Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1996 Sep;61(3):285–290. doi: 10.1136/jnnp.61.3.285

A non-selective (amitriptyline), but not a selective (citalopram), serotonin reuptake inhibitor is effective in the prophylactic treatment of chronic tension-type headache.

L Bendtsen 1, R Jensen 1, J Olesen 1
PMCID: PMC486552  PMID: 8795600

Abstract

OBJECTIVES: Although the tricyclic antidepressant amitriptyline is extensively used in the prophylactic treatment of chronic tension-type headache, only few studies have investigated the efficacy of this treatment and the results are contradictory. In addition, the new selective serotonin reuptake inhibiting antidepressants, which are widely used in depression and of potential value in pain management, have never been investigated in a placebo controlled study of tension-type headache. The aim was to evaluate the efficacy of amitriptyline and of the selective serotonin reuptake inhibitor citalopram in chronic tension-type headache. METHODS: Forty non-depressed patients with chronic tension type headache were included in a 32 week, double blind, placebo controlled, three-way crossover study. RESULTS: Thirty four patients completed the trial. Amitriptyline reduced area under the headache curve by 30% compared with placebo (P = 0.002), whereas citalopram had no significant effect (P = 0.68). Explanatory analyses showed that amitriptyline significantly reduced the duration of headache (P = 0.01), headache frequency (P = 0.01), and intake of analgesics (P = 0.02) but not headache intensity (P = 0.12). CONCLUSION: Although amitriptyline did not eliminate the headache, it provided a clinically important reduction of headache in the majority of otherwise treatment resistant patients. The differential effect of amitriptyline and citalopram indicates that mechanisms other than inhibition of serotonin reuptake are involved in the analgesic effect of the tricyclic antidepressants. Amitriptyline, but not citalopram, is valuable in the prophylactic treatment of chronic tension type headache.

Full text

PDF
285

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ardid D., Marty H., Fialip J., Privat A. M., Eschalier A., Lavarenne J. Comparative effects of different uptake inhibitor antidepressants in two pain tests in mice. Fundam Clin Pharmacol. 1992;6(2):75–82. doi: 10.1111/j.1472-8206.1992.tb00097.x. [DOI] [PubMed] [Google Scholar]
  2. Bech P., Cialdella P. Citalopram in depression--meta-analysis of intended and unintended effects. Int Clin Psychopharmacol. 1992 Jun;6 (Suppl 5):45–54. doi: 10.1097/00004850-199206005-00005. [DOI] [PubMed] [Google Scholar]
  3. Botney M., Fields H. L. Amitriptyline potentiates morphine analgesia by a direct action on the central nervous system. Ann Neurol. 1983 Feb;13(2):160–164. doi: 10.1002/ana.410130209. [DOI] [PubMed] [Google Scholar]
  4. Egbunike I. G., Chaffee B. J. Antidepressants in the management of chronic pain syndromes. Pharmacotherapy. 1990;10(4):262–270. [PubMed] [Google Scholar]
  5. Glaum S. R., Proudfit H. K., Anderson E. G. Reversal of the antinociceptive effects of intrathecally administered serotonin in the rat by a selective 5-HT3 receptor antagonist. Neurosci Lett. 1988 Dec 19;95(1-3):313–317. doi: 10.1016/0304-3940(88)90677-5. [DOI] [PubMed] [Google Scholar]
  6. Göbel H., Hamouz V., Hansen C., Heininger K., Hirsch S., Lindner V., Heuss D., Soyka D. Chronic tension-type headache: amitriptyline reduces clinical headache-duration and experimental pain sensitivity but does not alter pericranial muscle activity readings. Pain. 1994 Nov;59(2):241–249. doi: 10.1016/0304-3959(94)90077-9. [DOI] [PubMed] [Google Scholar]
  7. HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23:56–62. doi: 10.1136/jnnp.23.1.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hyttel J. Citalopram--pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity. Prog Neuropsychopharmacol Biol Psychiatry. 1982;6(3):277–295. doi: 10.1016/s0278-5846(82)80179-6. [DOI] [PubMed] [Google Scholar]
  9. Hyttel J. Neurochemical characterization of a new potent and selective serotonin uptake inhibitor: Lu 10-171. Psychopharmacology (Berl) 1977 Mar 16;51(3):225–233. doi: 10.1007/BF00431629. [DOI] [PubMed] [Google Scholar]
  10. Johansson F., von Knorring L. A double-blind controlled study of seratonin uptake inhibitor (Zimelidine) versus placebo in chronic pain patients. Pain. 1979 Aug;7(1):69–78. doi: 10.1016/0304-3959(79)90108-8. [DOI] [PubMed] [Google Scholar]
  11. Kunkel R. S. Fibrotic syndromes with chronic use of methysergide. Headache. 1971 Apr;11(1):1–5. doi: 10.1111/j.1526-4610.1971.hed1101001.x. [DOI] [PubMed] [Google Scholar]
  12. LANCE J. W., CURRAN D. A. TREATMENT OF CHRONIC TENSION HEADACHE. Lancet. 1964 Jun 6;1(7345):1236–1239. doi: 10.1016/s0140-6736(64)91866-5. [DOI] [PubMed] [Google Scholar]
  13. Magni G. The use of antidepressants in the treatment of chronic pain. A review of the current evidence. Drugs. 1991 Nov;42(5):730–748. doi: 10.2165/00003495-199142050-00002. [DOI] [PubMed] [Google Scholar]
  14. Matthews J. N., Altman D. G., Campbell M. J., Royston P. Analysis of serial measurements in medical research. BMJ. 1990 Jan 27;300(6719):230–235. doi: 10.1136/bmj.300.6719.230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Max M. B., Lynch S. A., Muir J., Shoaf S. E., Smoller B., Dubner R. Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. N Engl J Med. 1992 May 7;326(19):1250–1256. doi: 10.1056/NEJM199205073261904. [DOI] [PubMed] [Google Scholar]
  16. Nørregaard J., Volkmann H., Danneskiold-Samsøe B. A randomized controlled trial of citalopram in the treatment of fibromyalgia. Pain. 1995 Jun;61(3):445–449. doi: 10.1016/0304-3959(94)00218-4. [DOI] [PubMed] [Google Scholar]
  17. Onghena P., Van Houdenhove B. Antidepressant-induced analgesia in chronic non-malignant pain: a meta-analysis of 39 placebo-controlled studies. Pain. 1992 May;49(2):205–219. doi: 10.1016/0304-3959(92)90144-Z. [DOI] [PubMed] [Google Scholar]
  18. Panerai A. E., Monza G., Movilia P., Bianchi M., Francucci B. M., Tiengo M. A randomized, within-patient, cross-over, placebo-controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain. Acta Neurol Scand. 1990 Jul;82(1):34–38. doi: 10.1111/j.1600-0404.1990.tb01584.x. [DOI] [PubMed] [Google Scholar]
  19. Pfaffenrath V., Diener H. C., Isler H., Meyer C., Scholz E., Taneri Z., Wessely P., Zaiser-Kaschel H., Haase W., Fischer W. Efficacy and tolerability of amitriptylinoxide in the treatment of chronic tension-type headache: a multi-centre controlled study. Cephalalgia. 1994 Apr;14(2):149–155. doi: 10.1046/j.1468-2982.1994.1402149.x. [DOI] [PubMed] [Google Scholar]
  20. Rasmussen B. K., Jensen R., Olesen J. Impact of headache on sickness absence and utilisation of medical services: a Danish population study. J Epidemiol Community Health. 1992 Aug;46(4):443–446. doi: 10.1136/jech.46.4.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Russell M. B., Rasmussen B. K., Brennum J., Iversen H. K., Jensen R. A., Olesen J. Presentation of a new instrument: the diagnostic headache diary. Cephalalgia. 1992 Dec;12(6):369–374. doi: 10.1111/j.1468-2982.1992.00369.x. [DOI] [PubMed] [Google Scholar]
  22. Sacerdote P., Brini A., Mantegazza P., Panerai A. E. A role for serotonin and beta-endorphin in the analgesia induced by some tricyclic antidepressant drugs. Pharmacol Biochem Behav. 1987 Jan;26(1):153–158. doi: 10.1016/0091-3057(87)90548-x. [DOI] [PubMed] [Google Scholar]
  23. Saper J. R., Silberstein S. D., Lake A. E., 3rd, Winters M. E. Double-blind trial of fluoxetine: chronic daily headache and migraine. Headache. 1994 Oct;34(9):497–502. doi: 10.1111/j.1526-4610.1994.hed3409497.x. [DOI] [PubMed] [Google Scholar]
  24. Sharav Y., Singer E., Schmidt E., Dionne R. A., Dubner R. The analgesic effect of amitriptyline on chronic facial pain. Pain. 1987 Nov;31(2):199–209. doi: 10.1016/0304-3959(87)90036-4. [DOI] [PubMed] [Google Scholar]
  25. Sindrup S. H., Bjerre U., Dejgaard A., Brøsen K., Aaes-Jørgensen T., Gram L. F. The selective serotonin reuptake inhibitor citalopram relieves the symptoms of diabetic neuropathy. Clin Pharmacol Ther. 1992 Nov;52(5):547–552. doi: 10.1038/clpt.1992.183. [DOI] [PubMed] [Google Scholar]
  26. Sindrup S. H., Gram L. F., Brøsen K., Eshøj O., Mogensen E. F. The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms. Pain. 1990 Aug;42(2):135–144. doi: 10.1016/0304-3959(90)91157-E. [DOI] [PubMed] [Google Scholar]
  27. Sindrup S. H., Gram L. F., Skjold T., Grodum E., Brøsen K., Beck-Nielsen H. Clomipramine vs desipramine vs placebo in the treatment of diabetic neuropathy symptoms. A double-blind cross-over study. Br J Clin Pharmacol. 1990 Nov;30(5):683–691. doi: 10.1111/j.1365-2125.1990.tb03836.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Taiwo Y. O., Fabian A., Pazoles C. J., Fields H. L. Potentiation of morphine antinociception by monoamine reuptake inhibitors in the rat spinal cord. Pain. 1985 Apr;21(4):329–337. doi: 10.1016/0304-3959(85)90162-9. [DOI] [PubMed] [Google Scholar]
  29. Tfelt-Hansen P., Olesen J. Methodological aspects of drug trials in migraine. Neuroepidemiology. 1985;4(4):204–226. doi: 10.1159/000110232. [DOI] [PubMed] [Google Scholar]
  30. Tollison C. D., Kriegel M. L. Selected tricyclic antidepressants in the management of chronic benign pain. South Med J. 1988 May;81(5):562–564. doi: 10.1097/00007611-198805000-00004. [DOI] [PubMed] [Google Scholar]
  31. Tura B., Tura S. M. The analgesic effect of tricyclic antidepressants. Brain Res. 1990 Jun 4;518(1-2):19–22. doi: 10.1016/0006-8993(90)90948-b. [DOI] [PubMed] [Google Scholar]
  32. U'Prichard D. C., Greenberg D. A., Sheehan P. P., Snyder S. H. Tricyclic antidepressants: therapeutic properties and affinity for alpha-noradrenergic receptor binding sites in the brain. Science. 1978 Jan 13;199(4325):197–198. doi: 10.1126/science.202024. [DOI] [PubMed] [Google Scholar]
  33. Watson C. P., Evans R. J. A comparative trial of amitriptyline and zimelidine in post-herpetic neuralgia. Pain. 1985 Dec;23(4):387–394. doi: 10.1016/0304-3959(85)90009-0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES