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ARTICLES: Peter Zeeberg, Jes Olesen, and Rigmor Jensen Probable medication-overuse headache: The effect of a 2-month drug-free period Neurology 2006; 66: 1894-1898 [Abstract] [Full text] [PDF]

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Probable medication-overuse headache: The effect of a 2-month drug-free period

Marc Gotkine   (31 August 2006)

Reply from the Authors

Peter Zeeberg, Jes Olesen, Rigmor Jensen   (31 August 2006)

Probable medication-overuse headache: The effect of a 2-month drug-free period 31 August 2006
Marc Gotkine, Department of Neurology, Hadassah University Hospital P.O. Box 12000, Jerusalem 91120, Israel Send Correspondence to journal: Re: Probable medication-overuse headache: The effect of a 2-month drug-free period marcgotkine{at}gmail.com Marc Gotkine	I read the article by Zeeberg et al [1] with interest in which they emphasize the therapeutic importance of weaning patients suspected of suffering from medication overuse headache (MOH). Do the authors feel there is a possibility that the observed improvement in headache could be partially due to an "inverse" placebo effect? The placebo effect can be defined as "improvement in the condition of a patient that occurs in response to treatment but cannot be considered due to the specific treatment used." [2] Patients expecting an improvement in symptoms following the specific treatment of drug withdrawal may experience such an effect. It is scientifically appealing to conduct a double-blind controlled trial in which the "placebo" arm consists of patients continuing active pharmacological therapy while patients in the "active treatment" arm receive an inert substance. Although this is arguably the ideal way to establish MOH as a distinct clinical entity, the authors' pragmatic approach provides convincing evidence guiding the management of this problematic clinical situation. References 1. Zeeberg, P., J. Olesen, R. Jensen. Probable medication-overuse headache: the effect of a 2-month drug-free period. Neurology 2006;66:1894-1898. 2. Medline Plus Merriam Webster Dictionary. http://www2.merriam-webster.com/cgi-bin/mwmednlm?book=Medical&va=placebo%20effect. Accessed August 31, 2006. Disclosure: The author reports no conflicts of interest.
Reply from the Authors 31 August 2006
Peter Zeeberg, Danish Headache Center Dept. of Neurology, Univ. Copenhagen, Glostrup Hosp., Nordre Ringvej 57, DK-2600 Glostrup, DENMARK, Jes Olesen, Rigmor Jensen Send Correspondence to journal: Re: Reply from the Authors Peter.Zeeberg{at}Dadlnet.dk Peter Zeeberg, et al.	Dr. Gotkine’s question highlights an important aspect of all pain research – the placebo effect. Due to the uncontrolled open study design, we can not rule out the possibility of an "inverse" placebo effect. There are, however, several reasons to believe that this possible "inverse" placebo effect is minimal in our study. In prophylactic migraine trials, the reduction in migraine attacks due to placebo response has been estimated to 16.8% [3], but with large variation between studies. In acute migraine attacks, the average headache response rate to placebo is even higher (30%). [4] If a significant placebo effect was present, one would expect it to be evenly distributed among all patients and across different headache diagnoses. Our patients segregated into three groups following withdrawal: one with improvement (45%); one that stayed completely unchanged (48%); and a small group of 7% who deteriorated. Furthermore, there were marked differences between the diagnostic groups with a 67% median reduction in migraine, 0% in tension-type headache (TTH), 37% in mixed migraine and TTH and 0% in other headache diagnoses. These results strongly suggest the absence of a marked “inverse” placebo effect. References 3. van der Kuy PH, Lohman JJ. A quantification of the placebo response in migraine prophylaxis. Cephalalgia 2002;22:265-70. 4. Bendtsen L, Mattsson P, Zwart JA, Lipton RB. Placebo response in clinical randomized trials of analgesics in migraine. Cephalalgia 2003;23:487-90. Disclosure: The authors report no conflicts of interest.