The role of new antidepressants in clinical practice in Canada: a brief review of vortioxetine, levomilnacipran ER, and vilazodone

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-HT1A 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.

Effectiveness, tolerability, and dropout rates of vortioxetine in comorbid depression: A naturalistic study

“…Furthermore, vortioxetine showed a favorable profile in terms of sexual side effects in the studied sample: only one patient (4.5%) reported this specific side effect, and we could not exclude that it was related to other concomitant treatment. In other studies, vortioxetine showed a lower rate of sexual dysfunctions compared to other antidepressants, reported in <2% of vortioxetine‐treated patients (Baldwin et al, 2016; McIntyre, 2017). Although in the present study no significant differences among vortioxetine dosage groups were observed, in other trials, sexual dysfunction was found to be more frequent with higher doses, but always lower than those of selective serotonin reuptake inhibitors (SSRIs) (Jacobsen, Mahableshwarkar, Chen, Chrones, & Clayton, 2015).…”

“…Overall, two‐thirds of recruited patients did not report any side effects, while in the other third, the 72.7% experimented gastrointestinal side effects (mainly nausea, vomit, and diarrhea) and the 22.7% gastrointestinal ones associated with other side effects (mainly headache and sweating). Indeed, It is well established that vortioxetine's most common side effect is nausea (affecting more than one in 10 people) (EMA, 2014; McIntyre, 2017), generally with mild or moderate severity related to high dosage and usually decreasing or extinguishing in few weeks (De Bartolomeis, Fagiolini, & Maina, 2016). In the same direction, the duration of side effects, in the present study, slightly exceeded 4 weeks (37.17 ± 33.12 days): conversely, the reported severity of side effects was moderate–severe (36.4% moderate and 36.4% severe), and a worse tolerability was not associated with high doses of vortioxetine.…”

Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis

“…Even though the reasons for discontinuation are unclear from these data, common problems with SSRIs or SNRIs include sexual dysfunction, weight gain and sleep disturbances [9]. The more recent treatment options for GAD target a reduction of these side effects [12]. These newer compounds include the serotonin modulator and stimulator (SMS) vortioxetine, the melatonergic antidepressant agomelatine, and the serotonergic antidepressant vilazodone.…”

Antidepressant-Like Effects of Cistanche tubulosa Extract on Chronic Unpredictable Stress Rats Through Restoration of Gut Microbiota Homeostasis

“…This study evaluated the antidepressant activity of CTE in CUS rats, and confirmed the efficacy in in vivo models such as FST, SPT, OFT, and NSFT, and confirmed the anti-depressive activity of C. tubulosa in CUS rats which is frequently used for the treatment of kidney deficiency, impotence, and female infertility in TCM. Currently, the most commonly prescribed antidepressants are the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine, followed by the selective serotonin reuptake inhibitor (SSRI) FLX ( Thase et al, 2001 ; Mcintyre, 2017 ). However, these antidepressants have been shown to possess severe side effects including cardiac toxicity, blood pressure, sexual dysfunction, and sleep disorders ( Ferguson, 2001 ; Jin et al, 2015 ).…”