JA Zwart, G Dyb, K Hagen, S Svebak, L.J Stovner, J Holmen, Analgesicoveruse among subjects with headache, neck, and low-back pain Neurology2004;62:1540-1544
From the Department of Clinical Neuroscience (Drs. Zwart and Hagen), Sectionof Neurology, Department of Psychiatry and Behavioural Medicine (Drs. Dyband Svebak), and HUNT Research Centre (Dr. Holmen), Faculty of Medicine,Norwegian University of Science and Technology, Trondheim. Address correspondenceand reprint requests to Dr. J.-A. Zwart, Department of Clinical Neuroscience,Faculty of Medicine, Norwegian University of Science and Technology, 7006Trondheim, Norway; e-mail: john-anker.zwart@medisin.ntnu.no

Objectives: To examine the prevalence of chronic headache (>=15days/month) associated with analgesic overuse in relation to age and genderand the association between analgesic overuse and chronic pain (i.e., migraine,nonmigrainous headache, neck and low-back pain).  Methods: Inthe Nord–Trøndelag Health Study 1995 to 1997 (HUNT-2), a total of51,383 subjects responded to headache questions (Head-HUNT), of which 51,050completed questions related to musculoskeletal symptoms and 49,064 questionsregarding the use of analgesics. Results: The prevalence of chronicheadache associated with analgesic use daily or almost daily for >=1 monthwas 1% (1.3% for women and 0.7% for men) and for analgesic overuse durationof >=3 months 0.9% (1.2% for women and 0.6% for men). Chronic headachewas 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 to8.5). Upon analysis of the different chronic pain subgroups separately, theassociation 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 usefor all groups and was most evident among those with headache, especiallythose with migraine. Conclusions: Chronic headache associated withanalgesic overuse is prevalent and especially chronic migraine is more strongly associated with frequent intake of analgesics than other common pain conditionslike chronic neck and chronic low-back pain.

Takanaga H, Ohnishi A, Murakami H,Matsuo H, Higuchi S, Urae A, Irie S, Furuie H, Matsukuma K, Kimura M, KawanoK, Orii Y, Tanaka T, Sawada Y, Relationship between time after intakeof grapefruit juice and the effect on pharmacokinetics and pharmacodynamicsof nisoldipine in healthy subjects. Clin Pharmacol Ther, 2000 03, 67: 3,201-14

A clinical study was performed in eighthealthy volunteers to investigate the effect of various timing of grapefruitjuice intake on nisoldipine pharmacokinetics and pharmacodynamics, and tovalidate our pharmacokinetic model. The subjects were given 10 mg oral nisoldipinewith water (control), or 5 mg oral nisoldipine with 200 mL grapefruit juice(G0) or with water at 14 (G14), 38 (G38), 72 (G72) or 96 hours (G96) aftera 7-day period of thrice-daily intake of grapefruit juice. Grapefruit juiceingestion did not affect heart rate or the effect area during the first 8hours of heart rate after nisoldipine administration, although significantdecreases of systolic and diastolic blood pressure were caused in G0 by coadministrationof grapefruit juice with nisoldipine. Headaches were reported by 3, 2, and1 persons in G0, G14, and G38, respectively, but no subjects in G72 and G96reported headaches. Compared with the control group, the maximum plasma concentrationof nisoldipine was significantly increased after grapefruit juice intakein G0 and G14, and the plasma concentration was significantly increased ateach time in G0 to G72. Therefore the effect of grapefruit juice decreasedtime dependently and lasted for at least 3 days after intake. Furthermore,our model gave predicted values in good agreement with the observed values.It is therefore necessary to withhold grapefruit juice for at least 3 daysbefore administration of the drug to prevent grapefruit juice-nisoldipineinteraction.

Lipton RB, Stewart WF, Ryan RE Jr, Saper J, Silberstein S, Sheftell F, Efficacyand safety of acetaminophen, aspirin, and caffeine in alleviating migraineheadache pain: three double-blind, randomized, placebo-controlled trials.Arch Neurol, 1998 02, 55: 2, 210-7

OBJECTIVE: To assess the effectivenessof the nonprescription combination of acetaminophen, aspirin, and caffeinein alleviating migraine headache pain. DESIGN: Three double-blind, randomized,parallel-group, single-dose, placebo-controlled studies. SETTING: Privatepractice, referral centers, and general community. PATIENTS: Migraineurswith moderate or severe headache pain who met International Headache Societydiagnostic criteria for migraine with aura or without aura. The most severelydisabled segment of migraineurs, including those whose attacks usually requiredbed rest, or who vomited 20% or more of the time, were excluded. Of the 1357enrolled patients, 1250 took study medication and 1220 were included in theefficacy-evaluable data set. INTERVENTION: Two tablets of the nonprescriptioncombination of acetaminophen, aspirin, and caffeine or placebo taken orallyas a single-dose treatment of 1 eligible acute migraine attack. Main OutcomeMeasures: Pain intensity difference from baseline; percentage of patientswith pain reduced to mild or none. RESULTS: Significantly greater reductionsin migraine headache pain intensity 1 to 6 hours after dose were seen inpatients taking the acetaminophen, aspirin, and caffeine combination thanin those taking placebo in each of the 3 studies. Pain intensity was reducedto mild or none 2 hours after dose in 59.3% of the 602 drug-treated patientscompared with 32.8% of the 618 placebo-treated patients (P< .001; 95%confidence interval [CI], 55%-63% for drug, 29%-37% for placebo); at 6 hoursafter dose, 79% vs 52%, respectively, had pain reduced to mild or none (P<.001;95% CI, 75%-82% vs 48%-56%). In addition, by 6 hours after dose, 50.8% ofthe drug-treated patients were pain free compared with 23.5% of the placebo-treatedpatients (P<.001; 95% CI, 47%-55% for drug, 20%-27% for placebo). Othermigraine headache characteristics, such as nausea, photophobia, phonophobia,and functional disability, were significantly improved 2 to 6 hours aftertreatment with the acetaminophen, aspirin, and caffeine combination comparedwith placebo (P< or =.01). CONCLUSIONS: The nonprescription combinationof acetaminophen, aspirin, and caffeine was highly effective for the treatmentof migraine headache pain as well as for alleviating the nausea, photophobia,phonophobia, and functional disability associated with migraine attacks.This drug combination also has an excellent safety profile and is well tolerated.

Nelson CF, A Comparison of Medication, Chiropractic Therapy, and a CombinedTherapy in the Prophylaxis of Migraine Headache: A Randomized Clinical Trial  Proceedings of the Int'l Conference of Spinal Manipulation 1996 Oct:  66

Background and Objective: The burdenthat migraine headache imposes on society is substantial. The total economiccosts of migraine headache including health care costs and lost productivitydue to absenteeism is estimated to be between 5 billion and 17 billion dollarsannually in the US. Medical therapy for migraine headaches can be eitherabortive or prophylactic. Abortive therapies such as sumatriptan are intendedfor less frequent headaches while prophylactic medications such as amitriptylineare used for more frequent ( 3 or more episodes per month) headaches. Whiledata from a variety of sources indicate that migraine headache is a conditioncommonly treated by chiropractors and while there is abundant basic scienceevidence which implicates the cervical spine in migraine headache etiology,there is no reliable data on the effectiveness of spinal manipulation, amitriptyline,and those two therapies in combination for the treatment of migraine headache.Conclusion: Analysis of the outcome measure is ongoing.

Anderson A, Boline P, Bronfort G, Kassak K, Nelson C, Spinal Manipulationvs. Amitriptyline for the Treatment of Chronic Tension-Type Headaches: ARandomized Clinical Trial   Journal of Manipulative and PhysiolgicalTherapeutics 1995 ; 18(3): 148-54

Objective: To compare the effectivenessof spinal manipulation and pharmaceutical treatment (amitriptyline) for chronictension-type headache. Design: Randomized controlled trial using two parallelgroups. The study consisted of a 2-wk baseline period, a 6-wk treatment periodand a 4-wk posttreatement, follow-up period. Setting: Chiropractic collegeoutpatient clinic. Patients: One hundred and fifty patients between the agesof 18 and 70 with a diagnosis of tension-type headaches of at least 3 months'duration at a frequency of at least once per wk. Interventions: 6 wk of spinalmanipulative therapy provided by chiropractors or 6 wk of amitriptyline treatmentmanaged by a medical physician. Main Outcome Measures: Change in-patient-reporteddaily headache intensity, weekly headache frequency, over-the-counter medicationusage and functional health status (SF-36). Results: A total of 448 peopleresponded to the recruitment advertisements; 298 were excluded during thescreening process. Of the 150 patients who were enrolled in the study, 24(16%) dropped out: 5 (6.6%) from the spinal manipulative therapy and 19 (27.1%)from the amitriptyline therapy group. During the treatment period, both groupsimproved at very similar rates in all primary outcomes. In relation to baselinevalues at 4 wk after cessation of treatment, the spinal manipulation groupshowed reduction of 32% in headache intensity, 42% in headache frequency,30% in over-the-counter medication usage and an improvement of 16% in functionalhealth status. By comparison, the amitriptyline therapy group showed no improvementor a slight worsening from baseline values in the same four major outcomemeasures. Controlling for baseline differences, all group differences at4 wk after cessation of therapy were considered to be clinically importantand were statistically significant. Of the patients who finished the study,46 (82.1%) in the amitriptyline therapy group reported side effects thatincluded drowsiness, dry mouth and weight gain. Three patients (4.3%) inthe spinal manipulation group reported neck soreness and stiffness. Conclusion:The results of this study show that spinal manipulative therapy is an effectivetreatment for tension headaches. Amitriptyline therapy was slightly moreeffective in reducing pain at the end of the treatment period but was associatedwith more side effects. Four weeks after cessation of treatment, however,the patients who received spinal manipulative therapy experienced a sustainedtherapeutic benefit in all major outcomes in contrast to the patients thatreceived amitriptyline therapy, who reverted to baseline values. The sustainedtherapeutic benefit associated with spinal manipulation seemed to resultin a decreased need for over-the-counter medication. There is a need to assessthe effectiveness of spinal manipulative therapy beyond four weeks and tocompare spinal manipulative therapy to an appropriate placebo such as shammanipulation in future clinical trials.

Boline K, Boline P, One Year Follow-Up of Controlled Clinical Trial, SpinalAdjustments and Pharmaceutical Therapy   Proceedings ofthe Int'l Conference of Spinal Manipulation 1993 : 107

Background and Objectives: A randomizedtrial comparing chiropractic adjustive therapy and Amiltriptyline for thetreatment of chronic muscle contraction headaches was completed in February1992. The study consisted of a two week baseline period, with patients thencompleting a four week treatment course. A four week follow-up period concludedwith an exit interview. This study is a follow-up to that randomized, controlledclinical trial. One year after the exit interview the patients are beingcontacted by telephone and asked a standardized questionnaire to assess severityof headache pain, current headache frequency, headache frequency comparedto a year ago, over the counter medication use, other treatments utilized,and a global assessment of their own health. Thus, the primary objectiveis to measure patients long-term health status. Method: The patients arecurrently being contacted by telephone and asked a standardized questionnaire.Results: Results will include analysis of data from the one year follow-upand that compared with the four week follow-up data. Conclusions: Conclusionswill be presented and discussed.

Boline P, Chiropractic and Pharmaceutical Treatment for Chronic MuscleTension Headaches: A Randomized Clinical Trail   Transactionsof the Consortium for Chiropractic Research 1992  Jun; 7th: 45-7

Headache is a common problem. A populationsurvey in the United reported 14% of males and 28% of females with frequentand/or distressing headaches to 31 % of males and 44% of females with severeheadache. In a 1977-78 Ambulatory Care Survey, muscle tension headaches madeup 90% of all headache diagnoses. Muscle tension headaches do not cause theamount of incapacitating pain as do migraine headaches, but they are farmore frequent and result in a decreased level of productivity over time,a large consumption of over the counter and prescribed medication resultingin a subsequent diminished quality of life. Therefore, patients seek outa variety of treatment approaches which include chiropractic, medical andpsychological therapy.

Dhami M, Young K, The Efficacy ofCervical Manipulation as Opposed to Pharmacological Therapeutics in the Treatmentof Migraine Patients   Transactions of the Consortium forChiropractic Research 1987  Jun

Migraine has been defined in many differentways and several have been ascribed to it. In the most general sense, a migraineheadache is characterized by a prodromal phase of cerebral blood vessel vasoconstrictionwhich produces a painful headache. Many therapies are used to treat migraineheadaches including allopathic and chiropractic care. The wide variety ofpharmacological agents used, is ample evidence that the treatment and prophylaxismigraine continues to elude the efforts of medical doctors in many cases.Chiropractic treatment also has not been shown to be an acceptable treatmentmodality, although some patients do experience relief in duration, intensity,and frequency of migraine. Further research is indicated in order to determinethe efficacy of cervical manipulation as opposed to pharmacological therapeuticsin the treatment of migraine patients. Carefully controlled clinical trialscan establish guidelines as to the appropriate types of treatments for themigraine patient.

Chiropractic and Headache Related Literature