Dodick, DW

The best way to appreciate the efficacy of drug and behavioural therapy in the acute and prophylactic treatment of headache is to perform placebo-controlled randomized trials. In order to plan and conduct these studies in the most appropriate way, it is desirable to know which factors influence the placebo response. This paper reviews factors which influence the placebo response in clinical trials, such as expectation, blinding, route of application of drugs and age, gender and geographical distribution. Response rates of placebo in the treatment of acute headache episodes are higher than in headache prophylaxis. Invasive procedures such as injections have a higher placebo response compared with oral drugs. Variables known to influence the placebo response have to be taken into consideration to calculate properly the power of planned randomized trials.

The Act when Mild (AwM) Study has illustrated the benefits to migraineurs of taking triptan medication when their migraine pain is still mild and within 1 h of the onset of symptoms. Yet many patients wait until the attack has fully developed before taking their medication, with potentially inferior outcomes. In order to reproduce the benefits of early intervention using the AwM paradigm in daily practice, a number of key barriers need to be addressed at both the physician and patient level. Notable physician-related barriers to be overcome, particularly at the primary care level, include accuracy of an early diagnosis of migraine in newly presenting patients, communication skills that generate a therapeutic engagement with migraine patients and enhance patient confidence, the application of knowledge about up-to-date strategies to optimize treatment outcomes, and the setting of achievable goals to avoid unrealistic expectations. Patient-related obstacles that need to be identified and overcome encompass patient attitude, expectations, and behaviour. Migraine patients may be reluctant to consult their physician, and, of those who do, many stop consulting because they perceive that physicians can do little to improve their situation. For this reason, migraine patients need to be counselled about the most appropriate medication for their level of symptoms. Moreover, patients need to be confident before they will adhere routinely to the advice they receive, and high in the priority of advice is the use of medication, particularly triptans, at the first sign of a migraine attack, rather than waiting until their attack has progressed to moderate or severe intensity. Patients who adhere to this advice are likely to experience a notable reduction in the pain, disability and time lost that they would otherwise suffer. The beneficial effects of early triptan intervention illustrated in the AwM Study can therefore be best reproduced in the clinic if the correct advice given to patients is not only accepted and applied by them, but also followed up by their physician.

Initial studies indicate an increased prevalence of patent foramen ovale (PFO) in migraineurs with aura, and an increased prevalence of migraine and migraine with aura in persons with PFO. Retrospective analyses of PFO closure suggest clinically significant improvements in migraine patterns. The aim of this study was to examine the prevalence of migraine in patients with PFO, the prevalence of PFO in migraineurs, and the effect of PFO closure on migraine. We conducted a quantitative systematic review of articles on migraine and PFO that met inclusion criteria, then reviewed, appraised, and subjected them to data extraction. Of 134 articles identified, 18 met a priori selection criteria. The estimated strength of association between PFO and migraine, reflected by summary odds ratios (ORs), was 5.13 [95% confidence interval (CI) 4.67, 5.59], and between PFO and migraine with aura the OR was 3.21 (95% CI 2.38, 4.17). The grade of evidence was low. The association between migraine and PFO was OR 2.54 (95% CI 2.01, 3.08). The grade of evidence was low to moderate. Six studies of PFO closure suggested improvement in migraine, but had a very low grade of evidence. The low-to-moderate grade of evidence from observational studies supports an apparent association between PFO and migraine. Although PFO closure seemed to affect migraine patterns favourably, the very low grade of available evidence to support this association precludes definitive conclusions.

Migraineurs with frequent aura (≥1 per month) are at a 12-fold increased risk of posterior circulation infarctions. Although the mechanism is unclear, these lesions are located in the arterial borderzone of the cerebellum. This case illustrates, for the first time, crossed cerebellar diaschisis in a patient with migraine with prolonged aura, and raises the possibility that hypoperfusion may be responsible in part for the development of these lesions.

We set out to identify predictors for the prophylactic effect of placebo injections in subjects with migraine by post hoc analysis of 81 subjects with episodic migraine receiving single-blind placebo injections in a prospective trial of botulinum toxin. Possible predictors of placebo prophylaxis were compared among placebo responders (PRs) and placebo non-responders (PNRs). There were 34 PRs (42%) and 47 PNRs (58%). Male gender [odds ratio (OR) 5.83, 95% confidence interval (CI) 1.12, 30.14, P = 0.022], a history of opioid use (OR 4.44, 95% CI 1.47, 13.41, P = 0.005) and injections in the neck/shoulders (OR 2.44, 95% CI 0.93, 3.19, P = 0.033) were associated with placebo response. Of subjects with two or more of these signs, 88% were PRs compared with 31% of subjects with one or less. Male gender, opioid use and injections in the neck/shoulders are associated with placebo prophylaxis. These findings may have important implications for the design of future clinical trials and for the clinical management of migraineurs.

Occipital nerve stimulation (ONS) may be effective for the treatment of headaches that are recalcitrant to medical therapy. The objective of this study was to determine if response to occipital nerve block (ONB) predicts response to ONS in patients with chronic, medically intractable headaches. We evaluated 15 patients who underwent placement of occipital nerve stimulators for the treatment of chronic headaches. Data were collected regarding analgesic response to ONB and to ONS. Nine of 15 patients were ONS responders (≥50% reduction in headache frequency or severity). Thirteen patients had ONB prior to stimulator implantation. Ten of 13 who had ONB had significant relief of head pain lasting at least 24 h, and three were ONB non-responders. Of the three ONB non-responders, two were ONS responders. Of the two patients who did not have ONB prior to ONS, one was an ONS responder and one was an ONS non-responder. In conclusion, analgesic response to ONB may not be predictive of the therapeutic effect from ONS in patients with medically refractory chronic headaches.

The aim of this study was to examine the safety and efficacy of occipital nerve stimulation for medically intractable headache. Electrical stimulation of large sensory afferents has an antinociceptive effect. Occipital nerve stimulation may be effective for the treatment of medically intractable headache. Retrospective analysis was performed of 15 patients with medically refractory headache who underwent implantation of an occipital nerve stimulator. Pre- and postimplant data regarding headache frequency, severity, disability, depression and post-stimulator complications were collected. Twelve patients were female and three male. Ages ranged from 21 to 52 years (mean 39 years). Eight patients had chronic migraine, three chronic cluster, two hemicrania continua and two had post-traumatic headache. Eight patients underwent bilateral and seven had unilateral lead placement. Patients were measured after 5-42 months (mean 19). All six mean headache measures improved significantly from baseline ( P < 0.03). Headache frequency per 90 days improved by 25 days from a baseline of 89 days; headache severity (0-10) improved 2.4 points from a baseline of 7.1 points; MIDAS disability improved 70 points from a baseline of 179 points; HIT-6 scores improved 11 points from a baseline of 71 points; BDI-II improved eight points from a baseline of 20 points; and the mean subjective percent change in pain was 52%. Most patients (60%) required lead revision within 1 year. One patient required generator revision. Occipital nerve stimulation may be effective in some patients with intractable headache. Surgical revisions may be commonly required. Safety and efficacy results from prospective, randomized, sham-controlled studies in patients with medically refractory headache are needed.