Venlafaxine in the Treatment of Atypical Facial Pain: A Randomized Controlled Trial

Aims: To study in a randomized placebo-controlled design the effi-cacy of the antidepressant venlafaxine, a serotonin and a weak noradrenaline reuptake inhibitor, in the treatment of atypical facial pain (AFP). Methods: The study was a randomized, double-blind, crossover comparison of venlafaxine and a placebo. It con-sisted of 2 treatment periods, each of 4 weeks’ duration, separated by a 2-week washout period. Thirty patients suffering from chronic pain who had been diagnosed with AFP after a thorough clinical examination were recruited. Pain intensity and pain relief were registered at 6 visits. Anxiety, depression, and adverse effects were recorded. Venous blood samples were collected at the end of each treatment period for the determination of serum levels of venlafaxine and its metabolites. Results: Twenty patients com-pleted the trial. Eight patients discontinued because of adverse effects and 2 patients were excluded because of noncompliance. Two patients completed the trial but were excluded from the anal-ysis because they experienced no pain at the baseline visit. There was no significant difference in pain intensity reduction between the maximum tolerated dose of venlafaxine (75 mg in most cases) and the placebo. Pain relief was significantly greater with ven-lafaxine than with the placebo treatment. Significantly more escape medication was consumed during the placebo period com-pared with the venlafaxine period. No significant correlation was found between the serum concentration of the drug and the response to treatment. Anxiety and depression scores did not dif-fer between venlafaxine and placebo treatment. Adverse effects were equally common during both treatments. Conclusion: Venlafaxine was only modestly effective in the treatment of AFP.

antidepressants; atypical facial pain; chronic pain; neuropathic pain; venlafaxine

1. Pfaffenrath V, Rath M, Pöllmann W, Keeser W. Atypical facial pain—application of the IHS criteria in a clinical sample. Cephalalgia 1993;13:84–88.

2. Woda A, Pionchon P. A unified concept of idiopathic orofacial pain: Clinical features. J Orofacial Pain 1999;13: 172–184.

3. Tenenbaum HC, Mock D, Gordon AS, et al. Sensory and affective components of orofacial pain: Is it all in your brain? Crit Rev Oral Biol Med 2001;12:455–468.

4. Sharav Y. Orofacial pain. In: Wall PD, Melzack R (eds). Textbook of Pain (ed 4). London: Churchill Livingstone, 1999: 711–737.

5. Zakrzewska JM, Hamlyn PJ. Facial pain. In: Crombie IK (ed). Epidemiology of Pain. Seattle: IASP Press, 1999: 171–202.

6. Sessle BJ. The neurobiology of facial and dental pain: Present knowledge, future directions. J Dent Res 1987;66: 926–981.

7. Jääskeläinen SK, Forssell H, Tenovuo O. Electrophysio-logical testing of the trigeminofacial system: Aid in the diagnosis of atypical facial pain. Pain 1999;80:191–200.

8. Feinmann C, Harris M, Cawley R. Psychogenic facial pain: Presentation and treatment. Brit Med J 1984; 288:436–438.

9. Remick RA, Blasberg B. Psychiatric aspects of atypical facial pain. J Can Dent Assoc 1985;12:913–916.

10. Lascelles RG. Atypical face pain and depression. Br J Psychiatry 1966;112:651–659.

11. McQuay HJ, Tramer M, Nye BA, Carroll D, Wiffen PJ, Moore RA. A systematic review of antidepressants in neuropathic pain. Pain 1996;68:217–227.

12. Sindrup SH, Jensen TS. Efficacy of pharmacological treatments of neuropathic pain: An update and effect related to mechanism of drug action. Pain 1999;83:389–400.

13. Onghena P, Van Houdenhove B. Antidepressant–induced analgesia in chronic non–malignant pain: A meta-analysis of 39 placebo-controlled studies. Pain 1992;49:205–219.

14. Holliday SM, Benfield P. Venlafaxine. A review of its pharmacology and therapeutic potential in depression. Drugs 1995;49:280–294.

15. Ansari A. The efficacy of newer antidepressants in the treatment of chronic pain: A review of current literature. Harvard Rev Psychiatry 2000;7:257–277.

16. Mattia C, Paoletti F, Coluzzi F, Boanelli A. New antide-pressants in the treatment of neuropathic pain. A review. Minerva Anestesiol 2002;68:105–114.

17. Tasmuth T, Härtel B, Kalso E. Venlafaxine in neuropathic pain following treatment of breast cancer. Eur J Pain 2002;6:17–24.

18. Sindrup SH, Bach FW, Madsen C, Gram LF, Jensen TS. Venlafaxine versus imipramine in painful polyneuropathy. A randomized, controlled trial. Neurology 2003;60: 1284–1289.

19. Spielberger CD. The measurement of state and trait anxiety; conceptual and methodological issues. In: Levi L (ed). Emotions: Their Parameters and Measurement. New York: Raven, 1975:713–725.

20. Steer RA, Beck AT. Beck Depression Inventory (BDI). In: Sederer LI, Dickey B (eds). Outcomes Assessment in Clinical Practice. Baltimore: Williams & Wilkins, 1996: 100–103.

21. Reis M, Lundmark J, Bjork H, Bengtsson F. Therapeutic drug monitoring of racemic venlafaxine and its main metabolites in an everyday clinical setting. Ther Drug Monit 2002;24:545–553.

22. Littman GS, Walker BR, Scheider BE. Reassessment of verbal and visual analog ratings in analgesic studies. Clin Pharmacol Ther 1985;38:16–23.

23. Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94:149–158.

24. Smith D, Dempster C, Glanville J, Freemantle N, Anderson I. Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: A meta-analysis. Br J Psychiatry 2002; 180:396–404.

25. Richelson E. The pharmacology of antidepressants at the synapse: Focus on newer compounds. J Clin Psychiatry 1994;55:34–39.

26. Kalso E. Better standardisation will improve the quality of analgesic studies. Acta Anaesthesiol Scand 1996;40: 399–407.