Rheumatology Advance Access published online on November 5, 2008
Rheumatology, doi:10.1093/rheumatology/ken419
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Comment on: Is there any evidence to support the use of anti-depressants in painful rheumatological conditions? Systematic review of pharmacological and clinical studies & Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy
1Department of Physiology and Pharmacology, 2Department of Pharmacy, Universidade Federal do Ceara, Fortaleza and 3Department of Biophysiology and Pharmacology, Faculdade de Medicina de Juazeiro do Norte, Juazeiro do Norte, Brazil
Correspondence to:
F. H. C. Felix, Department of Biophysiology and Pharmacology, Faculdade de Medicina de Juazeiro do Norte, Av. Leão Sampaio Km 3 S/N Juazeiro do Norte CE 63040000, Brazil. E-mail: heldercfelix{at}gmail.com
SIR, The reviews of Perrot et al. [1] and Nishishinya et al. [2] brought new information about the usefulness of anti-depressants in rheumatic conditions, especially fibromyalgia syndrome (FMS). Many publications have recently emphasized the well-known association between old and newer anti-depressants and chronic pain relief [3–5]. For a long time, debate has existed upon how anti-depressants alleviate symptoms in chronic pain patients. Are they truly analgesic, or is their effect on higher cognitive pain-associative phenomena? Data from clinical and basic research have corroborated the first option: drugs that inhibit reuptake of catecholamines (noradrenaline and serotonin, sometimes dopamine) may have indeed an analgesic effect [5–8]. While the Perrot et al. and Nishishinya et al. data seem discordant, one must take care in drawing any analysis. Recently, the issues of long-term efficacy and tolerability have surfaced as critical when judging anti-depressant effectiveness as a whole and as analgesic drugs [9, 10]. Although previous data supported the indication of tricyclic anti-depressants (TCAs) as front-line pharmacological treatment for FMS, there was little information about the duration of its effect and tolerability issues seemed to be a major drawback [1, 5]. The review of Nishishinya, coupled with the recent clinical results of newer anti-depressants in FMS and neuropathic pain [4, 6], indicates that it is time to change the primary pharmacological indication for anti-depressants as analgesics from TCA to the serotonin and norepinephrine reuptake inhibitor (SNRI) class. This opinion is also supported by the Perrot review. This field is growing rapidly, and newer drugs are being developed that show better analgesic effect, exploring the same mechanism of anti-depressants: catecholamine reuptake inhibition. Particularly, it has been recently demonstrated that a triple reuptake inhibition mechanism may lead to more potent analgesic effect [11]. What may we conclude from this?
- Anti-depressants are good analgesics in selected chronic pain disorders. Their analgesic effect is not associated with their anti-depressant effect, but depends also on their catecholamine reuptake inhibition properties.
- There were recently reported caveats of tolerability and long-term efficacy for anti-depressants in general, and in their use for relief of chronic pain. Therefore, one must carefully design and analyse clinical trials of chronic pain drugs for inclusion of these as primary or secondary end-points.
- The recommended front-line anti-depressants for FMS treatment must be SNRI in the place of TCA. The use of the latter may even be discouraged in the face of its lack of long-term efficacy and excess of adverse events.
- As a pharmacological group, anti-depressants are frequently used as treatment for chronic pain in various diseases, although there is little evidence for many of these uses. It would probably be better to develop newer drugs that have the mechanism of action of the anti-depressants in nociception but lack any effect in mood (and, therefore, have less side-effects).
Disclosure statement: The authors have declared no conflicts of interest.
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[Abstract/Free Full Text] - Nishishinya B, Urrútia G, Walitt B, et al. Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy. Rheumatology (2008) Advance Access published August 12, 2008, doi: 10.1093/rheumatology/ken317.
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[Abstract/Free Full Text]
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  S. Perrot, R.-M. Javier, M. Marty, C. Le Jeunne, F. Laroche, and the Cercle d'Etude de la Douleur en Rhumatologie ( Comment on: Is there any evidence to support the use of anti-depressants in painful rheumatological conditions? Systematic review of pharmacological and clinical studies: reply Rheumatology, March 1, 2009; 48(3): 323 - 323. [Full Text] [PDF]
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G. Urrutia, B. Walitt, B. Nishishinya, A. Rodriguez, X. Bonfill, G. Darko, and C. Alegre Comment on: Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy: reply Rheumatology, March 1, 2009; 48(3): 323 - 324. [Full Text] [PDF]
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