A double-blind randomized controlled trial of low doses of propranolol, nortriptyline, and the combination of propranolol and nortriptyline for the preventive treatment of migraine

Abstract

-Few trials have evaluated combination of two or more drugs in the preventive treatment of migraine. In this study three therapeutic regimens were compared: (a) propranolol, at a dose of 40 mg per day, (b) nortriptyline, at a dose of 20 mg per day, and (c) the combination of these two drugs in these dosages. The groups were matched according to age, gender, and frequency of migraine attacks prior to treatment. The period of treatment was two months and the frequency and intensity of headache attacks of the 30 days pretreatment period were compared with the frequency of headaches in the treatment period. Fourteen patients in groups A and B and sixteen patients in group C have completed the study. Treatment with propranolol, alone or in combination, was shown to be effective. Treatment with nortriptyline alone was not effective. All three therapeutic regimens were safe and side effects were minimal. The frequency of discontinuation of the study was the same in the 3 groups but no patient left the study due to adverse reactions. The combined therapy proved to be as safe as the monotherapy. Further studies evaluating this and other possible combinations of drugs in higher doses and for longer periods, should more clearly elucidate the role of combined therapy in the treatment of migraine.Key Words: combined therapy, migraine, nortryptiline, propranolol.Estudo controlado, randomizado e duplo cego do uso de baixas doses de propranolol, nortriptilina e a combinação destas duas drogas no tratamento preventivo da migrânea Resumo -Poucos ensaios clínicos têm avaliado o tratamento preventivo da migrânea através da combinação de drogas. Neste estudo, três regimes terapêuticos foram comparados: (a) popranolol, na dose de 40 mg por dia, (b) nortriptilina, na dose de 20 mg por dia e (c) combinação destas duas drogas nestas dosagens. os grupos foram pareados de acordo com idade, sexo e freqüência de crises previamente ao tratamento. o período de tratamento foi de dois meses e a frequência e a intensidade das crises de cefaléia do período pré-tratamento foram comparadas com as do período de tratamento. Concluíram o estudo 14 pacientes do grupo A, 14 do grupo B e 16 do grupo C. os tratamentos com propranolol, isolado ou em associação mostraram-se eficazes. o tratamento com nortriptilina isolada não se mostrou eficaz para a redução do número de dias com cefaléia. Todos os três regimes terapêuticos foram seguros e os efeitos colaterais foram mínimos. A freqüência de abandono do estudo foi a mesma nos 3 grupos e nenhum paciente abandonou o estudo devido a reações adversas. A terapia combinada mostrou-se tão segura quanto a monoterapia. estudos futuros avaliando esta e outras possíveis combinações de drogas, em doses maiores e por períodos mais longos, deverão elucidar mais claramente o papel da terapia combinada no tratamento da migrânea.PAlAvrAs-ChAve: migrânea, nortriptilina, propranolol, tratamento combinado.

Quality of Life of Migraine Patients Treated With Combined Propranolol and Topiramate

“…It neither showed added effect of this combination in decreasing the frequency of headache nor its severity (15). Another study for evaluation of presence or intensity of headache showed that propranolol was effective both alone and in combination with nortryptyline (16).…”

“…Although, single drug treatment has been extensively studied, a few studies have evaluated the effect of combined prevention treatment with two or more drugs. As in a randomized control trial (RCT), propranolol was added to topiramate in patients with inadequate controlled chronic migraine with topiramate alone, showed no adequate evidence for its benefits (15), while another RCT showed the effectiveness of the combined nortryptyline and propranolol in migraine prophylaxis (16). Theoretically, combined drug therapy could have more advantages, because each drug could pathophysiologically targets different aspects of the disease (17).…”

Is Low Dose Combination Therapy Effective for Migraine Prophylaxis ? A Case Series Study

“…Some data are available that suggest the efficiency of lower dose compared with higher doses. Domingues and colleague (2009) found that combination of low dose propranolol (40 mg / day) and nortriptyline (20 mg / day) is effective for migraine prophylaxis without more intolerance or higher rate of side effects [25]. One report in 2006 explained two trials done on topiramate and placebo and showed that the best result for migraine prevention was achieved both in 100 mg / day and 200 mg / day topiramate with no difference in efficacy [26].…”

Controversies in migraine: monotherapy

“…No difference in efficacy was evident in other two controlled studies: low doses of propranolol and propranolol ? nortriptyline gave similar results [21]; polytherapy was not superior to monotherapy in patients treated with topiramate alone, amitriptyline alone or a combination of these drugs, although combination treatment lead to a higher patient satisfaction [22]. Only a recently published trial both the reduction in migraine days and the proportion of patients with headache response were significantly higher in patients in polytherapy with topiramate ?…”