Adjunctive vortioxetine for SSRI-resistant major depressive disorder: a real-world chart review study

Objective: Selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of treatment of major depressive disorder (MDD). However, non-response is common, often necessitating combination strategies. The present study assessed the efficacy of vortioxetine as an add-on therapy in patients with SSRI-resistant MDD. Methods: The charts of 36 adult outpatients with DSM-IV-TR MDD who had not achieved a response after at least 8 weeks of treatment with an SSRI were reviewed retrospectively. Subjects were treated with vortioxetine (5-20 mg/day) for 8 weeks added to the current SSRI. The main outcome measures were change from baseline in total Hamilton Scale for Depression (HAM-D) score and the rate of response (a 50% or greater reduction in HAM-D score and a Clinical Global Impression ‐ Improvement module [CGI-I] score of 1 or 2 at endpoint). HAM-D scores ≤ 7 were considered as remission. Additional outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS) and the Scale for Suicide Ideation (SSI). Results: 32 patients completed the 8 weeks of treatment. At 8 weeks, a significant reduction in HAM-D score was observed (p ≤ 0.001), with response obtained by 41.7% and remission by 33.3% of patients. Significant reductions in SHAPS and SSI were also observed (p ≤ 0.001 for both scales). Conclusions: Adjunctive vortioxetine may be useful and well-tolerated in stage I treatment-resistant depression. However, the limitations of this study (such as small sample size, absence of randomization and control group, retrospective design, etc.) must be considered.

The effect of vortioxetine on penicillin-induced epileptiform activity in rats / O efeito da vortioxetina sobre a atividade epileptiforme induzida pela penicilina em ratos

ABSTRACT Vortioxetine is a multimodal antidepressant agent that modulates 5-HT receptors and inhibits the serotonin transporter. It is indicated especially in cases of major depressive disorder related to cognitive dysfunction. There are many studies investigating the effects of antidepressants on the seizure threshold and short-term epileptic activity. However, the effect of vortioxetine on epileptic seizures is not exactly known. Our aim was to investigate the effects of vortioxetine on penicillin-induced epileptiform activity. Twenty-seven Wistar rats were divided into three groups: sham-control group, positive control group (diazepam), and vortioxetine group. After a penicillin-induced epilepsy model was formed in each of the three groups of animals, 0.1 ml of saline was administered to the control group, 0.1 ml (10 mg/kg) vortioxetine was administered in the vortioxetine group, and 0.1 mL (5 mg/kg) of diazepam was administered in the positive control group, intraperitoneally. The epileptic activity records were obtained for 120 minutes after the onset of seizure. There was no significant difference in spike wave activity between the vortioxetine and diazepam groups, whereas this was significantly reduced in the vortioxetine group compared with the controls. The administration of vortioxetine at a dose of 10 mg/kg immediately after the seizure induction significantly decreased the spike frequencies of epileptiform activity compared with the control group. No significant difference was found between the vortioxetine and positive controls. This study showed that vortioxetine reduces the number of acutely-induced epileptic discharges. Vortioxetine may be an important alternative for epileptic patients with major depressive disorder-related cognitive dysfunction.

RESUMO A vortioxetina é um agente antidepressivo multimodal que modula os receptores 5HT e inibe o transportador de serotonina. Está indicada, principalmente nos casos de transtorno depressivo maior (TDM), relacionado à disfunção cognitiva. Existem muitos estudos que investigam os efeitos dos antidepressivos no limiar convulsivo e na atividade epiléptica de curto prazo. No entanto, o efeito da vortioxetina nas crises epilépticas não é exatamente conhecido. Nosso objetivo é investigar os efeitos da vortioxetina sobre a atividade epileptiforme induzida pela penicilina. Vinte e sete ratos Wistar foram divididos em três grupos, grupo controle-sham, grupo controle positivo (Diazepam) e grupo vortioxetina. Depois, 0,1 mg (10 mg / kg) de vortioxetina foi administrado no grupo vortioxetina, e 0,1 ml (5 mg / kg) / kg) de diazepam foi administrado no grupo de controle positivo intraperitonealmente. Os registros de atividade epiléptica foram obtidos durante 120 minutos após o início da convulsão. Não houve diferença significativa na atividade de pico entre o grupo de voritoxetina e diazepam, embora tenha sido significativamente reduzida no grupo de vortioxetina em comparação com os controles. A administração de vortioxetina na dose de 10 mg / kg imediatamente após a indução das convulsões diminuiu significativamente as frequências de espícula da atividade epileptiforme em comparação com o grupo controle. Nenhuma diferença significativa foi encontrada entre a vortioxetina e controles positivos. Este estudo mostrou que a vortioxetina reduz o número de descargas epilépticas agudamente induzidas. A vortioxetina pode ser uma alternativa importante para pacientes epilépticos com disfunção cognitiva relacionada à TDM.