ORIGINAL CONTRIBUTION Management of Chronic Tension-Type Headache With Tricyclic Antidepressant Medication, Stress Management Therapy, and Their Combination A Randomized Controlled Trial Kenneth A. Holroyd, PhD Context Chronic tension-type headaches are characterized by near-daily head- Francis J. O’Donnell, DO aches and often are difficult to manage in primary practice. Behavioral and pharma- Michael Stensland, MS cological therapies each appear modestly effective, but data are lacking on their sepa- rate and combined effects. Gay L. Lipchik, PhD Objective To evaluate the clinical efficacy of behavioral and pharmacological thera- Gary E. Cordingley, MD, PhD pies, singly and combined, for chronic tension-type headaches. Bruce W. Carlson, PhD Design and Setting Randomized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio. ENSION-TYPE HEADACHES OF- Participants Two hundred three adults (mean age, 37 years; 76% women) with ten occur every day or nearly diagnosis of chronic tension-type headaches (mean, 26 headache d/mo). every day in individuals who 1-3 Interventions Participants were randomly assigned to receive tricyclic antidepres- seek treatment, but head- sant (amitriptyline hydrochloride, up to 100 mg/d, or nortriptyline hydrochloride, up Taches must occur 15 or more days per to 75 mg/d) medication (n=53), placebo (n=48), stress management (eg, relaxation, month for at least 6 months to meet In- cognitive coping) therapy (3 sessions and 2 telephone contacts) plus placebo (n=49), ternational Headache Society diagnos- or stress management therapy plus antidepressant medication (n=53). tic criteria for chronic rather than epi- Main Outcome Measures Monthly headache index scores calculated as the mean 4 sodic tension-type headache. The 1-year of pain ratings (0-10 scale) recorded by participants in a daily diary 4 times per day; num- prevalence rate for chronic tension- ber of days per month with at least moderate pain (pain rating $5), analgesic medica- type headache in the general popula- tion use, and Headache Disability Inventory scores, compared by intervention group. tion is about 3% in women and 1.5% in Results Tricyclic antidepressant medication and stress management therapy each pro- 5,6 men, with just less than half of those duced larger reductions in headache activity, analgesic medication use, and headache- with chronic tension-type headache re- related disability than placebo, but antidepressant medication yielded more rapid im- porting headache-related impairment in provements in headache activity. Combined therapy was more likely to produce clinically work performance. Chronic tension- significant ($50%) reductions in headache index scores (64% of participants) than type headaches are a risk factor for the antidepressant medication (38% of participants; P=.006), stress management therapy overuse of analgesic medications and (35%; P=.003), or placebo (29%; P=.001). On other measures the combined therapy and its 2 component therapies produced similar outcomes. thus the development of analgesic abuse headaches.2,4,6,7 Continuous headaches Conclusions Our results indicate that antidepressant medication and stress man- and frequent comorbid psychiatric or an- agement therapy are each modestly effective in treating chronic tension-type head- algesic use problems often render aches. Combined therapy may improve outcome relative to monotherapy. chronic tension-type headaches diffi- JAMA. 2001;285:2208-2215 www.jama.com cult to manage in primary practice.1,2,8,9 Tricyclic antidepressants are the pri- However, recent trials have reported Author Affiliations: Department of Psychology (Drs Holroyd, Lipchik, and Carlson and Mr Stensland) and mary drug therapy for chronic tension- little (#30%) or no improvement in College of Osteopathic Medicine (Dr Cordingley), Ohio type headache, with amitriptyline hy- chronic tension-type headaches13-15 with University, Athens; and Headache Treatment and Re- 2,9-12 search (Drs Holroyd, O’Donnell, and Lipchik) and Or- drochloride the first-line treatment. amitriptyline. Additional information thoNeuro (Dr O’Donnell), Westerville, Ohio. Dr Lip- is therefore needed to confirm the ben- chik is now with St Vincent Health Center, Erie, Pa. efits of this widely used medication for Corresponding Author and Reprints: Kenneth A. Hol- See also Patient Page. royd, PhD, 225 Porter Hall, Athens, OH 45701 (e-mail: chronic tension-type headache. [email protected]). 2208 JAMA, May 2, 2001—Vol 285, No. 17 (Reprinted) ©2001 American Medical Association. All rights reserved. Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013 ANTIDEPRESSANTS AND STRESS MANAGEMENT FOR HEADACHE Behavioral therapies, primarily re- Figure 1. Participant Flow in the Study laxation, biofeedback, and cognitive be- havior (stress management) therapies 409 Patients Evaluated appear to be effective in managing ten- 16-24 sion-type headache. However, tri- 206 Excluded als of behavioral therapies also have methodological shortcomings: results 203 Randomized typically have not been reported spe- cifically for participants with chronic 53 Assigned to Receive 49 Assigned to Receive 53 Assigned to Receive 48 Assigned to Receive Antidepressant Stress Management Antidepressant Placebo tension-type headache and few trials Medication Therapy Plus Placebo Medication Plus Stress have included placebo controls.25 Ad- Management Therapy ditional information is thus needed to 5 Dropped Out 11 Dropped Out 8 Dropped Out 10 Dropped Out confirm the effectiveness of behav- 1 Adverse Effects 1 Adverse Effects 1 Adverse Effects 2 Poor Response ioral therapy for chronic tension-type 1 Lost to Follow-up 2 Lost to Follow-up 1 Lost to Follow-up 2 Adverse Effects 3 Other 3 Lack of Time 3 Lack of Time 1 Lost to Follow-up headache. The possibility that behav- 5 Other 3 Other 1 Lack of Time ioral therapy can enhance outcomes ob- 4 Other tained with antidepressant medica- 13,24 48 Evaluated at 1 mo 38 Evaluated at 1 mo 45 Evaluated at 1 mo 38 Evaluated at 1 mo tion (AM) also needs to be evaluated. After Treatment (Dose After Treatment (Dose After Treatment (Dose After Treatment (Dose This study was intended to evaluate Adjustment) Phase Adjustment) Phase Adjustment) Phase Adjustment) Phase the separate and combined effects of tri- 4 Dropped Out 4 Dropped Out 5 Dropped Out 12 Dropped Out cyclic antidepressant (amitriptyline and 1 Poor Response 1 Poor Response 1 Poor Response 8 Poor Response 1 Lost to Follow-up 1 Lost to Follow-up 4 Other 1 Adverse Effects nortriptyline hydrochloride) medica- 2 Other 2 Other 3 Lost to Follow-up tion (AM) and brief stress manage- ment therapy (SMT) for chronic ten- 44 Evaluated at 6 mo 34 Evaluated at 6 mo 40 Evaluated at 6 mo 26 Evaluated at 6 mo After Treatment (Dose After Treatment (Dose After Treatment (Dose After Treatment (Dose sion-type headache. Adjustment) Phase Adjustment) Phase Adjustment) Phase Adjustment) Phase METHODS procedures approved by the Ohio Uni- sequent 6-month evaluation phase, clinic Participants versity Human Subjects Committee. visits were scheduled 1, 3, and 6 months Participants were recruited from pri- following completion of the treatment mary practice referrals and by local ad- Study Design and Treatments (dose adjustment) phase. The 1- and vertisements at 2 outpatient sites. In- After completing the baseline assess- 6-month evaluations included review of clusion criteria were age between 18 ment that included 1 month of head- 1 month of daily headache and medica- and 65 years and receipt of an Interna- ache and medication diary recordings, tion diaries, neurological evaluation, and tional Headache Society diagnosis of participants were randomly assigned in psychosocial testing. The 3-month chronic tension-type headache4 at 2 blocks of 4 participants to 4 treatments evaluation included only medication separate evaluations. Exclusion crite- (FIGURE 1): AM, placebo, SMT plus pla- checks and brief evaluation. ria were: International Headache Soci- cebo, and SMT plus AM. The AM and Tricyclic Antidepressant Medica- ety diagnosis of analgesic-abuse head- placebo therapies were administered in tion and Placebo. In this double-blind aches4; current use of AM or other a standard double-blind fashion. Treat- protocol, we attempted to maximize the prophylactic medication for head- ment conditions were blinded only for efficacy and tolerability of AM by using ache, or regular ($15 d/mo) use of anx- the medication component and not for a low starting dose and recommended iolytic medication; current psycho- the administration of SMT. This trial was target doses for the treatment of chronic therapy; current or planned pregnancy conducted between August 1995 and tension-type headache,11,26-29 by treat- or breastfeeding; medical contraindi- January 1998. ing participants who were unable to tol- cation to amitriptyline; migraine head- Each treatment protocol required 3 erate amitriptyline with nortriptyline and ache more than 1 day a month; pain dis- clinic visits and 2 telephone contacts by use of an adherence intervention de- order (eg, arthritis) other than headache during the 2-month treatment (dose ad- signed to increase AM adherence.30 as primary pain problem; psychiatric justment) phase, during which SMT was Treatment was initiated with 1 lead-in (eg, suicide risk) or medical disorder administered and the medication dose capsule of medication to be taken at bed- requiring immediate treatment; and fail- was adjusted. Clinic visits were sched- time (12.5