Major research findings

Duloxetine inhibits both serotonin and norepinephrine reuptake and is marketed as a treatment for both the core emotional symptoms and painful physical complaints that often accompany depression. 2 Some studies have found that duloxetine is efficacious in treating painful symptoms associated with depression but these findings have been inconsistent. 2 Several narrative review articles have reached positive conclusions about the efficacy of duloxetine as an analgesic in depression but there has been no quantitative systematic review regarding the impact of duloxetine on pain among this population. 2 A meta-analysis of data pertaining to duloxetine's purported analgesic effects on depressed patients was thus undertaken. 2

Duloxetine is a dual inhibitor of norepinephrine (NE) and serotonin (5-HT) uptake. 1 Initial trials conducted in depressed patients using regimens of 20 mg/day or less did not convincingly demonstrate its efficacy as an antidepressant. 1 The aim of this study was to assess the effects of duloxetine on the 5-HT and NE reuptake processes in healthy human volunteers. 1 Twenty-seven healthy young males without a history of psychiatric disorder were randomly assigned to four groups, each group receiving one of the following daily drug regimens: placebo, clomipramine (a potent 5-HT/NE reuptake blocker) 100 mg/day, duloxetine 20 mg/day, or duloxetine 60 mg/day. 1 In order to assess the NE reuptake process, the pressor response to intravenous tyramine (4 and 6 mg) was measured. 1 Determination of the whole blood 5-HT content was used to evaluate the 5-HT reuptake blockade. 1 These measurements were performed at baseline and repeated after 7 and 14 days of drug intake. 1 Both duloxetine, at doses of 20 to 60 mg/day, and clomipramine significantly interfered with the 5-HT reuptake process, as demonstrated by marked decreases in blood 5-HT concentrations. 1 However, the same doses of duloxetine, unlike clomipramine, failed to impede the usual increase in blood pressure that follows a tyramine intravenous infusion, indicating that clomipramine but not duloxetine blocked NE reuptake. 1 At doses tested in a population of healthy volunteers, duloxetine acted as a selective 5-HT reuptake inhibitor, having no clear effect on the NE reuptake process. 1 Nevertheless, given that the highest dose of duloxetine increased supine systolic blood pressure, it is possible that it represents the threshold regimen for NE reuptake inhibition. 1

To compare the effects of starting doses of duloxetine taken with or without food on tolerability and efficacy in patients with major depressive disorder (MDD). 3

Benefits and Risks

Benefit Summary

Duloxetine inhibits both serotonin and norepinephrine reuptake and is marketed as a treatment for both the core emotional symptoms and painful physical complaints that often accompany depression. 2

Risk Summary

Initial trials conducted in depressed patients using regimens of 20 mg/day or less did not convincingly demonstrate its efficacy as an antidepressant. 1 Given that the highest dose of duloxetine increased supine systolic blood pressure, it is possible that it represents the threshold regimen for NE reuptake inhibition. 1

Comparison of Studies

Commonalities of Studies

All three studies investigated the effects of duloxetine and assessed if it could be used as a serotonin and norepinephrine reuptake inhibitor. 2 1 3

Differences in Studies

These studies differed in study design, study population, and measured outcomes. 2 1 3 The meta-analysis was aimed at duloxetine's analgesic effects on depressed patients. 2 The study was conducted to assess the effects of duloxetine on the 5-HT and NE reuptake processes in healthy human volunteers. 1 The third study compared the effects of starting doses of duloxetine taken with or without food on tolerability and efficacy in patients with major depressive disorder (MDD). 3

Consistency and Inconsistency of Results

Duloxetine may be effective in treating pain in depressed patients, but these findings have been inconsistent. 2 Initial trials conducted in depressed patients using regimens of 20 mg/day or less did not convincingly demonstrate its efficacy as an antidepressant. 1

Real-life Application Notes

Duloxetine may be effective in treating pain in depressed patients, but these findings have been inconsistent. 2

Limitations of Current Research

These studies differed in study design, study population, and measured outcomes. 2 1 3

Future Research Directions

Further research is needed regarding duloxetine's analgesic effects on depressed patients. 2 Initial trials conducted in depressed patients using regimens of 20 mg/day or less did not convincingly demonstrate its efficacy as an antidepressant. 1

Conclusion

These studies suggest that duloxetine may be effective in treating pain in depressed patients, but further research is needed. 2 Initial trials conducted in depressed patients using regimens of 20 mg/day or less did not convincingly demonstrate its efficacy as an antidepressant. 1