Topiramate plus nortriptyline in the preventive treatment of migraine: a controlled study for nonresponders

A sizeable proportion of migraineurs in need of preventive therapy do not significantly benefit from monotherapy. The objective of the study is to conduct a randomized controlled trial testing whether combination therapy of topiramate and nortriptyline is useful in patients who had less than 50% decrease in headache frequency with the use of the single agents. Patients with episodic migraine were enrolled if they had less than 50% reduction in headache frequency after 8 weeks of using topiramate (TPM) (100 mg/day) or nortriptyline (NTP) (30 mg/day). They were randomized (blinded fashion) to have placebo added to their regimen, or to receive the second medication (combination therapy). Primary endpoint was decrease in number of headache days at 6 weeks, relative to baseline, comparing both groups. Secondary endpoint was proportion of patients with at least 50% reduction in headache frequency at 6 weeks relative to baseline. A total of 38 patients were randomized to receive combination therapy, while 30 continued on monotherapy (with placebo) (six drop outs in the combination group and three for each single drug group). For the primary endpoint, mean and standard deviation (SD) of reduction in headache frequency were 4.6 (1.9) for those in polytherapy, relative to 3.5 (2.3) for those in monotherapy. Differences were significant (p < 0.05]. Similarly, 78.3% of patients randomized to receive polytherapy had at least 50% headache reduction, as compared to 37% in monotherapy (p < 0.04). Finally we conclude that combination therapy (of TPM and NTP) is effective in patients with incomplete benefit using these agents in monotherapy

Migraine treatment: the doors for the future are open, but with caution and prudence

ABSTRACT Migraine is a burdensome disorder. Current treatments are far from ideal. Recent knowledge has been indicating targets whose antagonism may improve efficacy. It is particularly true with the calcitonin gene-related peptide (CGRP) and the monoclonal antibodies anti-CGRP can interfere with this pathway and decrease the frequency of migraine attacks. Erenumab, fremanezumab and galcanezumab have recently been approved and eptinezumab is likely to be, soon. Although efficacy figures were not spectacular, tolerability and potential higher adherence were noteworthy. However, caution must be exercised. The time frame after the studies was limited to three years and dose administration was restricted to three-monthly doses. The CGRP is present throughout the human body and migraine is a life-long disease, often requiring treatment for decades. It is not known whether this favorable profile can be maintained or will be safe in pregnant women or adolescents. In addition, there were deaths during the studies, which may have happened without a clear relationship. New treatments are welcome, but caution is warranted

Medication-overuse headache. Retrospective comparison of preventive treatments

ABSTRACT Objectives: Medication-overuse headache is commonly seen in tertiary centers. Limited evidence is available regarding treatment. We compared the use of one or two drugs, three drugs, or four pharmacological agents for the prevention of headache. Methods: This was a retrospective analysis of 149 consecutive patients. Sudden withdrawal and pharmacological prevention with one or more drugs were carried out. Adherence and the decrease of headache frequency of more than 50% were compared after four months between the one or two, three, and four drug groups. Results: There was no difference in adherence (p > 0.6). Headache frequency reduction was shown in 23 (54.8%, one or two drugs), 33 (70%, three drugs) and 11 (55%, four drugs); p = 0.13 and p = 0.98, not significant. There was a tendency towards significance between the one or two drug takers versus the three drug and four drug takers together (p = 0.09). Conclusions: The use of more drugs was not better at improving headache. However, there is the possibility that acting simultaneously on different sites may promote broader modulation and better outcome

Cefaléia crônica diária primária: a propósito de 52 casos

Apesar de a cefaléia crônica diária (CCD) ser frequentemente observada na prática cefaliátrica, o interesse pelo seu estudo é recente. Foram estudados 52 pacientes (48 mulheres e 4 homens) com idade entre 13 e 71 anos, que preencheram os critérios diagnósticos propostos por Silberstein e col. (1994) para CCD primária. A análise das principais características clínicas permitiu o diagnóstico de três modalidades da CCD: migrânea transformada (n=39; 75%), cefaléia do tipo tensional crônica (n=11; 21,1%) e cefaléia diária persistente de início súbito (n=2; 3,9%). Destes pacientes, 34 (65,4%) utilizavam de modo excessivo medicações sintomáticas e foram considerados como sofredores de cefaléia induzida por drogas. O esquema de tratamento utilizado incluiu, além da orientação à interrupção das medicações sintomáticas, o uso de amitriptilina isoladamente ou em associação ao propranolol, em doses crescentes, levando-se em conta a resposta e a tolerância a estes fármacos. Esse esquema revelou-se eficaz na diminuição da frequência da cefaléia na maioria dos pacientes com CCD. Os efeitos benéficos revelaram-se duradouros, persistindo mesmo após seis meses do início do acompanhamento. Na minoria dos pacientes na qual a terapêutica instituída não obteve êxito, constatou-se, de forma estatisticamente significativa, a persistência do uso excessivo de medicações sintomáticas