3. Preventive Treatment

Preventive treatment aims to reduce attack frequency and severity over the course of a cluster period (episodic CH) or indefinitely (chronic CH). For chronic sufferers, this is the treatment category that matters most day-to-day, and it is also the category where the gap between trial evidence and real-world/community practice is widest — most of these drugs have never been tested in a properly powered chronic-CH-only RCT.

Before the drug-by-drug detail, three structural facts shape everything below.

1. The randomised evidence base for CH prevention is astonishingly thin. A 2022 German review states that only verapamil and lithium have evidence from randomised studies at all, and grades even those as ++ (“moderate evidence”), with topiramate + (“low”), and gabapentin and melatonin (+) (“questionable”) (Drug Treatment of Cluster Headache, PMC8748342). peer-reviewed The 2016 American Headache Society evidence-based guideline found that after a full systematic review, the only preventive treatment achieving a Level A recommendation was suboccipital steroid injection — not verapamil, not lithium (Robbins MS, Starling AJ, Pringsheim TM, Becker WJ, Schwedt TJ. Headache 2016;56(7):1093–1106, DOI 10.1111/head.12866, PMID 27432623). peer-reviewed

2. Chronic CH is systematically worse-served than episodic CH. Every single agent below performs worse in chronic than episodic disease, and several drugs with positive episodic data have outright failed in chronic trials. This is the single most important pattern in this chapter for a daily-chronic patient, and it recurs so consistently that it is arguably a biological signal rather than a trial-design artefact.

3. The gap between guideline dosing and specialist/community practice is enormous — and the guidelines are, on the specific issue of verapamil dose, arguably the ones that are wrong. This is documented in an unusually explicit way in the German literature (see §1.6).