Treatment of primary headache in children: a multicenter hospital-based study in France

This was the second part of the Céleste study, the first cross-sectional, epidemiological, multicenter survey of primary headache in children and adolescents, conducted in France. The results presented in this article concentrated specifically on the therapeutic management of primary headache in children and adolescents, with a comparison between pre-referral and referral conditions.

Both migraine and tension-type headache require a comprehensive treatment plan, which may include acute and preventive therapy. The American Academy of Neurology recently reviewed the available evidence for both acute and preventive migraine therapies in detail, either behavioral or pharmaceutical, in a Practice Parameter [8]. In children of age 6–12 years, both paracetamol at 15 mg/kg per dose or the non-steroidal anti-inflammatory drug ibuprofen at 7.5–10 mg/kg per dose, taken when needed, are effective and well tolerated [9, 10]. For the acute treatment of migraine in adolescents of age 12–17 years, in addition to ibuprofen, sumatriptan nasal spray at doses of 5–20 mg is effective and well tolerated [11]. Triptans, migraine-specific medications, may be added to the treatment plan when children have a moderate-to-severe migraine, when the response to ibuprofen is either incomplete or ineffective. Management of tension-type headaches involves the use of intermittent analgesics coupled with behavior interventions such as stress management. Both paracetamol and non-steroidal anti-inflammatory drugs are effective first-line therapy for episodic tension-type headache [12]. The clinical characteristics and treatment options in cluster headache are globally similar to those of adult patients [13].

In France, the French Health Agency (Haute Autorité de Santé, HAS) published clinical guidelines for the therapeutic management of migraines in adults and children. These were distributed to each general practitioner (GP) in October 2002 [14]. The HAS recommended ibuprofen (7.5–10 mg/kg) as the mainstay drug for acute migraine attacks in children aged 6 months or older [14]. If ibuprofen proved ineffective, the HAS recommended the use of ergot derivatives from the age of 10 years onward, despite the absence of evidence of efficacy [15, 16], and the use of sumatriptan nasal spray from the age of 12 years onwards. In France, sumatriptan nasal spray is the only triptan approved for migraine treatment of children and adolescents 12 years or older. In this context, it is astonishing that paracetamol was largely preferred by GPs. Moreover, paracetamol was unsatisfactory in the majority of cases. Perhaps the most striking finding of our study was the fact that there was globally no distinct pattern of prescribing with respect to diagnosis. Paracetamol was the leading acute treatment that was indistinctly used for migraine, tension-type headache or other primary headaches. Specific antimigraine drugs were equally underused, although ergot alkaloids and triptans were prescribed slightly more frequently to patients assigned a diagnosis of migraine with or without aura by their physician. Not surprisingly, the acute treatment prescribed following the consultation in the neuropediatric department was more suited to the diagnosis and more in line with present recommendations, either by the HAS or the American Academy of Neurology, with a nearly sixfold increase in triptan prescription.

The decision to initiate prophylactic therapy must take into account the disability caused by the headache disorder. There is currently, however, no consensus on when to initiate preventive measures; but daily prophylactic therapy is warranted in about 20–30% of young migraineurs [17]. Most authors consider three to four migraines per month as the threshold for initiating prophylactic treatment in pediatric patients. Prophylactic pharmacological treatment should be also considered in chronic tension-type headache if non-pharmacological management is inadequate.

Prophylactic pharmacological headache treatments can be classified into antiepileptic medications, antidepressant medications, antiserotonergic medications and antihypertensive medications, including both beta blockers and calcium-channel blockers. Around 10% of children were prescribed a prophylactic therapy. There was slight difference with respect to diagnosis, the only exception being migraine with aura. GPs largely favored “old” prophylactic medications, with ergot alkaloids and serotonin antagonists being the two classes of drug they most often prescribed. Dihydroergotamine remains one of the drugs prescribed most often for childhood migraine prophylaxis in western European countries, such as France or Germany, despite lack of any proof of its efficacy. To our knowledge, only one controlled study with dihydroergotamine drops has been reported in a pediatric population, which found no statistical difference between placebo and dihydroergotamine [18]. Oxetorone, pizotifen and cyproheptadine were the serotonin antagonists prescribed by GPs. The Practice Parameter stated in its conclusions that pizotifen did not show efficacy and was not recommended and that there was insufficient evidence to make any recommendations concerning the use of cyproheptadine [8]. No study regarding the use of oxetorone in children is available. Nevertheless, the three drugs have been recommended by the HAS, which stated at the same time that there was actually no evidence of their efficacy [14]. In this setting it is not astonishing that the perceived efficacy by the patients was poor. Both serotonin antagonists and ergot alkaloids reduced frequency of headache frequency in less than a third of cases. Newer prophylactic drugs, such as antiepileptic medications, were rarely prescribed by GPs. While the number of children prescribed a prophylactic treatment nearly doubled following the consultation in the neuropediatric department, it is surprising that neuropediatricians also favored “old-fashioned” prophylactic medications. Antiserotonergic drugs were used most often, whereas newer ones such as antiepileptic medications, for which the evidence base for efficacy is considerably more solid, were infrequently prescribed.

Behavioral headache treatments include relaxation training, biofeedback training, cognitive-behavioral therapy or combinations of these treatments [19]. The availability of these therapies is limited in France and this may explain why few patients benefited from nonpharmacologic treatments at referral. Nevertheless, following the re-evaluation by a neuropediatrician, non-pharmacologic rather than drug treatments accounted for much of the increase in headache prevention therapy. Whereas there was a nearly 2-fold increase in the prescription of prophylactic medication, there was a 5-fold and a 23-fold increase for both psychotherapy and relaxation training, respectively, whereas biofeedback prescription increased from 0 to 8 patients, between pre-referral and referral. This may also indicate that there is a lack of knowledge of the possibility of these therapeutic options by GPs.

The reasons for our findings are difficult to understand, in view of scientific progress in the field of headache and the efforts made by professional societies to improve the standard of treatment [20]. GPs seem reluctant to be involved strongly or directly in the management of primary headache, especially in children, and prefer to delegate specialists to prescribe treatments that require a precise diagnosis [21].