Treatment of cluster headache with topiramate: effects and side-effects in five patients.
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Anticonvulsants↗
Biomedical subjects
S J Tepper
Publications and source records attributed to S J Tepper.
Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized, double-blind, placebo-controlled study.
Magnesium sulphate has been used in the acute treatment of migraines; some studies found it to be a highly effective medication in the acute control of migraine pain and associated symptoms. This randomized, double-blind, placebo-controlled study assesses the effect of magnesium sulphate on the pain and associated symptoms in patients with migraine without aura and migraine with aura. Sixty patients in each group were assigned at random to receive magnesium sulphate, 1000 mg intravenously, or 0.9% physiological saline, 10 ml. We used seven parameters of analgesic evaluation and an analogue scale to assess nausea, photophobia and phonophobia. In the migraine without aura group there was no statistically significant difference in the patients who received magnesium sulphate vs. placebo in pain relief. The analgesic therapeutic gain was 17% and number needed to treat was 5.98 at 1 h. There was also no statistical difference in relief of nausea. We did observe a significant lower intensity of photophobia and phonophobia in patients who received magnesium sulphate. In the migraine with aura group patients receiving magnesium sulphate presented a statistically significant improvement of pain and of all associated symptoms compared with controls. The analgesic therapeutic gain was 36.7% at 1 h. A smaller number of patients continued to have aura in the magnesium sulphate group compared with placebo 1 h after the administration of medication. Our data support the idea that magnesium sulphate can be used for the treatment of all symptoms in migraine with aura, or as an adjuvant therapy for associated symptoms in patients with migraine without aura.
Acute Disease↗
Hemicrania continua: comparison between two different classification systems.
Hemicrania continua is an uncommon primary headache disorder. This study of nine patients compares two different classification systems, proposed by Pareja et al. and Goadsby and Lipton. Although it seems logical to position the nosologic status of hemicrania continua under group 3 of the International Headache Society Classification, as proposed by Pareja et al., the Goadsby and Lipton classification is more clinically useful and should be included in future International Headache Society reclassification.
Adult↗
Long-term follow-up of patients treated for chronic daily headache with analgesic overuse.
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Adolescent↗
Chronic daily headache in a tertiary care population: correlation between the International Headache Society diagnostic criteria and proposed revisions of criteria for chronic daily headache.
The International Headache Society (IHS) has been criticized for its approach to classification of chronic daily headache (CDH); Silberstein and Lipton criteria provide an alternative to this approach. The aim of this study is to apply the alternative diagnostic approaches to a sample of CDH patients consulting in specialty care. Our sample consisted of 638 patients with CDH. Patients were classified according to both classification systems. Patients were predominantly female (65.0%), with ages ranging from 11 to 88 years. According to the Silberstein and Lipton classification, we found eight different diagnoses. The most common diagnosis was chronic migraine (87.4%), followed by new daily persistent headache (10.8%). Just six patients had chronic tension-type headache (CTTH). Applying the IHS criteria we found 14 different diagnoses. Migraine was found in 576 (90.2%) patients. CTTH occurred in 621 (97.3%), with only 10 (1.57%) having this as the sole diagnosis. We conclude that both systems allow for the classification of most patients with CDH when daily headache diaries are available. The main difference is that the IHS classification is cumbersome and requires multiple diagnoses. The Silberstein and Lipton system is easier to apply, and more parsimonious. These findings support revision of the IHS classification system to include chronic migraine.
Adolescent↗
Triptans are all different.
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Carbazoles↗
Safety and rational use of the triptans.
The safety of the triptans has been established, with more than 8 million patients treating greater than 340 million attacks with sumatriptan alone. All triptans narrow coronary arteries by 10% to 20% at clinical doses and should not be administered to patients with coronary or cerebrovascular disease. Some triptans have the potential for significant drug-drug interactions (sumatriptan, rizatriptan, and zomitriptan and monoamine oxidase inhibitors; rizatriptan and propanolol; zolmitriptan and cimetidine; and eletriptan and CYP3A4 metabolized medications and p-glycoprotein pump inhibitors). Rational use of triptans should be governed by the use of these medications for patients with disability associated with migraine. Patients with greater than 10 days of at least 50% disability during 3 months have benefited from treating with triptans as their first-line treatment for acute attacks. When the decision has been made to treat with a triptan, the patient should be instructed to treat early in the attack, when the pain is at a mild phase. This approach increases the likelihood of achieving a pain-free response, with fewer adverse events and lower likelihood of the headache recurring.
Adverse Drug Reaction Reporting Systems↗
Nefazodone for chronic daily headache prophylaxis: an open-label study.
OBJECTIVE: To assess effectiveness, tolerability, and safety of nefazodone as a prophylactic agent for chronic daily headache. BACKGROUND: Nefazodone is a potent, selective 5-HT2 antagonist with a distinct and atypical mechanism of action. The evolution of intermittent migraine to chronic daily headache has been linked to up-regulation of 5-HT2 receptors as well as other factors. Other effective migraine prophylactic medications are also 5-HT2 antagonists. Although research has shown nefazodone to be an effective antidepressant with a good tolerability and safety profile, its potential role in headache prophylaxis has not been tested. DESIGN: This was a two-center, open-label study with a 4-week baseline, followed by 12 weeks of treatment with nefazodone at a median dose of 300 mg (mean, 303.66 +/- 65.57 mg; range, 100 to 450 mg depending on tolerability). Potential patients were required to report more than 15 days of headache per month for at least 3 months prior to screening. Only patients with at least 15 days of recorded headache during baseline were included in the final sample (N=52). Most patients (n=48) had a history of migraine based on International Headache Society criteria; 4 had primarily chronic tension-type headache, but with more migrainous features than permitted by International Headache Society criteria for a primary chronic tension-type headache diagnosis. RESULTS: Significant improvement was demonstrated for all headache diary measures, with significance levels ranging from P<.00001 for average intensity, duration, headache index (intensity x duration), peak intensity, headache days per week, and peak impairment, to P<.0033 for severe headache days per week, and P<.0051 for rescue medication days. During the last month of treatment, 71% of the patients completing the study showed at least a 50% reduction in headache index compared to baseline, and 59% had at least a 75% improvement. Visual analog scales completed at 4-week intervals showed significant improvement in patient ratings of overall headache status, quality of life, sleep, mood (P<.00001), and sexual function (P<.00053). Significant improvements were also observed in the Pain Disability Index (P<.00007), Beck Depression Inventory-II (P<.00001), Hamilton Rating Scale for Depression (P<.0008), and Hamilton Psychiatric Rating Scale for Anxiety (P<.00007). Headache indices for patients in the top quartile on the depression and anxiety scales (clinical depression/anxiety) did not differ from the other patients during baseline. However, patients who were depressed or anxious showed significantly more improvement over the course of 12 weeks of treatment (P<.0006 or less for the depression scales, P<.026 for anxiety). Common mild to moderate adverse events reported by 10% or more of the patients included fatigue, nausea, dry mouth, dizziness, sleep disturbance, blurred vision, irritability/nervousness, and sedation. Only 5 of the 52 patients discontinued the study due to adverse events: headache (2 patients), and nausea, sleep disturbance, and a drugged feeling (1 patient each). CONCLUSIONS: These results provide preliminary support for the efficacy of nefazodone in the prophylaxis of chronic daily headache. In this sample, nefazodone was safe and generally well tolerated. Patient ratings of sexual function improved over the course of treatment, in contrast to what is generally observed with most antidepressants. Nefazodone may be particularly beneficial for patients with chronic daily headache and comorbid depression. Further research is indicated.
Adolescent↗
Differentiating the efficacy of 5-HT(1B/1D) agonists.
OBJECTIVE: To examine, for a set of published clinical trials of serotonin (5-HT(1B/1D)) agonists as acute treatments for migraine, whether transformation of efficacy data into therapeutic gain (TG) or number needed to treat (NNT) is useful. BACKGROUND: Pivotal clinical trials of 5-HT(1B/1D) agonists in migraine use a primary end point of change in pain score from 3 or 2 to 1 or 0. Placebo response rates among such studies are variable. Meta-analytic comparisons of 5-HT(1B/1D) agonists often employ TG and NNT as efficacy measures. METHODS: Data from US product labeling or published sources were converted into TG (TG = active response rate [%] - placebo response rate [%]) and NNT (NNT = 1/TG). Pivotal clinical trial data were compared before and after transformation. RESULTS: Therapeutic gain ranged from 17.5% to 51%. The transformation of TG into NNT yielded no clinically significant difference in efficacy estimate for the range of 17.5% to 47% (N = 29 clinical trials). However, NNT and TG had a nonlinear relationship for some secondary end points. When the relationship between the standard primary and secondary end points was compared, the correlation of TG with clinical disability (Pearson coefficient R = 0.93) was stronger than for NNT. Placebo response rates correlated more strongly with NNT (R = 0.66) than active response rates (R = 0.42; N = 29 clinical trials), although both TG and NNT were sensitive to placebo response rate. CONCLUSIONS: Transforming efficacy rates into TG or NNT adds no new information to placebo-controlled trials. The variables, TG and NNT, should not be used to compare members of this class of drugs. Migraine therapies can only be compared using well-designed head-to-head studies and not by meta-analysis. Broader measures of efficacy should be used to describe and compare 5-HT(1B/1D) efficacy.
Acute Disease↗
Migraine pharmacotherapy with oral triptans: a rational approach to clinical management.
The recent clinical development of a number of migraine specific 5-HT1B/1D agonist triptans with enhanced lipophilicity (TELs), relative to the first drug of this class sumatriptan, and with a range of different metabolic, pharmacokinetic and receptor affinity profiles, provides the potential for critically different clinical profiles. Eletriptan, naratriptan, rizatriptan and zolmitriptan display both increased stability to first pass metabolic inactivation by monoamine oxidase (MAO-A) and enhanced lipophilicity (4- to > 120-fold more than sumatriptan), leading to increased oral bioavailability (2- to 5-fold more than the 14% reported for oral sumatriptan). Central penetration and increased receptor affinity and selectivity for the neuronal (5-HT1D) receptor also combine to allow for lower total oral dosing (i.e., unit doses of 15 mg or less compared with 50-300 mg doses of sumatriptan) and reduced peripheral exposure to the coronary vasoconstrictor (5-HT1B) receptor. The notable exception being eletriptan, where an active P-glycoprotein blood-brain barrier efflux system effectively negates these benefits and requires an 80 mg oral dose. Differences in the metabolic balance between hepatic P450 (especially CYP 1A2) and MAO-A inactivation lead to potential drug interactions for all TELs with the oral contraceptive pill (OCP), fluvoxamine and the quinilone antibiotics (with increased triptan levels). An important but complex MAO-A interaction between a metabolite of propranolol and rizatriptan mandates dosage reduction (to 5 mg) for rizatriptan in the presence of propranolol treatment. There is also an absolute contraindication for the concurrent administration of the MAO-A inhibitor moclobemide and rizatriptan. All the new-marketed TELs have potential clinical benefits and were well-tolerated relative to sumatriptan. Both rizatriptan (10 mg) and zolmitriptan (2.5 mg and 5 mg) demonstrate at least equivalent efficacy to sumatriptan 25, 50 and 100 mg, respectively, making them suitable first line agents for moderate or severe migraine headaches. Rizatriptan has the fastest onset of effect of the TELs. Naratriptan would appear to have lower recurrent headache rate than sumatriptan, rizatriptan or zolmitriptan. Therefore, for headaches of long duration and with a tendency to recur naratriptan may be the most appropriate treatment. Thus, knowledge of the metabolic, pharmacokinetic and clinical profiles of the TELs facilitates the selection of a triptan which allows optimisation of the clinical benefits for individual patients, minimising the risk of drug interactions and a minimally effective dose to reduce potential adverse events (AEs).
Clinical Trials as Topic↗
A long-term study to maximise migraine relief with zolmitriptan.
Part 1 of this international study was a randomised, double-blind, placebo-controlled study of 2.5 mg and 5 mg zolmitriptan (Zomig) in the treatment of persistent migraine headache, two hours after an initial dose of 2.5 mg zolmitriptan. Part 2 was a non-comparative evaluation of long-term, unrestricted zolmitriptan use for treatment of initial, persistent and recurrent migraine headaches. In Part 1, following the treatment of moderate or severe persistent headache, two-hour headache response rates with 5 mg zolmitriptan (51.6%, n = 322), 2.5 mg zolmitriptan (49.7%, n = 324) and placebo (51.6%, n = 343) were not significantly different. However, the pain-free response rate following the treatment of persistent migraine headache of any intensity was significantly higher with 5 mg zolmitriptan than with placebo (36.0% vs. 25.5%; p < 0.001). This was predominantly due to effects in the subgroup of patients with mild headache. Thus, migraine relief in patients whose initial headache shows a partial response to 2.5 mg zolmitriptan may be maximised by a second 5 mg dose. In Part 2 (involving 2499 evaluable patients), 65.8% of attacks were treated with a single dose of zolmitriptan (2.5 mg or 5 mg). Of those migraine attacks initially treated with 2.5 mg zolmitriptan, 70.3% required no further dose, similarly 62.7% of migraine attacks treated initially with 5 mg zolmitriptan only required a single dose. Over the whole attack (i.e. initial and any persistent headache), headache response rates to one or two zolmitriptan doses were greater than 88.8%. 'Level of pain' was the primary factor influencing the choice of dose. Zolmitriptan provided consistent migraine headache relief in the majority of patients and was well tolerated.
Adolescent↗
A misleading cervical bruit in carotid occlusion.
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Auscultation↗
Diffuse bone marrow metastasis by glioblastoma: premortem diagnosis by peroxidase-antiperoxidase staining for glial fibrillary acidic protein.
Extraneural metastases from malignant glioma and glioblastoma are believed to be rare. The most common sites of metastases are lung, lymph nodes, bone, and liver. We recently encountered two patients with glioblastoma multiforme who presented with pain and thrombocytopenia caused by diffuse metastasis to bone marrow. A premortem diagnosis was established in the first patient with the aid of peroxidase-antiperoxidase staining of the bone marrow biopsy specimen for glial fibrillary acidic protein, a glial-specific marker. In the second patient glial fibrillary acidic protein staining confirmed the glial nature of the primary brain tumor as well as the metastatic tumor in bone marrow. The first patient also had metastatic nodules on the pleural surface and on the fifth rib. All three metastatic foci had similar cellular morphology, suggesting selection of a population of tumor cells with extraneural metastatic potential.
Adult↗
Prevalence of tardive dyskinesia.
Forty-four epidemiologic studies on tardive dyskinesia were evaluated as to whether they provided information on diagnostic criteria, objective scale and assessment, interobserver reliability, period of observation, and specific interhospital coordination. Studies which met these standards were reviewed for data on class of neuroleptic therapy, dose, duration, continuity of treatment, extrapyramidal toxicity, spontaneous dyskinesias, other drugs and treatment modalities, age and sex. A higher prevalence of tardive dyskinesia has been consistently noted in the elderly and in females. No other predisposing factors for tardive dyskinesia have been conclusively demonstrated thus far. Prevalence of tardive dyskinesia is estimated at 24-56% in chronic neuroleptic users.
Adolescent↗
Interaction of spatial and temporal summation in the warmth sense.
Two experiments explored the interaction of spatial and temporal summation in the perception of radiant heat. The first experiment showed that the absolute threshold for detecting two brief (0.1 sec) pulses of heat, one presented to each side of the forehead, is lower than the threshold for detecting a single pulse, even when the two pulses are separated in time by as muchas 0l75 sec. The second experiment showed that a single, 4-sec pulse of heat presented to one side of the forehead feels no warmer than two successive, 2-sec pulses, one to each side. Spatial and temporal summation appear to take place at least partly in the central nervous system.
Differential Threshold↗
Imaging spinal osteomyelitis and epidural abscess with short TI inversion recovery (STIR).
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Abscess↗
Sumatriptan suppositories for the acute treatment of migraine. S2B351 Study Group.
A randomised, double-blind, parallel-group, placebo-controlled trial was undertaken to assess the efficacy and tolerability of the sumatriptan suppository in 184 patients with acute migraine. Patients used a sumatriptan suppository (12.5 mg or 25 mg) or placebo at home for the treatment of a moderate or severe migraine attack and those who experienced headache recurrence within 24 hours of dosing had the option to repeat the dose. By 2 hours post-dose, 68% of patients in the sumatriptan 25 mg group and 47% of patients in the sumatriptan 12.5 mg group compared with 25% of placebo patients achieved headache relief. Relief rates 2 hours post-dose for nausea, vomiting, photophobia and phonophobia were similar to those reported 2 hours post-dose for headache. Post hoc review of the recurrence data showed that administration of a second suppository was effective in alleviating recurrent headache in over 80% of the sumatriptan-treated patients experiencing recurrence. No serious or unusual adverse events were reported, and the pattern and incidence of adverse events did not vary as a function of dose. These data demonstrate that the sumatriptan suppository is a well-tolerated, effective treatment for the acute treatment of migraine pain and its associated symptoms.
Administration, Rectal↗