Reply: Orbitofrontal cortex hypometabolism, medication overuse headache, substance abuse and migraine: key pathophysiological issues
Received March 4, 2006. Revised March 29, 2006. Accepted April 4, 2006.Sir, We thank Dr Gupta for his interest in our work and we will try to answer to his different remarks.
He states that only very few migraine patients regularly using analgesics develop medication overuse headache (MOH). There are several prospective studies dedicated to this topic. In a patient population consulting a specialized headache centre, 64 (14%) out of 450 patients developed chronic headache over 1 year; the most prominent risk factors were medication overuse and headache frequency (Katsarava et al., 2004
). In population-based studies, chronic headaches (at least 15 days/month) have a prevalence of 3–5%, among which 60–80% are attributed to acute medication overuse. In Norway, 11% of the population uses analgesics daily or weekly, and daily analgesic consumption during 6 months increased the risk of migraine chronification by a factor of 20 (Zwart et al., 2003). MOH is thus not a minor health problem, as suggested by Gupta.
Dr Gupta rightly underscores that there is no placebo-controlled trial showing that drug withdrawal ameliorates the headache in MOH. However, this is a widely documented clinical finding and the fact that both the duration of withdrawal headaches as well as that of overconsumption before MOH vary between triptans, ergotamine and analgesics favours a proper effect of these drugs on the headache aggravation (Katsarava et al., 2001; Limmroth et al., 2002). That the decrease in orbitofrontal cortex (OFC) metabolism found in our study is moreover not due to a placebo effect is highlighted by various studies showing that the placebo effect is associated with activation (not inactivation) of the OFC cortex (Wager et al., 2004; Petrovic et al., 2005).
Dr Gupta questions the relationship between drug dependence and MOH on the basis that the former is not associated with episodic or chronic pain. The clinical observation is indeed that chronification due to drug overuse occurs chiefly in headache patients, but it may not be strictly limited to such patients. The Norwegian Head-Hunt study mentioned above (Zwart et al., 2003) showed, for instance, that the risk of developing chronic pain was multiplied by 4 in subjects with low back pain who took daily analgesics for 6 months. Several recent studies have clearly identified behavioural characteristics of substance dependence in MOH patients (Fuh et al., 2005) and have shown that substance dependence is more prevalent in the personal and family history of such patients (Radat et al., 2005).
We excluded patients with overt depression in order to avoid the confounding effect on cerebral metabolism of depression. In migraine, and in MOH, the strongest association with psychiatric disorders is indeed found for depression and anxiety disorders (Verri et al., 1998; Mitsikostas and Thomas 1999; Radat et al., 2005), which were both excluded in our study. Nonetheless, overt psychiatric disease affects only a minority of patients among the whole group of MOH patients (including those who attend specialized headache clinics) as shown in this and other studies (Radat et al., 2005). We do, therefore, not agree with Dr Gupta’s criticism that our patient sample is not representative of MOH patients in the general population. By the way, these patients are not, as he believes, refractory. They have only developed a complication of migraine to which they could be predisposed, but which is perfectly reversible in most of them with adequate management.
The statements of Dr Gupta concerning the reliability of drug withdrawal and the role of the monoaminergic systems in migraine need no comment, as they have no scientific backing.
1 Departments of Neurology, University of Liège Liège, Belgium 2 Departments of Neuroanatomy, University of Liège Liège, Belgium 3 Department of Surgical, Pathophysiology and PET Unit Rigshospitalet Copenhagen, Denmark
Correspondence to: Arnaud Fumal, Department of Neurology, University of Liège, B-4000 Liège, Belgium E-mail: arnaud.fumal{at}ulg.ac.be
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