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Pain Relief in Depressive Disorders

A Meta-Analysis of the Effects of Antidepressants

Gebhardt, Stefan MD; Heinzel-Gutenbrunner, Monika PhD; König, Udo MSc

Journal of Clinical Psychopharmacology: December 2016 - Volume 36 - Issue 6 - p 658–668
doi: 10.1097/JCP.0000000000000604
Original Contributions

Background Pain is a common symptom in patients with depressive disorders, which, if present, worsens the prognosis. However, there is little empirical knowledge of the therapeutic effects of antidepressants on painful physical symptoms of patients with depressive disorders. Furthermore, tricyclic/tetracyclic antidepressants (TCAs) have not yet been included in existing meta-analyses.

Methods A broad, systematic search of PubMed literature on antidepressant drug treatment of patients with depressive disorders with comorbid pain symptoms was carried out. A random-effects meta-analysis has been performed among 3 different groups of drugs for the 2 end points: pain and depression.

Results Fourteen placebo-controlled studies with selective serotonin-noradrenaline reuptake inhibitors (SSNRIs) could be included, with 3 of them also investigating selective serotonin reuptake inhibitors (SSRIs). Three further placebo-controlled SSRI studies were identified, but only 2 placebo-controlled TCA studies.

Both SSNRIs and SSRIs, but not TCAs, were significantly superior to placebo as regards their analgesic effects. However, all effects were small. For SSNRIs, there was a strong positive correlation between their effectiveness for pain relief and their positive effect on the mood of the patients.

Discussion The analgesic effects of SSNRIs and SSRIs in patients with primary depressive disorders can be interpreted as largely equivalent. Because of a lack of placebo-controlled TCA studies, the results for TCAs would be comparable only to those of SSRIs and SSNRIs, if non–placebo-controlled TCA studies were included. The positive correlation found indicates a close relationship of pain relief and antidepressant treatment effects. These results refer merely to patients with primary depressive disorders, not to patients with primary pain disorders. Further studies comparing the effects of different types of antidepressant drugs on pain in depressive patients are warranted.

From the Departments of *Psychiatry and Psychotherapy and †Child and Adolescent Psychiatry, Philipps-University of Marburg, Marburg, Germany.

Received December 29, 2015; accepted after revision September 7, 2016.

Reprints: Stefan Gebhardt, MD, Department of Psychiatry and Psychotherapy, University of Marburg, Rudolf-Bultmann-Str. 8, D-35039 Marburg, Germany (e-mail:

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