Sir: One would naturally question the suggestion that an analgesic, e.g., acetaminophen or an opiate, that reduces pain severity in a patient with chronic pain, and thereby reduces the patient's dysphoria, would be implied to have an antidepressant property. It is in this context that the article by Leo and Barkin was written.1
To summarize, Leo and Barkin advise readers that studies assessing the efficacy of duloxetine among patients with major depressive disorder who are simultaneously somatically preoccupied does not necessarily imply an analgesic role of duloxetine. Use of a standard pain assessment instrument, such as the visual analog scale (VAS),2 in somatizing depressed patients is misleading. The VAS, a single-dimension pain-rating measure, is influenced by the vicissitudes of the rater's affect, prevailing mood, cognitions, and expectations. Each of these can be altered by the presence of a major depressive disorder, thereby leading to a magnification of pain severity ratings. Reduction in VAS scores is likely to be an artifact of the improvements in mood observed when depressed patients are given duloxetine. Thus, as depression is alleviated, so too is there a reduction in the amplification of somatic symptoms. Other studies have corroborated that the degree of physical symptom improvement among depressed patients is correlated with overall reduction of depression severity.3,4
Obviously, researchers at Eli Lilly are in agreement. To establish an analgesic effect of duloxetine in patients with diabetic neuropathy, they made certain to remove the potential confounds of comorbid depression. It is only when such confounds are controlled in experimental paradigms that one can begin to suggest that an agent like duloxetine exerts an analgesic effect. The suggestion that analgesic effects result from the effects of duloxetine on norepinephrine and serotonin neurotransmission is an interesting model but has, as yet, to be clarified. It may have been useful to study depressed and nondepressed patients with diabetic neuropathy. In this way, it might have been possible to demonstrate differences in the reductions in pain severity ratings between the 2 groups. Perhaps greater analgesia would be attained in those with depression as compared with those who are not depressed.
There is a continuum of depressive symptoms present among patients with chronic pain. Some patients have few depressive symptoms, while others may manifest the full gamut of symptoms to fulfill diagnostic criteria for a major depressive disorder or variant, e.g., dysthymic disorder. Use of duloxetine among chronic pain patients with comorbid depression would be a welcomed addition to the current armamentarium of antidepressants available for use among such patients. It would be an added benefit if duloxetine could be demonstrated to have an analgesic effect in selected pain disorders.
Preliminary animal studies,5 as well as a recent examination of pain-mitigating effects among patients with diabetic neuropathy6 (published after the submission of the 2003 Leo and Barkin article), suggest that duloxetine may have a role in pain management. However, many antidepressants and anticonvulsants have likewise demonstrated efficacy in neuropathy. Future research would be helpful in clarifying those patient subpopulations for whom duloxetine would be the preferred agent among the alternatives currently available. It may be possible to demonstrate the role of duloxetine in patients who have neuropathic pain with certain characteristics, e.g., dysesthetic or burning features, or certain neurovegetative symptoms of depression.
Footnotes
Dr. Leo reports no financial affiliation or other relationship relevant to the subject matter of this letter.
References
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- Goldstein DJ, Lu Y, and Iyengar S. et al. Duloxetine in the treatment of the pain associated with diabetic neuropathy. Presented at the 156th annual meeting of the American Psychiatric Association. 17–22May2003 San Francisco, Calif. [Google Scholar]