human psychopharmacology

Hum Psychopharmacol Clin Exp 2004; 19: S1–S2.

Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hup.617

EDITORIAL

Taking the pain out of depression: Dual action antidepressantsin the relief of pain in depression, fibromyalgia andother chronic pain syndromes

Much has been written about the relationship betweenpain and depression. Studies of patients with physicalillnesses, and especially those suffering pain, showconclusively that painful physical illnesses increasethe risk of depression. Conversely, we are unawareof any study of depressed patients that does not show,sometimes substantially, an increased rate of reportingof each and every pain symptom. Longitudinal studiesconfirm that the relationship is bi-directional—in thatpain increases the rate of depression, and depressionincreases the experience of pain. From the publichealth perspective also we should never lose sight ofthe fact that the powerful link between suicide anddepression is amplified by the presence of pain. Inthe introductory article of this supplement Jean-PierreLepine reviews the epidemiology of pain in depres-sion and explores the possible causal interrelation-ships between pain and depression.

The problem of pain syndromes remains just that, aproblem. Various medical specialties are associatedwith different pain syndromes—for example, dentaland oro-facial surgeons treat temporo-mandibulardisorder, cardiologists study atypical chest pain,gynaecologists see chronic pelvic pain and rheumatol-ogists are consulted for fibromyalgia. The boundariesbetween these painful conditions remain unclear, andall overlap with, but are not the same as, affective dis-orders such as depression (Wessely et al., 1999). Thisis not the place to enter into a debate on the nosologyof the pain syndrome. However, this supplementadopts the general position, to which we are increas-ingly drawn, that the neurobiological mechanisms anddifferences between pain and depression across all

these syndromes are more relevant than the differ-ences between the clinical conditions themselves,which may simply reflect artefacts of the various pro-fessional specializations.

The potential neurochemical bases of the functionand dysfunction of neural pathways and the interrela-tions of depression and pain at the neurochemicallevel are outlined by Stephen Stahl. The ascendingnoradrenergic and serotonergic pathways originatingfrom the locus coeruleus and raphe nuclei, respec-tively, control many of the psychological functionsthat are disturbed in depression. The descending path-ways from these same nuclei to the spinal cord areimplicated in the modulation of pain.

Animal models of chronic pain are particularlyuseful for understanding the role of the noradrenergicand serotonergic systems in pain and for indicatingcompounds that may be potentially active in themanagement of neuropathic pain. Daisuke Mochizukipresents a number of recent studies showing that speci-fic noradrenaline and serotonin reuptake inhibitor(SNRI) antidepressants such as milnacipran, venlafax-ine and duloxetine are particularly effective in control-ling chronic pain in a variety of different animalmodels.

The neurochemical rationale and the promisingresults from animal studies have led to an increasingexperimental clinical use of SNRIs in different clini-cal manifestations of neuropathic pain both associatedwith depression and independent of it. Mike Brileysummarizes the clinical trials, small studies and casereports that suggest the potential clinical usefulness ofmilnacipran, venlafaxine and duloxetine in the man-agement of pain.

Finally, Olivier Vitton describes a recentlycompleted placebo-controlled trial in fibromyalgiathat demonstrated a significant activity for the SNRI,milnacipran, resulting in a decrease of symptom

Copyright # 2004 John Wiley & Sons, Ltd. Received 30 June 2004

* Correspondence to: Dr S. Wessely, Academic Department ofPsychological Medicine, Institute of Psychiatry, King’s College,London, UK. E-mail: mike.briley@neurobiz.com

severity of at least 50% in 37% of patients (14% onplacebo).

While this volume might not be able to provide aparsimonious solution to removing the pain fromdepression, we hope it will help readers to increasetheir understanding of the neurophysiology and neu-rochemistry of the relationship between pain anddepression and also to provide some possible treat-ment regimens for use in the management of patientswith both pain and depression.

SIMON WESSELY1

AND IAN HINDMARCH2

1Academic Department of Psychological Medicine,Institute of Psychiatry, King’s College, London, UK2HPRU Medical Research Centre, University ofSurrey, Guildford, UK

REFERENCE

Wessely S, Nimnuan C, Sharpe M. 1999. Functional somatic syn-dromes: one or many? Lancet 354: 936–939.

S2 editorial

Copyright # 2004 John Wiley & Sons, Ltd. Hum Psychopharmacol Clin Exp 2004; 19: S1–S2.