Research paperThe effects of desvenlafaxine on neurocognitive and work functioning in employed outpatients with major depressive disorder
Introduction
Major Depressive Disorder (MDD) is currently one of the most common medical conditions worldwide (World Health Organization, 2008). People with MDD experience great personal distress, as well as significant impairments in their daily and occupational functioning (Kessler et al., 2006). With onset characteristically in late adolescence and early adulthood, MDD also disproportionately affects young and middle-aged adults in the prime of their working years, and is a leading cause of long-term disability and unemployment in this age group (World Health Organization, 2008; Ferrari et al., 2013).
Despite this large burden of disability, many people with MDD maintain gainful employment, though they may experience underemployment (Dooley et al., 2000), miss more hours and days of work (absenteeism) (Alonso et al., 2004), and have difficulty performing to their usual ability (also known as “presenteeism”) (Gilmour and Patten, 2007), as compared to their non-depressed peers (Adler et al., 2006, Valenstein et al., 2001). Depression-related presenteeism in the United States contributes to an estimated 200 million lost workdays annually, costing employers between $17 and $44 billion (Stewart et al., 2003). Moreover, impairment in work functioning is a primary concern for patients with MDD; in fact, patients rate functional recovery as a more important treatment outcome than remission of depressive symptoms (Zimmerman et al., 2006).
Cognition is likely a major determinant of work functioning. It is now well recognized that MDD is associated with significant cognitive dysfunction, which in turn can impact functional impairment (Greer and Hatt, 2016, Lam et al., 2014, Lam et al., 2015). A large body of research confirms that patients with MDD perform worse on neuropsychological tests compared to healthy comparison subjects, including information processing speed (Tsourtos et al., 2002), sustained and selective attention (Landrø et al., 2001, Porter et al., 2003), different aspects of learning and memory (Porter et al., 2003, Preiss et al., 2009), and executive function (Gohier et al., 2009, Henry and Crawford, 2005). However, there has been limited study of the relationships between cognitive and psychosocial functioning in MDD. A systematic review identified some studies showing significant correlations between neuropsychological tests and functional outcomes, but others did not find significant associations (Evans et al., 2014).
Problems in cognitive domains, including attention, memory, psychomotor speed, and executive functioning, would be expected to have a significant impact on work functioning (Greer and Hatt, 2016, Lam et al., 2015, McIntyre et al., 2015), but systematic reviews have found that the relationships between cognitive dysfunction and work functioning have not been well-studied (Evans et al., 2013). In particular, there are few studies of the effects of antidepressants on neurocognition (McIntyre et al., 2015) and no studies examining the relationship with functional outcomes, such as work functioning.
Desvenlafaxine is a serotonin and noradrenaline reuptake inhibitor (SNRI) that has established efficacy in the treatment of MDD (Liebowitz et al., 2008). Desvenlafaxine also has shown efficacy in improving symptom and functional outcomes in employed patients with MDD (Dunlop et al., 2011, Soares et al., 2009). We aimed to examine the relationship of neurocognitive dysfunction on work functioning in patients with MDD before and after treatment with flexibly-dosed desvenlafaxine 50–100 mg/day.
Section snippets
Participants
Participants were outpatients recruited through the Mood Disorders Center, a specialized psychiatric clinic in Vancouver, Canada. Inclusion criteria for the study were: (1) age 19–55 years, (2) Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR) major depressive episode, (3) current paid employment with a minimum of 15 work hours per week, (4) score ≥23 on the Montgomery-Asberg Depression Rating Scale (MADRS) (Montgomery and Asberg, 1979), indicating
Demographics and clinical characteristics
Of 55 individuals who were screened and eligible for the study, 40 enrolled and completed baseline assessment. Table 1 shows demographic and clinical characteristics of the sample. The mean estimated FSIQ score was significantly higher than the general population mean of 100 (single sample t-test, two-tailed, t(35)=8.14, p<0.001). There were no significant differences between men and women on any of the demographic or clinical variables.
Most patients (n=32, 78%) had experienced previous
Discussion
At baseline, this sample of employed outpatients with MDD had moderate severity of depression and moderate impairment in global and work functioning. They also had perceived cognitive impairment and mild impairment in neurocognitive performance, with significantly lower scores for the composite NCI and the Complex Attention domain compared to age- and sex-matched normative scores. It should be noted that our patient sample had more years of education and higher intelligence than the general
Conclusions
Depressed employed patients with MDD who report perceived cognitive complaints show mild impairment in neurocognitive performance. Treatment with 8 weeks of flexibly-dosed desvenlafaxine 50–100 mg/day led to significant improvement in clinical, functional, and neurocognitive measures. There were no significant correlations between measures of neurocognitive and work functioning at baseline, at post-treatment, or in change during treatment. Clinically significant improvement in neurocognitive
Acknowledgments
Role of the funding source: This study was funded by an investigator-initiated Grant from Pfizer Canada. The sponsor had no role in the design, conduct, analysis or publication of the study. CTRN: NCT01468610.
Author disclosures: RWL has received research support or consulting/speaking honoraria from: AstraZeneca, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Eli Lilly, Johnston and Johnston, Lundbeck, Lundbeck Institute, Mochida,
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