Propranolol vs flunarizine vs flunarizine plus propranolol in migraine without aura prophylaxis. a double-blind trial

Bordini, Carlos Alberto; Arruda, Marco Antônio; Ciciarelli, Marcelo Cedrinho; Speciali, José Geraldo

doi:10.1590/S0004-282X1997000400003

Abstracts

Fourty-five migraine without aura patients underwent a parallel double-blind trial aiming the comparison of the effects of propranolol 60 mg/day to flunarizine 10 mg/day and to propranolol 60 mg/day plus flunarizine 10 mg/day simultaneously. There were 3 groups, each one with 15 patients. After a 20-day-baseline period, each group received one kind of treatment during 120 days. Migraine index on propranolol was 23.4*. on flunarizine 18.7* and on both drugs 14.4*, mean frequency of attacks on propranolol was 1.26**, on flunarizine 1.2** and on both drugs 1.13** (*p<0.05, ** p < 0.01 compared to baseline) and global evaluation was reduced with all forms of treatment. It was not found statistical differences between groups, nevertheless there was a trend in the group using two drugs reaching lower values in migraine index, frequency of attacks and global evaluation. In individuals using flunarizine (alone or associated with propranolol) the therapeutic effect was largely maintained up to 45 days after drug withdrawal.

migraine trial; propranolol and migraine; flunarizine and migraine; migraine and polytheraphy

Quarenta e cinco pacientes com migrânea sem aura submeteram-se a ensaio paralelo e duplo-cego visando comparar os efeitos de propranolol (PPN), flunarizina (FNZ) e uso associado de propranolol mais flunarizina. Foram divididos em três grupos de 15 indivíduos. Após período preliminar de 20 dias sem a administração de qualquer droga, um grupo recebeu PPN 60 mg/dia, outro grupo FNZ 10 mg/dia, e o terceiro grupo PPN 60 mg/dia associado à FNZ 10 mg/dia. O tempo de tratamento foi 120 dias. O índice de dor no grupo sob PPN passou de 39,3 para 23,4 (p<0,05) no grupo sob FNZ de 33,7 para 18,7 (p<0,05) e no grupo recebendo ambas as drogas de 33,5 para 14,4 (p<0,05). Não houve diferenças entre os índices de dor dos três grupos após o tratamento. A frequência de crises no grupo sob PPN passou de 2,8 para 1,26 (p<0,01) no grupo sob FNZ de 2,6 para 1,2 (p<0,01) e no grupo recebendo ambas as drogas de 2,9 para 1,13 (p<0,01). Não houve diferenças entre as frequências de crises dos três grupos após o tratamento. Foram confirmadas as eficácias dessas drogas na profilaxia da migrânea sem aura. A associação das drogas não logrou benefício ulterior no que concerne à diminuição dos índices de dor ou da frequência de crises. Entretanto, na avaliação global por parte do paciente, os melhores resultados estavam entre os que usaram duas drogas. Nos grupos que usaram FNZ (isolada ou associada ao PPN), as melhoras alcançadas persistiram mesmo após 45 dias da retirada dos fármacos.

migrânea; propranolol na migrânea; flunarizina na migrânea; migrânea e politerapia

Propranolol vs flunarizine vs flunarizine plus propranolol in migraine without aura prophylaxis. a double-blind trial

Ensaio duplo-cego comparando propranolol, flunarizina e flunarizina associada ao propranolol na profilaxia da migrânea sem aura

Carlos Alberto Bordini^I; Marco Antônio Arruda^II; Marcelo Cedrinho Ciciarelli^II; José Geraldo Speciali^III

^IDepartamento de Neurologia da Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de São Paulo (USP), Ribeirão Preto, Brasil: Mestre e Doutor em Neurologia, Médico Assistente Responsável pelo Ambulatório de Cefaléia do Hospital das Clínicas da FMRP/USP

^IIDepartamento de Neurologia da Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de São Paulo (USP), Ribeirão Preto, Brasil: Mestre em Neurologia

^IIIDepartamento de Neurologia da Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de São Paulo (USP), Ribeirão Preto, Brasil: Professor Associado do Departamento de Neurologia da FMRP/USP

ABSTRACT

Fourty-five migraine without aura patients underwent a parallel double-blind trial aiming the comparison of the effects of propranolol 60 mg/day to flunarizine 10 mg/day and to propranolol 60 mg/day plus flunarizine 10 mg/day simultaneously. There were 3 groups, each one with 15 patients. After a 20-day-baseline period, each group received one kind of treatment during 120 days. Migraine index on propranolol was 23.4*. on flunarizine 18.7* and on both drugs 14.4*, mean frequency of attacks on propranolol was 1.26**, on flunarizine 1.2** and on both drugs 1.13** (*p<0.05, ** p < 0.01 compared to baseline) and global evaluation was reduced with all forms of treatment. It was not found statistical differences between groups, nevertheless there was a trend in the group using two drugs reaching lower values in migraine index, frequency of attacks and global evaluation. In individuals using flunarizine (alone or associated with propranolol) the therapeutic effect was largely maintained up to 45 days after drug withdrawal.

Key-words: migraine trial, propranolol and migraine, flunarizine and migraine, migraine and polytheraphy.

RESUMO

Quarenta e cinco pacientes com migrânea sem aura submeteram-se a ensaio paralelo e duplo-cego visando comparar os efeitos de propranolol (PPN), flunarizina (FNZ) e uso associado de propranolol mais flunarizina. Foram divididos em três grupos de 15 indivíduos. Após período preliminar de 20 dias sem a administração de qualquer droga, um grupo recebeu PPN 60 mg/dia, outro grupo FNZ 10 mg/dia, e o terceiro grupo PPN 60 mg/dia associado à FNZ 10 mg/dia. O tempo de tratamento foi 120 dias. O índice de dor no grupo sob PPN passou de 39,3 para 23,4 (p<0,05) no grupo sob FNZ de 33,7 para 18,7 (p<0,05) e no grupo recebendo ambas as drogas de 33,5 para 14,4 (p<0,05). Não houve diferenças entre os índices de dor dos três grupos após o tratamento. A frequência de crises no grupo sob PPN passou de 2,8 para 1,26 (p<0,01) no grupo sob FNZ de 2,6 para 1,2 (p<0,01) e no grupo recebendo ambas as drogas de 2,9 para 1,13 (p<0,01). Não houve diferenças entre as frequências de crises dos três grupos após o tratamento. Foram confirmadas as eficácias dessas drogas na profilaxia da migrânea sem aura. A associação das drogas não logrou benefício ulterior no que concerne à diminuição dos índices de dor ou da frequência de crises. Entretanto, na avaliação global por parte do paciente, os melhores resultados estavam entre os que usaram duas drogas. Nos grupos que usaram FNZ (isolada ou associada ao PPN), as melhoras alcançadas persistiram mesmo após 45 dias da retirada dos fármacos.

Palavras chave: migrânea, propranolol na migrânea, flunarizina na migrânea, migrânea e politerapia.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Aceite: 11-junho-1997.

Dr. Carlos Alberto Bordini - Departamento de Neurologia da Faculdade de Medicina de Ribeirão Preto - Campus Universitário USP -14048-900 Ribeirão Preto SP - Brasil. Fax 55 16 7611238

1. Chouza C, Scaramelli A, Caamano JL, De Medina O, Aljanati R, Romero S. Parkinsonism, tardive dyskinesia, akathisia and depression induced by flunarizine. Lancet 1986;8493:1303-1304.
2. Cortelli P, Sacquegna T, Albani F, Balbrat A D'Alessandro R, Baruzzi A, Lugaresi E. Propranolol plasma levels and the relief of migraine. Arch Neurol 1985; 42:46-48.
3. Diamond S, Kudrow L, Stevens J, Shapiro BD. Long-term study of propranolol in the treatment of migraine. Headache 1982;22:268-271.
4. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988;8(Suppl 7):19-20.
5. International Headache Society Committee on Clinical Trials of Drugs in Migraine. Guidelines for controlled trials in migraine. Cephalalgia 1991;11:1-12.
6. Lance JW. Mechanism and management of headache. 5Rev.ed. London: Butterworth, 1993:135.
7. Martínez-Lage JM. Flunarizine (Sibelium) in the prophylaxis of migraine: an open, long-term, multicenter trial. Cephalalgia 1988;8(Suppl 8):15-20 .
8. Mathew NT. Prophylaxis of migraine and mixed headache: a randomized controlled study. Headache 1981;21:105-109.
9. Olesen J. The role of beta-blockers in migraine. Cephalalgia 1986;6(Suppl 5):6.
10. Olesen J, Andersen AR, Hedman C. Sense of separating classic and common migraine. In Ferrari MD, Lataste X (eds). Migraine and other headaches. Casterton Hall: Partenon, 1989:139-144.
11. Prusinski A. Monotheraphy or polytheraphy in migraine. Neuroepidemiology 1987;6:186-189.
12. Sorensen PS, Hansen K, Olesen J. A placebo-controlled, double-blind, cross-over trial of flunarizine in common migraine. Cephalalgia 1986;6:7-14.
13. Tfelt-Hansen P, Standnes B, Kangasneimi P, Hakkarainen H, Olesen J. Timolol versus propranolol versus placebo in common migraine prophylaxis: a double-blind multicenter trial. Acta Neurol Scand 1984;69:1-8.
14. Vanhoutte PM, Paoletti R. The WHO classification of calcium antagonists. Tips 1987;8:4-5.
15. Wauquier A, Ashton D, Edmond HL. Protection against cerebral anoxia by antimigraine drugs. In: Amery MD, Van Neuten STM, Wauquier A. (eds) The pharmacological basis of migraine theraphy. London: Pittman, 1984:134-148.
16. Wilkinson M. The nonsense of separating classic and common migraine. In Ferrari MD, Lataste X (eds). Migraine and other headaches. Casterton Hall: Partenon,1989;145-150.

Publication Dates

Publication in this collection
18 Oct 2010
Date of issue
Sept 1997

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Chouza C, Scaramelli A, Caamano JL, De Medina O, Aljanati R, Romero S. Parkinsonism, tardive dyskinesia, akathisia and depression induced by flunarizine. Lancet 1986;8493:1303-1304.

[2] 2. Cortelli P, Sacquegna T, Albani F, Balbrat A D'Alessandro R, Baruzzi A, Lugaresi E. Propranolol plasma levels and the relief of migraine. Arch Neurol 1985; 42:46-48.

[3] 3. Diamond S, Kudrow L, Stevens J, Shapiro BD. Long-term study of propranolol in the treatment of migraine. Headache 1982;22:268-271.

[4] 4. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988;8(Suppl 7):19-20.

[5] 5. International Headache Society Committee on Clinical Trials of Drugs in Migraine. Guidelines for controlled trials in migraine. Cephalalgia 1991;11:1-12.

[6] 6. Lance JW. Mechanism and management of headache. 5Rev.ed. London: Butterworth, 1993:135.

[7] 7. Martínez-Lage JM. Flunarizine (Sibelium) in the prophylaxis of migraine: an open, long-term, multicenter trial. Cephalalgia 1988;8(Suppl 8):15-20 .

[8] 8. Mathew NT. Prophylaxis of migraine and mixed headache: a randomized controlled study. Headache 1981;21:105-109.

[9] 9. Olesen J. The role of beta-blockers in migraine. Cephalalgia 1986;6(Suppl 5):6.

[10] 10. Olesen J, Andersen AR, Hedman C. Sense of separating classic and common migraine. In Ferrari MD, Lataste X (eds). Migraine and other headaches. Casterton Hall: Partenon, 1989:139-144.

[11] 11. Prusinski A. Monotheraphy or polytheraphy in migraine. Neuroepidemiology 1987;6:186-189.

[12] 12. Sorensen PS, Hansen K, Olesen J. A placebo-controlled, double-blind, cross-over trial of flunarizine in common migraine. Cephalalgia 1986;6:7-14.

[13] 13. Tfelt-Hansen P, Standnes B, Kangasneimi P, Hakkarainen H, Olesen J. Timolol versus propranolol versus placebo in common migraine prophylaxis: a double-blind multicenter trial. Acta Neurol Scand 1984;69:1-8.

[14] 14. Vanhoutte PM, Paoletti R. The WHO classification of calcium antagonists. Tips 1987;8:4-5.

[15] 15. Wauquier A, Ashton D, Edmond HL. Protection against cerebral anoxia by antimigraine drugs. In: Amery MD, Van Neuten STM, Wauquier A. (eds) The pharmacological basis of migraine theraphy. London: Pittman, 1984:134-148.

[16] 16. Wilkinson M. The nonsense of separating classic and common migraine. In Ferrari MD, Lataste X (eds). Migraine and other headaches. Casterton Hall: Partenon,1989;145-150.