Antidepressants and pain

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Tricyclic antidepressants, together with anticonvulsants, are considered to be first-line drugs for the treatment of neuropathic pain. Antidepressants are analgesic in patients with chronic pain and no concomitant depression, indicating that the analgesic and antidepressant effects occur independently. The analgesia induced by these drugs seems to be centrally mediated but consistent evidence also indicates a peripheral site of action. Several pharmacological mechanisms account for their antinociceptive effect but the inhibition of monoamine transporters (and, consequently, the facilitation of descending inhibition pain systems) is implicated on the basis of mechanistic and knockout-mouse studies. However, pain is a common symptom of depression, and depression is frequent in chronic pain patients, supporting the hypothesis that pain and depression share some common biochemical mechanisms. We suggest that antidepressants have a genuine analgesic effect and that research into their mechanisms of action will help to facilitate the development of new drugs.

Section snippets

Why use an antidepressant to relieve pain?*

‘Why do I have to take an antidepressant to relieve pain if I am not depressed?’ This question could be asked of a physician by a patient suffering from pain when prescribed an antidepressant as an analgesic. This is a reasonable question from the patient's perspective, and the physician should answer that the antidepressant is prescribed for its analgesic action rather than its antidepressant action. The patient's next questions might be: ‘are antidepressants pain killers?’ and ‘how is that

Tricyclic antidepressants versus selective amine-reuptake inhibitors and new dual antidepressants

Just as there is virtually an agreement that neuropathic pain is most responsive to the analgesic action of antidepressants [10], a consensus also exists that the well-known tricyclic antidepressants have the greatest analgesic efficacy 8, 9 (Table 1). Among these, particular mention should go to amitriptyline, the gold standard of analgesic antidepressants. This does not mean that other tricyclic antidepressants are less effective but that most available clinical evidence has been obtained for

Mechanism of the analgesic action of antidepressants

Most information regarding the mechanism of the analgesic action of antidepressants has been obtained in animals (rats and mice). It should be noted that the results of research into the antinociceptive action of antidepressants using acute pain tests in which different noxious stimuli (thermal, chemical, mechanical or electric) are applied cannot be extrapolated to human clinical pain [16]. In fact, antidepressants are never used to treat acute pain in humans, except for experimental research.

Impact of antidepressants on pain as a physical symptom of depression

Pain and depression are often linked, and several studies have indicated that pain and depression share common neurochemical mechanisms 26, 27. Clinical depression is common in patients with persistent chronic pain: 30–54% [28]. Conversely, pain is among the most common physical symptoms in patients with depression, and a common complaint reported to specialists [29]. Relapses into a depressive state are more common in such patients and make total symptom remission difficult, closing a vicious

Concluding remarks and future perspectives

Antidepressants have become, in their own right, common drugs for the treatment of chronic, mainly neuropathic, pain, even though their efficacy is limited. Research in this field has evolved substantially in recent years but there are still many issues to be elucidated in both preclinical and clinical research. From a clinical viewpoint, consistent criteria are required for selection of the type of antidepressant to be used, in addition to the dosage, depending on symptoms, pain type and

Acknowledgements

This study was supported by Fondo de Investigación Sanitaria (PI031430), Ministère Français de l'Enseignement Supérieur et de la Recherche, INSERM and Institut Paul Hamel.

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