[Chronic pain treatment with antidepressants--metaanalysis]

Both preclinical and clinical evidence support the usefulness of antidepressants in chronic pain treatment. Monoamine uptake inhibitors influence the neurotransmissions of noradrenaline (NA) and/or serotonin (5-HT); their effect on nociception is thought to take place predominantly within the spinal cord. Antidepressant drugs seem to differ in their properties as analgesics and as thymoleptics. The present work is aimed at correlating the special mechanism of action of antidepressants in diminishing nocicepetion with the pharmacological profile of these drugs in clinical pain treatment. From a preclinical, experimental point of view, it can be expected, that mixed type uptake blockers should be superior to selective NA or 5-HT uptake inhibitors. The analgesic profile of antidepressants was established by a metaanalysis of clinical trials on the effect of these drugs, given alone or in combination with other analgetics, in chronic pain syndromes. 57 Clinical trials were separated into 5 groups according to their scientific quality: [1] placebo-controlled double-blind studies with high power; [2] placebo-controlled double-blind studies with low power; [3-4] open controlled studies or studies with historical controls; [5] case reports. A study was positive if the tested antidepressant was more effective than placebo or the compared drug or seemed beneficial with respect to the interval of its previous absence. The most effective antidepressants in chronic pain treatment only included unselective monoamine reuptake inhibitors in the following rank order: amitriptyline > clomipramine > or = desipramine > or = imipramine > or = doxepin. A statement about the appropriate dosage of these drugs in chronic pain treatment, however, must wait for properly conducted dose finding studies which include the measurement of plasma concentrations.