Vol. 10, No 3, 2003 pp. 106 - 110
UC 616-084:616.857  
PROPHYLACTIC TREATMENT OF MIGRAINE BY VALPROATE
Mirjana Spasić, Miroslava Živković, Stevo Lukić
Clinic of Neurology, Clinical centre, Faculty of Medicine, Niš, Serbia and Montenegro
E-mail: stevol@junis.ni.ac.yu
Summary. Migraine is a common episodic headache disorder. A comprenhensive headache treatment plan includes acute attack treatment to releive pain and impairment and long-term preventive therapy to reduce attack frequency, severity and duration. Circumstances that might warrant preventive treatment include very frequent and severe migraine that interferes with the patient's daily routine,  failure to acute treatment, special circumstances such as hemiplegic migraine or patient preference. The drug has to be started at a low dose and each treatment has to be given an adequate trial with avoiding interfering overused and contraindicated drugs. Co-morbidity has to be considered. Drugs that have documented high efficacy and mild to moderate adverse events include beta-blockers, amitiriptyline and valproates.
Valproate has been shown to be an effective prophylactic teratment in migraine. Investigation of the mechanism of its antimigraine action is difficult due to the broad range of its biochemical effects and the complex nature of migraine pathophysiology. Valptoate increases brain GABA levels and may suppress migraine related events in the cortex, perivascular parasympathetics or trigeminal nucleus caudalis. There is experimental evidence that it suppresses neurogenic inflamation and directly attenuates nociceptive neurotransmission. In addiion, valproate reportedly alters levels of excitatory and inhibitory neurotransmitters and exerts direct effects on neuronal membranes in vitro. Valproate's observed effects may ultimately result from a combination of actions at different loci.
Key words: Migraine, prophylaxis, valproate
PROFILAKTIČKI TRETMAN MIGRENE VALPROATIMA
Kratak sadržaj: Migrena je epizodična glavobolja. Plan lečenja glavobolje uključuje akutni tretman sa ciljem prekidanja bola i neurološke oštete i dugotrajni preventivni tretman sa ciljem smanjivanja učestalosti, jačine i trajanja bola. Okolnosti koje zahtevaju preventivnu terapiju uključuju vrlo česte i snažne migrene koje remete pacijentove svakodnevne aktivnosti, neuspešnost akutnog tretmana, specijalne okolnosti kao što je hemiplegična migrena ili je to želja pacijenta. Lečenje treba započeti malom dozom, a svako lečenje treba da traje adekvatno dugo uz izbegavanje interakcija, predoziranja i kontraindikovanih lekova. Treba razmotiti i komorbiditet. Među lekovima koji imaju dokazanu visoku efikasnost a blage ili umerene sporedne efekte spadaju beta blokatori, amitriptilin i valproati.
Valproati su se pokazali kao efikasan lek u profilaktičnom tretmanu migrene. Istraživanje mehanizma njihovog antimigrenskog dejstva je teško zbog širokog spektra njihove biohemijske aktivnosti i komplikovane patofiziologije migrene. Valproati povećevaju nivo GABA i mogu suprimirati migrenske događaje u korteksu, perivaskularnoj parasimpatičkoj mreži ili u kaudalnom jedru trigeminusa. Postoji eksperimentalni dokaz da suprimiraju neurogenu inflamaciju i direktno slabe nociceptivnu neurotransmisiju. Takođe, valproati menjaju nivoe ekscitatornih i inhibitornih neurotransmitera i pokazuju direktne efekte na membranu neurona in vitro. Efekti valproata rezultiraju iz kombinacije aktivnosti na različitim mestima.
Ključne reči: Migrena, profilaktički tretman, valproati