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A comparison of psychological and pharmacological treatment of pediatric migraine
BEHAVIOUR RESEARCH AND THERAPY
PERGAMON
Behaviour Research and Therapy 36 (1998) 1155±1170
A comparison of psychological and pharmacological treatment of pediatric migraine G. Sartory a, *, B. MuÈller a, J. Metsch a, R. Pothmann b a
Clinical Psychology, University of Wuppertal, Max-Horkheimer Strasse 20, D-42097, Wuppertal, Germany b Sociopediatric Unit, Lutheran Hospital Oberhausen, Oberhausen, Germany Received 3 March 1998
Abstract A comparison was carried out of the ecacy of psychological and drug treatments for children with migraine. Forty-three children aged between 8 and 16 years (mean age: 11.3 years) who suered from migraine received either progressive relaxation or cephalic vasomotor feedback, both with stress management training, or metoprolol, a beta-blocker. Psychological treatment was administered in ten sessions lasting six weeks and the drug treatment lasted ten weeks. Relaxation and stress management training reduced the headache index (frequency intensity of headache episodes), more eectively than metoprolol with cephalic vasomotor feedback and stress management training in between. An overall improvement over time was found with regard to frequency and intensity of headache episodes and analgesics intake. When comparing pre- to post-treatment data, children treated with relaxation training improved signi®cantly in headache frequency and intensity, whereas those treated with cephalic vasomotor feedback improved signi®cantly in headache frequency and duration as well as mood. The clinical improvement was stable at an 8-months follow-up. # 1998 Elsevier Science Ltd. All rights reserved.
1. Introduction Epidemiological surveys among children indicate that the prevalence of migraine has increased over the last decades (SillanpaÈaÈ and Anttila, 1996). An early Swedish study yielded a prevalence rate of 4% (Bille, 1962) whereas a rate of 10.7% was found in a recent German one (Pothmann et al., 1994). It is as yet unclear at what age migraine sets in, as younger children tend to be less reliable in describing symptoms and the diagnosis of migraine rests upon selfreport. * Corresponding author. Fax: +49-202-2824. 0005-7967/98/$19.00 # 1998 Elsevier Science Ltd. All rights reserved. PII: S 0 0 0 5 - 7 9 6 7 ( 9 8 ) 0 0 0 8 1 - 3
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Psychological interventions have been successful in lowering the number of migraine attacks in the short term and favorably in¯uencing their long-term course as was concluded in a recent meta-analysis of eects (Holroyd and Penzien, 1994). Fewer treatment trials have been carried out in children suering from migraine than in adults. However, Hermann et al. (1995) located 38 behavioral treatment trials with a group design which they included in their meta-analysis of eect size. After eliminating outliers, they found that thermal biofeedback had the greatest eect size (3.3) which was similar to that of combined thermal biofeedback and relaxation training but signi®cantly greater than that of relaxation training alone (1.4). Psychological placebo treatment was no more eective than the waiting list control condition (0.6). Multicomponent treatment approaches which combine relaxation training with information and cognitive therapy were found to be less ecacious (1.4) than biofeedback but more so than control conditions. Two more biofeedback treatment trials in children (Osterhaus et al., 1993; LabbeÂ, 1995) have been published recently which were not included in the Hermann et al. (1995) meta-analysis but are broadly in agreement with their outcome. There are only few studies of the ecacy of propranolol in children and their results are not consistent. Ludvigsson (1974) reported good results in comparison with placebo whereas other authors found no dierences (Forsythe et al., 1984; Olness et al., 1987). Besken et al. (1992) compared another beta-blocker, metoprolol, with an ergotamine medication and failed to ®nd signi®cant dierences between the improvement rates of the two groups. A within-group timeseries analysis, however, yielded a signi®cant percentage of responders in the metoprolol and not in the ergotamine group. Apart from the study by Olness et al. (1987) who used a sequential treatment design, no treatment studies have been reported in children in which pharmacological treatment has been compared directly with psychological treatment and the present study was therefore designed to ®ll that gap. Being a prophylactic agent, metoprolol is appropriate for comparison with the eects of biofeedback and relaxation training, both in combination with stress management training. Biofeedback training was chosen because children responded well to thermal feedback and, when administered on its own, even better so than adults (Blanchard, 1992; Hermann et al., 1995); the eect of cephalic vasomotor feedback of the temporal artery has so far not been reported in pediatric migraine. In adults, it was originally reported to require fewer treatment sessions than thermal biofeedback in order to achieve clinical improvement (Friar and Beatty, 1976) and was therefore preferred over the latter method in the present study. Progressive relaxation training still represents an inexpensive alternative to biofeedback training as it requires no equipment and was therefore used as a control treatment. Originally applied in tension headache (Holroyd et al., 1977), cognitive methods such as stress and pain management training have also been evaluated in the treatment of migraine (Birbaumer et al., 1984). McGrath et al. (1992) developed a version that was suitable for children and adolescents with migraine and found it to be more eective than conventional treatment. There is indication that stress management training may extend the eectiveness of psychological treatment when administered toward the end of the biofeedback training in adults (Birbaumer et al., 1984). It was added to the two treatment conditions to maximize their prophylactic eect in comparison with the pharmacological treatment. One of the diculties arising from a direct comparison of fundamentally dierent treatment approaches results from the dierences in their administration which has to be approximated
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so as to become comparable. Some of the ecacy of the treatment approach is sometimes lost in the process. The main dierence in administration between psychological and pharmacological treatment of migraine concerns the duration of the intervention. Thus, betablockers are usually administered for 12 weeks or longer to develop their full clinical eect while few sessions of psychological treatment or minimal contact could be successful (Rowan and Andrasik, 1996). In order to approximate the duration of treatments a compromise was reached by administering metoprolol for 10 weeks and psychological treatments for 6 weeks in the present study. The aim of the present study was to compare the ecacy of a beta blocker, metoprolol, a prophylactic drug treatment with two psychological treatments of pediatric migraine namely, progressive relaxation training and vasomotor feedback, both combined with stress management training.
2. Methods 2.1. Subjects Forty-three children, 17 of them girls, with a mean age of 11.3 years (SD = 2.1; range: 8±16 years) took part in the treatment trial. They had suered from migraine headache for a mean of 4.6 years (SD = 2.6). Sixteen of them had migraine with aura and 29 of them suered from non-migraine headache. The children were recruited from the out-patient clinic of a pediatric hospital and through information in local newspapers and radio broadcasts. Headache diagnoses were con®rmed by the pediatrician author (R.P.) according to the IHS (1988) criteria, i.e., at least 5 headache attacks lasting for 2 to 48 h with two of the following symptoms or more: lateralized headache, pulsing pain of moderate to high intensity, exacerbation by eortful physical activity; nausea or vomiting, in addition to photo- and phonophobia. The minimal duration of the disorder had to be 6 months with at least two attacks having taken place during the last month. Children with secondary headache and also those with a neurological or developmental disorder were excluded. Children and one of their parents gave their informed consent before entering the treatment trial. 2.2. Design of the treatment trial Children were allocated randomly to one of three treatment groups; two of the groups received psychological treatment and the third one received metoprolol, a beta-blocker (N = 13). Psychological treatment consisted of either cephalic vasomotor training (N = 15) or relaxation training (N = 15). Additionally, a standardized stress management training was administered as a complement to both psychological treatment groups. The trial started with a pre-treatment phase which lasted four weeks to be followed by the treatment phase lasting for 6 weeks in case of the psychological treatments and for 10 weeks in case of the pharmacological treatment. The four weeks following treatment constituted the post-treatment phase. The follow-up assessment took place at least 8 months after completion of the trial.
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2.3. Procedure The ®rst appointment took place in the presence of a parent. The aim and nature of the trial was explained and informed consent requested. The previously made medical diagnosis of migraine was veri®ed by means of a diagnostic interview. Children were then shown how to complete the headache diary and mothers were asked to assist children if necessary. Three further weekly appointments were given before the start of treatment. Diary entries and related problems were discussed at these occasions. The headache diary had the dual function of providing information about headache activity and material for psychological treatment. Thus, children were asked to indicate whether they had experienced headache episodes but also whether anything pleasant or unpleasant had occurred during that day, whether they had missed school and how their mood state had been. Having completed the daily entry, a humorous sticker could be selected and placed underneath as a reward. The diary was maintained throughout the duration of the trial and was posted to the children for follow-up assessment. 2.4. Treatment Metoprolol was administered orally as a single daily dose of 50 mg to children with a bodyweight of under 40 kg and a dose of 100 mg to those above. The medication was introduced at half that dose during the ®rst week of the treatment phase. It was stopped abruptly at the end of treatment. Children of this group were seen weekly at the clinic when the prescription was renewed. Psychological treatment (Fig. 1) consisted of 10 individual sessions, twice weekly during the ®rst four weeks and single weekly sessions during the last two weeks. Each session lasted for an hour. The ®rst half of the session was devoted to either cephalic vasomotor training or relaxation and during the second half, both groups received stress management training. During the ®rst session, all children were given a treatment rationale based on a model of stress changing vasomotor activity which, in turn, triggered migraine attacks. 2.4.1. Stress management training A standardized program based on a manual by McGrath et al. (1992) was used. During the ®rst session an agreement was formally signed by both child and therapist whereby the child consented to turn up to the treatment sessions, carry out the homework assignments and complete the headache diary regularly. The therapist, in turn, promised to be punctual, introduce something new in every session and give the child a small present at the end of treatment. Next, the concept and schematic cut-out ®gure of a headache `crab' was introduced. Its black color was supposed to signify the child's headache, a part of which could be `blotted out' by sticking on multi-colored paper every-time the homework assignments had been carried out. During the following three sessions, the various situations the child considered stressful were explored as well as the bodily and cognitive reactions to these situations. Diary entries of the previous week were used as source material. Another three sessions were given over to the training of stress management skills such as thought stopping and the use of self verbalization,
Fig. 1. Design of the psychological treatments: group I received cephalic vasomotor feedback with increasingly more phases of self-control (SELF), i.e., without feedback (FB) toward the end of treatment. Group II was administered progressive muscle relaxation with the tensing phases being omitted toward the end of treatment. Both groups carried out their coping technique, i.e., either vasoconstriction or relaxation while imagining or being administered stressors during the last two treatment sessions. Additionally, both groups received a standardized program of stress management training.
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as well as imagery and distraction as pain management techniques. The ®nal three sessions were devoted to practicing the skills while imagining stressful situations. 2.4.2. Cephalic vasomotor feedback The training was carried out with equipment (KUK-VKT1) developed by Falkenstein et al. (1984). A photoplethysmograph was placed on the temporal artery of the more severely aected side of the head. The sensor was fastened with an adhesive disk and a headband. Calibration of the blood-volume pulse amplitude signal was adjusted anew for each child and session. The signal was recorded, ®ltered, ampli®ed and fed back visually on a screen as a vertical beam whose width varied with vasodilatation and -constriction. The child sat in a comfortable chair at a distance of 2 m from the screen. Following calibration of the signal, children were instructed to render the beam more narrow. The process was aided by means of imagery, e.g. of going through a tunnel, and verbal praise whenever children were successful. Each feedback phase lasted for 3 min and was separated from the next one by a rest period of 1 min. Phases of `self-control', i.e., without feedback, were introduced early on and lasted also for 3 min. As shown in Fig. 1, the ®rst session served to introduce children to the equipment and in the second through to the sixth session, an initial self-control phase was followed by 4 feedback phases and ended with a ®nal self-control phase. The self-control phases were gradually increased over sessions. During the last two sessions, only one feedback
Fig. 2. Mean percent change from before to after treatment of headache variables in the three groups. The indicated signi®cance levels are the result of pre- to post-treatment comparisons, separately for each group and variable.
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phase was administered and children were instructed to carry out vasoconstriction exercises under conditions of stress such as an intrusively noisy radio program or eort-demanding tasks. At the end of each session, children were given homework assignments which were noted on a sheet. They were asked to repeat at home the exercises which had been carried out during the session. This training schedule has been reported to by successful in adults (Falkenstein et al., 1986). 2.4.3. Progressive relaxation training Children sat in a comfortable chair with their feet on the ground. Muscle groups were alternately tensed and relaxed. All exercises were demonstrated by the therapist who sat at a right angle to the child. A treatment rationale was given during the ®rst session together with a demonstration of tensing and relaxing the muscles in both arms. In the following sessions, exercises were extended to the legs, the back, chest, abdomen, and neck and shoulders, as well as the face. During the ®fth session, tensing was to be carried out only partly, with half or quarter of the full eort. In the sixth session, cued relaxation was introduced whereupon relaxation exercises were carried out without tensing phases as from the seventh session. During the eighth session, relaxation was practiced during standing and walking. The remaining two sessions were devoted to carrying out relaxation during the application of stressors that were similar to the ones used in the ®nal biofeedback sessions. Children were given homework assignments which were noted in a sheet. They were asked to practice the exercises repeatedly which had been carried out during the sessions. 2.5. Measures The headache diary was completed during a 4-week base-line and post-treatment phase by the three groups. A headache index based on frequency and intensity of headache activity was used, in addition to separate analyses of frequency, duration and intensity as well as vasomotor activity. The clinical relevance of headache improvement was assessed by calculating the proportion of patients who achieved a 50% improvement. As the majority of the children suered from both migraine and non-migrainous headaches, additional analyses were performed for each of the two types. 2.5.1. Headache diary Children were asked to complete the headache diary daily. Apart from questions as to the occurrence of headache, there were also questions as to the quality, duration and site of the pain as well as additional symptoms indicative of an aura, nausea and phono- or photophobia. Diary entries were scored for the four weeks baseline and post-treatment phase as well as the two weeks of follow-up assessment. The following variables were extracted: Frequency: The number of headache episodes per week. Intensity: Children were asked to indicate the intensity of headache on a scale of 1 (light) to 10 (overbearing). The weekly sum of the indicated intensities was divided by number of headache episodes. Duration: Children were asked to tick all hours during which headache had occurred. The sum total of the weekly hours was divided by the number of episodes.
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Analgesics intake: The weekly number of headache episodes during which analgesic medication was taken. Mood: The mood scale consisted of 5 schematic faces whose expression varied from being smiling (1) to looking upset (5). Children indicated the face that resembled their overall state of mood best. The mean weekly rating was entered into further analysis. A mean score was computed for each variable of the entries of the 4-week baseline and posttreatment period and a 2-week follow-up phase eight months later. The therapeutic eect was expressed in terms of percent change from pre- to post-treatment. As noted above, a headache index was derived based on the combination of frequency and intensity, as both will presumably cause a patient to seek professional help. Those improving by at least 50% from before to after treatment with regard to the headache index were considered responders in each group. An attempt was made to determine whether or not the dierent treatment modes had a speci®c eect on either migraine or non-migrainous headache. All headache activity reported in the diary was therefore categorized into episodes with and without migraine symptoms, i.e., headache episodes without aura symptoms or nausea were considered non-migrainous. Frequency, intensity and duration of the two kinds of headache were entered into analysis. As there were only 5 children in the metoprolol group suering from non-migraine headache, this analysis was carried out in children of the two psychologically treated groups only. 2.5.2. Vasomotor activity Blood-volume pulse amplitude was recorded only in the two groups receiving psychological treatment. At the beginning and end of the ®rst, sixth and tenth treatment session, pulse volume amplitude was recorded during a base-line phase of 2 min and an additional phase of 3 min during which the biofeedback group was asked to practice vasoconstriction in the absence of feedback and the relaxation group was instructed to relax. Data were recorded with a polygraph (Nihon Khoden) with a digitizing rate of 100 Hz; they were stored on hard disk to be analyzed o line. Mean pulse volume amplitude was evaluated for each 30 s epoch. A program routine controlling for artifacts rejected all amplitude data which occurred with a probability of 5%. The ®rst epoch served as reference. All subsequent epochs were expressed in terms of percent change.
3. Results 3.1. Headache diary 3.1.1. Base-line Subject characteristics and headache variables of the 4 weeks pre-treatment phase are displayed in Table 1. Group between treatment groups using univariate analyses of variance yielded no signi®cant dierences with regard to age, weekly headache frequency, intensity of headache or mood. The in¯ated mean headache duration of the relaxation group was due to one single outlier and proved not signi®cant. However, treatment groups diered signi®cantly with regard to frequency of analgesics intake (F(2,40) = 4.37, p < 0.02) in that subjects in the
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Table 1 Subject and headache characteristics and baseline diary data of the three treatment groups
N Migraine with aura Combined headache Age Female/male Duration of headache disorder (years) Headache diary: Frequency/week Duration/episode (h) Intensity/episode (1±10) Analgesics/episode Mood (1±5)
Relaxation
Biofeed
Metoprolol
15 7/15 11/15 11.4 (2.4) 6/9 4.13 (2.29)
15 5/15 13/15 11.8 (2.0) 7/8 5.07 (3.37)
13 4/15 5/13 10.5 (1.9) 4/9 4.92 (1.85)
2.24 (1.89) 19.56 (25.98) 5.09 (1.35) 0.27 (0.34) 2.04 (0.54)
1.77 9.35 4.37 0.18 2.14
1.33 9.10 5.34 0.50 2.00
(1.17) (8.07) (2.25) (0.23) (0.64)
(0.62) (4.67) (1.88) (0.31) (0.58)
metroprolol group were taking medication signi®cantly more often than those in the biofeedback group (t = 3.17, df = 26, p < 0.01) with the relaxation group in between, not diering signi®cantly from either. 3.1.2. Therapeutic eects Fig. 2 shows mean percent change from before to after treatment of frequency, duration and intensity of headache, mood and analgesics intake. One child in the metoprolol group failed to indicate duration of headache episodes during the post-treatment phase and was therefore excluded from analyses of this variable. Base-line and post-treatment data of frequency, duration, intensity and analgesics intake were entered into multivariate analysis of variance (MANOVA) comparing groups (3) prepost measurement occasions (2). There was a marginally signi®cant pre to post eect (F(1,37) = 3.77, p < 0.06) but no signi®cant group dierence or group pre to post interaction eect. Next, individual variables were entered into analysis of variance with a 3 (groups) 2 (pre-post) design. Headache frequency showed a signi®cant reduction from pre to post treatment (F(1,39) = 20.61, p < 0.01) with neither the group nor the interaction eect being signi®cant. Headache intensity was also signi®cantly lowered (F(1,39) = 10.32, p < 0.01) from before to after treatment with neither the group nor the interaction eect being signi®cant. Analgesics intake was signi®cantly reduced (F(1,39) = 4.28, p < 0.05) and groups diered signi®cantly with regard to intake (F(2,39) = 6.78, p < 0.01) while the interaction eect was not signi®cant. Eects were not signi®cant with regard to duration. Within-group analyses (pre±post) were also performed for each treatment group. Given the skewed distribution of measures, the Wilcoxon matched-pairs signed-ranks test was used (all Pvalues are 2-tailed). The relaxation group showed signi®cant improvement from before to after treatment with regard to frequency (Z = 2.98, p < 0.01) and intensity (Z = 2.42, p < 0.02) with the improvement in duration being only marginally signi®cant. The biofeedback group also showed signi®cant improvement with regard to frequency (Z = 2.45, p < 0.02), duration (Z = 1.98, p < 0.05) and mood (Z = ÿ 2.16, p < 0.05). The metoprolol group showed no signi®cant changes overtreatment.
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3.1.3. Type of headache Frequency, intensity and duration of migraine and non-migraine headache of the two psychologically treated groups were entered into univariate analysis of variance comparing headache type (2) treatment (2) pre±post (2). Frequency of headache showed a signi®cant reduction regardless of treatment type which was signi®cant only for migraine headache (F(1,28) = 7.33, p < 0.02) in the individual analysis. Migraine headache was of higher intensity than non-migraine headache (F(1,28) = 42.6, p < 0.01) and also of longer duration (F(1,28) = 19.8, p < 0.01). Regardless of treatment type, the pain intensity was signi®cantly reduced between pre and post measurement for migraine but not for non-migraine headache (headache type pre-post: F(1,28) = 7.6, p < 0.01) (Fig. 3). 3.1.4. Clinical improvement A comparison was made between the number of patients of each group who had improved by 50% or more with regard to change in the headache index (percent change from baseline to post-treatment of frequency intensity). Fig. 4 displays the percentage of children who had improved with regard to the headache index for each group. The children in the relaxation as compared to those in the metoprolol group were signi®cantly more improved (chi-
Fig. 3. Change in pain intensity of migraine and non-migraine headache in the two psychologically treated groups. Migraine headache was more intense and responded better to treatment than non-migraine headache. The metoprolol group was not included in this analysis as it contained too few children suering from combined headache.
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Fig. 4. Percentage of patients who improved by more than 50% in the headache index (frequency intensity of headache episodes) after treatment. Group comparisons were carried out with the chi-square test.
square = 4.2, p < 0.04). Neither of these groups diered signi®cantly from the biofeedback group. 3.1.5. Cephalic vasomotor activity (Fig. 5) Each of three subsequent 30 s epochs were combined resulting in three 90 s epochs. They were entered into analysis of variance comparing groups (2) sessions (3) pre±post (2) epochs (3). The biofeedback group showed marginally more vasoconstriction than the relaxation group (F(1,23) = 3.23, p < 0.1) with none of the other eects being signi®cant. 3.1.6. Follow-up (Table 2) Sixteen children could not be contacted for follow-up assessment or failed to return the diary. Group means of the successfully contacted children are shown in Table 2. A 3 (groups) 3 (pre±post-follow-up) analysis of variance yielded a signi®cant measurement occasion eect for frequency of headache (F(6,42) = 6.37, p < 0.01) and duration of headache (F(6,44) = 4.12, p < 0.03). None of the other eects were signi®cant. Analysis of variance comparing groups (3) post-treatment-follow up (2) revealed no signi®cant results for main eects nor interactions.
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Fig. 5. Means of the vasomotor activity of the temporal artery in the two groups who received either relaxation or cephalic vasomotor feedback. The data represent averages over 6 measurement occasions (pre-, mid- and posttreatment, at the beginning and end of the each respective session). Three subsequent 90 s epochs were referred to a 30 s baseline. The biofeedback group was instructed to practice vasoconstriction and the relaxation group to relax.
Table 2 Group means (M) and SDs of headache variables of the three treatment groups at the three measurement occasions (baseline, post treatment and follow-up). Sixteen children could not be contacted at follow-up. Only children with a complete data set are included in these groups
N Frequency ± baseline ± post ± follow-up Duration ± baseline ± post ± follow-up Intensity ± baseline ± post ± follow-up Analgesics ± baseline ± post ± follow-up
Relaxation (M, SD)
Biofeedback (M, SD)
Metoprolol (M, SD)
11
10
6
1.75 (1.44) 0.82 (1.15) 1.14 (1.19)
1.73 (1.25) 0.80 (0.95) 1.05 (0.72)
1.46 (0.9) 1.03 (0.78) 1.25 (0.82)
11.74 (12.47) 7.05 (12.81) 6.68 (6.38) 5.24 (1.18)
8.32 3.01 6.27 4.65
10.9 6.61 7.82 4.63
3.37 (2.68) 2.98 (2.65) 0.34 (0.37)
2.51 (2.37) 3.09 (1.67) 0.22 (0.24)
5.02 (2.22) 4.19 (2.42) 0.41 (0.34)
0.13 (0.31) 0.09 (0.20)
0.02 (0.05) 0.18 (0.33)
0.42 (0.38) 0.15 (0.34)
(5.42) (3.60) (5.82) (2.57)
(5.54) (6.78) (3.52) (2.28)
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3.1.7. Relationship between measures Age was correlated positively with duration of headache disorder and a worsening in terms of frequency and duration of episodes and mood of the baseline phase. However, children's age was unrelated to any dierence scores from before to after treatment. Intensity of headache at baseline was not signi®cantly correlated with any of the other headache variables while frequency and duration were highly correlated (r = 0.85, p < 0.01). Improvement, i.e., pre-post dierence scores of the three headache variables were signi®cantly interrelated (r = 0.31±0.67) and they were also signi®cantly correlated with improvement in mood (0.31±0.46). Correlating baseline headache data with extent of improvement yielded no signi®cant results when taking into account all three groups. The separate analysis in the psychologically treatment groups revealed a positive correlation between initial medication and its change over treatment (r = 0.40; p < 0.03) and a negative correlation between initial mood rating and change in medication (r = ÿ 0.36, p < 0.05). The latter correlation indicates that the better the mood state the greater the change in medication.
4. Discussion The overall results of the study showed that relaxation training combined with stress management training was signi®cantly more eective in reducing the headache index than treatment with the betablocker metoprolol. The eectiveness of cephalic feedback combined with stress management training was falling in between these two groups, but did not dier signi®cantly from any of them. The headache index was derived from frequency of headache episodes and intensity of their painfulness. The relaxation group did not dier at baseline from the other two groups with regard to these two variables and baseline dierences cannot therefore account for the treatment eect. Relaxation and stress management training resulted in signi®cant improvement in both variables whereas the biofeedback treatment aected only frequency which would account for its less favorable outcome with regard to the combined variable. Cephalic vasomotor feedback and stress management resulted in signi®cant reduction of the duration of headache episodes and also in improved mood, which was not the case in the two other treatments. It could be argued that a headache index derived from frequency and duration of headache would have shown the biofeedback rather than the relaxation group to have the best outcome. Combining frequency and pain intensity is however more meaningful statistically as well as clinically. The two variables were uncorrelated unlike frequency and duration. Both high frequency of migraine attacks and intense pain will cause disruption in the children's daily life and therefore deserves clinical attention. Combining the two aspect in the assessment of clinical ecacy therefore appears more appropriate than an index based on headache frequency and duration. The results are partly in keeping with those reported previously. In a recent meta-analytic review of studies, Hermann et al. (1995) concluded that relaxation combined with other treatment components (e.g. McGrath et al., 1992) constituted an eective intervention in pediatric migraine. Unlike the outcome of the present study, Hermann et al. (1995) found biofeedback training to have the greatest therapeutic ecacy in pediatric migraine. A number of factors could account for the inconsistency. The studies summarized by Hermann et al.
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(1995) used thermal biofeedback whereas cephalic feedback was used in the present study. It is conceivable that a change in hand temperature is more easily achieved than cephalic vasoconstriction and therefore more eective in this age group. Temperature changes of the hands are associated with more pronounced interoceptive cues than vasoconstriction of the temporal artery which may facilitate their controllability. Most of the previous studies (Labbe and Williamson, 1983; Fentress et al., 1986) have also used more training sessions than the present study. As one of the aims of the present study was to generate and evaluate a compact and inexpensive treatment for pediatric migraine, it was outlined after the short treatment schedule reported to be successful for adult migraineurs by Falkenstein et al. (1986). If children need more extensive treatment than adults, then the present treatment study may not have constituted an appropriate trial of the eectiveness of cephalic vasomotor feedback in pediatric migraine. Comparing the improvement rate of some recent studies with the present one, Osterhaus et al. (1993) found a similar 41% improvement in headache frequency after a combination of relaxation, temperature feedback and cognitive therapy; yet other authors reported an average 75% (LabbeÂ, 1995) and 63 or 85% reduction in headache frequency (Fentress et al., 1986). Labbe (1995) used a short course of autogenic training and thermal feedback whereas Fentress et al. (1986) used muscular relaxation and EMG feedback. Both of these forms of feedback are designed to enhance relaxation. Administering relaxation and cognitive treatment separately, Richter et al. (1986) reported improvements of 40 and 46% respectively, in headache frequency in severely aected patients. Less severely aected ones showed less improvement. Active treatment was found to be more eective than control conditions. Most authors reported no change in frequency in waiting list control groups (e.g. ÿ2% Ð Osterhaus et al., 1993; 4% Ð Fentress et al., 1986) with, however, exceptions such as Labbe (1995) who reported a 24% reduction in frequency in her waiting list control group. Psychological placebo treatment, such as recognizing and labelling emotions as in non-directive therapy, resulted in a 7% reduction in frequency (Richter et al., 1986). Although less often reported, the present improvement with regard to intensity of headache compares well with that of other studies. Richter et al. (1986) reported similar 26 and 32% for relaxation and cognitive therapy and Osterhaus et al. (1993) failed to ®nd a change. Unlike the other treatments, relaxation signi®cantly reduced headache intensity in the present study. Relaxation is an eective pain reducing technique in the management of other chronic pain disorders. It has been suggested that if both migraine and non-migraine headache episodes occur, it is the latter that respond better to relaxation (Mizener et al., 1992), presumably because pain in non migrainous headaches is partly caused by increased muscle tension. Comparing the change in headache activity between the two types, it was however, migraine rather than non-migraine headache that responded best to the two psychological treatments. The former was also initially rated as being more intense and longer lasting and could therefore improve more than the latter. Children in the biofeedback group showed greater constriction of the temporal artery than the relaxation group who were instructed to relax. However, extent of vasoconstriction did not increase with training nor did it dier across treatment sessions. The crudity of the measure, i.e., the dependence of assessing reactivity of the blood-volume pulse amplitude relative to an arbitrary baseline level, may have obscured changes over treatment sessions. Measuring blood
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¯ow velocity by means of transcranial Doppler technique, McGrady et al. (1994) and Wauquier et al. (1995) found signi®cant slowing in the middle cerebral artery following feedback training of the frontalis EMG and of ®nger temperature, autogenic training and diaphragmatic breathing. Abnormalities of the middle cerebral artery have previously been implicated in the occurrence of migraine (Oleson, 1991). So far, it is however, unclear, whether or not cephalic vasomotor feedback induces similar changes or indeed, which component of the treatment package was responsible for the ones reported by McGrady et al. (1994) and Wauquier et al. (1995). The medication with metoprolol had little eect on the children's headache activity in the present study. In a previous treatment trial it proved eective unlike ergotamine (Besken et al., 1992). These results were based on within-group time-series analysis of diary data which may constitute of more sensitive way of analyzing repeated measures. Other drugs, such as ¯unarizine, a calcium-channel blocker, may have been more eective (for a review, see Hermann et al., 1995). Metoprolol is generally regarded to have a prophylactic eect and was therefore presumed to be similar to psychological treatment. Drawing conclusions from follow-up data in the present study, it should be noted that a number of clients from the metoprolol group could not be traced or failed to respond to the request for follow-up information. Obtaining diary information about headache activity for only two rather than four weeks also reduced the reliability of the follow-up data. However, the two psychologically treated groups showed no signi®cant changes over the follow-up period and the treatment eect could thus be said to be maintained over time. A ten-year follow-up of patients who were originally encouraged to use coping techniques rather than medication, found 73% to be still suering from headache with, however, 81% being much improved (Dooley and Bagnell, 1995). Current psychological techniques are thus unlikely to prevent further migraine attacks altogether but alleviate their severity long-term and in a manner that is free of unwanted side eects which makes them particularly suited for the treatment of pediatric migraine.
Acknowledgements This study was supported by the Bundesminister fuÈr Forschung und Technologie (BMFT; Federal Minister for Research and Technology, Germany). We gratefully acknowledge the contribution to carrying out the trial of the following: Angela Elvermann, Dagmar Haase, Wiebke Otremba and Irene Vormbaum.
References Besken, E., Pothmann, R., Niederberger, U., Plump, U. & Sartory, G. (1992). Metoprolol- und Dihydroergotaminprophylaxe kindlicher MigraÈne. In B. KoÈhler, and R. Keimer (Eds.), Aktuelle NeuropaÈdiatrie (pp. 440±442) Springer Verlag Berlin, Heidelberg. Bille, B. (1962). Migraine in school children. Acta Paediatrica Scandinavica, 51, 1±151. Birbaumer, N., Gerber, D., Miltner, W., Lutzenberger, W. & Kluck, M. (1984). Start with biofeedback and continue with behavior therapy in migraine. Proceeding of the 15th Annual Meeting of Biofeedback Society of America (pp. 33±36) Albuquerque.
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Blanchard, E. B. (1992). Psychological treatment of benign headache disorders. Journal of Consulting and Clinical Psychology, 60, 537± 551. Dooley, J., & Bagnell, A. (1995). The prognosis and treatment of headaches in children ± a ten-year follow-up. Canadian Journal of Neurological Science, 22, 47±49. Falkenstein, M., Hoormann, J., WeitkaÈmper, B., & ZuÈlch, J. (1984). Signalverarbeitung bei fotoelektrischer GefaÈûplethysmographie. Biomedizinische Technik, 29, 213±214. Falkenstein, M., ZuÈlch, J., & Hoormann, J. (1986). Stress coping and vasoconstriction training in migraine therapy. A controlled evaluation. Schmerz ± Pain ± Douleur, 2, 60±67. Fentress, D. W., Masek, B. J., Mehegan, J. E., & Benson, H. (1986). Biofeedback and relaxation-response training in the treatment of paediatric migraine. Developmental Medicine Child Neurology, 28, 139±146. Forsythe, W. I., Gillies, D., & Sills, M. A. (1984). Propranolol (Inderal) in the treatment of childhood migraine. Developmental Medicine Child Neurology, 26, 737±741. Friar, L. R., & Beatty, J. (1976). Management of migraines by trained control of vasoconstriction. Journal of Consulting and Clinical Psychology, 44, 46±53. Hermann, C., Kim, M., & Blanchard, E. B. (1995). Behavioral and prophylactic pharmacological intervention studies of pediatric migraine: An exploratory meta-analysis. Pain, 60, 239±256. Holroyd, K. A., Andrasik, F., & Westbrook, T. (1977). Cognitive control of tension headache. Cognitive Therapy and Research, 1, 121± 133. Holroyd, K. A., & Penzien, D. B. (1994). Psychosocial interventions in the management of recurrent headache disorders 1: Overview and eectiveness. Behavioral Medicine, 20, 53±63. International Headache Society (1988). Classi®cation and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia, 8(Suppl. 7), 19±25. LabbeÂ, E. E., & Williamson, D. A. (1983). Temperature biofeedback in the treatment of children with migraine headaches. Journal of Pediatric Psychology, 8, 317±326. LabbeÂ, E. E. (1995). Treatment of childhood migraine with autogenic training and skin temperature biofeedback: A component analysis. Headache, 35, 10±13. Ludvigsson, J. (1974). Propanolol uses in prophylaxis of migraine children. Acta Neurol. Scand., 50, 109±115. McGrady, A., Wauquier, A., McNeil, A., & Gerard, G. (1994). Eect of biofeedback-assisted relasation on migraine headache and changes in cerebral blood ¯ow velocity in the middle cerebral artery. Headache, 34, 424±428. McGrath, P. J., Humphreys, P., Keene, D., Goodman, J. T., Lascelles, M. A., Cunningham, S. J., & Firestone, P. (1992). The ecacy and eciency of a self-administered treatment for adolescent migraine. Pain, 49, 321±324. Mizener, D., Thomas, M.R.&Dasgupta, B. (1992). Biofeedback vs cognitive therapy in the treatment of migraine headache: A controlled outcome study. Second congress of the International Society of Behavioral Medicine, Hamburg. Oleson, J. (1991). Review of current of drugs for migraine. Journal of Neurology, 238 (Suppl. 1), 23±27. Oleson, J. (1991). Cerebral and extracraniale circulatory disturbance in migraine. Pathophysiological Implications, Cerebrovasc. Brain metab. ref., 3, 1±28. Olness, K., MacDonald, J. T., & Uden, D. L. (1987). Comparison of self-hypnosis and propranolol in the treatment of juvenile classic migraine. Pediatrics, 79, 593±597. Osterhaus, S. O. L., Passchier, J., van der Helm-Hylkema, H., de Jong, K. T., Orlebeke, J. F., de Grauw, A. J. C., & Dekker, P. H. (1993). Eects of behavioral psychophysiological treatment on schoolchildren with migraine in a nonclinical setting: Predictors and process variables. Journal of Pediatric Psychology, 18, 697±715. Pothmann, R., Frankenberg, S. V., MuÈller, B., Sartory, G., & Hellmeier, W. (1994). Epidemiology of headache in children and adolescents: Evidence of high prevalence of migraine among girls unter 10. International Journal of Behavioral Medicine, 1, 76±89. Richter, I. L., McGrath, P. J., Humphreys, P. J., Goodman, J. T., Firestone, P. & Keene, D. (1986). Cognitive and relaxation treatment of paediatric migraine. Pain, 25, 195±203. Rowan, A. B., & Andrasik, F. (1996). Ecacy and cost-eectiveness of minimal therapist contact treatments of chronic headaches: A review. Behavior Therapy, 27, 207±234. SillanpaÈaÈ, M., & Anttila, P. (1996). Increasing prevalence of headache in 7-year-old children. Headache, 36, 466±470. Wauquier, A., McGrady, A., Aloe, L., Klausner, T., & Collins, B. (1995). Changes in cerebral blood ¯ow velocity associated with biofeedback-assisted relaxation treatment of migraine headaches are speci®c for the middle cerebral artery. Headache, 35, 358±362.
PERGAMON
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A comparison of psychological and pharmacological treatment of pediatric migraine G. Sartory a, *, B. MuÈller a, J. Metsch a, R. Pothmann b a
Clinical Psychology, University of Wuppertal, Max-Horkheimer Strasse 20, D-42097, Wuppertal, Germany b Sociopediatric Unit, Lutheran Hospital Oberhausen, Oberhausen, Germany Received 3 March 1998
Abstract A comparison was carried out of the ecacy of psychological and drug treatments for children with migraine. Forty-three children aged between 8 and 16 years (mean age: 11.3 years) who suered from migraine received either progressive relaxation or cephalic vasomotor feedback, both with stress management training, or metoprolol, a beta-blocker. Psychological treatment was administered in ten sessions lasting six weeks and the drug treatment lasted ten weeks. Relaxation and stress management training reduced the headache index (frequency intensity of headache episodes), more eectively than metoprolol with cephalic vasomotor feedback and stress management training in between. An overall improvement over time was found with regard to frequency and intensity of headache episodes and analgesics intake. When comparing pre- to post-treatment data, children treated with relaxation training improved signi®cantly in headache frequency and intensity, whereas those treated with cephalic vasomotor feedback improved signi®cantly in headache frequency and duration as well as mood. The clinical improvement was stable at an 8-months follow-up. # 1998 Elsevier Science Ltd. All rights reserved.
1. Introduction Epidemiological surveys among children indicate that the prevalence of migraine has increased over the last decades (SillanpaÈaÈ and Anttila, 1996). An early Swedish study yielded a prevalence rate of 4% (Bille, 1962) whereas a rate of 10.7% was found in a recent German one (Pothmann et al., 1994). It is as yet unclear at what age migraine sets in, as younger children tend to be less reliable in describing symptoms and the diagnosis of migraine rests upon selfreport. * Corresponding author. Fax: +49-202-2824. 0005-7967/98/$19.00 # 1998 Elsevier Science Ltd. All rights reserved. PII: S 0 0 0 5 - 7 9 6 7 ( 9 8 ) 0 0 0 8 1 - 3
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Psychological interventions have been successful in lowering the number of migraine attacks in the short term and favorably in¯uencing their long-term course as was concluded in a recent meta-analysis of eects (Holroyd and Penzien, 1994). Fewer treatment trials have been carried out in children suering from migraine than in adults. However, Hermann et al. (1995) located 38 behavioral treatment trials with a group design which they included in their meta-analysis of eect size. After eliminating outliers, they found that thermal biofeedback had the greatest eect size (3.3) which was similar to that of combined thermal biofeedback and relaxation training but signi®cantly greater than that of relaxation training alone (1.4). Psychological placebo treatment was no more eective than the waiting list control condition (0.6). Multicomponent treatment approaches which combine relaxation training with information and cognitive therapy were found to be less ecacious (1.4) than biofeedback but more so than control conditions. Two more biofeedback treatment trials in children (Osterhaus et al., 1993; LabbeÂ, 1995) have been published recently which were not included in the Hermann et al. (1995) meta-analysis but are broadly in agreement with their outcome. There are only few studies of the ecacy of propranolol in children and their results are not consistent. Ludvigsson (1974) reported good results in comparison with placebo whereas other authors found no dierences (Forsythe et al., 1984; Olness et al., 1987). Besken et al. (1992) compared another beta-blocker, metoprolol, with an ergotamine medication and failed to ®nd signi®cant dierences between the improvement rates of the two groups. A within-group timeseries analysis, however, yielded a signi®cant percentage of responders in the metoprolol and not in the ergotamine group. Apart from the study by Olness et al. (1987) who used a sequential treatment design, no treatment studies have been reported in children in which pharmacological treatment has been compared directly with psychological treatment and the present study was therefore designed to ®ll that gap. Being a prophylactic agent, metoprolol is appropriate for comparison with the eects of biofeedback and relaxation training, both in combination with stress management training. Biofeedback training was chosen because children responded well to thermal feedback and, when administered on its own, even better so than adults (Blanchard, 1992; Hermann et al., 1995); the eect of cephalic vasomotor feedback of the temporal artery has so far not been reported in pediatric migraine. In adults, it was originally reported to require fewer treatment sessions than thermal biofeedback in order to achieve clinical improvement (Friar and Beatty, 1976) and was therefore preferred over the latter method in the present study. Progressive relaxation training still represents an inexpensive alternative to biofeedback training as it requires no equipment and was therefore used as a control treatment. Originally applied in tension headache (Holroyd et al., 1977), cognitive methods such as stress and pain management training have also been evaluated in the treatment of migraine (Birbaumer et al., 1984). McGrath et al. (1992) developed a version that was suitable for children and adolescents with migraine and found it to be more eective than conventional treatment. There is indication that stress management training may extend the eectiveness of psychological treatment when administered toward the end of the biofeedback training in adults (Birbaumer et al., 1984). It was added to the two treatment conditions to maximize their prophylactic eect in comparison with the pharmacological treatment. One of the diculties arising from a direct comparison of fundamentally dierent treatment approaches results from the dierences in their administration which has to be approximated
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so as to become comparable. Some of the ecacy of the treatment approach is sometimes lost in the process. The main dierence in administration between psychological and pharmacological treatment of migraine concerns the duration of the intervention. Thus, betablockers are usually administered for 12 weeks or longer to develop their full clinical eect while few sessions of psychological treatment or minimal contact could be successful (Rowan and Andrasik, 1996). In order to approximate the duration of treatments a compromise was reached by administering metoprolol for 10 weeks and psychological treatments for 6 weeks in the present study. The aim of the present study was to compare the ecacy of a beta blocker, metoprolol, a prophylactic drug treatment with two psychological treatments of pediatric migraine namely, progressive relaxation training and vasomotor feedback, both combined with stress management training.
2. Methods 2.1. Subjects Forty-three children, 17 of them girls, with a mean age of 11.3 years (SD = 2.1; range: 8±16 years) took part in the treatment trial. They had suered from migraine headache for a mean of 4.6 years (SD = 2.6). Sixteen of them had migraine with aura and 29 of them suered from non-migraine headache. The children were recruited from the out-patient clinic of a pediatric hospital and through information in local newspapers and radio broadcasts. Headache diagnoses were con®rmed by the pediatrician author (R.P.) according to the IHS (1988) criteria, i.e., at least 5 headache attacks lasting for 2 to 48 h with two of the following symptoms or more: lateralized headache, pulsing pain of moderate to high intensity, exacerbation by eortful physical activity; nausea or vomiting, in addition to photo- and phonophobia. The minimal duration of the disorder had to be 6 months with at least two attacks having taken place during the last month. Children with secondary headache and also those with a neurological or developmental disorder were excluded. Children and one of their parents gave their informed consent before entering the treatment trial. 2.2. Design of the treatment trial Children were allocated randomly to one of three treatment groups; two of the groups received psychological treatment and the third one received metoprolol, a beta-blocker (N = 13). Psychological treatment consisted of either cephalic vasomotor training (N = 15) or relaxation training (N = 15). Additionally, a standardized stress management training was administered as a complement to both psychological treatment groups. The trial started with a pre-treatment phase which lasted four weeks to be followed by the treatment phase lasting for 6 weeks in case of the psychological treatments and for 10 weeks in case of the pharmacological treatment. The four weeks following treatment constituted the post-treatment phase. The follow-up assessment took place at least 8 months after completion of the trial.
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2.3. Procedure The ®rst appointment took place in the presence of a parent. The aim and nature of the trial was explained and informed consent requested. The previously made medical diagnosis of migraine was veri®ed by means of a diagnostic interview. Children were then shown how to complete the headache diary and mothers were asked to assist children if necessary. Three further weekly appointments were given before the start of treatment. Diary entries and related problems were discussed at these occasions. The headache diary had the dual function of providing information about headache activity and material for psychological treatment. Thus, children were asked to indicate whether they had experienced headache episodes but also whether anything pleasant or unpleasant had occurred during that day, whether they had missed school and how their mood state had been. Having completed the daily entry, a humorous sticker could be selected and placed underneath as a reward. The diary was maintained throughout the duration of the trial and was posted to the children for follow-up assessment. 2.4. Treatment Metoprolol was administered orally as a single daily dose of 50 mg to children with a bodyweight of under 40 kg and a dose of 100 mg to those above. The medication was introduced at half that dose during the ®rst week of the treatment phase. It was stopped abruptly at the end of treatment. Children of this group were seen weekly at the clinic when the prescription was renewed. Psychological treatment (Fig. 1) consisted of 10 individual sessions, twice weekly during the ®rst four weeks and single weekly sessions during the last two weeks. Each session lasted for an hour. The ®rst half of the session was devoted to either cephalic vasomotor training or relaxation and during the second half, both groups received stress management training. During the ®rst session, all children were given a treatment rationale based on a model of stress changing vasomotor activity which, in turn, triggered migraine attacks. 2.4.1. Stress management training A standardized program based on a manual by McGrath et al. (1992) was used. During the ®rst session an agreement was formally signed by both child and therapist whereby the child consented to turn up to the treatment sessions, carry out the homework assignments and complete the headache diary regularly. The therapist, in turn, promised to be punctual, introduce something new in every session and give the child a small present at the end of treatment. Next, the concept and schematic cut-out ®gure of a headache `crab' was introduced. Its black color was supposed to signify the child's headache, a part of which could be `blotted out' by sticking on multi-colored paper every-time the homework assignments had been carried out. During the following three sessions, the various situations the child considered stressful were explored as well as the bodily and cognitive reactions to these situations. Diary entries of the previous week were used as source material. Another three sessions were given over to the training of stress management skills such as thought stopping and the use of self verbalization,
Fig. 1. Design of the psychological treatments: group I received cephalic vasomotor feedback with increasingly more phases of self-control (SELF), i.e., without feedback (FB) toward the end of treatment. Group II was administered progressive muscle relaxation with the tensing phases being omitted toward the end of treatment. Both groups carried out their coping technique, i.e., either vasoconstriction or relaxation while imagining or being administered stressors during the last two treatment sessions. Additionally, both groups received a standardized program of stress management training.
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as well as imagery and distraction as pain management techniques. The ®nal three sessions were devoted to practicing the skills while imagining stressful situations. 2.4.2. Cephalic vasomotor feedback The training was carried out with equipment (KUK-VKT1) developed by Falkenstein et al. (1984). A photoplethysmograph was placed on the temporal artery of the more severely aected side of the head. The sensor was fastened with an adhesive disk and a headband. Calibration of the blood-volume pulse amplitude signal was adjusted anew for each child and session. The signal was recorded, ®ltered, ampli®ed and fed back visually on a screen as a vertical beam whose width varied with vasodilatation and -constriction. The child sat in a comfortable chair at a distance of 2 m from the screen. Following calibration of the signal, children were instructed to render the beam more narrow. The process was aided by means of imagery, e.g. of going through a tunnel, and verbal praise whenever children were successful. Each feedback phase lasted for 3 min and was separated from the next one by a rest period of 1 min. Phases of `self-control', i.e., without feedback, were introduced early on and lasted also for 3 min. As shown in Fig. 1, the ®rst session served to introduce children to the equipment and in the second through to the sixth session, an initial self-control phase was followed by 4 feedback phases and ended with a ®nal self-control phase. The self-control phases were gradually increased over sessions. During the last two sessions, only one feedback
Fig. 2. Mean percent change from before to after treatment of headache variables in the three groups. The indicated signi®cance levels are the result of pre- to post-treatment comparisons, separately for each group and variable.
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phase was administered and children were instructed to carry out vasoconstriction exercises under conditions of stress such as an intrusively noisy radio program or eort-demanding tasks. At the end of each session, children were given homework assignments which were noted on a sheet. They were asked to repeat at home the exercises which had been carried out during the session. This training schedule has been reported to by successful in adults (Falkenstein et al., 1986). 2.4.3. Progressive relaxation training Children sat in a comfortable chair with their feet on the ground. Muscle groups were alternately tensed and relaxed. All exercises were demonstrated by the therapist who sat at a right angle to the child. A treatment rationale was given during the ®rst session together with a demonstration of tensing and relaxing the muscles in both arms. In the following sessions, exercises were extended to the legs, the back, chest, abdomen, and neck and shoulders, as well as the face. During the ®fth session, tensing was to be carried out only partly, with half or quarter of the full eort. In the sixth session, cued relaxation was introduced whereupon relaxation exercises were carried out without tensing phases as from the seventh session. During the eighth session, relaxation was practiced during standing and walking. The remaining two sessions were devoted to carrying out relaxation during the application of stressors that were similar to the ones used in the ®nal biofeedback sessions. Children were given homework assignments which were noted in a sheet. They were asked to practice the exercises repeatedly which had been carried out during the sessions. 2.5. Measures The headache diary was completed during a 4-week base-line and post-treatment phase by the three groups. A headache index based on frequency and intensity of headache activity was used, in addition to separate analyses of frequency, duration and intensity as well as vasomotor activity. The clinical relevance of headache improvement was assessed by calculating the proportion of patients who achieved a 50% improvement. As the majority of the children suered from both migraine and non-migrainous headaches, additional analyses were performed for each of the two types. 2.5.1. Headache diary Children were asked to complete the headache diary daily. Apart from questions as to the occurrence of headache, there were also questions as to the quality, duration and site of the pain as well as additional symptoms indicative of an aura, nausea and phono- or photophobia. Diary entries were scored for the four weeks baseline and post-treatment phase as well as the two weeks of follow-up assessment. The following variables were extracted: Frequency: The number of headache episodes per week. Intensity: Children were asked to indicate the intensity of headache on a scale of 1 (light) to 10 (overbearing). The weekly sum of the indicated intensities was divided by number of headache episodes. Duration: Children were asked to tick all hours during which headache had occurred. The sum total of the weekly hours was divided by the number of episodes.
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Analgesics intake: The weekly number of headache episodes during which analgesic medication was taken. Mood: The mood scale consisted of 5 schematic faces whose expression varied from being smiling (1) to looking upset (5). Children indicated the face that resembled their overall state of mood best. The mean weekly rating was entered into further analysis. A mean score was computed for each variable of the entries of the 4-week baseline and posttreatment period and a 2-week follow-up phase eight months later. The therapeutic eect was expressed in terms of percent change from pre- to post-treatment. As noted above, a headache index was derived based on the combination of frequency and intensity, as both will presumably cause a patient to seek professional help. Those improving by at least 50% from before to after treatment with regard to the headache index were considered responders in each group. An attempt was made to determine whether or not the dierent treatment modes had a speci®c eect on either migraine or non-migrainous headache. All headache activity reported in the diary was therefore categorized into episodes with and without migraine symptoms, i.e., headache episodes without aura symptoms or nausea were considered non-migrainous. Frequency, intensity and duration of the two kinds of headache were entered into analysis. As there were only 5 children in the metoprolol group suering from non-migraine headache, this analysis was carried out in children of the two psychologically treated groups only. 2.5.2. Vasomotor activity Blood-volume pulse amplitude was recorded only in the two groups receiving psychological treatment. At the beginning and end of the ®rst, sixth and tenth treatment session, pulse volume amplitude was recorded during a base-line phase of 2 min and an additional phase of 3 min during which the biofeedback group was asked to practice vasoconstriction in the absence of feedback and the relaxation group was instructed to relax. Data were recorded with a polygraph (Nihon Khoden) with a digitizing rate of 100 Hz; they were stored on hard disk to be analyzed o line. Mean pulse volume amplitude was evaluated for each 30 s epoch. A program routine controlling for artifacts rejected all amplitude data which occurred with a probability of 5%. The ®rst epoch served as reference. All subsequent epochs were expressed in terms of percent change.
3. Results 3.1. Headache diary 3.1.1. Base-line Subject characteristics and headache variables of the 4 weeks pre-treatment phase are displayed in Table 1. Group between treatment groups using univariate analyses of variance yielded no signi®cant dierences with regard to age, weekly headache frequency, intensity of headache or mood. The in¯ated mean headache duration of the relaxation group was due to one single outlier and proved not signi®cant. However, treatment groups diered signi®cantly with regard to frequency of analgesics intake (F(2,40) = 4.37, p < 0.02) in that subjects in the
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Table 1 Subject and headache characteristics and baseline diary data of the three treatment groups
N Migraine with aura Combined headache Age Female/male Duration of headache disorder (years) Headache diary: Frequency/week Duration/episode (h) Intensity/episode (1±10) Analgesics/episode Mood (1±5)
Relaxation
Biofeed
Metoprolol
15 7/15 11/15 11.4 (2.4) 6/9 4.13 (2.29)
15 5/15 13/15 11.8 (2.0) 7/8 5.07 (3.37)
13 4/15 5/13 10.5 (1.9) 4/9 4.92 (1.85)
2.24 (1.89) 19.56 (25.98) 5.09 (1.35) 0.27 (0.34) 2.04 (0.54)
1.77 9.35 4.37 0.18 2.14
1.33 9.10 5.34 0.50 2.00
(1.17) (8.07) (2.25) (0.23) (0.64)
(0.62) (4.67) (1.88) (0.31) (0.58)
metroprolol group were taking medication signi®cantly more often than those in the biofeedback group (t = 3.17, df = 26, p < 0.01) with the relaxation group in between, not diering signi®cantly from either. 3.1.2. Therapeutic eects Fig. 2 shows mean percent change from before to after treatment of frequency, duration and intensity of headache, mood and analgesics intake. One child in the metoprolol group failed to indicate duration of headache episodes during the post-treatment phase and was therefore excluded from analyses of this variable. Base-line and post-treatment data of frequency, duration, intensity and analgesics intake were entered into multivariate analysis of variance (MANOVA) comparing groups (3) prepost measurement occasions (2). There was a marginally signi®cant pre to post eect (F(1,37) = 3.77, p < 0.06) but no signi®cant group dierence or group pre to post interaction eect. Next, individual variables were entered into analysis of variance with a 3 (groups) 2 (pre-post) design. Headache frequency showed a signi®cant reduction from pre to post treatment (F(1,39) = 20.61, p < 0.01) with neither the group nor the interaction eect being signi®cant. Headache intensity was also signi®cantly lowered (F(1,39) = 10.32, p < 0.01) from before to after treatment with neither the group nor the interaction eect being signi®cant. Analgesics intake was signi®cantly reduced (F(1,39) = 4.28, p < 0.05) and groups diered signi®cantly with regard to intake (F(2,39) = 6.78, p < 0.01) while the interaction eect was not signi®cant. Eects were not signi®cant with regard to duration. Within-group analyses (pre±post) were also performed for each treatment group. Given the skewed distribution of measures, the Wilcoxon matched-pairs signed-ranks test was used (all Pvalues are 2-tailed). The relaxation group showed signi®cant improvement from before to after treatment with regard to frequency (Z = 2.98, p < 0.01) and intensity (Z = 2.42, p < 0.02) with the improvement in duration being only marginally signi®cant. The biofeedback group also showed signi®cant improvement with regard to frequency (Z = 2.45, p < 0.02), duration (Z = 1.98, p < 0.05) and mood (Z = ÿ 2.16, p < 0.05). The metoprolol group showed no signi®cant changes overtreatment.
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3.1.3. Type of headache Frequency, intensity and duration of migraine and non-migraine headache of the two psychologically treated groups were entered into univariate analysis of variance comparing headache type (2) treatment (2) pre±post (2). Frequency of headache showed a signi®cant reduction regardless of treatment type which was signi®cant only for migraine headache (F(1,28) = 7.33, p < 0.02) in the individual analysis. Migraine headache was of higher intensity than non-migraine headache (F(1,28) = 42.6, p < 0.01) and also of longer duration (F(1,28) = 19.8, p < 0.01). Regardless of treatment type, the pain intensity was signi®cantly reduced between pre and post measurement for migraine but not for non-migraine headache (headache type pre-post: F(1,28) = 7.6, p < 0.01) (Fig. 3). 3.1.4. Clinical improvement A comparison was made between the number of patients of each group who had improved by 50% or more with regard to change in the headache index (percent change from baseline to post-treatment of frequency intensity). Fig. 4 displays the percentage of children who had improved with regard to the headache index for each group. The children in the relaxation as compared to those in the metoprolol group were signi®cantly more improved (chi-
Fig. 3. Change in pain intensity of migraine and non-migraine headache in the two psychologically treated groups. Migraine headache was more intense and responded better to treatment than non-migraine headache. The metoprolol group was not included in this analysis as it contained too few children suering from combined headache.
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Fig. 4. Percentage of patients who improved by more than 50% in the headache index (frequency intensity of headache episodes) after treatment. Group comparisons were carried out with the chi-square test.
square = 4.2, p < 0.04). Neither of these groups diered signi®cantly from the biofeedback group. 3.1.5. Cephalic vasomotor activity (Fig. 5) Each of three subsequent 30 s epochs were combined resulting in three 90 s epochs. They were entered into analysis of variance comparing groups (2) sessions (3) pre±post (2) epochs (3). The biofeedback group showed marginally more vasoconstriction than the relaxation group (F(1,23) = 3.23, p < 0.1) with none of the other eects being signi®cant. 3.1.6. Follow-up (Table 2) Sixteen children could not be contacted for follow-up assessment or failed to return the diary. Group means of the successfully contacted children are shown in Table 2. A 3 (groups) 3 (pre±post-follow-up) analysis of variance yielded a signi®cant measurement occasion eect for frequency of headache (F(6,42) = 6.37, p < 0.01) and duration of headache (F(6,44) = 4.12, p < 0.03). None of the other eects were signi®cant. Analysis of variance comparing groups (3) post-treatment-follow up (2) revealed no signi®cant results for main eects nor interactions.
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Fig. 5. Means of the vasomotor activity of the temporal artery in the two groups who received either relaxation or cephalic vasomotor feedback. The data represent averages over 6 measurement occasions (pre-, mid- and posttreatment, at the beginning and end of the each respective session). Three subsequent 90 s epochs were referred to a 30 s baseline. The biofeedback group was instructed to practice vasoconstriction and the relaxation group to relax.
Table 2 Group means (M) and SDs of headache variables of the three treatment groups at the three measurement occasions (baseline, post treatment and follow-up). Sixteen children could not be contacted at follow-up. Only children with a complete data set are included in these groups
N Frequency ± baseline ± post ± follow-up Duration ± baseline ± post ± follow-up Intensity ± baseline ± post ± follow-up Analgesics ± baseline ± post ± follow-up
Relaxation (M, SD)
Biofeedback (M, SD)
Metoprolol (M, SD)
11
10
6
1.75 (1.44) 0.82 (1.15) 1.14 (1.19)
1.73 (1.25) 0.80 (0.95) 1.05 (0.72)
1.46 (0.9) 1.03 (0.78) 1.25 (0.82)
11.74 (12.47) 7.05 (12.81) 6.68 (6.38) 5.24 (1.18)
8.32 3.01 6.27 4.65
10.9 6.61 7.82 4.63
3.37 (2.68) 2.98 (2.65) 0.34 (0.37)
2.51 (2.37) 3.09 (1.67) 0.22 (0.24)
5.02 (2.22) 4.19 (2.42) 0.41 (0.34)
0.13 (0.31) 0.09 (0.20)
0.02 (0.05) 0.18 (0.33)
0.42 (0.38) 0.15 (0.34)
(5.42) (3.60) (5.82) (2.57)
(5.54) (6.78) (3.52) (2.28)
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3.1.7. Relationship between measures Age was correlated positively with duration of headache disorder and a worsening in terms of frequency and duration of episodes and mood of the baseline phase. However, children's age was unrelated to any dierence scores from before to after treatment. Intensity of headache at baseline was not signi®cantly correlated with any of the other headache variables while frequency and duration were highly correlated (r = 0.85, p < 0.01). Improvement, i.e., pre-post dierence scores of the three headache variables were signi®cantly interrelated (r = 0.31±0.67) and they were also signi®cantly correlated with improvement in mood (0.31±0.46). Correlating baseline headache data with extent of improvement yielded no signi®cant results when taking into account all three groups. The separate analysis in the psychologically treatment groups revealed a positive correlation between initial medication and its change over treatment (r = 0.40; p < 0.03) and a negative correlation between initial mood rating and change in medication (r = ÿ 0.36, p < 0.05). The latter correlation indicates that the better the mood state the greater the change in medication.
4. Discussion The overall results of the study showed that relaxation training combined with stress management training was signi®cantly more eective in reducing the headache index than treatment with the betablocker metoprolol. The eectiveness of cephalic feedback combined with stress management training was falling in between these two groups, but did not dier signi®cantly from any of them. The headache index was derived from frequency of headache episodes and intensity of their painfulness. The relaxation group did not dier at baseline from the other two groups with regard to these two variables and baseline dierences cannot therefore account for the treatment eect. Relaxation and stress management training resulted in signi®cant improvement in both variables whereas the biofeedback treatment aected only frequency which would account for its less favorable outcome with regard to the combined variable. Cephalic vasomotor feedback and stress management resulted in signi®cant reduction of the duration of headache episodes and also in improved mood, which was not the case in the two other treatments. It could be argued that a headache index derived from frequency and duration of headache would have shown the biofeedback rather than the relaxation group to have the best outcome. Combining frequency and pain intensity is however more meaningful statistically as well as clinically. The two variables were uncorrelated unlike frequency and duration. Both high frequency of migraine attacks and intense pain will cause disruption in the children's daily life and therefore deserves clinical attention. Combining the two aspect in the assessment of clinical ecacy therefore appears more appropriate than an index based on headache frequency and duration. The results are partly in keeping with those reported previously. In a recent meta-analytic review of studies, Hermann et al. (1995) concluded that relaxation combined with other treatment components (e.g. McGrath et al., 1992) constituted an eective intervention in pediatric migraine. Unlike the outcome of the present study, Hermann et al. (1995) found biofeedback training to have the greatest therapeutic ecacy in pediatric migraine. A number of factors could account for the inconsistency. The studies summarized by Hermann et al.
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(1995) used thermal biofeedback whereas cephalic feedback was used in the present study. It is conceivable that a change in hand temperature is more easily achieved than cephalic vasoconstriction and therefore more eective in this age group. Temperature changes of the hands are associated with more pronounced interoceptive cues than vasoconstriction of the temporal artery which may facilitate their controllability. Most of the previous studies (Labbe and Williamson, 1983; Fentress et al., 1986) have also used more training sessions than the present study. As one of the aims of the present study was to generate and evaluate a compact and inexpensive treatment for pediatric migraine, it was outlined after the short treatment schedule reported to be successful for adult migraineurs by Falkenstein et al. (1986). If children need more extensive treatment than adults, then the present treatment study may not have constituted an appropriate trial of the eectiveness of cephalic vasomotor feedback in pediatric migraine. Comparing the improvement rate of some recent studies with the present one, Osterhaus et al. (1993) found a similar 41% improvement in headache frequency after a combination of relaxation, temperature feedback and cognitive therapy; yet other authors reported an average 75% (LabbeÂ, 1995) and 63 or 85% reduction in headache frequency (Fentress et al., 1986). Labbe (1995) used a short course of autogenic training and thermal feedback whereas Fentress et al. (1986) used muscular relaxation and EMG feedback. Both of these forms of feedback are designed to enhance relaxation. Administering relaxation and cognitive treatment separately, Richter et al. (1986) reported improvements of 40 and 46% respectively, in headache frequency in severely aected patients. Less severely aected ones showed less improvement. Active treatment was found to be more eective than control conditions. Most authors reported no change in frequency in waiting list control groups (e.g. ÿ2% Ð Osterhaus et al., 1993; 4% Ð Fentress et al., 1986) with, however, exceptions such as Labbe (1995) who reported a 24% reduction in frequency in her waiting list control group. Psychological placebo treatment, such as recognizing and labelling emotions as in non-directive therapy, resulted in a 7% reduction in frequency (Richter et al., 1986). Although less often reported, the present improvement with regard to intensity of headache compares well with that of other studies. Richter et al. (1986) reported similar 26 and 32% for relaxation and cognitive therapy and Osterhaus et al. (1993) failed to ®nd a change. Unlike the other treatments, relaxation signi®cantly reduced headache intensity in the present study. Relaxation is an eective pain reducing technique in the management of other chronic pain disorders. It has been suggested that if both migraine and non-migraine headache episodes occur, it is the latter that respond better to relaxation (Mizener et al., 1992), presumably because pain in non migrainous headaches is partly caused by increased muscle tension. Comparing the change in headache activity between the two types, it was however, migraine rather than non-migraine headache that responded best to the two psychological treatments. The former was also initially rated as being more intense and longer lasting and could therefore improve more than the latter. Children in the biofeedback group showed greater constriction of the temporal artery than the relaxation group who were instructed to relax. However, extent of vasoconstriction did not increase with training nor did it dier across treatment sessions. The crudity of the measure, i.e., the dependence of assessing reactivity of the blood-volume pulse amplitude relative to an arbitrary baseline level, may have obscured changes over treatment sessions. Measuring blood
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¯ow velocity by means of transcranial Doppler technique, McGrady et al. (1994) and Wauquier et al. (1995) found signi®cant slowing in the middle cerebral artery following feedback training of the frontalis EMG and of ®nger temperature, autogenic training and diaphragmatic breathing. Abnormalities of the middle cerebral artery have previously been implicated in the occurrence of migraine (Oleson, 1991). So far, it is however, unclear, whether or not cephalic vasomotor feedback induces similar changes or indeed, which component of the treatment package was responsible for the ones reported by McGrady et al. (1994) and Wauquier et al. (1995). The medication with metoprolol had little eect on the children's headache activity in the present study. In a previous treatment trial it proved eective unlike ergotamine (Besken et al., 1992). These results were based on within-group time-series analysis of diary data which may constitute of more sensitive way of analyzing repeated measures. Other drugs, such as ¯unarizine, a calcium-channel blocker, may have been more eective (for a review, see Hermann et al., 1995). Metoprolol is generally regarded to have a prophylactic eect and was therefore presumed to be similar to psychological treatment. Drawing conclusions from follow-up data in the present study, it should be noted that a number of clients from the metoprolol group could not be traced or failed to respond to the request for follow-up information. Obtaining diary information about headache activity for only two rather than four weeks also reduced the reliability of the follow-up data. However, the two psychologically treated groups showed no signi®cant changes over the follow-up period and the treatment eect could thus be said to be maintained over time. A ten-year follow-up of patients who were originally encouraged to use coping techniques rather than medication, found 73% to be still suering from headache with, however, 81% being much improved (Dooley and Bagnell, 1995). Current psychological techniques are thus unlikely to prevent further migraine attacks altogether but alleviate their severity long-term and in a manner that is free of unwanted side eects which makes them particularly suited for the treatment of pediatric migraine.
Acknowledgements This study was supported by the Bundesminister fuÈr Forschung und Technologie (BMFT; Federal Minister for Research and Technology, Germany). We gratefully acknowledge the contribution to carrying out the trial of the following: Angela Elvermann, Dagmar Haase, Wiebke Otremba and Irene Vormbaum.
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