The mainstay of the management of breakthrough pain episodes is the use of so-called “rescue medication” (“breakthrough medication”). Rescue medication is taken as required, rather than on a regular basis: rescue medication should be taken at the onset of the pain, although may be taken in advance of pain in cases of volitional incident pain or procedural pain (i.e. pre-emptive treatment) [1]. In most cases the most appropriate rescue medication will be an opioid analgesic, rather than a non-opioid or an adjuvant analgesic [1].

The characteristics of an “ideal” rescue medication include:

1. Good efficacy
2. Rapid onset of action
3. Short duration of effect
4. Good tolerability
5. Easy to use
6. Acceptable to the patient
7. Available
8. Affordable

Oral rescue medication
Traditionally, the most common form of rescue medication has been a fixed dose of an oral “normal-release” / “immediate-release” formulation of morphine. However, the pharmacodynamic profile of oral morphine does not tend to mirror the temporal characteristics of most breakthrough pain episodes. Thus, the slow onset of action (onset of analgesia: 20-30 min; peak analgesia: 60-90 min) [2] results in delayed / ineffective analgesia, whilst the prolonged duration of effect (3-6 hr) [2] results in ongoing adverse effects (see Figure 1). In other words, oral morphine is not the optimal rescue medication for most breakthrough pain episodes [1,3]. Moreover, these factors apply equally to the oral normal-release formulations of similar opioid analgesics (e.g. hydromorphone, oxycodone) [2].

Figure 1 – Temporal relationship between breakthrough pain episode and oral morphine treatment.

Nevertheless, oral morphine may have a role in the management of breakthrough pain: it may be useful in the management of breakthrough pain episodes lasting for more than 60 min, and may be considered in the pre-emptive management of volitional incident pain or procedural pain [1]. However, if oral morphine is used in the latter scenario, then it needs to be taken at least 30 min, and probably 60 min, before the relevant precipitant of the pain [1]. It should be noted that an effervescent oral formulation of morphine has been developed, and this novel oral formulation is reported to have a quicker onset of analgesia than conventional oral formulations [4].

References
[1]. Davies AN, Dickman A, Reid C, Stevens AM, Zeppetella G. The management of cancer-related breakthrough pain: recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland. European Journal of Pain 2009; 13: 331-8.
[2]. Bailey F, Farley A. Oral opioid drugs. In: Davies A, editor. Cancer-related breakthrough pain. Oxford: Oxford University Press; 2006. p. 43-55.
[3]. Mercadante S, Radbruch L, Caraceni A et al. Episodic (breakthrough) pain. Consensus conference of an Expert Working Group of the European Association for Palliative Care. Cancer 2002; 94: 832-9.
[4]. Freye E, Levy JV, Braun D. Effervescent morphine results in faster relief of breakthrough pain in patients compared to immediate release morphine sulfate tablet. Pain Practice 2007; 7: 324-31.