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Observational study: Matricaria chamomilla may improve symptoms of attention-deficit hyperactivity disorder.

Abstract

Objective: Noradrenaline and serotonin reuptake inhibitors have been proven to be effective in some cases of ADHD. In this open trial, Matricaria chamomilla, a serotonin and noradrealine reuptake inhibitor, actually used as an antidepressant, has been checked for this indication.

Method: Three 14-16-year-old male psychiatric outpatients, diagnosed with attention-deficit disorder (ADHD) have been rated at baseline and while taking Matricaria chamomilla to determine its efficacy as a treatment for ADHD. Improvement was valuated using comparisons of Conners' parent ratings.

Results: Patients' mean scores improved for Conners' hyperactivity, inattention and immaturity factors.

Conclusions: Although the sample size is very small and therefore generalization is very difficult, this observation indicates that Matricaria chamomilla might be a slightly effective treatment also for ADHD.

[C]2008 Elsevier GmbH. All rights reserved.

Keywords: Observational study; Attention-deficit disorder (ADHD); Matricaria chamomilla

Introduction

D-amphetamine, the mixed preparation of D, L-amphe-tamine (Swanson et al., 1998), and methylphenidate (Greenhill et al., 1996) are first-line agents for the treatment of attention-deficit disorder (ADHD). Despite the impressive track record for the stimulants in the treatment of ADHD, they fail in 25% of patients due to lack of efficacy or the emergence of unwanted side effects (Crenshaw et al, 1999). The de novo onset of tics has also been documented in placebo-controlled, multiple-dose stimulant trials that excluded children with tic disorders (Barkley et al., 1992).

With respect to nonstimulants in treatment of ADHD, the [Alpha.sub.2]-receptor agonist clonidine has been used for more than 20 years (Cohen et al., 1979). The findings from controlled studies, however, have been somewhat inconsistent, showing benefit (Connor et al., 2000) and negative results (Singer et al., 1995). The noradrenaline reuptake inhibitor Desipramine has also shown some benefit (Singer et al., 1995). The novel antidepressant bupropion was found to be superior to placebo (Conners et al., 1996).

Niederhofer could demonstrate, that also drugs, affecting the serotonine system, may improve some symptoms associated with ADHD (Niederhofer, 2004).

Atomoxetine is a selective norepinephrine reuptake inhibitor (SNRI), and is a unique ADD/ADHD medication, as it affects only norepinephrine, rather than dopamine. Norepinephrine and Dopamine are structurally very similar, differing only in the presence of a hydroxyl group. As a result, Atomoxetine has a lower abuse potential than psychostimulants (Wee and Wool-verton, 2004).

We found no study, investigating the efficacy of Matricaria chamomilla treating children suffering from ADHD. For that reason, this observation was conducted to examine the effects of Matricaria chamo-milla on a variety of target behaviors in a patient with ADHD.

Methods

After completing the screening procedures and a 7-day washout period, two 14-16-year-old male patients diagnosed with ADHD disattention type after having excluded combined disorders like hyperthyroidism, anxiety disorder, bipolar disorder, psychosis, EEG abnormalities and suicidality, who suffered from ADHD for at least 6 years, received, after informed consent was obtained, Matricaria chamomilla (3 times/ daily oral administration of tablets containing 100 mg Levomenol (Extract 1:4.0 with Ethanol 96%) and essential oil 0.19 g each) for 4 weeks and than Placebo for 4 weeks and one patient received first Placebo and then Matricaria chamomilla. Prior to that medication they received Methylphenidate 20 mg daily for 6 years, which improved symptomatology, but led to insomnia and weight loss. They were recruited from our clinic. Before study entry, the patients were seen for a detailed clinical evaluation by an interdisciplinary team consisting of a psychiatrist, and a psychologist.

The diagnose of ADHD was made on the basis of this clinical interview and Rating Scales (DuPaul et al., 1998a). The patients (WISC-R IQ = 95-102) were free, of all psychotropic medication for 1 week and free of any medical problem. They did not suffer from tic symptoms (Yale Global Tic Severity Scale (Leckman et al., 1989) total tic score >22) or obsessive-compulsive symptoms (Children's Yale-Brown Obsessive Compulsive Scale (Scahill et al., 1997) total score > 15).

An interview and Youth Self Report were conducted to exclude anxiety disorder, depression, and psychosis. The DSM-IV diagnosis of ADHD was based on a review of the ADHD Rating Scale (DuPaul et al., 1998a).

The screening included routine laboratory tests, ECG, measurement of pulse and blood pressure, height and weight measurement, medical history, and a physical examination. An interview and Youth Self Report were conducted to exclude anxiety disorder, depression, and psychosis. The DSM-IV diagnosis of ADHD was based on a review of the ADHD Rating Scale (DuPaul et al., 1998a).

Results

The ADHD Rating Scale (DuPaul et al., 1998b) is an 18-item measure of inattention and hyperactive/impulsive symptoms derived from DSM-IV. Each symptom was scored by the child, its parents and its teacher from 0 to 3 (0 = never [or rarely], 1 = sometimes, 2 = often, and 3 = very often). The scale yields three scores: an inattention score and a hyperactive/impulsive score (range = 0-27 for each score) and a total score (range = 0-54). The means of the three scores were compared. An improvement was observed for the inattention score (drop from 14 to 9), the hyperactive/ impulsive score (drop from 13 to 7), and the total score (drop from 27 to 16). Placebo showed scores similar to those of the before-treatment period: inattention score: 12; hyperactive/impulsive score 13, and the total score 25.

The Clinical Global Impression of improvement score compares current symptom severity to baseline severity (Conners and Barkley, 1985; Guy, 1976). A score of 1 corresponds with very much improved and 2 with much improved, 3 denotes minimal change, and 4 represents no change. Scores of 5, 6 or 7 indicate deterioration (minimally worse, much worse, or very much worse, respectively). In the verum period, there was an improvement of 2 in ADHD symptoms rated by an clinician, who did not have any information about the Matricaria chamomilla medication.

To limit practice effects, the Conners Continuous Performance Test (CPT) (Rosvold et al., 1956) was undertaken at baseline (screening) and at the end of the 4-week treatment period. Further testing sessions during treatment itself were not used, in order to minimize practice effects. The most recent version of the Conners CPT is a computer-administered and -scored measure of sustained visual attention and motor response inhibition (DuPaul et al., 1998b). The test takes about 15 min to administer and yields measures of omissions, commissions, and reaction time. Norms are available for the test. The test has been used to evaluate drug response. Matricaria chamomilla was not associated with an improvement (baseline 6 omission errors, 17 commission errors; at the end of the 4-week treatment period 7 omission errors, and 15 commission errors), although impressingly improvement has been reported e.g. for Methylphenidate. This observation might be due to the fact, that the improvement of this single case observation was not strong enough to change CPT score.

Adverse effects were systematically assessed at each visit by the primary clinician using a modified version of the Systematic Assessment for Treatment of Emergent Events (SAFTEE) (Levine and Schooler, 1986). The assessment for adverse effects also included questions about concomitant medications and concurrent illness. No serious side effects were observed. There were no alterations in laboratory test results, and the patient showed no clinically meaningful change in cardiac conduction. She complained of mild sedation, which relented soon. There were no changes in weight from baseline to endpoint. To evaluate cardiovascular effects, we compared blood pressure changes at each visit and could not detect any change.

Discussion

To our knowledge, this is the first study of Matricaria chamomilla in children with ADHD. The observed improvement is lower than the 50-60% improvement reported in stimulant trials, studied in a sample of 76 children (Rapport et al., 1994), but is similar than the level of improvement observed in other nonstimulant studies such as that of Desipramine, studied in a group of 62 patients (Biederman et al., 1989). These finding also raises questions about the utility of combining Matricaria chamomilla with a stimulant. In patients with ADHD, this combination might permit lower doses of the stimulant. Furthermore, Matricaria chamomilla could provide protection against tics. Questions about these effects can be answered only with further placebo-controlled, randomized studies with larger samples, that focuses on safety and efficacy in monotherapy with Matricaria chamomilla in this population.

References

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* Tel.: +-39348 9360281; fax: + 39047 1466609.

E-mail address: hclmutnicdcrhofer@yahoo.de.

H. Niederhofer *

Child and Adolescent Psycholatry. Regional Hospital Bozen, Via Guncina 541A, 39100 Bulzuno, Italy

doi:10.1016,/j.phymed.2008.10.006
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Title Annotation:SHORT COMMUNICATION
Author:Niederhofer, H.
Publication:Phytomedicine: International Journal of Phytotherapy & Phytopharmacology
Article Type:Report
Geographic Code:4EUIT
Date:Apr 1, 2009
Words:2063
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