Abstract
BackgroundPain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics.DiscussionIn this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy.SummaryMultitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves) to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies.
Highlights
Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing
Summary: Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors to customize treatment to the patient’s specific needs
We describe the scientific evidence for the superior efficacy of fixed-dose combinations [10] and discuss their role in the pharmacotherapy of pain and of headaches
Summary
2.1 Multi-target approach It is important to note that the distinction between a single drug with a single pharmacological activity and a combination drug with combined pharmacological activities is not absolute [11]. Over pilot study almotriptan (12.5 mg) + aceclofenac (100 mg) almotriptan (12.5 mg) + placebo single dose These observations were confirmed in randomized controlled clinical trials, which demonstrated that multimechanism acute therapy for migraine, combining a triptan (sumatriptan) and an analgesic (naproxen sodium) offers improved clinical benefits over monotherapy with these selected standard antimigraine treatments [26]. The benefit of this combination existed in the lowest headache recurrence rate and in significantly superior pain relief (2-hour pain response) [26]. In six randomized, controlled double-blind studies (Table 2), this combination was superior both to placebo and to the control therapies sumatriptan (50 mg) [60], ibuprofen (400 mg) [61], ASA + paracetamol [57,59], ASA [57,59], paracetamol [59],
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