Abstract
Dear Sir We have read the article ‘Prednisone vs. placebo in withdrawal therapy following medication overuse headache’ by Pageler et al. in the February issue of Cephalalgia and found it extremely interesting (1). The basis of medication overuse headache treatment continues to be the interruption of all overused medications. The high prevalence of this condition in headache clinics results in many patients suffering from withdrawal symptoms and headache intensification (2). Due to this remarkably uncomfortable process, many patients fail to complete withdrawal therapy (3). Any method that enables patients to tolerate this therapy will be welcome. We would like to comment on some aspects of the article in order to assist and simplify future studies.
Although intended to be a pilot study, the study population and protocol should have been described in more detail, in order to allow the precise reproduction of the study and to avoid dispute. Exclusion criteria should include the presence of active peptic ulcer and other severe disorders, subsequently increasing safety prior to the use of such a high dose of prednisone in a larger population. These additional criteria were used in two previous studies that included a high dose of prednisone in withdrawal therapy, but in a lower and tapering dose (4, 5). We are not considering the hypothesis of peptic ulceration caused by steroids, whose evidence is fogged by conflicting data (6). Rather, we have in mind that a supraphysiological dose of steroids may inhibit the healing of pre-existent lesions, which can be caused by the overused medication (2). Besides, it is tempting to speculate that nine patients do not constitute a meaningful sample size to demonstrate adverse events and to prove the safety of the therapy of choice.
Moreover, the article should have clearly described the method used to record headache characteristics before withdrawal therapy. Retrospective reports on chronic pain patients indicate a tendency to present inaccurate information and suggest that reliance on medication increases the divergence between reported and actual pain severity (7). Studies in children and adults imply that a combination of clinical interviews and the use of diagnostic headache diaries provides a more precise diagnosis (both quantitatively and qualitatively) than a clinical interview alone (8, 9). Our experience with children and adolescents, comparing chronic daily headache severity prior to and following the use of a headache diary, has confirmed the superior diagnostic potential of the combination of the two methods (especially in a population such as this, prone to recall bias, placebo effect and previous overestimation) (10). A reliable baseline headache severity should have been documented in a diary or calendar in order to reduce bias and to increase the accuracy of description, which would strengthen the comparison after withdrawal therapy (11). Furthermore, if patients 6 and 10 (shown in Table 1 of Pageler et al.) (1) had been asked to complete a baseline headache diary, they would probably not have been included in the study or submitted to withdrawal therapy at all.
In conclusion, we are optimistic about this approach (with a high dose of prednisone) to the treatment of withdrawal symptoms and headache intensification. There is still the need for a double-blind, randomized, placebo-controlled study with the use of prednisone, which takes the above-mentioned suggestions into consideration. A larger, multicentre, Phase III study has been initiated in various European centres (1), and these results are eagerly expected by patients who previously failed to complete withdrawal therapy and by their doctors.