CNS drugs
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Refractory status epilepticus (RSE) is the most severe manifestation of status epilepticus (SE), often requiring intensive care and therapeutic coma. It is associated with prolonged intensive care unit (ICU) and hospital stays, as well as increased morbidity and mortality. Treatment involves both intravenous anaesthetics and antiepileptic drugs (AEDs) that can be administrated intravenously, by nasogastric tube or by percutaneous endoscopic gastrostomy. Experience with some of the newer AEDs for the treatment of RSE is restricted and higher-class evidence regarding tolerability and efficacy is lacking. Topiramate is a potent broad-spectrum AED with several modes of action, including blockade of the ionotropic glutamatergic AMPA receptor, which is likely to be an important mechanism for the treatment of SE. While there is no commercially available intravenous formulation, topiramate can be administered enterally, which may make it suitable for the treatment of RSE. ⋯ Treatment with enterally administered topiramate was feasible, well tolerated and had a good safety profile in patients with RSE in this observational, single-centre, cohort study. Refractory SE was terminated in the majority of patients within 3 days after initiation of topiramate. Prospective studies are warranted to further evaluate topiramate for the treatment of RSE.
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Controversy exists about the safety of substituting generic antiepileptic drugs (AEDs). Lamotrigine, the prototypical newer AED, is often used for psychiatric and neurological conditions other than epilepsy. The safety of generic substitution of lamotrigine in diverse populations of AED users is unclear. ⋯ A statistically significant increase in ED visits, hospitalizations or condition-specific encounters was not observed following the switch from brand to generic lamotrigine, although a type II error cannot be ruled out.
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The prevalence of cluster headache is 0.1% and cluster headache is often not diagnosed or misdiagnosed as migraine or sinusitis. In cluster headache there is often a considerable diagnostic delay - an average of 7 years in a population-based survey. Cluster headache is characterized by very severe or severe orbital or periorbital pain with a duration of 15-180 minutes. ⋯ For most cluster headache patients there are fairly good treatment options both for acute attacks and for prophylaxis. The big problem is the diagnosis of cluster headache as demonstrated by the diagnostic delay of 7 years. However, the relatively short-lasting attack of pain in one eye with typical associated symptoms should lead the family doctor to suspect cluster headache resulting in a referral to a neurologist or a headache centre with experience in the treatment of cluster headache.
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Based on preclinical and clinical studies, the neuropeptide calcitonin gene-related peptide (CGRP) is proposed to play a central role in the underlying pathology of migraine. CGRP and its receptor are widely expressed in both the peripheral and central nervous systems by multiple cell types involved in the regulation of inflammatory and nociceptive responses. Peripheral release of CGRP from trigeminal nerve fibres within the dura and from the cell body of trigeminal ganglion neurons is likely to contribute to peripheral sensitization of trigeminal nociceptors. ⋯ Towards this end, the non-peptide CGRP receptor antagonists olcegepant and telcagepant have been shown to be effective in the acute treatment of migraine. While telcagepant is being pursued as a frontline abortive migraine drug in a phase III clinical trial, an oral formulation of a novel CGRP receptor antagonist, BI 44370, is currently in phase II clinical trials. Encouragingly, data from clinical studies on these compounds have clearly demonstrated the potential therapeutic benefit of this class of drugs and support the future development of CGRP receptor antagonists to treat migraine and possibly other types of chronic pain.