vortioxetine and Depressive-Disorder

This paper reviews recent research on late-life depression (LLD) pharmacotherapy, focusing on updated information for monotherapy and augmentation treatments. We then review new research on moderators of clinical response and how to use the information for improved efficacy.. A recent review shows that sertraline, paroxetine, and duloxetine were superior to placebo for the treatment of LLD. There is concern that paroxetine could have adverse outcomes in the geriatric population due to anticholinergic properties; however, studies show no increases in mortality, dementia risk, or cognitive measures. Among newer antidepressants, vortioxetine has demonstrated efficacy in LLD, quetiapine has demonstrated efficacy especially for patients with sleep disturbances, and aripiprazole augmentation for treatment resistance in LLD was found to be safe and effective. Researchers have also been identifying moderators of LLD that can guide treatment. Researchers are learning how to associate moderators, neuroanatomical models, and antidepressant response. SSRI/SNRIs remain first-line treatment for LLD. Aripiprazole is an effective and safe augmentation for treatment resistance. Studies are identifying actionable moderators that can increase treatment response.

Topics: Antidepressive Agents; Aripiprazole; Depression; Depressive Disorder; Drug Resistance; Duloxetine Hydrochloride; Humans; Paroxetine; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Sertraline; Vortioxetine

Topics: Animals; Antidepressive Agents; Depressive Disorder; Humans; Piperazines; Sulfides; Vortioxetine

Post-stroke depression (PSD) is a common and serious complication after stroke, occurring in nearly one third of stroke survivors, and affecting mortality rate, functional outcome, rehabilitation results and quality of life. However, in the common clinical practice only a minority of patients are properly treated. A relatively small number of scientific reports are available on clinical usefulness and safety of antidepressants (ADs) in PSD. Areas covered: This report provides an updated review about pharmacological state of art of PSD, including efficacy and safety of different drugs and their role on prevention, treatment and functional outcome. Expert opinion: Even if currently an antidepressant treatment can improve depressive symptoms, neither the optimal drug nor the optimal lengths of treatment, have been identified. Serotonergic drugs are preferable because of their better safety profile, but in the recent years there has been an important debate on possible association between selective serotonin reuptake inhibitor use and increased mortality. Another issue is the potential role of ADs for improving functional recovery. Newer ADs have interesting properties, in particular vortioxetine, due to its properties of enhancing cognitive functions, but further research is needed to clarify its/their role in treatment of PSD.

Topics: Antidepressive Agents; Cognition; Depression; Depressive Disorder; Humans; Piperazines; Quality of Life; Selective Serotonin Reuptake Inhibitors; Stroke; Sulfides; Vortioxetine

We recently conducted a comprehensive review of the psychiatric inclusion/exclusion criteria used in 170 placebo-controlled antidepressant efficacy trials (AETs) published during the past 20 years and found that the criteria of more recent studies were significantly more restrictive than prior studies. Vortioxetine is the most recently approved medication for the treatment of major depressive disorder (MDD). We compared the inclusion/exclusion criteria of the vortioxetine studies to the criteria used in other AETs, and discuss the broader issue of the generalizability of AETs and the implications this might have for the labeling of antidepressants receiving FDA approval.. We conducted a comprehensive literature review of placebo-controlled AETs published from January, 1995 through December, 2014. We identified 170 AETs published during this 20 year period and compared the inclusion/exclusion criteria used in the 12 studies of vortioxetine to those used in the nonvortioxetine studies. A second analysis compared vortioxetine to the 3 antidepressants most recently approved prior to vortioxetine (desvenlafaxine, levomilnacipran extended release, vilazodone).. Compared to the nonvortioxetine AETs, the vortioxetine studies significantly more often excluded patients with any comorbid Axis I disorder (p<.001) and more often required the current depressive episode to be longer than the DSM minimum symptom duration requirement of 2 weeks (p<.01). The cutoff on the Montgomery Asberg Depression Rating Scale required for inclusion in the vortioxetine studies was higher than the cutoff used in the other AETs (p<.01).. A limitation of the present analysis is that it was based on published placebo-controlled studies of antidepressants.. The inclusion/exclusion criteria in the studies of vortioxetine were more restrictive than the criteria used in other AETs. Inconsistent with FDA guidelines on the labeling of medications, the label of vortioxetine does not include a description of the limits to the group of patients with MDD for whom the medication has been shown to be effective.

Topics: Adult; Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Female; Humans; Male; Patient Selection; Piperazines; Product Labeling; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Sulfides; Vortioxetine

The development of new antidepressants has had mixed results over the past decade, with several notable failures. This paper reviews a number of major initiatives in the development of new antidepressant agents. Traditional strategies to build on agents that have monoaminergic effects at the synapse (e.g., vilazodone and ketamine) have been complemented with efforts that have emphasized devices and brain circuits (e.g., deep brain stimulation and transcranial magnetic stimulation) or chemical agents that modulate neuroendocrine systems (e.g., glucocorticoid antagonists, mixed melatonin agonists/serotonin type-2 receptor antagonists). Interestingly, chemical agents, such as onabotulinumtoxin A, may affect brain circuits as well. We present data from recent studies in drug and device development--reviewing progress made, stumbling blocks encountered, and issues that need to be addressed in future studies.

Topics: Antidepressive Agents; Benzofurans; Deep Brain Stimulation; Depressive Disorder; Drug Discovery; Humans; Indoles; Ketamine; Nerve Net; Neurosecretory Systems; Piperazines; Placebo Effect; Sulfides; Transcranial Magnetic Stimulation; Vilazodone Hydrochloride; Vortioxetine

5-HT(1A) receptor is a receptor of surprises. Buspirone, an anxiolytic drug with a then yet unidentified mechanism of action had been marketed for years when it was discovered that it is a 5-HT(1A) partial agonist. Several more years had to pass before it was accepted that this receptor plays the key role in the action mechanism of buspirone. This was followed by further surprises. It was discovered that in spite of its anxiolytic effect buspirone activates the hypothalamic-pituitary-adrenal (HPA) stress axis, furthermore, it increases peripheral noradrenaline and adrenaline concentration via a central mechanism. Thus activation of this receptor leads to ACTH/corticosterone and catecholamine release and also increases beta-endorphine, oxytocin and prolactin secretion while decreasing body temperature, increasing food uptake, eliciting characteristic behavioural responses in rodents and also playing a role in the development of certain types of epilepsy. Human genetic studies revealed the role of 5-HT(1A) receptors in cognitive processes playing a role in the development of depression such as impulsiveness or response to environmental stress. This exceptionally wide spectrum of effects is attributable to the presence of 5-HT1A receptors in serotonergic as well as other, for example glutamatergic, cholinergic, dopaminergic and noradrenergic neurons. The majority of the effects of 5-HT(1A) receptors is manifested via the mediation of Gi proteins through the hyperpolarisation or inhibition of the neuron carrying the receptor. 5-HT(1A) receptors on serotonergic neurons can be found in the somatodendritic area and play a significant role in delaying the effects of antidepressants which is an obvious disadvantage. Therefore the newest serotonergic antidepressants including vilazodone and vortioxetine have been designed to possess 5-HT(1A) receptor partial agonist properties. In the present paper we focus primarily on the role of 5-HT(1A) receptors in stress and antidepressant response.

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Buspirone; Depression; Depressive Disorder; Depressive Disorder, Major; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Piperazines; Pituitary-Adrenal System; Receptor, Serotonin, 5-HT1A; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists; Stress, Psychological; Sulfides; Vilazodone Hydrochloride; Vortioxetine

This article presents a brief review and summarizes current therapies for the treatment of chronic obstructive pulmonary disease, major depression, and rheumatoid arthritis. One new pharmaceutical agent is highlighted for each of the topics.

Topics: Anti-Anxiety Agents; Arthritis, Rheumatoid; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Depressive Disorder; Fluticasone; Humans; Nursing Process; Piperazines; Piperidines; Protein Kinase Inhibitors; Pulmonary Disease, Chronic Obstructive; Pyrimidines; Pyrroles; Sulfides; United States; Vortioxetine

To evaluate the effect of vortioxetine combined with cognitive behaviour intervention on the level of brain-derived neurotrophic factor (BDNF) in the serum of patients with depression and its therapeutic effect.. A total of 82 depressive patients treated at the School of Basic Medicine, Heilongjiang University of Chinese Medicine from January 2017 to June 2017 were randomised into a control group (n = 41) and intervention group (n = 41) according to a random number table. Both groups were given vortioxetine treatment, while the intervention group adopted an additional cognitive-behavioural therapy at the same time. The therapeutic effect was evaluated using the Hamilton Depression Scale (HAMD). The cognitive function was evaluated using continuous performance test (CPT) and Wisconsin card sorting test (WCST). The changes of BDNF level were detected with the use of enzyme-linked immunosorbent assay.. The HAMD score of the intervention group was obviously lower than that of the control group after treatment (P < 0.001). WCST test showed that the number of trials, perseverative errors and non-perseverative errors in the intervention group were significantly lower than those in the control group, while the correct matching number and the number of categories achieved were significantly higher than those in the control group (all P < 0.001). Results of CPT showed that the correct number of responses to stimulus, the verbal fluency and the fluency of classification in the intervention group were significantly higher than those in the control group (all P < 0.05). Moreover, after treatment, the serum BDNF level of the intervention group was significantly higher than that in the control group (P < 0.001).. Vortioxetine combined with cognitive behavioural therapy has a good clinical effect and can largely improve the cognitive function of depressive patients.

Topics: Adult; Brain-Derived Neurotrophic Factor; Cognitive Behavioral Therapy; Cognitive Dysfunction; Combined Modality Therapy; Depressive Disorder; Female; Humans; Male; Outcome Assessment, Health Care; Selective Serotonin Reuptake Inhibitors; Vortioxetine

The primary objectives of this study were to evaluate the pharmacokinetics (PK) and tolerability of single and multiple doses of vortioxetine in children and adolescents with a depressive or anxiety disorder and to provide supportive information for appropriate dosing regimens for pediatric clinical trials.. This prospective, open-label, multinational, multisite, multiple-dose trial enrolled 48 patients (children and adolescents; 1:1 ratio) divided into 8 cohorts (4 adolescent and 4 child), with each cohort including 6 patients. The cohorts in each age group were assigned to receive one of four dosing regimens: vortioxetine 5, 10, 15, or 20 mg q.d. for 14 days. The total treatment period lasted 14-20 days with patients in the higher dose cohorts uptitrated over 2-6 days. Plasma samples for PK analysis were obtained on the first and last days of dosing.. Among children and adolescents, respectively, 62% and 92% had depression and 58% and 33% had anxiety disorder. Comorbid attention-deficit/hyperactivity disorder (ADHD) was present in 50% of children and 38% of adolescents. After 14 days q.d. at the target dose, the PK of vortioxetine concentrations was generally proportional to the dose in both age groups. Exposure, as assessed by maximum plasma concentrations and area under the plasma concentration-time curve from time 0 to 24 hours, was 30%-40% lower in adolescents than in children. There was no significant relationship between sex, height, or ADHD diagnosis and PK parameters. Most adverse events were mild in severity and consistent with those seen in adults.. The results suggest that the dosages of vortioxetine evaluated (5-20 mg q.d.; approved for treatment in adults) and the uptitration schedule used are appropriate for pediatric efficacy and safety trials.

Topics: Adolescent; Anti-Anxiety Agents; Anxiety Disorders; Attention Deficit Disorder with Hyperactivity; Child; Comorbidity; Depressive Disorder; Dose-Response Relationship, Drug; Female; Humans; Male; Piperazines; Sulfides; Vortioxetine

The aim of this study was to investigate the antidepressant activity of vortioxetine in a tryptophan (TRP) depletion female rat model of depression and compare it to that of paroxetine using doses that fully occupy the serotonin transporter (SERT). We evaluated the effects of vortioxetine on potential biomarkers associated with TRP depletion including serum aldosterone, corticosterone and IL-6 levels together with indirect indicators of glutamate neurotransmission. Female Sprague-Dawley rats were randomized to control, low TRP, low TRP/paroxetine or low TRP/vortioxetine groups. Vortioxetine and paroxetine were administered via diet (10mg/kg/day) and drinking water (10mg/kg/day) respectively for 14days. Vortioxetine but not paroxetine reversed TRP depletion-induced depressive-like behavior. Vortioxetine reduced TRP depletion-induced increases of serum corticosterone, aldosterone, IL-6 and N-methyl-d-aspartate and α7-nicotinic acetylcholine receptor expression in the amygdala and hippocampus, respectively. Paroxetine demonstrated little effect except a reduction of aldosterone. Vortioxetine but not paroxetine reversed TRP depletion-induced reductions of serum and brain kynurenic acid. In conclusion, vortioxetine, but not paroxetine, enabled reversals of TRP depletion-induced changes of depression-like behavior and markers of glutamatergic activity. These observations support the hypothesis that vortioxetine's antidepressant activity may involve mechanisms beyond SERT inhibition.

Topics: Administration, Oral; Animals; Biomarkers; Depressive Disorder; Disease Models, Animal; Female; Glutamic Acid; Paroxetine; Random Allocation; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Vortioxetine

We studied the effects of the multi-modal antidepressant, vortioxetine and the SSRI, paroxetine on pineal melatonin and monoamine synthesis in a sub-chronic tryptophan (TRP) depletion model of depression based on a low TRP diet. Female Sprague-Dawley rats were randomised to groups a) control, b) low TRP diet, c) low TRP diet+paroxetine and d) low TRP diet+vortioxetine. Vortioxetine was administered via the diet (0.76mg/kg of food weight) and paroxetine via drinking water (10mg/kg/day) for 14days. Both drugs resulted in SERT occupancies >90%. Vortioxetine significantly reversed TRP depletion-induced reductions of pineal melatonin and serotonin (5-HT) and significantly increased pineal noradrenaline NA. Paroxetine did none of these things. Other studies suggest pineal melatonin synthesis may involve N-methyl-d-aspartate (NMDA) receptors and glutamatergic modulation. Here observed changes may be mediated via vortioxetine's strong 5-HT reuptake blocking action together with possible additional effects on glutamate neurotransmission in the pineal via NMDA receptor-modulation and possibly with added impetus from increased NA output.

Topics: Administration, Oral; Animals; Antidepressive Agents, Second-Generation; Depressive Disorder; Disease Models, Animal; Female; Glutamic Acid; Melatonin; Norepinephrine; Paroxetine; Pineal Gland; Piperazines; Random Allocation; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; RNA-Binding Proteins; Selective Serotonin Reuptake Inhibitors; Serotonin; Sulfides; Tryptophan; Vortioxetine

The mechanisms mediating ketamine's antidepressant effect have only been partly resolved. Recent preclinical reports implicate serotonin (5-hydroxytryptamine; 5-HT) in the antidepressant-like action of ketamine. Vortioxetine is a multimodal-acting antidepressant that is hypothesized to exert its therapeutic activity through 5-HT reuptake inhibition and modulation of several 5-HT receptors.. The objective of this study was to evaluate the therapeutic-like profiles of S-ketamine, vortioxetine, and the serotonin reuptake inhibitor fluoxetine in response to manipulation of 5-HT tone.. Flinders Sensitive Line (FSL) rats, a genetic model of depression, were depleted of 5-HT by repeated administration of 4-chloro-DL-phenylalanine methyl ester HCl (pCPA). Using pCPA-pretreated and control FSL rats, we investigated the acute and sustained effects of S-ketamine (15 mg/kg), fluoxetine (10 mg/kg), or vortioxetine (10 mg/kg) on recognition memory and depression-like behavior in the object recognition task (ORT) and forced swim test (FST), respectively.. The behavioral phenotype of FSL rats was unaffected by 5-HT depletion. Vortioxetine, but not fluoxetine or S-ketamine, acutely ameliorated the memory deficits of FSL rats in the ORT irrespective of 5-HT tone. No sustained effects were observed in the ORT. In the FST, all three drugs demonstrated acute antidepressant-like activity but only S-ketamine had sustained effects. Unlike vortioxetine, the antidepressant-like responses of fluoxetine and S-ketamine were abolished by 5-HT depletion.. These observations suggest that the acute and sustained antidepressant-like effects of S-ketamine depend on endogenous stimulation of 5-HT receptors. In contrast, the acute therapeutic-like effects of vortioxetine on memory and depression-like behavior may be mediated by direct activity at 5-HT receptors.

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Behavior, Animal; Depressive Disorder; Disease Models, Animal; Fluoxetine; Ketamine; Locomotion; Male; Memory Disorders; Piperazines; Rats; Recognition, Psychology; Selective Serotonin Reuptake Inhibitors; Sulfides; Swimming; Vortioxetine