom Pat. % Pat. % Pat. % Pat. %

No information 8 0.9 eight 0.9 4 0.4 six 0.6

Absent one hundred 10.9 272 29.6 57 6.2 273 29.7

Mild 166 18.1 418 45.5 92 10.0 430 46.8

Moderate 347 37.8 169 18.4 327 35.6 170 18.5

Severe 258 28.1 41 4.5 381 41.5 33 3.6

Very severe 39 4.3 10 1.1 57 6.21 6 0.7

Total 918 100 918 100 918 one hundred 918 100

Table 2. Investigators' assessment with the tolerability of the valerian/

lemon balm combination

Tolerability Individual figures Percentage

Very excellent (1) 571 62.2

Good (2) 317 34.5

Satisfactory (3) 18 1.9

Adequate (4) 3 0.3

Poor (5) one 0.1

No information 8 0.9

Total 918 100.00

Table 3. reasons regarding early discontinuation during the study

Reason with regard to discontinuation Patients Percentage

Treatment will no longer required 74 47.1

Parents request 64 40.8

Poor tolerability 0 0.00

Other 41 26.1

No reasons provided 3 1.91

Total 182 (a)

(a) Multiple answers possible.

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