Ciro Pio Rosario Coccia

Similarities and differences between chronic migraine and episodic migraine

Objective.—To quantify and characterize the similarities and the differences between chronic migraine (CM) patients with medication overuse and episodic migraine (EM) patients with only occasional analgesic use.

Past, present, and future prospects of medication-overuse headache classification.

The 1988 classification by the International Headache Society (IHS) first defined drug‐induced headache as a specific disorder, belonging to secondary headaches, subtype 8.2 (headache induced by chronic substance use or exposure). In 2004 ICHD‐II, this definition was replaced by medication‐overuse headache (MOH). It was established that a definite diagnosis of MOH required the improvement of the disorder after cessation of medication overuse. The specific characteristics of the various subforms were also indicated. Later revisions have first eliminated these headache characteristics and then the diagnosis of probable MOH. The diagnosis of MOH has therefore become more useful to clinical aims. However, the last revision has eliminated the need to prove that the disorder is caused by drugs, that is, the headache improves after cessation of medication overuse. The classification of MOH as a secondary headache has therefore been modified, too. Clinical trials can consequently include in the same group patients with primary headache and drug overuse and patients with MOH.

Pharmacokinetics of sumatriptan in non-respondent and in adverse drug reaction reporting migraine patients

Sumatriptan is a selective agonist of 5HT1 (1B/1D) receptors, which has proved to be effective and safe for the acute treatment of migraine attacks. Nevertheless, its use by migraine sufferers is still limited and some patients consider adverse reactions related to sumatriptan, especially chest symptoms, unacceptable even if not serious. Moreover, in clinical trials, almost one third and one sixth of patients, respectively, fail to experience headache relief either after oral or after subcutaneous sumatriptan administration. Our aim was to verify whether differencies in sumatriptan pharmacokinetics could explain non–response and/or adverse drug reactions. Sumatriptan levels were determined by HPLC with electrochemical detection. Pharmacokinetic parameters were calculated using a computer program (PK Solutions 2.0; non compartmental Pharmacokinetics Data Analysis). After oral administration, sumatriptan is rapidly absorbed and sometimes displays multiple peaks of plasma concentration. This “multiple peaking” gives rise to considerable inter–subject variability in the time of reaching maximum plasma concentration. Pharmacokinetic parameters of sumatriptan, both after oral and subcutaneous administration, were similar in the three patient groups. Blood pressure and heart rate did not show any significant differences between groups. Pharmacokinetic parameters and bioavailability of sumatriptan did not seem to be correlated either to the lack of efficacy or the appearance of side effects. These results could depend on the limited number of patients studied.

Pharmacokinetics and interactions of headache medications, part I: introduction, pharmacokinetics, metabolism and acute treatments

Recent progress in the treatment of primary headaches has made available specific, effective and safe medications for these disorders, which are widely spread among the general population. One of the negative consequences of this undoubtedly positive progress is the risk of drug–drug interactions. This review is the first in a two-part series on pharmacokinetic drug–drug interactions of headache medications. Part I addresses acute treatments. Part II focuses on prophylactic treatments. The overall aim of this series is to increase the awareness of physicians, either primary care providers or specialists, regarding this topic. Pharmacokinetic drug–drug interactions of major severity involving acute medications are a minority among those reported in literature. The main drug combinations to avoid are: i) NSAIDs plus drugs with a narrow therapeutic range (i.e., digoxin, methotrexate, etc.); ii) sumatriptan, rizatriptan or zolmitriptan plus monoamine oxidase inhibitors; iii) substrates and inhibitors of CYP2D6 (i.e., chlorpromazine, metoclopramide, etc.) and -3A4 (i.e., ergot derivatives, eletriptan, etc.), as well as other substrates or inhibitors of the same CYP isoenzymes. The risk of having clinically significant pharmacokinetic drug–drug interactions seems to be limited in patients with low frequency headaches, but could be higher in chronic headache sufferers with medication overuse.

Pharmacokinetics and interactions of headache medications, part II: prophylactic treatments.

The present part II review highlights pharmacokinetic drug–drug interactions (excluding those of minor severity) of medications used in prophylactic treatment of the main primary headaches (migraine, tension-type and cluster headache). The principles of pharmacokinetics and metabolism, and the interactions of medications for acute treatment are examined in part I. The overall goal of this series of two reviews is to increase the awareness of physicians, primary care providers and specialists regarding pharmacokinetic drug–drug interactions (DDIs) of headache medications. The aim of prophylactic treatment is to reduce the frequency of headache attacks using β-blockers, calcium-channel blockers, antidepressants, antiepileptics, lithium, serotonin antagonists, corticosteroids and muscle relaxants, which must be taken daily for long periods. During treatment the patient often continues to take symptomatic drugs for the attack, and may need other medications for associated or new-onset illnesses. DDIs can, therefore, occur. As a whole, DDIs of clinical relevance concerning prophylactic drugs are a limited number. Their effects can be prevented by starting the treatment with low dosages, which should be gradually increased depending on response and side effects, while frequently monitoring the patient and plasma levels of other possible coadministered drugs with a narrow therapeutic range. Most headache medications are substrates of CYP2D6 (e.g., β-blockers, antidepressants) or CYP3A4 (e.g., calcium-channel blockers, selective serotonin re-uptake inhibitors, corticosteroids). The inducers and, especially, the inhibitors of these isoenzymes should be carefully coadministered.