Switching to duloxetine in selective serotonin reuptake inhibitor non- and partial-responders: Effects on painful physical symptoms of depression

Abstract

Painful physical symptoms (PPS) are common in patients with depression. Our objective was to evaluate the presence of PPS in a sample of SSRI non- or partial-responders with MDD and examine the effect of a switch to duloxetine on those PPS. Outpatients who met criteria for MDD despite having taken an SSRI antidepressant for at least 6 weeks, and who had a Hamilton depression rating scale total score of at least 15 and a clinical global impression of severity score of at least 3, were randomized to switch to duloxetine by either a direct switch or a start-taper switch method. PPS were assessed at baseline and at the study endpoint using various measures including six visual analog scales (VAS) for pain (overall pain, headache, back pain, shoulder pain, interference with daily activities, and time in pain while awake), the pain subscale of the symptom questionnaire-somatic subscale, and the bodily pain subscale of the short form-36 item health survey. Clinically significant levels of pain (mean baseline VAS scores >30 mm) were seen across all VAS pain measures prior to switching. Switch to duloxetine was associated with significant improvements on all pain measures regardless of switch method, and there was evidence for an earlier reduction in pain in the start-taper switch group. In summary, MDD patients who were non- or partial-responders to SSRI treatment were found to have clinically significant pain which improved significantly following switch to duloxetine regardless of the switch method utilized.

Introduction

Depression is known to present with a wide variety of emotional and somatic symptoms including low mood, anhedonia, anxiety, sleep, and appetite disturbance. In addition, pain is increasingly recognized as a symptom of depression, and recent evaluations of the prevalence and character of painful physical symptoms (PPS) associated with depression suggest that such symptoms are common, and treatment of these symptoms plays an important role in achieving optimal outcomes including improved remission and functioning (Kroenke et al., 1994, Karp et al., 2004, Ohayon, 2004, Fava et al., 2004). In one study, approximately 65% of patients with depression in primary care settings were reported to have concomitant pain, (Bair et al., 2003) and in a population-based telephone survey, subjects with major depressive disorder (MDD) were found to be at a four times greater risk of suffering from a chronic painful physical condition than those without MDD (Ohayon and Schatzberg, 2003). In a recent presentation of data from a post-hoc analysis of prevention of recurrent episodes of depression with Venlafaxine XR (PREVENT) study, the authors reported that moderate to severe PPS were highly prevalent in outpatients with MDD and were highly significantly associated with anxiety and depression severity (Ahmed et al., 2007). Additionally, the coexistence of depression and pain often leads to decreased productivity and results in lower rates of help seeking (Demyttenaere et al., 2006). The presence of PPS can also negatively impact longer-term depression treatment outcomes, with a significantly shorter time to depressive recurrence seen in patients with residual PPS compared with those without (Judd et al., 1998).

Dysregulation of serotonin (5-HT) and norepinephrine (NE) neurotransmission, which is believed to play a role in depression, may also lead to an hyperalgesic state in patients with depression (Stahl, 2002) due to the role of 5-HT and NE in the modulatory descending spinal pain pathways (Fields et al., 1991, Jones, 1991). Consistent with this, duloxetine (a serotonin and norepinephrine reuptake inhibitor, or SNRI), has been shown to be effective in treating PPS associated with depression (Brannan et al., 2005, Goldstein et al., 2004) as well as core emotional depressive symptoms.

In general, patients presenting with an episode of depression are treated initially with antidepressant monotherapy, often selective serotonin reuptake inhibitors (SSRIs). As evidenced by numerous studies including the recent STAR-D study (Rush et al., 2006), however, suboptimal response to the initial antidepressant agent is common, and in the event of suboptimal treatment response, there are a number of possible approaches that can be employed including increasing the dose (e.g. Bauer et al., 2002), augmentation with another antidepressant (e.g. Fava and Rush, 2006), or switching within the same class or to another class of antidepressant (Peselow et al., 1989, Fava, 2000, Thase et al., 2002). A variety of different ways of switching between antidepressants may be employed, some of which have been studied in clinical trials (e.g. Fava et al., 2001, Kreider et al., 1995). Previous switching studies have not however studied in detail what happens to PPS associated with depression following antidepressant switch.

Our objective therefore was to evaluate the presence of PPS in SSRI non- or partial-responders, and to examine the impact of a switch to the SNRI duloxetine on these painful symptoms. Previously, we have reported on overall changes in depression and pain (Perahia et al., 2008). Herein, we focus on the time course of improvement in pain as well as changes in specific pain symptoms. For context, the overall findings from Perahia et al (2008) are briefly repeated.