Introduction
Major depressive disorder (MDD) has a profound negative impact on patient functioning across all aspects of daily life.Reference Sheehan, Nakagome, Asami, Pappadopulos and Boucher1, Reference Malhi and Mann2 Patients with MDD experience difficulties performing routine activities of daily living as well as in their personal relationships, social life, and working life.Reference Sheehan, Nakagome, Asami, Pappadopulos and Boucher1 In particular, the impact of MDD on a person’s ability to work and workplace productivity appears greater than that of many other common health disorders.Reference de Graaf, Tuithof, van Dorsselaer and ten Have3–Reference Rojanasarot, Bhattacharyya and Edwards5 MDD is one of the most prevalent health problems in the working populationReference Rojanasarot, Bhattacharyya and Edwards5–Reference Chokka, Bender and Brennan7 and is a major cause of absenteeism and presenteeism in the workplace worldwide.Reference Evans-Lacko and Knapp8 The economic impact of MDD in the workplace is also substantial,Reference Evans-Lacko and Knapp8 with estimated workplace costs and lost productivity accounting for the largest proportion of the economic burden of MDD in the USA.Reference Greenberg, Fournier, Sisitsky, Simes, Berman, Koenigsberg and Kessler6
There is strong evidence to suggest that work is beneficial for overall health and well-being,Reference Chokka, Bender and Brennan7, Reference Waddell and Burton9 highlighting the importance of therapeutic interventions that can help patients with MDD remain in or return to work. Indeed, patients consider a return to their usual level of functioning to be one of the most important factors contributing to remission from MDD.Reference Zimmerman, McGlinchey, Posternak, Friedman, Attiullah and Boerescu10 Functional recovery is consequently an important treatment goal.Reference Lam, McIntosh and Wang11–Reference Yang, Gao and Li13 However, functional impairment frequently persists in patients with MDD after other core depressive symptoms have resolved.Reference de Vries, Koeter, Nieuwenhuijsen, Hees and Schene14–Reference Vicent-Gil, Serra-Blasco, Navarra-Ventura, Trujols, Balanzá-Martínez, Portella and Cardoner19 In a recent study, approximately 40% of patients with MDD who achieved symptomatic remission (defined as Montgomery–Åsberg Depression Rating Scale [MADRS] total score ≤ 12) failed to meet the criterion for functional recovery (Sheehan Disability Scale [SDS] total score ≤ 6).Reference Papalexi, Galanopoulos and Roukas18 This is of clinical significance, as residual functional impairment following remission of mood symptoms in patients with MDD has been shown to be a predictor of subsequent relapse.Reference IsHak, Greenberg and Cohen20
Vortioxetine demonstrates broad efficacy across the spectrum of symptoms experienced by patients with MDD, including functional impairment.Reference Thase, Mahableshwarkar, Dragheim, Loft and Vieta21–Reference Christensen, McIntyre, Adair, Florea, Loft and Fagiolini31 Vortioxetine has also been shown to be effective in patients with MDD and common comorbidities, such as generalized anxiety disorderReference Christensen, Schmidt and Grande32, Reference Almeida, Christensen, Simonsen and Adair33 and dementia.Reference Christensen, Schmidt and Grande34, Reference Cumbo, Adair, Åstrom and Christensen35
A meta-analysis of data from 9 short-term, randomized, placebo-controlled clinical trials demonstrated significant improvements in overall functioning (as assessed by the SDS) in patients with MDD treated with vortioxetine 5–20 mg/day, with the greatest benefits seen at a dose of 20 mg/day.Reference Florea, Loft and Danchenko24 Clinically relevant improvements in overall functioning have also been reported in patients with MDD receiving longer-term treatment with vortioxetine in routine care settings.Reference Chin, Zain and Hemrungrojn36–Reference Watanabe, Sumiyoshi and Kato43 Similarly, improvements in overall functioning and work productivity have been reported in working patients with MDD during treatment with vortioxetine.Reference Chin, Zain and Hemrungrojn36–Reference Mattingly, Ren and Christensen38, Reference Wang, Si, Rieckmann, Ma and Christensen42–Reference Chokka, Tvistholm, Bougie, Clerzius and Ettrup46
VIVRE was a large multinational study undertaken to directly compare the efficacy of vortioxetine with that of the serotonin–norepinephrine reuptake inhibitor (SNRI) desvenlafaxine in patients with MDD experiencing a partial response to initial selective serotonin reuptake inhibitor (SSRI) monotherapy. The overall study findings have been reported previously.Reference McIntyre, Florea, Pedersen and Christensen47 Vortioxetine was demonstrated to be non-inferior to desvenlafaxine for the primary study endpoint of improvement in core depressive symptoms, assessed by mean change from baseline in MADRS total score after 8 weeks of treatment. However, significantly more patients treated with vortioxetine achieved symptomatic and functional remission defined using the Clinical Global Impressions–Severity of Illness (CGI-S) scale. Vortioxetine-treated patients also experienced significantly greater improvements in daily and social functioning assessed using the Functioning Assessment Short Test (FAST) than those treated with desvenlafaxine and reported significantly greater satisfaction with their medication as assessed by the Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).
The FAST is a clinician-administered questionnaire specifically developed for the detailed assessment of psychosocial functioning in patients with mental health disorders.Reference Rosa, Sánchez-Moreno and Martínez-Aran48 This paper presents the results of additional post-hoc analyses undertaken to further explore the differences observed between vortioxetine and desvenlafaxine in the VIVRE study in terms of improvement in functioning as assessed by FAST total, domain, and individual item scores. Analyses were conducted for the overall study population and for the large subgroup of working patients. Correlations between improvements in FAST total, domain and item scores, and other assessment scale scores were also assessed.
Methods
Study design and participants
VIVRE (NCT04448431) was a multinational, randomized, double-blind, active-controlled, parallel-group, 8-week study of vortioxetine (10 or 20 mg/day) versus desvenlafaxine (50 mg/day) in outpatients aged 18–65 years with MDD who had experienced a partial response to initial SSRI monotherapy. The study design has been reported in detail previously.Reference McIntyre, Florea, Pedersen and Christensen47 In brief, the study was conducted at 77 sites across 12 countries (Argentina, Belgium, Bulgaria, Czech Republic, Estonia, Latvia, Mexico, Russia, Slovakia, Spain, Sweden, and Ukraine) from June 2020 to February 2022. Key inclusion criteria were a primary diagnosis of MDD according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria (confirmed by the Mini-International Neuropsychiatric Interview), duration of current major depressive episode of ≥ 3 and < 12 months, and MADRS total score ≥ 24 following prior treatment with escitalopram, sertraline, paroxetine, or citalopram at the approved dosage for ≥ 6 weeks. All patients were, in the investigator’s opinion, suitable candidates for switching to another drug for depression. Patients with other current DSM-5 psychiatric or Axis I disorders, treatment-resistant depression (ie, inadequate response to at least 2 drugs for depression for the treatment of the current major depressive episode), a history of alcohol/substance use within the past 6 months, and/or considered at clinically significant risk of suicide were excluded.
The prior SSRI monotherapy was discontinued before the baseline visit, with dose tapering if required. Study drugs were administered in accordance with local prescribing information. Vortioxetine was initiated at the recommended starting dosage of 10 mg/day, with the dosage increased to 20 mg/day in all patients after 1 week. Further dose adjustments were permitted until week 4, after which the vortioxetine dosage was fixed. Desvenlafaxine was administered at the recommended dosage of 50 mg/day. To maintain the blind, desvenlafaxine dose adjustment could be requested up to week 4 based on patient response and the investigator’s clinical judgment; however, the administered dosage was not changed.
The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines, was approved by the local ethics committee at each study site, and all patients provided written informed consent.
Study assessments
The overall severity of core depressive symptoms at baseline and weeks 1, 4, and 8 was assessed using the MADRS total score. Overall disease severity and its impact on global patient functioning were also assessed at these time points using the CGI-S.
Detailed assessment of patient functioning was undertaken at baseline and week 8 using the FAST.Reference Rosa, Sánchez-Moreno and Martínez-Aran48 The FAST comprises a total of 24 items divided into 6 different functional domains: autonomy (4 items), occupational functioning (5 items), cognitive functioning (5 items), financial issues (2 items), interpersonal relationships (6 items), and leisure time (2 items). For each item, clinicians rate the degree of impairment experienced by the patient over the past 14 days on a 4-point scale: 0 (no impairment), 1 (mild impairment), 2 (moderate impairment), or 3 (severe impairment). Scores for the individual items are summed to yield the FAST total score; this ranges from 0 to 72 points, with higher scores indicating greater impairment. FAST total scores of 12–20, 21–40, and > 40 indicate mild, moderate, and severe functional impairment, respectively.Reference Bonnín, Martínez-Arán and Reinares49 For the purposes of this analysis, a combined score was also generated for the sum of the autonomy, cognitive functioning, and interpersonal relationships domains. These were the FAST domains shown to be most sensitive to early improvement, defined as a significant improvement from baseline after 3 weeks of treatment, in a validation study in patients with bipolar disorder.Reference Rosa, Reinares and Amann50
Health-related quality of life was assessed at baseline and week 8 please keep together on 1 line using the long form of the Q-LES-Q.Reference Endicott, Nee and Harrison51 This patient-rated scale provides a comprehensive assessment of health-related quality of life across 10 domains: physical health/activities, subjective feelings, work, leisure time activities, social relations, general activities, satisfaction with medication, overall satisfaction and contentment, household duties, and school/course work. Q-LES-Q domain scores are expressed as a percentage of the maximum score possible; higher scores signify better health-related quality of life.
Statistical analysis
The population for this additional analysis comprised all randomized patients who received at least 1 dose of study medication and who had MADRS total score data at baseline and at least 1 post-baseline assessment time point (full analysis set). Analyses were performed for the overall study population and in the subgroup of patients who were in paid employment or self-employed at baseline. All analyses were conducted on observed cases; missing data were not replaced.
Mean percentage changes from baseline to week 8 in FAST total score, FAST domain scores, and the sum of the FAST autonomy, cognitive functioning, and interpersonal relationships domain scores (ie, the FAST subscore) were analyzed by treatment group using an analysis of covariance model (ANCOVA), including baseline score and country. Patients with a baseline score of 0 for FAST total score or a specific FAST domain or item were excluded from the respective analysis. A similar ANCOVA was applied to analyze the difference in the mean percentage change from baseline to week 8 between the 2 treatment groups for all individual FAST item scores.
Correlation analyses were performed to investigate the relationship between the absolute mean change from baseline to week 8 in FAST total, domain, and item scores and: (i) MADRS total and individual item scores; (ii) CGI-S score; and (iii) all Q-LES-Q domain scores except for the school/course work domain. Only patients with data for both scales were included in the respective correlation analyses. Spearman’s correlations (rs) are reported, with associated P-values.
All statistical analyses were performed using R version 4.2.1. Significance was set at P < 0.05 (2-sided) and no adjustment for multiple comparisons was applied.
Results
Patient characteristics
Of the 603 patients who were randomized and received at least 1 dose of study medication, 602 were eligible for inclusion in the full analysis set (309 in the vortioxetine treatment group and 293 in the desvenlafaxine group). One patient in the vortioxetine group was excluded from the full analysis set as they did not have any valid post-baseline data for MADRS total score. Key baseline demographics and clinical characteristics for the patients included in the full analysis set are summarized in Supplementary Table 1. Patients were mostly female (70.8%), with a mean (SD) age of 43.3 (12.8) years, and over half of all patients (59.8%) were in paid employment or self-employed. On average, patients had moderate-to-severe depression and severely impaired functioning at baseline. Mean (SD) duration of the current depressive episode was 23.7 (9.2) weeks. The most common prior SSRIs used were escitalopram (received by 41.4% of patients) and sertraline (35.5%).
Efficacy: overall patient population
Marked improvements in patient functioning, as assessed by the FAST, were seen in both groups over the 8 weeks of treatment (Figure 1A), with numerically greater improvements seen in vortioxetine- versus desvenlafaxine-treated patients across almost all FAST domains and items (Table 1). The mean percentage reduction in FAST total score from baseline to week 8 was significantly greater in vortioxetine-treated patients than in those who received desvenlafaxine (37.2% vs 31.8%, respectively; P = 0.04). Compared with desvenlafaxine, significantly greater improvements relative to baseline were also seen in patients treated with vortioxetine for the FAST autonomy, cognitive functioning, and interpersonal relationships domain scores (all P < 0.05 vs desvenlafaxine). The mean percentage reduction in the sum score for these 3 domains from baseline to week 8 was 36.7% in the vortioxetine group compared with 28.7% in the desvenlafaxine group (P < 0.01). Significantly greater percentage reductions in mean score at week 8 relative to baseline were also seen in vortioxetine-treated patients compared with desvenlafaxine-treated patients for the following individual FAST items: “taking responsibility for a household,” “ability to concentrate on a book or film,” “maintaining friendships,” “participating in social activities,” and “having satisfactory sexual relationships” (all P < 0.05 vs desvenlafaxine).
Table 1. Mean percentage change from baseline to week 8 in FAST domain and individual item scores (overall population, full analysis set)
Note: Patients with a baseline score of 0 for FAST total score or a specific FAST domain or item were excluded from the relevant analyses.
Significant treatment differences (P-values) are shown in bold.
a Sum of the autonomy, cognitive functioning, and interpersonal relationships domain scores. BL, mean score at baseline; CI, confidence interval; FAST, Functioning Assessment Short Test; SE, standard error.
Figure 1. Mean (SE) percentage change from baseline to week 8 in FAST total and individual domain scores in (A) the overall patient population and (B) working patients (full analysis set). The FAST subscore is the sum of the autonomy, cognitive functioning, and interpersonal relationships domain scores. Note: Patients with a baseline score of 0 for FAST total score or a specific FAST domain or item were excluded from the relevant analyses. *P < 0.05; **P ≤ 0.01 vs desvenlafaxine. FAST, Functioning Assessment Short Test; SE, standard error.
Efficacy: working patients
Of the 602 patients included in the full analysis set, 360 (59.8%) were in paid employment or self-employed at baseline (179 in the vortioxetine group and 181 in the desvenlafaxine group) (Supplementary Table 1). The 2 treatment groups were well-matched in terms of baseline disease characteristics (data not shown). In working patients, the mean (SD) MADRS score was 30.5 (3.7) in those treated with vortioxetine and 30.6 (3.9) in those who received desvenlafaxine. The mean (SD) CGI-S score was 4.5 (0.6) in both groups, and the mean (SD) FAST total score was 40.0 (12.3) and 40.3 (12.1), respectively.
In working patients, the mean percentage reduction in FAST total score from baseline to week 8 was significantly greater in working patients treated with vortioxetine than in those who received desvenlafaxine (38.7% vs 32.1%, respectively; P = 0.04) (Figure 1B). As in the overall patient population, numerically greater percentage improvements relative to baseline were also seen in working patients treated with vortioxetine compared with those who received desvenlafaxine across almost all FAST domains and items (Supplementary Table 2). Mean percentage reductions in FAST autonomy and cognitive functioning domain scores relative to baseline were also significantly greater in vortioxetine-treated working patients than in those who received desvenlafaxine (38.7% vs 17.2% [P < 0.01] and 34.6% vs 26.8% [P = 0.04], respectively). Vortioxetine-treated patients also achieved significantly greater improvement in the FAST subscore from baseline (mean percentage reduction from baseline to week 8, 41.2% vs 31.9% in the desvenlafaxine group, P = 0.01). Significantly greater percentage reductions relative to baseline in favor of vortioxetine versus desvenlafaxine were also seen for the following individual FAST items (Supplementary Table 2): “taking responsibility for a household,” “occupational earnings,” “ability to concentrate on a book or film,” “ability to solve a problem adequately,” and “participating in social activities” (all P < 0.05 vs desvenlafaxine).
Correlation analyses
As shown in Figure 2, significant positive correlations were seen between the mean change from baseline to week 8 for FAST total score and MADRS total score (rs = 0.57; P < 0.001) and all individual MADRS item scores (rs values ranging from 0.47 for MADRS item 7 [lassitude] to 0.13 for MADRS item 10 [suicidal thoughts]; all P < 0.01). Significant correlations were also seen between the improvements in all FAST domain scores and MADRS total score (rs values ranging from 0.50 for the FAST interpersonal relationships domain to 0.18 for the FAST financial issues domain; all P < 0.001), as well as between all FAST individual item scores and MADRS total score (rs values ranging from 0.44 for “participating in social activities” in the interpersonal relationships domain to 0.15 for the “spending money in a balanced way” item in the financial issues domain; all P < 0.001) (data not shown).
Figure 2. Correlations between absolute mean change from baseline to week 8 in FAST total score and MADRS total and individual item scores (n = 574) and CGI-S score (n = 572). **P < 0.01; ***P < 0.001. CGI-S, Clinical Global Impressions–Severity of Illness; FAST, Functioning Assessment Short Test; MADRS, Montgomery–Åsberg Depression Rating Scale.
A significant positive correlation was seen between the mean change from baseline to week 8 in FAST total score and CGI-S score (rs = 0.48; P < 0.001) (Figure 2), with significant correlations also seen between CGI-S score and all FAST domain and individual item scores (all P < 0.05) (data not shown). As for MADRS total score, the weakest correlations were between CGI-S score and the FAST financial issues domain and its component item scores.
Significant negative correlations were seen between the mean change from baseline to week 8 in FAST total score and all Q-LES-Q domain scores (rs values ranging from −0.68 for the feelings and household duties scores to −0.47 for the satisfaction with medication score; all P < 0.001) (Figure 3). Significant correlations were also observed between all FAST domain and individual item scores and all Q-LES-Q domain scores (all P < 0.05) (data not shown).
Figure 3. Correlations between absolute mean change from baseline to week 8 in FAST total score and Q-LES-Q domain scores (n = 291). Note: The main reason for exclusion was missing data for Q-LES-Q work and/or satisfaction with medication scores. ***P < 0.001. FAST, Functioning Assessment Short Test; Q-LES-Q, Quality of Life Enjoyment and Satisfaction Questionnaire.
Discussion
These additional analyses of data from the VIVRE study further demonstrate that patients with MDD with only a partial response to initial SSRI therapy experienced significantly greater improvements in many aspects of functioning when subsequently treated with vortioxetine compared with desvenlafaxine. After 8 weeks of treatment, the mean percentage change in total FAST score from baseline was greater than the proposed minimal clinically important difference in both the vortioxetine and the desvenlafaxine treatment groups.Reference Christensen, Schmidt and Grande52 Compared with desvenlafaxine-treated patients, vortioxetine-treated patients experienced significantly greater improvements in overall functioning relative to baseline as assessed by FAST total score, as well as in daily, social, and cognitive functioning as assessed by the relevant FAST domain scores. The improvement in these 3 domains combined (ie, autonomy, cognitive functioning, and interpersonal relationships) was also significantly greater in patients treated with vortioxetine than in those who received desvenlafaxine. Significantly greater improvements were also seen in vortioxetine-treated patients for several individual FAST items; namely, “taking responsibility for a household,” “ability to concentrate on a book or film,” “maintaining friendships,” “participating in social activities,” and “having satisfactory sexual relationships.”
These findings confirm and elaborate on the results of the primary analysis of the VIVRE study.Reference McIntyre, Florea, Pedersen and Christensen47 Our findings are also in line with those of the randomized, double-blind, placebo-controlled CONNECT study that evaluated the efficacy and safety of vortioxetine versus the SNRI duloxetine in patients with MDD.Reference Mahableshwarkar, Zajecka, Jacobson, Chen and Keefe53, Reference Christensen, Loft and McIntyre54 In that study, significantly greater improvement in overall patient functioning was seen in vortioxetine-treated patients compared with those who received duloxetine as assessed by the University of California San Diego Performance-based Skills Assessment (UPSA) composite score.Reference Mahableshwarkar, Zajecka, Jacobson, Chen and Keefe53 In addition, significantly more vortioxetine- than duloxetine-treated patients achieved symptomatic and functional response (defined as ≥ 50% reduction in MADRS total score from baseline and UPSA score ≥ 7).Reference Christensen, Loft and McIntyre54
The significantly greater improvement in sexual relationships seen in vortioxetine-treated patients compared with those who received desvenlafaxine in the overall population in the present analysis is also noteworthy. Sexual dysfunction is common in patients with MDD and is also often reported as a treatment-related adverse event in patients receiving certain drugs for depression, particularly SSRIs and SNRIs.Reference Clayton, El Haddad, Iluonakhamhe, Ponce Martinez and Schuck55–Reference Atmaca57 Other studies have also reported a significant improvement in sexual function in patients switching to vortioxetine after experiencing sexual dysfunction during treatment with other drugs for depression.Reference Jacobsen, Mahableshwarkar, Chen, Chrones and Clayton58–Reference Montejo, Sánchez-Sánchez and De Alarcón60 In a pooled analysis of data from short-term clinical trials, rates of treatment-emergent sexual dysfunction in patients with MDD receiving vortioxetine were similar to those in patients who received placebo.Reference Jacobsen, Mahableshwarkar, Palo, Chen, Dragheim and Clayton61 Vortioxetine has also been shown to have a lower propensity for treatment-emergent sexual side effects than paroxetine in healthy volunteers.Reference Jacobsen, Zhong, Nomikos and Clayton62
The beneficial effects of vortioxetine on functioning in working patients in the present analysis were generally more pronounced than those observed in the overall study population. After 8 weeks of treatment, significantly greater improvements in overall functioning, daily functioning, cognitive functioning, and the FAST subscore (ie, the sum of the autonomy, cognitive functioning, and interpersonal relationships domain scores) were seen in working patients treated with vortioxetine compared with those who received desvenlafaxine. Significantly greater improvements in FAST items assessing occupational earnings and the ability to solve problems were also observed in vortioxetine-treated patients.
Our findings add to the growing body of evidence demonstrating the effectiveness of vortioxetine for the treatment of functional impairment in working patients with MDD. Results of an 8-week, randomized, placebo-controlled study (FOCUS) showed vortioxetine to have pronounced beneficial effects on executive functioning, speed of processing, verbal learning, and memory in working patients with MDD, with the greatest improvement seen in patients in managerial or professional positions.Reference McIntyre, Florea, Tonnoir, Loft, Lam and Christensen44 In another 8-week study (ReMind WORK), significant improvements versus placebo in overall functioning assessed by the FAST were seen in working patients with MDD treated with vortioxetine, but not in those who received paroxetine.Reference Baune, Sluth and Olsen63
Long-term improvements in functioning and productivity have also been reported in working patients with MDD treated with vortioxetine for 52 weeks, including those switching to vortioxetine due to an inadequate response to prior therapy with other drugs for depression.Reference Chokka, Bougie, Proulx, Tvistholm and Ettrup45, Reference Chokka, Tvistholm, Bougie, Clerzius and Ettrup46 Significant improvements in workplace functioning and productivity have also been reported in several large observational studies of patients with MDD receiving treatment with vortioxetine in real-world settings.Reference Chin, Zain and Hemrungrojn36–Reference Mattingly, Ren and Christensen38, Reference Wang, Si, Rieckmann, Ma and Christensen42, Reference Watanabe, Sumiyoshi and Kato43 These findings are noteworthy, as patients with MDD often continue to work despite the functional impairments they experience.Reference Greenberg, Fournier, Sisitsky, Simes, Berman, Koenigsberg and Kessler6
Moderately strong positive correlations were seen between the mean absolute changes from baseline in FAST total, domain, and individual item scores and depressive symptom severity assessed by MADRS total and individual item scores and CGI-S score. Stronger negative correlations were generally seen between the mean changes from baseline in FAST scores and health-related quality of life assessed using the Q-LES-Q, highlighting the impact of functional impairment in MDD on all aspects of patients’ daily lives and the importance of functional recovery as a treatment goal. For all scales, the lowest correlations were seen with the FAST financial domain and its component item scores, suggesting that the difficulties patients with MDD may experience in handling finances are not covered by these other assessment scales.
The clinically significant improvements in overall patient functioning seen in patients with MDD during treatment with vortioxetine have been shown to be mediated by the drug’s procognitive effects.Reference McIntyre, Florea, Tonnoir, Loft, Lam and Christensen44, Reference Chokka, Bougie, Proulx, Tvistholm and Ettrup45 The direct beneficial effects of vortioxetine on cognition and functioning are likely due to its multimodal mechanism of action, particularly its ability to modulate the activity of other neurotransmitters in addition to serotonin (namely, norepinephrine, dopamine, acetylcholine, histamine, gamma-aminobutyric acid, and glutamate).Reference Sanchez, Asin and Artigas64, Reference Gonda, Sharma and Tarazi65 For example, norepinephrine plays an important role in executive functioning, cognition, and motivation,Reference Moret and Briley66 while dopamine has been implicated in the regulation of motivation and the experience of pleasure and reward.Reference Dunlop and Nemeroff67, Reference Belujon and Grace68
Study limitations include that this was a post-hoc analysis of data from the VIVRE study and the relatively short study duration (8 weeks), as patients with MDD generally require long-term treatment. However, the therapeutic benefits of vortioxetine on core depressive symptoms, patient functioning, and health-related quality of life have been shown to be maintained and further improved over treatment durations of up to 52 weeks in both clinical trials and real-world clinical practice.Reference Mattingly, Ren and Christensen38, Reference Wang, Xiao and Ren40, Reference Wang, Si, Rieckmann, Ma and Christensen42, Reference Watanabe, Sumiyoshi and Kato43, Reference Chokka, Bougie, Proulx, Tvistholm and Ettrup45, Reference Chokka, Tvistholm, Bougie, Clerzius and Ettrup46, Reference Mattingly, Necking, Schmidt, Reines and Ren69 In addition, the potential for systematic bias due to missing data was not assessed. As patients with a baseline score of 0 for FAST total score or a specific FAST domain were excluded from the analyses of relative change from baseline, the percentage change from baseline in FAST total, domain, and item scores can therefore only be interpreted for patients with baseline scores greater than 0 for the respective domains. However, as this limitation applies to both treatment groups, we do not expect this to have introduced significant bias into the comparison of treatment effect.
Conclusion
In summary, vortioxetine was associated with significantly greater relative improvements in overall functioning and daily, social, and cognitive functioning than the SNRI desvenlafaxine in patients with MDD with an inadequate response to prior SSRI therapy. The observed greater improvements in functioning relative to baseline in vortioxetine-treated patients appeared more pronounced in working patients than in the overall study population. When considered together with the evidence of clinical benefit reported in the primary analysis of this study,Reference McIntyre, Florea, Pedersen and Christensen47 our findings provide further support for the functional benefits of vortioxetine in patients with MDD, particularly working patients. The observed correlations between improvements in patient functioning and improvements in depression severity and health-related quality of life highlight the impact of functional impairment on all aspects of daily life in patients with MDD and the importance of functional recovery as a treatment goal.
Supplementary material
The supplementary material for this article can be found at http://doi.org/10.1017/S1092852924000610.
Acknowledgments
Under the authors’ direction, medical writing assistance was provided by Jennifer Coward for Piper Medical Communications Ltd, funded by H. Lundbeck A/S.
Author contribution
All authors contributed to the conceptualization and interpretation of the analyses, contributed to the scientific content of the manuscript, and approved the final version of the manuscript for submission. Andreas Rieckmann performed the statistical analyses.
Financial support
The VIVRE study and the analyses reported in this paper were funded by H. Lundbeck A/S, Valby, Denmark, whose personnel contributed to the data analysis, review of the data, and preparation and review of the manuscript.
Competing interest
Drs. Christensen and Rieckmann are employees of H. Lundbeck A/S. Dr. Grande has received grants and has served as a consultant, advisor, or CME speaker for the following entities (unrelated to the present work): Adamed, Angelini, Casen Recordati, Esteve, Ferrer, Gedeon Richter, Janssen Cilag, Lundbeck, Lundbeck-Otsuka, Luye, SEI Healthcare, Viatris. She also receives royalties from Oxford University Press, Elsevier, and Editorial Médica Panamericana. Dr. Grande has also received support from the Spanish Ministry of Science and Innovation (MCIN) (PI23/00822 y PI19/00954) integrated into the Plan Nacional de I + D + I and co-financed by the ISCIII-Subdirección General de Evaluación y confinanciado por la Unión Europea (FEDER, FSE, Next Generation EU/Plan de Recuperación Transformación y Resiliencia_PRTR); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); and the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2021 SGR 01358), CERCA Programme/Generalitat de Catalunya, as well as the Fundació Clínic per la Recerca Biomèdica (Pons Bartran 2022-FRCB_PB1_2022). Dr. Chokka has served as a speaker and received consultant fees from AbbVie, Janssen, Lundbeck, Otsuka, Purdue, and Takeda, and has received research/grant support from AbbVie, Janssen, Lundbeck, Otsuka, Takeda, Telus, and Mitacs.
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