11.1 Introduction

The treatment of acute cluster headache attacks is based on clinical trials and on empirical data. In the last decades, we also learnt more about the pathophysiology of cluster headache leading to new substances for both acute and prophylactic treatment. Although cluster headache is a very impressive somatic disorder, it has to be considered that drug treatment in cluster headache shows a placebo rate similar to that observed in migraine treatment [1]. There are treatment guidelines available published for different parts of the world [2, 3], and the superiority of guideline-adherent treatment over purely intuitive treatment in cluster headache has been shown [4].

11.2 Attack Treatment

After the first published report on the use of oxygen to abort cluster headache attacks [5], the use of oxygen in cluster headache has been proposed for decades. The first controlled clinical trial was published in the 1980s [6]. The most recent trial showed that inhalation of pure (100%) oxygen with a flow of at least 12 L/min is effective in abortion of acute cluster headache attacks [7]. Oxygen should be inhaled for 15 min in a sitting, upright position by demand valve oxygen (full facial mask) [8]. There are no contraindications known for the use of oxygen. It is safe and without side effects. More than 70% of all cluster headache patients respond to this treatment with a significant pain reduction within 30 min.

In double-blind, placebo-controlled trials, the 5-HT1_B/D agonist sumatriptan injected subcutaneously was effective in about 75% of all cluster headache patients (i.e., pain free within 20 min) [9, 10]. It is safe and without side effects in most of the patients even if it is taken nearly daily as some cluster headache patients do off-label [11]. Contraindications are cardio- and cerebrovascular disorders and untreated arterial hypertension. The most unpleasant side effects are chest pain and distal paraesthesia. Even 3 mg subcutaneous sumatriptan is effective in the majority of patients [12]. Zolmitriptan 5 mg nasal spray has also been shown to be effective in two placebo-controlled trials and has been approved by the EMA for the acute treatment of cluster headache [13, 14]. In one single open and one double-blind, placebo-controlled trial, sumatriptan nasal spray 20 mg was also effective in the abortion of attacks [15, 16]. These triptan nasal sprays should be installed into the contralateral nostril as ipsilateral rhinorrhea might hamper the uptake of the drug by the nasal mucosa. Finally, oral zolmitriptan 10 mg was also effective within 30 min [17]. However, oral use of triptans in the approved dose is not recommended for cluster headache attacks, since the onset of efficacy is too late.

Oral and intranasal ergotamine tartrate has been used in the treatment of acute cluster headache attacks for more than 60 years [18] and is probably effective when given very early in the attack. However, placebo-controlled trials are missing. Short-term prophylaxis with ergotamine is not recommended anymore because of severe side effects. The intranasal application of dihydroergotamine in cluster headache attacks was not superior to placebo in a single trial [19]. The intravenous application of 1 mg dihydroergotamine over 3 days has been shown to be effective in the abortion of severe cluster attacks in an open retrospective trial [20].

The nasal installation of lidocaine into the ipsilateral nostril (1 mL with a concentration of 4–10%; the head should be reclined by 45° and rotated to the affected side by 30–40°) is effective in at least one third of the patients [21–23].

One hundred microgramme subcutaneous octreotide has been shown to be effective in the treatment of acute cluster headache attacks in a double-blind, placebo-controlled trial [24].

The use of the so-called peripheral analgesics and of opioids is not recommended in the treatment of cluster headache attacks [2]. Although controlled trials on these substances in cluster headache are lacking, there is expert consensus that they are ineffective or show much lower efficacy than the substances discussed above.

Although the (nearly) daily intake of acute drugs to abort cluster headache attacks is safe and without further complications in most cluster headache patients, the induction of medication overuse headache cannot be excluded, in particular in those patients with concomitant migraine or migraine in their family [25]. Therefore, the intake of acute drugs should be restricted to 10 days per month which is possible in nearly all patients with successful prophylactic treatment.

11.3 Future Developments

New drugs affecting the CGRP pathways are under development for the treatment of cluster headache. The so-called CGRP antagonists (class group of gepants), which are given orally, might be an option for long-lasting cluster headache attacks; however, no clinical trials have been performed so far. The class of CGRP antibodies is mainly investigated for the prevention of cluster headache attacks; however, for very severe cluster attacks, a parenteral application could be efficacious.

Stimulation techniques to treat cluster headache focus on the prevention of attacks. However, the acute treatment of attacks has also been investigated. In a first unblinded, but sham-controlled pilot study on sphenopalatine ganglion stimulation in the acute attack, 67% of 28 patients showed significant pain relief by this stimulation [26]. However, in the largest trial on this stimulation technique, there was no significant difference in the primary endpoint (responder rates) between verum and sham stimulation with only maximal 26.7% responders, and patients with episodic cluster headache responded significantly better [27]. Another technique under development for acute attack treatment is the transdermal vagal nerve stimulation [28], suggesting an efficacy also for the acute attack abortion. However, further trials with a real sham control have to follow, before these techniques can be recommended.