Grobbee, D.E. (Diederick)

Ottervanger, J.P. (Jan Paul)

Stricker, B.H.Ch. (Bruno)

Valkenburg, H.A. (Hans)

Erasmus University Digital Repository

Eur J Clin Pharmacol (1996) 50 : 353–355 © Springer-Verlag 1996PHARMACOEPIDEMIOLOGY AND PRESCRIPTIONJ. P. Ottervanger · H. A. Valkenburg · D. E. GrobbeeB. H. Ch. StrickerPattern of sumatriptan use and overuse in general practiceReceived: 24 July 1995/Accepted in revised form: 5 October 1995Abstract Objective: To investigate the frequency of useand misuse of sumatriptan, and to explore the char-acteristics of patients reporting overuse.Setting: A postmarketing cohort study on adverse reactions to sumatriptan, performed with the assis-tance of drug-dispensing general practitioners in theNetherlands.Methods: Questionnaires were sent to patients on suma-triptan of drug-dispensing general practitioners in theNetherlands. Use of sumatriptan was classified into fivegroups: < 1, 1–10, 11–20 and 21–30 times per monthand a group of patients who reported daily use ofsumatriptan more than 10 times per week. Patients inthe latter group were regarded as “overusers”.Results: The request to the 1720 patients yielded aresponse rate of 1202 (70%). Of 952 (79%) of thesepatients, details of their sumatriptan intake were avail-able. Most patients (718, 75%) took sumatriptan 1–10times each month. However, 36 patients (4%, 95% CI2.8–5.2%) took sumatriptan daily or more than 10times each week. The group with the highest intakeconsisted mainly of males, and many patients whoreported a poor efficacy of sumatriptan. Age was notrelated to use of sumatriptan.Conclusions: A small group of patients (4%) used suma-triptan too often. A high intake was associated withboth male gender and a reported poor efficacy of suma-triptan, but not with age, reported adverse reactions,or headache attributed to sumatriptan. It is importantto explain to patients that sumatriptan is only for thetreatment of acute attacks, and not for prophylacticuse. Drug consumption patterns have to be evaluated,in particular in patients who report low efficacy ofsumatriptan.Key words Sumatriptan, Postmarketing surveillance,Migraine; overuse, pharmacoepidemiologyThe serotonin-1 agonist sumatriptan is a relatively newdrug used in the treatment of acute attacks of migraineand cluster headache [1]. Adverse drug reactions attrib-uted to sumatriptan in the postmarketing periodinclude acute myocardial infarction [2, 3], depression[4] and skin reactions [5]. A characteristic feature is therecurrence of headache within 24 h after administra-tion of sumatriptan [6]. Since marketing of the drug,several patients have been observed who developed anincrease in the frequency of migraine attacks with con-sequent dependence and misuse, after use of suma-triptan [7–9]. Preliminary results of a postmarketingstudy based on pharmacy records have also shown mis-use of sumatriptan by approximately 1% of consumers[10]. We investigated the frequency of use and misuseof sumatriptan in a postmarketing cohort study, andexplored the characteristics of patients reportingoveruse.Methods and data analysisIn May 1991, sumatriptan was registered in the Netherlands for the treatment of acute attacks of migraine and cluster headache. InJuly 1992, we conducted an enquiry and all 687 drug-dispensinggeneral practitioners (GPs) in the Netherlands were contacted, toobtain the date of birth and gender of every person to whom they had dispensed sumatriptan since marketing. Subsequently, they were asked to send a questionnaire to the patients who hadused sumatriptan, to be completed at home. The questionnaireswere sent via the GP in prestamped envelopes with a standardletter from our centre. In the questionnaire, the patients were askedJ. P. Ottervanger · B. H. Ch. Stricker (*)Netherlands Centre for Monitoring of Adverse Reactions toDrugs, P.O. Box 5406, NL-2280 HK Rijswijk, The NetherlandsJ. P. OttervangerDepartment of Internal Medicine II, University HospitalDijkzigt, Rotterdam, The NetherlandsH. A. Valkenburg · D. E. Grobbee · B. H. Ch. StrickerDepartment of Epidemiology and Biostatistics,Pharmacoepidemiology Unit, Erasmus University MedicalSchool, Rotterdam, The Netherlandswhether they had indeed used sumatriptan and, if so, how oftensumatriptan was used, what the efficacy of sumatriptan was andwhether they had observed any adverse reaction after use of suma-triptan. No adverse reactions were mentioned by name in the ques-tionnaire. Some details of the study have been published previously[11, 12].Use of sumatriptan was classified into five groups: < 1, 1–10, 11–20 and 21–30 times per month, and a fifth group ofpatients who reported daily sumatriptan use or use more than 10 times each week. Patients in the latter group were regarded as“overusers”.Differences between group means were tested by Student’s t-test.A chi-square test was used to assess differences between propor-tions, with use of Fisher’s exact test if there was an expected cell value of less than 5. All calculated P values are two-tailed.Statistical significance was defined as a two-sided P-value of less than 0.05. Relative risks (RR) were calculated with 95%confidence intervals (95% CI).ResultsOf the 589 Dutch GPs (86%) who participated in thisstudy, 474 had dispensed sumatriptan on at least oneoccasion to a total of 1727 patients (24% males, 76%females). During the study period, seven patients werelost to follow-up, all from change of address. Of the1720 remaining patients, 1202 (70%) returned the ques-tionnaire. With 952 (79%) of these patients full detailsof their sumatriptan intake were available.Basic characteristics of the study population aresummarized in Table 1. A total of 34 patients (4%)reported (rebound) headache due to use of sumatrip-tan, 6 males and 28 females (gender distribution notsignificantly different from the other patients). In Fig. 1 the consumption of sumatriptan is depicted.Most patients (718, 75%) consumed sumatriptan 1–10times each month. Thirty-six patients (4%, 95% CI2.8–5.2%) used sumatriptan daily or more than 10 times each week, and were regarded as “overusers”,of whom 17 patients used sumatriptan once every day,14 patients took sumatriptan 2 times each day, 3patients three times each day, and 2 patients reportedthat they used sumatriptan more than 10 times eachweek (not specified per day). Of the 36 patients, 13(36%) were males, which was more than in the patientswho used sumatriptan less than 10 times per month(192 males, relative risk 1.9, 95% CI 1.0–3.7). Therewere no differences in age, duration of headache com-plaints or  route of administration between the fiveintake groups. Of the 36 patients who took sumatrip-tan daily or more than 10 times each week, 6 patientsreported the efficacy of sumatriptan as poor, comparedto 49 patients of the 916 patients who used sumatrip-tan less than 30 times each month (RR = 3.3 95% CI1.4–7.5). One or more adverse reactions were reportedby 18 patients (50%) of the overusers, compared to 511patients (56%) of the others (P = 0.5). Headache as anadverse reaction to sumatriptan was reported by 1“overuser” (2.8%), compared to 33 patients in the othergroups (3.6%; not significantly different).354Table 1 Basic characteristics of 952 patients with information onsumatriptan consumption (SD standard deviation)Characteristic Number or meanAge (years) 44 (SD: 11)Males 224 (24%)Reported efficacy of sumatriptan– Good 729 (77%)– Moderate 77 (8%)– Poor 55 (6%)– Not reported 91 (9%)Route of administration– Oral 318 (33%)– Subcutaneous 458 (48%)– Both routes 82 (9%)– Missing 94 (10Average duration ofheadache complaints (years) 21 (SD: 13)Any adverse reaction 529 (56%)Headache after sumatriptan 34 (4%)Fig. 1 Consumption ofsumatriptan in 952 patients ofdrug-dispensing generalpractitioners. Consumptionwas classified into five groups:< 1, 1–10, 11–20 and 21–30times per month and a groupof patients who reported dailyuse sumatriptan or use morethan 10 times each weekDiscussionWe found that a small proportion (4%) of the con-sumers used sumatriptan daily or more than 10 timeseach week. Since sumatriptan is a drug for acute attacksof migraine or cluster headache, and not for prophy-lactic use, we regarded this group as “overusers”. It haspreviously been recommended that patients withheadaches should never take analgesics every day, andthat ergotamine should not be taken more than 10 timesa month [13]. Overuse in our study was significantlymore frequently observed in males, and in patients whoreported the efficacy of sumatriptan as poor.Analyses of medication consumption based ondispensing or reimbursement data have two major lim-itations: (1) no information is available on non-com-pliance and (2) no information is available on drugswhich are bought “over the counter”. Furthermore,these pharmacy record based studies do not providedirect information on efficacy, clinical events or adversedrug reactions observed by consumers. In our post-marketing study we used information of drug useobtained directly from consumers. Because of strict pri-vacy rules in the Netherlands, we were not able to val-idate these data by evaluating the records of the drug-dispensing general practitioners. We think, however,that these data give good insight into the consumptionof sumatriptan in these patients, although negativemisclassification may exist.Several explanations for overuse may be considered.The most important reason for more frequent use ofsumatriptan is possibly a higher attack rate of migraineor cluster headache, but information on attack rateswas not available in our study. However, it was demon-strated in our study that an observed low efficacy ofsumatriptan accompanied more frequent overuse.Previously, headache recurrence after sumatriptan usewas reported [14–16]. It has been suggested that therebound headache may be the underlying mechanismof over-use of sumatriptan [10, 15]. However, the(rebound) headache was not associated with overuse inour study. Another explanation, more compatible withour data, is that some patients use sumatriptan in toolow a dose or that in some patients the activity of suma-triptan is too short.In conclusion, we found that 4% of patients con-suming sumatriptan used this drug daily or more than10 times per week. Overuse was associated with areported poor efficacy of sumatriptan and with malegender, but not with (rebound) headache after suma-triptan use. Drug consumption patterns of sumatrip-tan have to be evaluated in all patients, but in particularin patients who report low efficacy of sumatriptan.Acknowledgement The authors are very grateful for the coopera-tion of Dutch drug-dispensing general practitioners in collecting thedata for this study.References1. Plosker GL, McTavish D (1994) Sumatriptan: a reappraisal ofits pharmacology and therapeutic efficacy in the acute treat-ment of migraine and cluster headache. Drugs 47:622–6512. Ottervanger JP, Paalman HJA, Boxma GL, Stricker BHCh(1993) Transmural myocardial infarction with sumatriptan.Lancet 341:861–8623. Weidmann B, Jansen W, Bojko P, Hänseler Th, Hinzmann S,Tauchert M (1994) Sumatriptan-induzierter Myokardinfarkt.Intensivmedizin 31:3534. La Porta LD (1995) Recurrent depression after sumatriptanadministration for treatment of migraine. J Clin Psychopharma-col 15:81–825. Black P, Caldwell J (1994) Skin sensitivity to sumatriptan [let-ter]. NZ Med J 107:20–216. Brown EG, Endersby CA, Smith RN, Talbot JCC (1991) Thesafety and tolerability of sumatriptan: an overview. Eur Neurol31:339–3447. Osborne MJ, Austin RCT, Dawson KJ, Lance L (1994) Is therea problem with long term use of sumatriptan in acute migraine?BMJ 308:1138. Kaube H, May A, Diener HC, Pfaffenrath V (1994) Sumatrip-tan. BMJ 308:1573–15749. Pini LA, Trenti T (1994) Does chronic use of sumatriptaninduce dependence? Headache 34:60010. Gaist D, Sindrup S, Hallas J, Gram LF (1994) Misuse of suma-triptan. Lancet 344:109011. Ottervanger JP, Witsen van TB, Valkenburg HA, Stricker BHC(1993) Postmarketing study of cardiovascular adverse reactionsassociated with sumatriptan. BMJ 307:118512. Ottervanger JP, Valkenburg HA, Grobbee DE, Stricker BHCh(1994) Adverse reactions attributed to sumatriptan: a post-marketing study in general practice. Eur J Clin Pharm47:305–30913. Olesen J (1995) Analgesic headache. A common, treatable con-dition that deserves more attention. BMJ 310:479–48014. Dahlof C (1992) Headache recurrence after subcutaneous suma-triptan. Lancet 339:425–42615. Sucherowsky O (1993) Rebound headaches due to sumatrip-tan. Neurology 43 (Suppl 2) :A32616. Anonymous (1995) Sumatriptan: rebound headache andmigraine exacerbation. Can Adv Drug React Newslett 5:1355

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