The role of new antidepressants in clinical practice in Canada: a brief review of vortioxetine, levomilnacipran ER, and vilazodone
Bibliographic record
Abstract
Abstract: Although many branded and generic antidepressants are approved for the treatment of major depressive disorder (MDD) in Canada, efficacy and tolerability differ among patients, and new treatment options are needed. Symptom types (eg, fatigue, energy/motivation, cognition, and functioning), medication type, treatment duration, and the need for maintenance therapy are factors that may influence treatment effectiveness. Three antidepressants, vortioxetine, levomilnacipran extended-release (ER), and vilazodone have recently become available in Canada. The aim of this review is to contextualize differences in their mechanistic and clinical profiles, thereby providing practitioners with knowledge to support treatment decisions. In trials versus placebo, each drug improved depressive symptoms in adult patients with MDD. The antidepressant effect of vortioxetine may be related to enhanced serotonergic activity via reuptake inhibition and agonism and/or antagonism of various serotonin receptors. Vortioxetine may also improve cognitive functioning in MDD, and has proven efficacious in relapse prevention. Nausea was the most commonly reported adverse event (AE); rates of sexual dysfunction were low and abrupt discontinuation was well tolerated. Levomilnacipran ER, a serotonin norepinephrine reuptake inhibitor, demonstrated greater improvement versus placebo in functional impairment as well as depressive symptoms; in post hoc analyses, improvement in symptoms of motivation and energy were observed. Nausea was the most commonly reported AE; gradual discontinuation is recommended to avoid discontinuation syndrome. Vilazodone is a serotonin reuptake inhibitor and partial serotonergic 5-HT 1A receptor agonist. In addition to improvement in depressive symptoms, evidence suggests that vilazodone may be particularly well suited for depressed patients with high anxiety levels. Diarrhea, nausea, and headache were the most common AEs; low rates of sexual dysfunction were reported. The 2016 Canadian Network for Mood and Anxiety Treatments guidelines for MDD includes vortioxetine as a first-line treatment; levomilnacipran ER and vilazodone are considered as second-line treatments due to lack of relapse prevention data at the time of approval. Keywords: serotonin reuptake inhibitor, norepinephrine reuptake inhibitor, depression, major depressive disorder
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.010 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.009 | 0.013 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".