Barbiturate withdrawal following Internet purchase of Fioricet.

Romero CE, Baron JD, Knox AP, Hinchey JA, Ropper AH.

Neurology Service, St Elizabeth's Medical Center, 736 Cambridge Street, Boston, MA 02135, USA.

BACKGROUND: The Internet enables businesses to advertise their pharmaceutical products and services without medical supervision. The Internet also allows for the unsupervised purchase of medications that may have neurologic consequences. OBJECTIVE: To describe acute withdrawal delirium following the abrupt discontinuation of Fioricet. PATIENT: The patient was a 37-year-old woman with a history of depression and migraine headaches but not drug abuse. She developed a florid withdrawal delirium following the discontinuation of a drug she purchased online. The medication, which contained butalbital, was self-administered in escalating doses for the treatment of chronic headaches. Daily doses of up to 750 mg to 1000 mg were reported. RESULTS: The patient was admitted to the hospital for the treatment of unexplained seizures that were followed by several days of an intense withdrawal syndrome. Little improvement was noted after the administration of benzodiazepines and phenothiazine. After parenteral phenobarbital administration, her symptoms resolved. CONCLUSIONS: The withdrawal state from barbiturates is similar to that from ethanol. Tolerance can develop with prolonged abuse, leading to escalating drug doses to achieve the desired effect. The suggested management of both types of withdrawal syndromes is similar, but the relative resistance of the behavioral and autonomic features in patients was remarkable. Physicians should be aware of the ease with which medications can be purchased without supervision from Internet pharmacies. The magnitude of the number of drugs that are made available through this means creates a proclivity to withdrawal states.

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Assay for the simultaneous determination of acetaminophen-caffeine-butalbital in human serum using a monolithic column.

Pistos C, Stewart JT.

Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602-2352, USA.

A fast and sensitive high performance liquid chromatography (HPLC) assay was developed on a C18 monolithic column for the simultaneous determination of acetaminophen-caffeine-butalbital in human serum. Serum samples were treated with a solid phase extraction procedure. The analytes were separated using a mobile phase of 95:5 (v/v) 0.1M potassium phosphate monobasic (pH 2.41)-acetonitrile on the C18 monolithic column with detection at 220 nm. Benzoic acid was used as the internal standard (IS). The method was validated over the range of 1.25-100 microg/ml for each drug and found to be linear (r > 0.995, n = 12) with RSD less than 8.3%. The method proved to be accurate (percent bias for all calibration samples varied from -14.6 to -1.3%) and precise (ranged from 2.9 to 13.4%). The mean percent absolute recoveries from serum were 89.7 +/- 3.6 for acetaminophen, 95.5 +/- 4.5 for caffeine, 99 +/- 5.2 for butalbital and 83.4 +/- 3.9% for the internal standard.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=&dopt=Abstract butalbital fioricet barbiturate




MIGRAINE TREATMENT.

[No authors listed]

Wenzel R, Dortch M, Cady R, Loland JH, Diamond S. Migraine headache misconceptions: barriers to effective care. Pharmacotherapy. 2004;24:638-648. Migraine headaches affect 12% of the adult population in the United States and cause a significant economic loss due to decreased workplace productivity. Although interactions between pharmacists and individuals with headache are common, few pharmacists receive adequate training regarding migraine therapy. We refute several misconceptions that hinder effective care, such as that migraine is a vascular disease, triptans cause rampant cardiac-related morbidity and even mortality, a best oral triptan exists, sinus and tension headaches are prevalent, and migraine is a minor economic problem. Our pathophysiologic understanding demonstrates that migraine is a neurologic process of the trigeminovascular system, of which vascular effects are secondary. This process can result in a myriad of clinical signs and symptoms, often leading to a misdiagnosis of sinus or tension headache. The last decade's experience with triptans in more than half a billion people worldwide reveals a benign adverse-effect profile, particularly when taken early in an attack. Published reports and real-world experiences illustrate that these drugs do not merit fears of triptan-induced cardiac consequences in appropriately selected individuals. Society's productivity loss due to migraine is measured in billions of dollars. Restoring a patient's ability to function normally is now recognized as the primary treatment goal, not merely relieving pain. Thus, the overreliance on "pain killer" drugs such as butalbital-containing products and the continued underutilization of migraine-specific drugs need to be addressed. Opportunities exist for pharmacists and other health care providers to dispel continually propagated migraine misconceptions and familiarize themselves with advances in therapy. Such actions will benefit patients, the health care system, and society as a whole. Comment: This is a marvelous review for residents and primary care practitioners.-Stewart J. Tepper This is a thought provoking article which deserves to be widely discussed. It contains many home truths which should have considerable impact for health care practitioners and will provide useful ammunition for patient groups and headache physicians battling to access resources for headache patients. We reached similar conclusions following our U.K. population survey of headache treatment and health care utilization. Undoubtedly, pharmacists and other health care professionals can act as important conduits to facilitate the prompt effective treatment of headache.-David S. Millson Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, Roewer N, IMPACT Investigators. a factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004;350:2441-2451. Background: Untreated, one-third of patients who undergo surgery will have postoperative nausea and vomiting. Although many trials have been conducted, the relative benefits of prophylactic antiemetic interventions given alone or in combination remain unknown. Methods: We enrolled 5199 patients at high risk for postoperative nausea and vomiting in a randomized, controlled trial of factorial design that was powered to evaluate interactions among as many as three antiemetic interventions. Of these patients, 4123 were randomly assigned to 1 of 64 possible combinations of six prophylactic interventions: 4 mg of ondansetron or no ondansetron; 4 mg of dexamethasone or no dexamethasone; 1.25 mg of droperidol or no droperidol; propofol or a volatile anesthetic; nitrogen or nitrous oxide; and remifentanil or fentanyl. The remaining patients were randomly assigned with respect to the first four interventions. The primary outcome was nausea and vomiting within 24 hours after surgery, which was evaluated blindly. Results: Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26%. Propofol reduced the risk by 19%, and nitrogen by 12%; the risk reduction with both of these agents (ie, total intravenous anesthesia) was thus similar to that observed with each of the antiemetics. All the interventions acted independently of one another and independently of the patients' baseline risk. Consequently, the relative risks associated with the combined interventions could be estimated by multiplying the relative risks associated with each intervention. Absolute risk reduction, though, was a critical function of patients' baseline risk. Conclusions: Because antiemetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients. Comment: We do not know the mechanism of postop nausea, but it is likely to be both medication-induced and central, with potential central generators being nucleus tractus solitariuus and medullary area postrema. Both dopamine and serotonin are clearly involved, and probably Substance P, and we also do not know the relation between migrainous nausea and iatrogenic nausea. Although ondansetron, a 5-HT3-receptor antagonist was included in the randomization, aprepitant, the Substance P/NK1 antagonist antinauseant, synthesized by Richard Hargreaves and team, was not in the study. I included this article as food for thought: which of these medications should we use for our migraine patients, and should we combine multiple medications? I believe a randomized controlled trial of antinauseants alone in treatment of migraine nausea is in order.-Stewart J. Tepper I agree with Dr. Tepper that a randomized comparator trial is urgently needed for treatment of nausea in migraine. I was a little puzzled to see fentanyl and remifentanil described as potential antinausea agents. I would have assumed they are less effective or may actually cause nausea as predicted by their pharmacology. The early studies with ondansetron suggested a potential role in the acute treatment of migraine. However, later work using an early headache classifications and trial designs failed to confirm efficacy (Ferrari MD. 5-HT3-receptor antagonists and migraine. J Neurol. 1991;238:S53-S56). Perhaps the newer antinauseants deserve revisiting given recent developments with the IHS classification and trial designs.-David S. Millson Dodick DW, Martin V. Triptans and CNS side-effects: pharmacokinetic and metabolic mechanisms. Cephalalgia. 2004;24:417-424. Triptans are the treatment of choice for acute migraine. While seemingly a homogenous group of drugs, results from a meta-analysis reveal significant differences in efficacy and tolerability among oral triptans. The incidence of drug-related central nervous system (CNS) side-effects with some triptans is as high as 15% and may be associated with functional impairment and reduced productivity. The occurrence of adverse events associated with triptans in general, and CNS side-effects in particular, may lead to a delay in initiating or even avoidance of an otherwise effective treatment. Potential explanations for differences among triptans in the incidence of CNS side-effects may relate to pharmacological and pharmacokinetic differences, including receptor binding, lipophilicity, and the presence of active metabolites. Of the triptans reviewed, at clinically relevant doses, almotriptan 12.5 mg, naratriptan 2.5 mg, and sumatriptan 50 mg had the lowest incidence of CNS side-effects, while eletriptan 40 and 80 mg, rizatriptan 10 mg, and zolmitriptan 2.5 and 5 mg had the highest incidence. The most likely explanations for the differences in CNS side-effects among triptans are the presence of active metabolites and high lipophilicity of the parent compound and active metabolites. Eletriptan, rizatriptan, and zolmitriptan have active metabolites, while lipophilicity is lowest for almotriptan and sumatriptan. If CNS side-effects are a clinically relevant concern in the individual patient, use of a triptan with a low incidence of CNS side-effects may offer the potential for the earlier initiation of treatment and more effective outcomes. Comment: This article raises more questions than it answers. CNS penetration and liphophilicity do indeed go hand in hand as described by Professor Peter Goadsby in his review (Goadsby P. A triptan too far? J Neurol Neurosurg Psychiatry. 1999;66:121). However, this relationship is questionable in relation to naratriptan which is at least as liphophilic as zolmitriptan and rizatriptan. For naratriptan the FDA mandated a maximum daily dose of 5 mg due to concerns relating to CNS toxicity with higher doses. This also explains why the subcutaneous formulation was abandoned. I do not believe that active metabolites contribute significantly to CNS activity unless they accumulate (which is not the case). Triptan metabolites are usually less liphophilic generated by first pass through the liver (in many cases N-demethylation) which renders them more water soluble and enhances renal elimination. CNS side-effects are also related to onset of action with a trade-off for increased efficacy within 30 minutes with oral formulations of eletriptan, rizatriptan, and zolmitriptan versus the slower onset of naratriptan and frovatriptan. Other factors predicting CNS penetration relate to uptake and competition for the P-gp phospho glycoprotein pump which facilitates the exclusion of lipophilic drugs from the CNS and for which eletriptan is a substrate.-David S. Millson Sender J, Bradford S, Watson D, Lipscombe S, Rees T, Manley R, Dowson AJ. Setting up a Specialist Headache Clinic in primary care: general practitioners with a special interest in headache. Headache Care. 2004;1:165-171. Part of the National Health Service modernization process is to develop General Practitioners with Special Interest (GPwSI) services for intermediate care. Management of headache is currently poor in the United Kingdom due to a lack of trained health care professionals, patients not accessing care, and a reliance on ineffective medications. This warrants the development of GPwSI in headache services. The Royal College of General Practitioners has produced a framework document for the development of an intermediate care service for headache. While this describes what needs to be present in such a service, it does not address the practicalities of implementing it. This article provides organizational and practical guidance for setting up such a service. The majority of headache patients can be managed by multidisciplinary GP- or GPwSI-based care teams located in Primary Care Trusts. Relatively few patients need to referred to secondary care services. The processes of headache management are the same for the whole case mix, involving initial screening, diagnosis, assessment of severity, prescription of therapies tailored to the individual patient's needs, and proactive follow-up. However, the successful implementation of such services poses significant economic and professional challenges to both health care providers and physicians that must be overcome for this program to be successful. Comment: As an American who travels to the United Kingdom a bit, and counts many British as friends, let me try to summarize how this works. The UK National Health Service (NHS) is hierarchical, and specialists are limited in number and often difficult to access for general practitioners (GPs), especially in the hinterlands. Since GPs provide the majority of care in the United Kingdom, control has been placed regionally in Primary Care Trusts run by primary care doctors. A provision has been instituted to allow GPs with special interest in particular specialties to train to provide care in place of specialists, to reduce the burden of referrals to the overtaxed specialists. These GPs with Special Interest (GPwSIs, pronounced "gypsies") have the potential to give outstanding and badly needed care, and headache is an obvious need. The training would be similar to what Dr. Andy Dowson has championed with his Migraine in Primary Care Advisors (MIPCA) in the United Kingdom, and Roger Cady and the Primary Care Network (PCN) provides to primary care practitioners in the United States, but longer and with more bureaucratic documentation. In the United States, certified headache fellowships exist, and we do not distinguish between the training of the doctors at onset-any interested licensed physician can do a headache fellowship. US qualifying Headache Boards, in the works, may also be allowed for licensed physicians who have completed certified fellowships.-Stewart J. Tepper Sang CN, Ramadan NM, Wallihan RG, Chappell AS, Freitag FG, Smith TR, Silberstein SD, Johnson KW, Phebus LA, Bleakman D, Ornstein PL, Arnold B, Tepper SJ, Vandenhende F. LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine. Cephalalgia. 2004;24:596-602. Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY293558, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA) receptor antagonist, is effective in preclinical models of migraine. We therefore tested LY293558 in acute migraine. We conducted a randomized, triple-blind, parallel-group, double-dummy, multicenter trial of 1.2 mg/kg intravenous (IV) LY293558, 6 mg subcutaneous (SC) sumatriptan, or placebo in the treatment of acute migraine. The primary efficacy variable was the headache response rate, ie, headache score improvement from moderate/severe at baseline to mild/none at 2 hour. Of 45 enrolled patients, 44 patients (20:24 [M:F]; mean age +/- SD = 40 +/- 9 years) completed the study. Response rates were 69% for LY293558 (P= .017 vs. placebo), 86% for sumatriptan (P < .01 vs. placebo), and 25% for placebo. LY293558 and sumatriptan were superior to placebo (P < .01 for all comparisons) on all other measures of improvement in pain and migraine-associated symptoms. Fifteen percent of patients who took LY293558 reported adverse events (AEs) (n = 2; 1 mild, 1 severe). Fifty-three percent of patients who took sumatriptan (n = 8; 7 mild, 1 moderate) and 31% of those who received placebo reported AEs (n = 5; 4 mild, 1 severe). The efficacy and safety results of LY293558 in this small migraine proof of concept trial, together with supportive preclinical data, provide evidence for a potential role of nonvasoactive AMPA/KA antagonists in treating migraine. Larger trials are needed to further test the hypothesis. Comment: This is a seminal proof of concept study for the first AMPA/KA antagonist demonstrating potential efficacy approaching that of subcutaneous (SC) sumatriptan in acute migraine. I would be intrigued to know if the adverse events (AEs) relating to SC sumatriptan were perceived by patients with prior triptan experience (difficult to avoid in the United States!) and may have allowed them to identify treatment. The important next step must be to dose range the new agent and to identify either a rapidly acting oral formulation or parenteral route (eg, intranasal, transdermal). This small scale efficacy trial, if confirmed for a nonvasoactive AMPA/KA antagonist, may pave the way for an alternative to the triptans. -David S. Millson.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=&dopt=Abstract butalbital fioricet barbiturate




Efficacy and safety of sumatriptan 50 mg in patients not responding to standard care, in the treatment of mild to moderate migraine. The Sumatriptan 50 mg Italian Study Group.

Pini LA, Fabbri L, Cavazzuti L.

Headache Center, University of Modena, Italy.

The tolerability and efficacy of oral sumatriptan 50 mg for the treatment of mild to moderate migraine attacks were assessed in a double-blind, multicenter placebo-controlled study on a group of patients who had not responded sufficiently to analgesic preparations. Three-hundred-and-twenty-eight migraine sufferers treated a first migraine attack with a nontriptan standard care medication: a mixture containing phenazone, butalbital and caffeine (optalidon) or indomethacin plus prochlorperazine plus caffeine (difmetre) or paracetamol 100 mg (tachipirine), depending on their habits. Of these patients, 32.6% reported headache relief with this treatment and were not included in phase II of the study. The 219 patients not reporting relief during the first phase of the study entered the second phase and were randomized to sumatriptan 50 mg or to placebo; 167 of these patients treated a second attack according to the protocol and were evaluated for efficacy. Of the patients with migraine taking sumatriptan, 58% reported headache relief compared with 35% of placebo-treated patients (p = 0.008). The reduction of nausea and vomiting was significantly better in the sumatriptan group. No differences were detected for the recurrence rate, while rescue medication was used more by the placebo group. The safety profile of sumatriptan 50 mg was confirmed. This study demonstrates the usefulness of this dose of oral sumatriptan against the pain and the accompanying symptoms of mild and moderate migraine.

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CHRONIC DAILY HEADACHE AND MEDICATION-OVERUSE HEADACHE.

[No authors listed]

Bentsen L, Jensen R. Mirtazapine is effective in the prophylactic treatment of chronic tension-type headache. Neurology. 2004;62:1706-1711. Background: The tricyclic antidepressant amitriptyline is the only drug with prophylactic efficacy for chronic tension-type headache. However, amitriptyline is only moderately effective, with headache reduction of approximately 30%, and treatment is often hampered by side effects. Mirtazapine is a relatively new so-called noradrenergic and specific serotonergic antidepressant, which is more specific and therefore generally better tolerated. Objective: To evaluate the efficacy of mirtazapine. Methods: Twenty-four nondepressed patients with chronic tension-type headache were included in a randomized, double-blind, placebo-controlled, crossover trial. All patients had tried numerous other treatments. Mirtazapine 15 to 30 mg/day or placebo was each given for 8 weeks separated by a 2-week wash-out period. Results: Twenty-two patients completed the study. The primary efficacy variable, area-under-the-headache curve (AUC; duration x intensity), was lower during treatment with mirtazapine (843) than during treatment with placebo (1275) (P= .01). Mirtazapine also reduced the secondary efficacy variables headache frequency (P= .005), headache duration (P= .03), and headache intensity (P= .03) and was well tolerated. Conclusions: Mirtazapine reduced AUC by 34% more than placebo in difficult-to-treat patients. This finding is clinically relevant and may stimulate the development of prophylactic treatments with increased efficacy and fewer side effects for tension-type headache and other types of chronic pain. Comment: I am happy to see these results on mirtazepine for chronic tension-type headache (CTTH), and I look forward to prescribing it for daily headache, despite its occasional adverse events of weight gain and somnolence, similar to amitriptyline. It is probably not quite right to state, as the authors did, that "the tricyclic antidepressant amitriptyline is the only drug with prophylactic efficacy for CTTH." For example, here are two randomized controlled studies suggesting efficacy for two very different medications for CTTH: * Saper JR, Silberstein SD, Lake AE III, Winters ME. Double-blind trial of fluoxetine: chronic daily headache and migraine. Headache. 1994;34:497-502. * Saper JR, Lake AE III, Cantrell DT, Winner PK, White JR. Chronic daily headache prophylaxis with tizanidine: a double-blind, placebo-controlled, multicenter outcome study. Headache. 2002;42:470-482.-Stewart J. Tepper Zwart J-A, Hagen K, Svebak S, Stovner LJ, Holmen J. Analgesic overuse among subjects with headache, neck, and low-back pain. Neurology. 2004;62:1540-1544. Objectives: To examine the prevalence of chronic headache (>/=15 days/month) associated with analgesic overuse in relation to age and gender and the association between analgesic overuse and chronic pain (ie, migraine, nonmigrainous headache, neck, and low-back pain). Methods: In the Nord-Trondelag Health Study 1995 to 1997 (HUNT-2), a total of 51 383 subjects responded to headache questions (Head-HUNT), of which 51 050 completed questions related to musculoskeletal symptoms and 49 064 questions regarding the use of analgesics. Results: The prevalence of chronic headache associated with analgesic use daily or almost daily for >/=1 month was 1% (1.3% for women and 0.7% for men) and for analgesic overuse duration of 3 months 0.9% (1.2% for women and 0.6% for men). Chronic headache was more than seven times more likely among those with analgesic overuse (>/=1 month) than those without (odds ratio [OR]= 7.5; 95%CI: 6.6 to 8.5). Upon analysis of the different chronic pain subgroups separately, the association with analgesic overuse was strongest for chronic migraine (OR = 10.3; 95%CI: 8.1 to 13.0), intermediate for chronic nonmigrainous headache (OR = 6.2; 95%CI: 5.3 to 7.2), and weakest for chronic neck (OR = 2.6, 95%CI: 2.3 to 2.9) and chronic low-back (OR = 3.0; 95%CI: 2.7 to 3.3) pain. The association became stronger with increasing duration of analgesic use for all groups and was most evident among those with headache, especially those with migraine. Conclusions: Chronic headache associated with analgesic overuse is prevalent and especially chronic migraine is more strongly associated with frequent intake of analgesics than other common pain conditions such as chronic neck and chronic low-back pain. Esposito SB, Gherpelli JL. Chronic daily headaches in children and adolescents: a study of clinical characteristics. Cephalalgia. 2004;24(6):476-482. The clinical characteristics of chronic daily headache were studied in 40 children and adolescents, as well as the associated factors responsible for maintenance of the continuous headache pattern. The study of the clinical headache characteristics, showed a female preponderance (75%), mean age of 11 years old at the first consultation, and onset of headache symptomatology at a mean age of 8.5 years old. The average time interval for the evolution of sporadic headache into chronic daily headache was 1.4 years, and psychosocial stressors were present, acutely or chronically, during the period of headache-frequency increase in 47% of the children. Headaches were classified as transformed migraine (65%), mixed pattern (17.5%), and chronic tension-type headache (17.5%). Sixty percent of patients had mothers with migraine. Data regarding common analgesic use showed an average intake of 11.2 days/month. Romero CE, Baron JD, Knox AP, Hinchey JA, Ropper AH. Barbiturate withdrawal following internet purchase of fioricet. Arch Neurol. 2004;61:1111-1112. Background: The Internet enables businesses to advertise their pharmaceutical products and services without medical supervision. The internet also allows for the unsupervised purchase of medications that may have neurologic consequences. Objective: To describe acute withdrawal delirium following the abrupt discontinuation of Fioricet. Patient: The patient was a 37-year-old woman with a history of depression and migraine headaches but not drug abuse. She developed a florid withdrawal delirium following the discontinuation of a drug she purchased online. The medication, which contained butalbital, was self-administered in escalating doses for the treatment of chronic headaches. Daily doses of up to 750 to 1000 mg were reported. Results: The patient was admitted to the hospital for the treatment of unexplained seizures that were followed by several days of an intense withdrawal syndrome. Little improvement was noted after the administration of benzodiazepines and phenothiazine. After parenteral phenobarbital administration, her symptoms resolved. Conclusions: The withdrawal state from barbiturates is similar to that from ethanol. Tolerance can develop with prolonged abuse, leading to escalating drug doses to achieve the desired effect. The suggested management of both types of withdrawal syndromes is similar, but the relative resistance of the behavioral and autonomic features in patients was remarkable. Physicians should be aware of the ease with which medications can be purchased without supervision from the Internet pharmacies. The magnitude of the number of drugs that are made available through this means creates a proclivity to withdrawal states. Comment: There are two take-home lessons here. The first lesson is that abrupt butalbital discontinuation can produce life-threatening barbiturate withdrawal. Drs. Elizabeth Loder and David Biondi wrote an indispensable guide to safe withdrawal of these patients in 2003 (Loder E, Biondi D. Oral phenobarbital loading: a safe and effective method of withdrawing patients with headache from butalbital compounds. Headache. 2003;43:904-909). The second lesson is that habituating, potentially life-threatening medications are available with ease on the internet, and we must be vigilant about asking our patients if they supplement our prescriptions. Dr. Steve Peroutka has written eloquently on headache information available on the internet (Peroutka S. Analysis of internet sites for headache. Cephalalgia. 2001;21:20-24). Romero et al's article describes sites for obtaining drugs.-Stewart J. Tepper Bigal ME, Rapoport AM, Sheftell FD, Tepper SJ, Lipton RB. Transformed migraine and medication overuse in a tertiary headache centre-clinical characteristics and treatment outcomes. Cephalalgia. 2004;24:483-490. Studies suggest that a substantial proportion of headache sufferers presenting to headache clinics may overuse acute medications. In some cases, overuse may be responsible for the development or maintenance of a chronic daily headache (CDH) syndrome. The objectives of this study are to evaluate patterns of analgesic overuse in patients consulting a headache centre and to compare the outcomes in a group of patients who discontinued medication overuse to those of a group who continued the overuse, in patients with similar age, sex, and psychological profile. We reviewed charts of 456 patients with transformed migraine (TM) and acute medication overuse defined by one of the following criteria: (1) simple analgesic use (>1000 mg ASA/acetaminophen) > 5 days/week; (2) combination analgesics use (caffeine and/or butalbital) > 3 tablets a day for > 3 days a week; (3) opiate use > 1 tablet a day for > 2 days a week; (4) ergotamine tartrate use: 1 mg PO or 0.5 mg PR for > 2 days a week. For triptans, we empirically considered overuse > 1 tablet per day for > 5 days per week. Patients who were able to undergo detoxification and did not overuse medication (based on the above definition) after 1 year of follow-up were considered to have successful detoxification (Group 1). Patients who were not able to discontinue offending agents, or returned to a pattern of medication overuse within 1 year were considered to have unsuccessful detoxification (Group 2). We compared the following outcomes after 1 year of follow-up: number of days with headache per month; intensity of headache; duration of headache; headache score (frequency x intensity). The majority of patients overused more than one type of medication. Numbers of tablets taken ranged from 1 to 30 each day (mean of 5.2). Forty-eight (10.5%) subjects took more than 10 tablets per day. Considering patients seen in the last 5 years, we found the following overused substances: butalbital containing combination products, 48%; acetaminophen, 46.2%; opioids, 33.3%; ASA, 32.0%; ergotamine tartrate, 11.8%; sumatriptan, 10.7%; nonsteroidal anti-inflammatory medications other than ASA, 9.8%; zolmitriptan, 4.6%; rizatriptan, 1.9%; naratriptan, 0.6%. Total of all triptans, 17.8%. Of 456 patients, 318 (69.7%) were successfully detoxified (Group 1) and 138 (30.3%) were not (Group 2). The comparison between groups 1 and 2 after 1 year of follow-up showed a decrease in the frequency of headache of 73.7% in group 1 and only 17.2% in group 2 (P < .0001). Similarly, the duration of head pain was reduced by 61.2% in group 1 and 14.8% in group 2 (P < .0001). The headache score after 1 year was 18.8 in group 1 and 54 in group 2 (P < .0001). A total of 225 (70.7%) successfully detoxified subjects in Group 1 returned to an episodic pattern of migraine, compared to 21 (15.3%) in Group 2 (P < .001). More rigorous prescribing guidelines for patients with frequent headaches are urgently needed. Successful detoxification is necessary to ensure improvement in the headache status when treating patients who overuse acute medications. Comment: This study highlights the difficulties faced in trying to obtain outpatient provision for successful detoxification. Isn't it about time the FDA took a fresh look at the risk/benefits for butobarbital combinations, which are still surprisingly available in the United States? Surely this must signal the death knell for these products. The New England Center for Headache have a tremendous database of knowledge on which to base pragmatic prescribing guidelines. I would endorse their concern and commend the approach they have taken.-David S. Millson Torbey MT, Geocadin RG, Razumovsky AY, Rigamonti D, Williams MA. Utility of CSF pressure monitoring to identify idiopathic intracranial hypertension without papilledema in patients with chronic daily headache. Cephalalgia. 2004;24:495-502. The aim of the present study was to report on the utility of continuous Pcsf monitoring in establishing the diagnosis of idiopathic intracranial hypertension without papilledema (IIHWOP) in chronic daily headache (CDH) patients. We report a series of patients (n = 10) with refractory headaches and suspected IIHWOP referred to us for continuous Pcsf monitoring between 1991 and 2000. Pcsf was measured via a lumbar catheter and analyzed for mean, peak, highest pulse amplitude, and abnormal waveforms. A 1 to 2 day trial of continuous controlled CSF drainage (10 cc/hour) followed Pcsf monitoring. Response to CSF drainage was defined as improvement in headache symptoms. Patients with abnormal waveforms underwent a ventriculoperitoneal (VPS) or lumboperitoneal (LPS) shunt insertion. All patients had normal resting Pcsf (8 +/- 1 mmHg) defined as ICP < 15 mmHg. During sleep, all patients had B-waves and 90% had plateau waves or near plateau waves. All patients underwent either a VPS or LPS procedure. All reported improvement of their headache after surgery. Demonstration of pathological Pcsf patterns by continuous Pcsf monitoring was essential in confirming the diagnosis of IIHWOP, and provided objective evidence to support the decision for shunt surgery. Increased Pcsf was seen mostly during sleep and was intermittent, suggesting that Pcsf elevation may be missed by a single spot-check LP measurement. The similarity between IIHWOP and CDH suggests that continuous Pcsf monitoring in CDH patients may have an important diagnostic role that should be further investigated. Comment: This study confirms that elevated CSF pressure, as measured by continuous CSF pressure monitoring, may be linked to CDH.-Stewart J. Tepper.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=&dopt=Abstract butalbital fioricet barbiturate