Letter to the editor regarding “Efficacy and tolerability of combination treatment of topiramate and greater occipital nerve block versus topiramate monotherapy for the preventive treatment of chronic migraine: A randomized controlled trial”

Dear editor,

We have read with great interest the paper by Chowdhury et al., entitled “Efficacy and tolerability of combination treatment of topiramate and greater occipital nerve block versus topiramate monotherapy for the preventive treatment of chronic migraine: A randomized controlled trial” (1).

Greater Occipital Nerve (GON) block represents a useful and not expensive therapeutic option for managing migraine in both the adult and pediatric population (2,3). Moreover, a previous neurophysiological study found that GON block-induced response could also be predicted by early changes in serotonergic brainstem firing measured by intensity dependence of auditory evoked potentials (4).

Authors presented this paper as a comparison randomized control trial between two different kinds of GON block added to topiramate (one arm with steroid and lidocaine and one with only lidocaine), compared to topiramate alone. To date, there is no consensus about an additional beneficial role of steroid added to anesthetic, therefore rigorous studies, as randomized clinical trials, on this topic are very needed.

We wonder whether steroid contribution is really that marginal, as authors concluded from this study. Authors concluded that the steroid did not add a clinical benefit compared with lidocaine alone, since the head-to-head comparison between the two arms was not different.

However, as per study design, from the second administration on, steroid was withdrawn and only lidocaine administered. GON block was repeated twice with monthly period.

Looking at results in this paper, interestingly, steroid-lidocaine combination appeared to be more often significantly effective than lidocaine alone when compared with topiramate in many secondary outcomes (e.g., the rate of >50% responders or monthly headache days).

In this sense, also the timing of the GON block administration is noteworthy. The mean duration of the GON block is very variable but the real-world studies showed that its effect (when steroid is also administered) could last 30 days or more (2,3). In the paper by Puledda et al., in particular, the mean duration of the clinical benefit of steroid plus anesthetic was nine weeks (3). For this reason, maybe, the 1-month administration could favor the lidocaine arm rather that the combination one, while steroid-lidocaine combination might be administered with longer time laps.

This could be important since the main reason for avoiding multiple administration of steroid was the risk of side effects. In the paper by Chowdhury et al., a case of Cushing syndrome is reported as possible severe adverse events, however, three large observational studies including about 580 GON injections in either migraine (both episodic and chronic) or cluster headache did not report such adverse events, even when the administration was repeatedly performed (2,3,5). Moreover, since the GON block performed with a combination of steroid and lidocaine has a longer effect with respect to a injection with sole lidocaine, the time lap between injections could be even expanded if the beneficial effect resulted by the injection would be greater.

In conclusion, we praise Chowdhury et al. for increasing the level of evidence of the GON block in the management of chronic migraine. However, considering the novelty of this trial and the fact that samples were not powered enough to allow a direct comparison between the two arms (as discussed by the authors), we believe that steroid plus lidocaine combination should not be dismissed before a specific comparison trial on a possible additive effect of steroid.