Skip to main content

Individualized strategies for depression: narrative review of clinical profiles responsive to vortioxetine

Abstract

Background

Depression is a highly heterogeneous disorder, often resulting in suboptimal response and remission rates. This underscores the need for more nuanced clinical characterization of patients to tailor individualized treatment plans. Emerging evidence highlights the critical role of cognitive and emotional dysfunction in major depression, prompting the exploration of novel therapeutic interventions that target these specific symptom domains.

Main text

Vortioxetine, a multimodal antidepressant, enhances serotonergic activity while also modulating several other neurotransmitter systems involved in depressive symptoms such as emotional blunting, anhedonia, and cognitive dysfunction. Numerous randomized, placebo-controlled trials have demonstrated vortioxetine’s efficacy and safety in treating depression, particularly in specific subgroups of depressed patients, including those with cognitive deficits and comorbid anxiety symptoms or disorders. Although not randomized or placebo-controlled, studies have also shown vortioxetine’s efficacy in depressed patients with emotional blunting or anhedonia. Vortioxetine’s ability to effectively treat a range of depressive symptoms, including anhedonia, emotional blunting, anxiety, and cognitive dysfunction, provides an individualized treatment solution for depressed individuals suffering from these symptoms. The purpose of this paper is to identify clinical profiles of patients who may benefit from vortioxetine, with the goal of optimizing therapeutic outcomes.

Conclusion

Vortioxetine has been shown to be effective for patients with depression and symptoms such as anhedonia, emotional blunting, anxiety, and cognitive dysfunction. Tailoring treatment plans to individual needs and personalizing treatment choices based on the specific symptoms presented by depressed patients improve treatment outcomes.

Background

The treatment of depression presents several challenges: (a) Varying contributions of biological, psychological, and environmental factors in each individual making it difficult to identify the specific cause and necessitating treatments that address multiple factors [1, 2]. (b) Stigma and barriers to help-seeking behavior [3]. (c) Individual variability, as depression manifests differently across individuals. There is no one-size-fits-all treatment, and what works for one person may not be as effective for another [4]. (d) Comorbidity with other mental or physical health conditions, complicating treatment and requiring a holistic approach [5]. (e) Treatment resistance [6]. (f) Limited access to mental health services particularly in low-income areas, leading to disparities in mental health care [7]. (g) Medication side effects, making it challenging to find the right balance between efficacy and tolerability [8, 9]. (h) Relapse prevention as maintenance and follow-up care are critical for sustaining long-term improvements in mental health [10]. (i) Lack of objective measures, unlike some physical illnesses, as there are no clear biomarkers or diagnostic tests for depression [11]. Diagnosis often relies on self-report and clinical assessment, making it difficult to objectively measure treatment progress. l) Patient engagement and adherence, including motivating individuals to actively participate in their treatment consistently take medications and make lifestyle changes.

Addressing depression’s multifaceted challenges requires a comprehensive and multidisciplinary approach involving mental health professionals, support networks, and policy changes to improve access to mental health care [12]. Ongoing research and advancements in understanding depression are crucial for developing more effective and personalized treatment strategies. Major depressive disorder (MDD) treatment challenges include delayed pharmacotherapy response, adverse effects, and persistent cognitive dysfunction affecting executive function, memory, and attention, which can hinder recovery even during remission [13, 14].

MDD’s complexity may benefit from personalized clinical approaches [15, 16], yet current treatment choices are often based on trial-and-error strategies, leading to a lack of remission in many cases and treatment resistance in about 30% of patients [16].

Vortioxetine, approved for MDD, offers a unique mechanism of action, modulating neurotransmission in multiple systems [17].

This narrative review explores the impact of vortioxetine on various clinical presentations of patients with MDD who may benefit from this medication.

Materials and methods

For the purposes of this expert opinion paper, we appraised and selected studies to report and comment on the existing literature that we considered most relevant for a qualitative summary and interpretation of our perceived perspectives on the impact of vortioxetine on the treatment armamentarium for major depressive disorder. As a narrative review, this manuscript is primarily based on articles selected according to our personal knowledge, experience, and perspective, with the goal of sharing our clinical or research experiences and perspectives.

We conducted a search strategy in PubMed to identify relevant studies using the following search string: ((vortioxetine[title/abstract]) AND (major depressive disorder[title/abstract] OR depression[title/abstract])) AND (efficacy[title/abstract] OR tolerability[title/abstract] OR adverse effects[title/abstract] OR symptoms[title/abstract]). We read the titles and abstracts of the 314 papers resulting from our search strategy. The full text of 41 papers considered most relevant to the topic of this paper were retrieved from PubMed or other databases, analyzed, and discussed in this paper. We maintained a narrative review approach, as 10 additional papers were retrieved from the references of the above papers and included in our critical review.

Pharmacological profile of vortioxetine

Vortioxetine, approved for MDD in adults, is administered at doses ranging from 5 to 20 mg/day, with a recommended starting dose of 10 mg/day for those under 65 and 5 mg/day for older adults [13]. This antidepressant is distinguished by its multimodal mechanism of action, influencing various neuroreceptor systems [18]. Originating from a drug discovery program, vortioxetine’s development was inspired by hypotheses combining SERT inhibition and 5-HT1A receptor modulation [19]. Classified under a new system for psychotropic medications, vortioxetine uniquely combines serotonin (5-HT) receptor activity modulation with SERT inhibition across its dosage spectrum [13, 19]. Its action is primarily through serotonergic receptor modulation and SERT inhibition [20]. Preclinical studies reveal vortioxetine’s broad receptor activity, including antagonism at 5-HT3, 5-HT7, and 5-HT1D receptors, partial agonism at 5-HT1B receptors, and agonism at 5-HT1A receptors, alongside SERT inhibition. This extensive modulation impacts neurotransmission across multiple systems, including serotonin, norepinephrine, dopamine, histamine, acetylcholine, GABA, and glutamate, contributing to its antidepressant and anxiolytic effects, as well as cognitive function enhancement observed in animal studies [21]. Vortioxetine’s SERT saturation is dose-dependent, contrasting with selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). Positron emission tomography (PET) studies using 5-HT transporter ligands (11 C-MADAM or 11 C-DASB) demonstrated that 5-HT transporter occupancy in the raphe nuclei is around 50% at 5 mg/day, 65% at 10 mg/day, and over 80% at 20 mg/day [22]. This is significant compared to SNRIs and SSRIs, where serotonin reuptake transporter occupancy is typically over 80% even at the lowest effective doses, explaining the limited efficacy increase but worsened tolerability profile at higher doses of these medications [23].

Clinical profiles responsive to Vortioxetine

Clinical trials and meta-analyses have consistently demonstrated vortioxetine’s effectiveness in MDD. A meta-analysis of 11 randomized, placebo-controlled trials found significant reductions in Montgomery–Åsberg Depression Rating Scale (MADRS) scores across vortioxetine doses (5–20 mg/day), indicating a dose-dependent antidepressant effect [24]. Further, pooled analyses and studies have corroborated these findings, demonstrating greater efficacy and rapid symptomatic response at higher doses [25, 26].

Vortioxetine has been demonstrated to significantly improve most depressive symptoms, including cognitive impairment [27,28,29,30,31,32,33,34,35,36,37,38,39], anhedonia [40,41,42], and emotional blunting [43]. It has also proven efficacious in improving depressive symptoms in patients with comorbid anxiety [44,45,46,47], and psychiatric comorbidities such as early-stage dementia [46].

Efficacy for patients with cognitive dysfunction

Vortioxetine’s pro-cognitive effects have been demonstrated in several studies. Animal and preclinical studies indicate its potential to enhance synaptic plasticity and cortical activity, impacting cognitive functions [27,28,29]. Clinical trials using cognitive assessments like the Rey Auditory Verbal Learning Test (RAVLT) and Digit Symbol Substitution Test (DSST) have shown significant improvements in cognitive performance in MDD patients treated with vortioxetine, independent of depressive symptom improvement [30, 31, 33]. These effects are particularly pronounced in working patients, highlighting vortioxetine’s role in improving work productivity and quality of life [34, 35, 48]. Meta-analyses further reinforce vortioxetine’s superiority in enhancing cognitive functions compared to other antidepressants [36,37,38,39]. In a study involving 100 patients with Alzheimer’s disease (AD) and depression, vortioxetine was not significantly superior to placebo in reducing depressive symptoms or cognitive impairment. However, overall tolerability and patient safety were similar to placebo. The authors concluded that additional studies are needed to replicate the efficacy and tolerability of vortioxetine in AD patients with depression [49]. The effectiveness and tolerability of vortioxetine in improving depressive symptoms, cognitive performance, functioning, and quality of life in patients with MDD and comorbid early-stage dementia, were studied in 82 patients who received vortioxetine for 12 weeks. A significant improvement was shown in depressive symptom severity, cognitive performance, functioning, and quality of life. Vortioxetine was well tolerated [46]. A prospective, randomized, 12 month, parallel-group study investigated the efficacy of vortioxetine compared to other conventional antidepressants on cognitive functions in AD patients with depressive symptoms. The study concluded that vortioxetine had a beneficial effect on cognition and mood in elderly AD patients and was safe and well tolerated [50].

Efficacy for patients with anhedonia and emotional blunting

Vortioxetine has been shown to be effective in treating anhedonia, a core symptom of depression, as evidenced by improvements in the Snaith-Hamilton Pleasure Scale (SHAPS) and MADRS anhedonia factor scores [40, 41]. Its long-term efficacy in reducing anhedonia-related symptoms has been supported over 52 weeks of treatment [42]. In addition, vortioxetine has shown promise in alleviating emotional blunting in patients with MDD, particularly those with a partial response to SSRIs/SNRIs [43]. Although these studies were not randomized or placebo-controlled, improvements in anhedonia and emotional blunting were statistically significant.

Efficacy for patients with comorbid anxiety

Vortioxetine effectively reduces anxiety symptoms in MDD, as demonstrated in a meta-analysis of trials with high baseline anxiety levels [44] and an update pooled analysis of fixed-dose studies [45].

The RECONNECT study and a subgroup analysis of the RELIEVE study further validated vortioxetine’s efficacy in patients with severe depression and comorbid generalized anxiety disorder (GAD) [46, 47]. Moreover, vortioxetine’s effectiveness extends to patients with MDD and comorbidities like alcohol use disorder and substance use disorder. In these populations, vortioxetine has been shown to significantly improve depressive symptoms and functional impairment [51, 52]. These findings highlight the potential of vortioxetine as a treatment option for patients with MDD and various comorbid conditions, particularly those involving anxiety and substance use disorders.

Efficacy for patients with physical comorbidities

Vortioxetine has been shown to be well-tolerated and efficacious in patients with MDD and comorbid physical conditions, such as cardiovascular disease, diabetes mellitus, Parkinson’s disease [53] and, to a lesser extent, chronic obstructive pulmonary disorders (COPD) [54]. Notably, vortioxetine’s effectiveness and tolerability extend to older populations, who often deal with multiple comorbidities and polypharmacy [55]. This is particularly relevant, as the presence of physical comorbidities can complicate the management of MDD and negatively impact treatment outcomes.

Recent evidence suggests that vortioxetine may have beneficial effects beyond its direct impact on depressive symptoms. A recent meta-analysis [66] demonstrated that vortioxetine significantly improved physical symptoms associated with depression, such as pain, sleep disturbances, and somatic anxiety. The multimodal mechanism of action of vortioxetine, involving modulation of several neurotransmitter systems, may contribute to its ability to alleviate these somatic correlates of depression. Furthermore, preclinical studies have revealed that vortioxetine possesses anti-inflammatory and antioxidative properties. There is some evidence that vortioxetine exerts anti-inflammatory and immunomodulatory effects on human monocytes and macrophages, possibly through its actions on the serotonergic system and direct inhibition of cyclooxygenases [67]. These findings suggest that vortioxetine’s anti-inflammatory activity may be particularly relevant in the context of post-COVID-19 depression. Patients with post-COVID-19 major depressive episodes treated with vortioxetine experienced significant improvements in physical and cognitive symptoms, as well as a reduction in inflammatory markers [68]. Given the high prevalence and clinical implications of post-COVID-19 depression, further research on the potential benefits of vortioxetine in this population is warranted (Table 1).

Table 1 Summary of Vortioxetine clinical findings

Safety and tolerability profile of vortioxetine

Vortioxetine, at doses of 5–20 mg/day, has been shown to be generally safe and well-tolerated in treating MDD, as evidenced by several studies [56,57,58]. A pooled analysis of ten randomized, double-blind, placebo-controlled, short-term (6–8 weeks) clinical trials revealed that most treatment-emergent adverse events (TEAEs) in MDD patients receiving vortioxetine were mild or moderate in severity (89.3% for vortioxetine vs. 90.5% for placebo) [19]. Nausea, the most common TEAE, was dose-dependent and transient, with a median duration of 10 to 16 days [59]. The most frequent TEAEs (incidence 5%) occurring at twice the frequency of placebo were nausea and vomiting, plateauing at 15 mg/day [13, 60]. Other common antidepressant TEAEs such as headache, dry mouth, dizziness, and insomnia occurred at placebo levels without a dose effect. Suicidal ideation rates were similar between vortioxetine and placebo groups, including patients aged 18–24 years [13, 60]. A meta-analysis in elderly patients (aged 55–88) found vortioxetine effective and well-tolerated, with common side effects including nausea, dizziness, and headache, but no significant impact on biochemical parameters, vital signs, or body weight [55, 60]. Withdrawal rates due to TEAEs ranged from 4.5 to 7.8% for vortioxetine, which were lower than those for venlafaxine (14.2%) and duloxetine (8.8%) [60].

Patients treated with antidepressants often face key tolerability concerns, including sexual function, weight changes, and cardiac/cardiovascular safety:

  1. 1.

    Sexual Dysfunction: TEAEs related to sexual dysfunction were low in patients receiving vortioxetine (1.6–1.8%) compared to placebo (1.0) Moreover, vortioxetine has been shown to improve sexual function in patients with SSRI-induced sexual dysfunction [60, 61].

  2. 2.

    Weight Changes: In short-term treatment, mean weight changes were similar for vortioxetine and placebo, with no significant weight gain or loss observed [60].

  3. 3.

    Cardiac and Cardiovascular Safety: Vortioxetine demonstrated no clinically significant effects on ECG parameters, including QT intervals, in both MDD patients and healthy subjects [59, 60, 62].

The low incidence of these key tolerability concerns with vortioxetine treatment highlights its potential as a well-tolerated antidepressant option for a wide range of patients, including those with specific tolerability concerns or medical comorbidities.

Drug-drug interactions

Vortioxetine’s favorable cytochrome P450 (CYP) enzyme inhibitory profile reduces the risk of clinically relevant interactions, especially compared to other antidepressants like fluoxetine, paroxetine, duloxetine, and bupropion [21]. Unlike some SSRIs and SNRIs, vortioxetine does not significantly increase bleeding risks when co-administered with warfarin, aspirin, or other anticoagulants. This has been demonstrated in studies evaluating vortioxetine’s effects on the pharmacokinetics and pharmacodynamics of aspirin and warfarin. However, caution is always advisable during co-administration of any medications with potential interactions [63, 64].

Vortioxetine’s minimal impact on CYP enzymes and its low potential for clinically significant drug-drug interactions are important advantages, particularly for patients with comorbid conditions requiring multiple medications. This favorable interaction profile may contribute to improved treatment adherence and reduced risk of adverse events related to polypharmacy.

Dosage and formulations

A clear dose-response relationship has been observed for vortioxetine in both clinical practice and clinical trials. Vortioxetine 20 mg/day demonstrated significant differences from placebo in improving total depressive symptomatology as early as week two, whereas vortioxetine 10 mg showed separation from placebo only from week four onward. At week eight, the mean change from baseline in MADRS total score was significantly greater for vortioxetine 20 mg/day compared to 10 mg/day. Notably, the incidence of adverse events did not increase in patients receiving vortioxetine 20 mg/day versus 10 mg/day. In flexible-dose studies, 48.0% of patients had their dose increased to 20 mg/day after one week and 64.3% maintained a final dose of 20 mg/day [25].

The administration of vortioxetine at a daily dose of 20 mg provides a faster and more sustained symptomatic improvement compared to the 10 mg/day dose in individuals diagnosed with MDD, without adversely affecting tolerability [25].

In our clinical experience, the most common side effect of vortioxetine is nausea. A slow titration (i.e., reaching the 10 mg dose in 5–10 days) further improves the tolerability profile and reduces the risk of nausea [65]. This can be easily achieved in countries where a liquid formulation is available.

Conclusions

Vortioxetine can play a key role in the treatment of certain subgroups of depressed patients, such as those with anhedonia, emotional blunting, cognitive dysfunction, and comorbid anxiety. The drug effectively addresses a range of depressive symptoms, including cognitive problems, anhedonia, and emotional blunting. Vortioxetine’s safety and tolerability profile, including relatively low rates of sexual dysfunction and minimal weight effects, enhance its viability for long-term treatment of MDD. Additionally, its limited drug-drug interactions are beneficial for patients treated with other medications. In conclusion, vortioxetine can provide relief across a broad spectrum of symptoms, including anhedonia, emotional blunting, cognitive dysfunction, and comorbid anxiety symptoms, while maintaining a relatively favorable safety profile.

This makes vortioxetine a valuable treatment option for patients with MDD who present with these specific symptom profiles, allowing for a more personalized approach to treatment.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

MDD:

Major Depressive Disorder

MADRS:

Montgomery–Åsberg Depression Rating Scale

RAVLT:

Rey Auditory Verbal Learning Test

DSST:

Digit Symbol Substitution Test

AD:

Alzheimer’s disease

SHAPS:

Snaith-Hamilton Pleasure Scale

GAD:

Generalized Anxiety Disorder

COPD:

Chronic Obstructive Pulmonary Disorders

TEAEs:

Treatment-Emergent Adverse Events

References

  1. Uher R. The implications of gene-environment interactions in depression: will cause inform cure? Mol Psychiatry. 2008;13(12):1070–8.

    Article  CAS  PubMed  Google Scholar 

  2. Kendler KS, Gardner CO. A longitudinal etiologic model for symptoms of anxiety and depression in women. Psychol Med. 2011;41(10):2035–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Arnaez JM, Krendl AC, McCormick BP, Chen Z, Chomistek AK. The association of depression stigma with barriers to seeking mental health care: a cross-sectional analysis. J Ment Health Abingdon Engl. 2020;29(2):182–90.

    Article  Google Scholar 

  4. van Eeden WA, van Hemert AM, Carlier IVE, Penninx BW, Giltay EJ. Severity, course trajectory, and within-person variability of individual symptoms in patients with major depressive disorder. Acta Psychiatr Scand. 2019;139(2):194–205.

    Article  PubMed  Google Scholar 

  5. Arnaud AM, Brister TS, Duckworth K, Foxworth P, Fulwider T, Suthoff ED, et al. Impact of treating Depression on Associated comorbidities: a systematic literature review. Prim Care Companion CNS Disord. 2023;25(1):22r03330.

    Article  PubMed  Google Scholar 

  6. Kasper S, Frazer A. Editorial for treatment-resistant depression (TRD). Int J Neuropsychopharmacol. 2019;22(2):83–4.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Latimer EA, Bond GR, Drake RE. Economic approaches to improving access to evidence-based and recovery-oriented services for people with severe mental illness. Can J Psychiatry Rev Can Psychiatr. 2011;56(9):523–9.

    Article  Google Scholar 

  8. Cole JO, Bodkin JA. Antidepressant drug side effects. J Clin Psychiatry. 1990;51:21–6.

    PubMed  Google Scholar 

  9. Carvalho AF, Sharma MS, Brunoni AR, Vieta E, Fava GA. The Safety, Tolerability and Risks Associated with the use of newer generation antidepressant drugs: a critical review of the literature. Psychother Psychosom. 2016;85(5):270–88.

    Article  PubMed  Google Scholar 

  10. Beshai S, Dobson KS, Bockting CLH, Quigley L. Relapse and recurrence prevention in depression: current research and future prospects. Clin Psychol Rev. 2011;31(8):1349–60.

    Article  PubMed  Google Scholar 

  11. Harsanyi S, Kupcova I, Danisovic L, Klein M. Selected biomarkers of Depression: what are the effects of cytokines and inflammation? Int J Mol Sci. 2022;24(1):578.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Forbes A, Keleher MR, Venditto M, DiBiasi F. Assessing patient adherence to and Engagement with Digital interventions for Depression in clinical trials: systematic literature review. J Med Internet Res. 2023;25:e43727.

    Article  PubMed  PubMed Central  Google Scholar 

  13. de Bartolomeis A, Fagiolini A, Maina G. [Vortioxetine in the treatment of major depression]. Riv Psichiatr. 2016;51(6):215–30.

    PubMed  Google Scholar 

  14. Bortolato B, Miskowiak KW, Köhler CA, Maes M, Fernandes BS, Berk M, et al. Cognitive remission: a novel objective for the treatment of major depression? BMC Med. 2016;14:9.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Maj M. Why the clinical utility of diagnostic categories in psychiatry is intrinsically limited and how we can use new approaches to complement them. World Psychiatry off J World Psychiatr Assoc WPA. 2018;17(2):121–2.

    Google Scholar 

  16. Maj M, Stein DJ, Parker G, Zimmerman M, Fava GA, De Hert M, et al. The clinical characterization of the adult patient with depression aimed at personalization of management. World Psychiatry off J World Psychiatr Assoc WPA. 2020;19(3):269–93.

    Google Scholar 

  17. Chen G, Højer AM, Areberg J, Nomikos G. Vortioxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2018;57(6):673–86.

    Article  PubMed  Google Scholar 

  18. Gonda X, Sharma SR, Tarazi FI. Vortioxetine: a novel antidepressant for the treatment of major depressive disorder. Expert Opin Drug Discov. 2019;14(1):81–9.

    Article  CAS  PubMed  Google Scholar 

  19. Sanchez C, Asin KE, Artigas F. Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data. Pharmacol Ther. 2015;145:43–57.

    Article  CAS  PubMed  Google Scholar 

  20. Pehrson AL, Cremers T, Bétry C, van der Hart MGC, Jørgensen L, Madsen M, et al. Lu AA21004, a novel multimodal antidepressant, produces regionally selective increases of multiple neurotransmitters–a rat microdialysis and electrophysiology study. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol. 2013;23(2):133–45.

    Article  CAS  Google Scholar 

  21. Spina E, Santoro V. Drug interactions with vortioxetine, a new multimodal antidepressant. Riv Psichiatr. 2015;50(5):210–5.

    PubMed  Google Scholar 

  22. Bennabi D, Haffen E, Van Waes V. Vortioxetine for cognitive enhancement in Major Depression: from animal models to Clinical Research. Front Psychiatry. 2019;10:771.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Meyer JH. Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. J Psychiatry Neurosci JPN. 2007;32(2):86–102.

    PubMed  Google Scholar 

  24. Thase ME, Mahableshwarkar AR, Dragheim M, Loft H, Vieta E. A meta-analysis of randomized, placebo-controlled trials of vortioxetine for the treatment of major depressive disorder in adults. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol. 2016;26(6):979–93.

    Article  CAS  Google Scholar 

  25. Christensen MC, McIntyre RS, Florea I, Loft H, Fagiolini A. Vortioxetine 20 mg/day in patients with major depressive disorder: updated analysis of efficacy, safety, and optimal timing of dose adjustment. CNS Spectr. 2023;28(1):90–7.

    Article  PubMed  Google Scholar 

  26. Christensen MC, McIntyre RS, Adair M, Florea I, Loft H, Fagiolini A. Clinical benefits of vortioxetine 20 mg/day in patients with major depressive disorder. CNS Spectr. 2023;28(6):693–701.

    Article  PubMed  Google Scholar 

  27. Dale E, Zhang H, Leiser SC, Xiao Y, Lu D, Yang CR, et al. Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus. J Psychopharmacol Oxf Engl. 2014;28(10):891–902.

    Article  CAS  Google Scholar 

  28. Leiser SC, Pehrson AL, Robichaud PJ, Sanchez C. Multimodal antidepressant vortioxetine increases frontal cortical oscillations unlike escitalopram and duloxetine–a quantitative EEG study in rats. Br J Pharmacol. 2014;171(18):4255–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Conen S, McKie S, Smallman RP, Dutta A, Dawson GR, Smith J et al. P. 2. f. 014 effects of vortioxetine on resting-state activity in subjects remitted from depression and healthy controls. Eur Neuropsychopharmacol. 2015;(25):S442.

  30. Katona C, Hansen T, Olsen CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder. Int Clin Psychopharmacol. 2012;27(4):215–23.

    Article  PubMed  Google Scholar 

  31. McIntyre RS, Lophaven S, Olsen CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol. 2014;17(10):1557–67.

    Article  CAS  PubMed  Google Scholar 

  32. Mahableshwarkar AR, Zajecka J, Jacobson W, Chen Y, Keefe RSEA, Randomized P-C. Active-Reference, Double-Blind, flexible-dose study of the efficacy of Vortioxetine on cognitive function in major depressive disorder. Neuropsychopharmacol off Publ Am Coll Neuropsychopharmacol. 2015;40(8):2025–37.

    Article  CAS  Google Scholar 

  33. Harrison JE, Lophaven S, Olsen CK. Which cognitive domains are improved by treatment with Vortioxetine? Int J Neuropsychopharmacol. 2016;19(10):pyw054.

    Article  PubMed  PubMed Central  Google Scholar 

  34. McIntyre RS, Florea I, Tonnoir B, Loft H, Lam RW, Christensen MC. Efficacy of Vortioxetine on cognitive functioning in working patients with Major Depressive Disorder. J Clin Psychiatry. 2017;78(1):115–21.

    Article  PubMed  Google Scholar 

  35. Chokka P, Bougie J, Proulx J, Tvistholm AH, Ettrup A. Long-term functioning outcomes are predicted by cognitive symptoms in working patients with major depressive disorder treated with vortioxetine: results from the AtWoRC study. CNS Spectr. 2019;24(6):616–27.

    Article  PubMed  Google Scholar 

  36. McIntyre RS, Harrison J, Loft H, Jacobson W, Olsen CK. The effects of Vortioxetine on cognitive function in patients with major depressive disorder: a Meta-analysis of three randomized controlled trials. Int J Neuropsychopharmacol. 2016;19(10):pyw055.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Huang IC, Chang TS, Chen C, Sung JY. Effect of Vortioxetine on cognitive impairment in patients with major depressive disorder: a systematic review and Meta-analysis of Randomized controlled trials. Int J Neuropsychopharmacol. 2022;25(12):969–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Rosenblat JD, Kakar R, McIntyre RS. The Cognitive effects of antidepressants in Major Depressive disorder: a systematic review and Meta-analysis of Randomized clinical trials. Int J Neuropsychopharmacol. 2015;19(2):pyv082.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Baune BT, Brignone M, Larsen KG. A Network Meta-Analysis comparing effects of various antidepressant classes on the Digit Symbol Substitution Test (DSST) as a measure of cognitive dysfunction in patients with major depressive disorder. Int J Neuropsychopharmacol. 2018;21(2):97–107.

    Article  PubMed  Google Scholar 

  40. Cao B, Park C, Subramaniapillai M, Lee Y, Iacobucci M, Mansur RB, et al. The efficacy of Vortioxetine on Anhedonia in patients with Major Depressive Disorder. Front Psychiatry. 2019;10:17.

    Article  PubMed  PubMed Central  Google Scholar 

  41. McIntyre RS, Loft H, Christensen MC. Efficacy of Vortioxetine on Anhedonia: results from a pooled analysis of short-term studies in patients with major depressive disorder. Neuropsychiatr Dis Treat. 2021;17:575–85.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Mattingly GW, Necking O, Schmidt SN, Reines E, Ren H. Long-term safety and efficacy, including anhedonia, of vortioxetine for major depressive disorder: findings from two open-label studies. Curr Med Res Opin. 2023;39(4):613–9.

    Article  CAS  PubMed  Google Scholar 

  43. Fagiolini A, Florea I, Loft H, Christensen MC. Effectiveness of Vortioxetine on emotional blunting in patients with major depressive disorder with inadequate response to SSRI/SNRI treatment. J Affect Disord. 2021;283:472–9.

    Article  CAS  PubMed  Google Scholar 

  44. Baldwin DS, Florea I, Jacobsen PL, Zhong W, Nomikos GG. A meta-analysis of the efficacy of vortioxetine in patients with major depressive disorder (MDD) and high levels of anxiety symptoms. J Affect Disord. 2016;206:140–50.

    Article  CAS  PubMed  Google Scholar 

  45. Adair M, Christensen MC, Florea I, Loft H, Fagiolini A. Vortioxetine in patients with major depressive disorder and high levels of anxiety symptoms: an updated analysis of efficacy and tolerability. J Affect Disord. 2023;328:345–54.

    Article  CAS  PubMed  Google Scholar 

  46. Christensen MC, Schmidt S, Grande I. Effectiveness of vortioxetine in patients with major depressive disorder comorbid with generalized anxiety disorder: results of the RECONNECT study. J Psychopharmacol Oxf Engl. 2022;36(5):566–77.

    Article  CAS  Google Scholar 

  47. Almeida SS, Christensen MC, Simonsen K, Adair M. Effectiveness of vortioxetine in patients with major depressive disorder and co-morbid generalized anxiety disorder in routine clinical practice: a subgroup analysis of the RELIEVE study. J Psychopharmacol Oxf Engl. 2023;37(3):279–88.

    Article  CAS  Google Scholar 

  48. Chokka P, Bougie J, Rampakakis E, Proulx J. Assessment in Work Productivity and the relationship with cognitive symptoms (AtWoRC): primary analysis from a Canadian open-label study of vortioxetine in patients with major depressive disorder (MDD). CNS Spectr. 2019;24(3):338–47.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Jeong HW, Yoon KH, Lee CH, Moon YS, Kim DH. Vortioxetine Treatment for Depression in Alzheimer’s Disease: a Randomized, Double-blind, placebo-controlled study. Clin Psychopharmacol Neurosci off Sci J Korean Coll Neuropsychopharmacol. 2022;20(2):311–9.

    Article  CAS  Google Scholar 

  50. Cumbo E, Cumbo S, Torregrossa S, Migliore D. Treatment effects of Vortioxetine on cognitive functions in mild Alzheimer’s Disease patients with depressive symptoms: a 12 Month, Open-Label, Observational Study. J Prev Alzheimers Dis. 2019;6(3):192–7.

    CAS  PubMed  Google Scholar 

  51. Di Nicola M, Pepe M, Panaccione I, Moccia L, Dattoli L, Molinaro M, et al. Effect of vortioxetine in subjects with major depressive and alcohol use disorders: a 6-month retrospective analysis. CNS Spectr. 2022;27(1):73–81.

    Article  PubMed  Google Scholar 

  52. Basurte-Villamor I, Vega P, Roncero C, Martínez-Raga J, Grau-López L, Aguilar L, et al. A feasibility study of patients with Major Depression and Substance Use disorders: Vortioxetine as maintenance treatment. Neuropsychiatr Dis Treat. 2022;18:965–76.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Santos García D, Alonso Losada MG, Cimas Hernando I, Cabo López I, Yáñez Baña R, Alonso Redondo R, et al. Vortioxetine improves depressive symptoms and cognition in Parkinson’s Disease patients with Major Depression: an open-label prospective study. Brain Sci. 2022;12(11):1466.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Baldwin DS, Necking O, Schmidt SN, Ren H, Reines EH. Efficacy and safety of vortioxetine in treatment of patients with major depressive disorder and common co-morbid physical illness. J Affect Disord. 2022;311:588–94.

    Article  CAS  PubMed  Google Scholar 

  55. Nomikos GG, Tomori D, Zhong W, Affinito J, Palo W. Efficacy, safety, and tolerability of vortioxetine for the treatment of major depressive disorder in patients aged 55 years or older. CNS Spectr. 2017;22(4):348–62.

    Article  PubMed  Google Scholar 

  56. Alvarez E, Perez V, Artigas F. Pharmacology and clinical potential of vortioxetine in the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2014;10:1297–307.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Al-Sukhni M, Maruschak NA, McIntyre RS. Vortioxetine: a review of efficacy, safety and tolerability with a focus on cognitive symptoms in major depressive disorder. Expert Opin Drug Saf. 2015;14(8):1291–304.

    Article  CAS  PubMed  Google Scholar 

  58. Kelliny M, Croarkin PE, Moore KM, Bobo WV. Profile of vortioxetine in the treatment of major depressive disorder: an overview of the primary and secondary literature. Ther Clin Risk Manag. 2015;11:1193–212.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Baldwin DS, Serenko M, Palo W, Lophaven S, Matz J. The safety and tolerability of vortioxetine (Lu AA21004) in the treatment of adults with major depressive disorder (MDD): a pooled analysis. International Journal of Psychiatry in Clinical Practice. INFORMA HEALTHCARE ℡EPHONE HOUSE; 2013. pp. 69–77. PAUL STREET, LONDON EC2A 4LQ, ENGLAND.

  60. Baldwin DS, Chrones L, Florea I, Nielsen R, Nomikos GG, Palo W, et al. The safety and tolerability of vortioxetine: analysis of data from randomized placebo-controlled trials and open-label extension studies. J Psychopharmacol Oxf Engl. 2016;30(3):242–52.

    Article  CAS  Google Scholar 

  61. Jacobsen PL, Mahableshwarkar AR, Chen Y, Chrones L, Clayton AH. Effect of Vortioxetine vs. Escitalopram on sexual functioning in adults with well-treated Major Depressive Disorder Experiencing SSRI-Induced sexual dysfunction. J Sex Med. 2015;12(10):2036–48.

    Article  CAS  PubMed  Google Scholar 

  62. Wang Y, Nomikos GG, Karim A, Munsaka M, Serenko M, Liosatos M, et al. Effect of Vortioxetine on Cardiac Repolarization in healthy adult male subjects: results of a thorough QT/QTc study. Clin Pharmacol Drug Dev. 2013;2(4):298–309.

    Article  CAS  PubMed  Google Scholar 

  63. Chen G, Zhang W, Serenko M. Lack of effect of multiple doses of vortioxetine on the pharmacokinetics and pharmacodynamics of aspirin and warfarin. J Clin Pharmacol. 2015;55(6):671–9.

    Article  CAS  PubMed  Google Scholar 

  64. Spina E, Trifirò G, Caraci F. Clinically significant drug interactions with newer antidepressants. CNS Drugs. 2012;26(1):39–67.

    Article  CAS  PubMed  Google Scholar 

  65. Fagiolini A, Cuomo A, Barillà G, Cattolico M, Koukouna D, Mariantoni E, Pardossi S, Pierini C, Pinzi M, Piumini G. Clinical Benefits, efficacy and tolerability of slowly titrated vortioxetine oral drops solution. 32nd European Congress of Psychiatry 2024, E-Poster EPV0425 European Psychiatry. in press.

  66. Christensen MC, Florea I, Lindsten A, et al. Efficacy of vortioxetine on the physical symptoms of major depressive disorder. J Psychopharmacol. 2018;32:1086–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Talmon M, Rossi S, Pastore A, et al. Vortioxetine exerts anti-inflammatory and immunomodulatory effects on human monocytes/macrophages. Br J Pharmacol. 2018;175:113–24.

    Article  CAS  PubMed  Google Scholar 

  68. Di Nicola M, Pepe M, Montanari S, et al. Vortioxetine improves physical and cognitive symptoms in patients with post-COVID-19 major depressive episodes. Eur Neuropsychopharmacol. 2023. https://doi.org/10.1016/j.euroneuro.2023.02.001. Epub ahead of print 3 February 2023.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

An Independent Medical Writing assistance and Open Access fee were funded by Lundbeck Italia S.p.A (Milan, Italy).

Author information

Authors and Affiliations

Authors

Contributions

All authors participated in reviewing the literature, drafting and finalizing the manuscript.

Corresponding author

Correspondence to Alessandro Cuomo.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

Andrea Fagiolini is /has been a consultant and/or a speaker and/or has received research grants from Angelini, Apsen, Biogen, Boheringer Ingelheim, Idorsia Italfarmaco, Lundbeck, Janssen, Medicamenta, Mylan, Otsuka, Pfizer, Recordati, Sunovion, ViatrisAlessandro Cuomo is /has been a consultant and/or a speaker and/or has received research grants from Angelini, Boheringer Ingelheim, Idorsia Italfarmaco, Lundbeck, Janssen, Medicamenta, Mylan, Otsuka, Pfizer, Recordati, Sunovion, ViatrisNo other authors have conflicts of interest to declare. Alessandro Cuomo is /has been a consultant and/or a speaker and/or has received research grants from Angelini, Boheringer Ingelheim, Idorsia Italfarmaco, Lundbeck, Janssen, Medicamenta, Mylan, Otsuka, Pfizer, Recordati, Sunovion, Viatris. No other authors have conflicts of interest to declare.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cuomo, A., Aguglia, A., De Berardis, D. et al. Individualized strategies for depression: narrative review of clinical profiles responsive to vortioxetine. Ann Gen Psychiatry 23, 20 (2024). https://doi.org/10.1186/s12991-024-00505-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12991-024-00505-1

Keywords