Efficacy, Tolerability, and Safety of Toludesvenlafaxine for the Treatment of Major Depressive Disorder—A Narrative Review

Abstract

The estimated rate of treatment-resistant major depressive disorder (TRD) remains higher than 30%, even after the discovery of multiple classes of antidepressants in the last 7 decades. Toludesvenlafaxine (ansofaxine, LY03005, or LPM570065) is a first-in-class triple monoaminergic reuptake inhibitor (TRI) that has reached clinical use. The objective of this narrative review was to summarize clinical and preclinical evidence about the efficacy, tolerability, and safety of toludesvenlafaxine. Based on the results of 17 reports retrieved in the literature, the safety and tolerability profiles of toludesvenlafaxine were good in all clinical trials, and the pharmacokinetic parameters were well described in the phase 1 trials. The efficacy of toludesvenlafaxine was demonstrated in one phase 2 and one phase 3 trial, both on primary and secondary outcomes. In conclusion, this review highlights the favorable clinical results of toludesvenlafaxine in only two short-term trials that enrolled patients with major depressive disorder (MDD) (efficacy and tolerability were good for up to eight weeks), indicating the need for more good quality, larger-sample, and longer-term trials. Exploring new antidepressants, such as TRI, can be considered a priority for clinical research due to the high rates of TRD, but also due to the significant percentages of relapse in patients with MDD.

Innovation at the Intersection: Emerging Translational Research in Neurology and Psychiatry

“…The first paper by Vasiliu provides a narrative review of the efficacy, tolerability, and safety of toludesvenlafaxine, a novel antidepressant that belongs to the class of serotonin and norepinephrine reuptake inhibitors (SNRIs) [89]. The author summarizes the results of preclinical and clinical studies that evaluated the pharmacokinetics, pharmacodynamics, and therapeutic effects of toludesvenlafaxine in comparison with other SNRIs, such as venlafaxine, duloxetine, and desvenlafaxine.…”

Neurodegeneration in Cognitive Impairment and Mood Disorders for Experimental, Clinical and Translational Neuropsychiatry

“…The integration and interpretation data derived from various origins and modes, including genetics, epigenetics, proteomics, metabolomics, imaging, electrophysiology, and neuropsychology [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. The development and validation of novel methods, such as NIBS, artificial intelligence, and drug repurposing, which necessitate thorough examination and assessment of their safety, effectiveness, and mechanisms [ 11 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ]. Addressing these challenges requires collaborative efforts among researchers, clinicians, patients, and policymakers from various fields to enhance our understanding and improve the treatment of neurodegeneration underlying cognitive impairment and mood disorders [ 55 , 56 , 57 , 58 ].…”

Oxidative and Excitatory Neurotoxic Stresses in CRISPR/Cas9-Induced Kynurenine Aminotransferase Knock-Out Mice: A Novel Model for Experience-Based Depression and Post-traumatic Stress Disordertabolism: Insights From Novel Kynurenine Aminotransferase

“…Moreover, they offer crucial insights into changes in structure and imaging techniques in clinical cases (140)(141)(142)(143)(144)(145)(146)(147)(148)(149)(150)(151)(152)(153)(154)(155)(156)(157)(158). Preclinical and clinical research collaboratively contribute to innovative therapeutics and personalized medicine (159)(160)(161)(162)(163)(164).…”