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more side‐effects than an aspirin‐metoclopramide combination (Tfelt‐Hansen, 2008; Lipton
et al, 2004).
A combination of sumatriptan‐naproxen as a single tablet for acute migraine, was superior to
monotherapy with each component drug alone or placebo, in terms of pain‐free outcome
from 2 to 24 hours, with an adverse effects profile no worse than sumatriptan alone (Brandes
et al, 2007 Level II).
The most frequent adverse events associated with triptans are dizziness, fatigue, sleepiness,
nausea, chest tightness and paraesthesiae. The average incidence of any adverse events
reported using various triptans ranged from approximately 18% to 50%. Sumatriptan has the
greatest incidence and range of reported adverse events in placebo‐controlled trials (Dahlof,
2002). Triptans may have significant sensory side effects, particularly an increase in light touch‐
evoked allodynia and thermal sensitivity (Linde, 2004).
Concern about adverse cardiac events is the main reason why only 10% of patients with
migraine receive a triptan for acute therapy (Dahlof, 2002). A sensation of chest tightness
occurred in 0.1 to 0.2% of patients who received almotriptan compared with 3 to 5% of
patients on sumatriptan (Dahlof, 2002). There is no association between a lifetime history of
migraine, with or without aura, and coronary artery disease related angina (Rose et al, 2004).
However, chest tightness may not always be due to a cardiac cause (Dahlof, 2002). In a positron
emission tomography study, sumatriptan did not affect myocardial perfusion or the ECG in
migraine patients who had no history of ischaemic heart disease (Lewis et al, 1997).
Frequent use of triptans may lead to triptan‐induced rebound headaches (Silberstein & Welch,
2002; Limmroth et al, 2002).
Ergot derivatives
Ergotamine and dihydroergotamine preparations have been used for many years to treat
migraine, although they are rapidly being superseded by the triptans.
Intranasal (IN) dihydroergotamine (2 mg) has a NNT of 2.5 for 2‐hour headache response in
migraine (Oldman et al, 2002 Level I). As a single agent, parenteral dihydroergotamine may not
be as effective as other migraine treatments (Colman et al, 2005 Level I). It was less effective
than chlorpromazine (Bell et al, 1990 Level II) or sumatriptan (Winner et al, 1996 Level II), with
CHAPTER 9 increased side effects (Bell et al, 1990 Level II). However, when dihydroergotamine was
combined with an antiemetic such as metoclopramide, the efficacy of this combination was
similar to valproate, ketorolac and opioids (Colman et al, 2005 Level I).
Opioids and tramadol
Opioids are of limited benefit in the treatment of migraine. Morphine without an antiemetic
was no more effective than placebo (Nicolodi, 1996 Level II). Butorphanol was effective when
given by the IN or IM route (Elenbaas et al, 1991 Level II; Diamond et al, 1992 Level II; Hoffert et al,
1995 Level II).
Pethidine in particular, is not recommended for the treatment of migraine, due to lack of
evidence of efficacy and the risk of developing dependency. Pethidine was less effective than
dihydroergotamine or antiemetics for the treatment of migraine; however, it was of similar
efficacy to ketorolac (Friedman et al, 2008 Level I). Pethidine was no more effective than
dihydroergotamine, chlorpromazine, dimenhydrinate, metoclopramide, promethazine or
NSAIDs (Lane et al, 1989 Level II; Stiell et al, 1991 Level II; Davis et al, 1995 Level II; Scherl & Wilson,
1995 Level II).
IM tramadol was similar to diclofenac for pain response at 2 hours in migraine (approximately
80% of patients) (Engindeniz et al, 2005 Level II).

264 Acute Pain Management: Scientific Evidence