The relationship between functional outcomes and the treatment of anxious and painful somatic symptoms in patients with generalized anxiety disorder

ABSTRACT

Objective: To examine the relationship between global functional impairment and the treatment of anxious symptoms and painful somatic symptoms (PSS) in patients with generalized anxiety disorder (GAD).

Research design and methods: Data from two double-blind, placebo-controlled trials in adult outpatients meeting DSM-IV criteria for GAD were pooled. In the first trial (9-week, fixed-dose treatment period), patients were randomized to duloxetine 60 mg QD (n = 168), duloxetine 120 mg QD (n = 170), or placebo (n = 175). In the second trial (10-week, flexible-dose treatment period), patients were randomized to 60–120 mg QD of duloxetine (n = 168) or placebo (n = 159). Path analysis was used to assess the relative contributions of changes in psychic and somatic anxiety and PSS on improved functional outcomes. Clinical trial registration information: Study 1: NCT00122824; Study 2: study completed before registration required.

Main outcome measures: Sheehan Disability Scale (SDS), Hamilton Anxiety Rating Scale (HAMA), and Visual Analog Scale for overall pain (VAS).

Results: There was a moderate correlation (0.45, p < 0.05) at endpoint between changes in global functional impairment and changes in psychic anxiety (controlling for somatic anxiety and PSS); whereas the correlation between changes in global functional impairment and changes in somatic anxiety (controlling for psychic anxiety and PSS) was weak (0.09, p < 0.05). The correlation between changes in global functional impairment and changes in PSS (controlling for psychic and somatic anxiety) was weak (0.27, p < 0.05). Path analysis revealed that 37% of the total improvement in functional impairment (Sheehan Disability Scale total score) due to duloxetine treatment was independent of improvement in the Hamilton Anxiety Rating Scale (HAMA) psychic and somatic anxiety subscale scores or Visual Analog Scale for overall pain (VAS) score. Improvement in psychic anxiety accounted for 47% of the total treatment effect on improvement of functional impairment, whereas 7% and 9% of the improvement in functional impairment was accounted for by improvements in somatic anxiety and overall pain, respectively.

Limitations: This was a post-hoc exploratory analysis. Patients with co-morbid Major Depressive Disorder (MDD) or significant depressive symptoms were excluded from these GAD studies.

Conclusions: In patients with GAD, there was a moderate correlation between improvement in psychic anxiety symptoms and improvement in global functional impairment, whereas the correlation between improvements in somatic anxiety or PSS and improvement in global functional impairment was low. Most of the treatment effect of duloxetine in improvement of functional impairment was mediated through improvement in psychic anxiety, with smaller contributions through improvement in somatic anxiety and PSS. Some of the improvement in functional impairment for duloxetine-treated patients was independent of improvement through any of these domains.

Key Words::

• Disability
• Duloxetine
• Functional impairment
• GAD
• Sheehan Disability Scale
• Somatic symptoms

Acknowledgments

Declaration of interest: This work was sponsored by Eli Lilly and Company. J.M.R. and R.W.S. conceived of the study, participated in its design and coordination, and interpreted the study data. A.L.M. and C.H.M. performed the statistical analysis and interpreted the data. D.V.S. and M.J.R. helped interpret the data. A.P. interpreted the data and drafted the manuscript. All authors critically reviewed and approved the final manuscript. A.L.M., A.P., C.H.M., M.J.R., R.W.S., and J.M.R. are stock shareholders and full-time employees of Eli Lilly and Company. D.V.S. has been affiliated with or received honoraria and travel expenses related to consultant activities from numerous government and commercial entities.

Notes

* Data in this paper were presented in part as an oral presentation at the annual meeting of the American Psychiatric Association, San Diego, CA, USA, May 21, 2007