Current antidepressants used to treat pediatric patients have the disadvantage of limited efficacy and potentially serious side effects. The purpose of this study was to assess the efficacy of vitamin C as an adjuvant agent in the treatment of pediatric major depressive disorder in a six-month, double-blind, placebo-controlled pilot trial.
Antidepressant drugs such as selective serotonin re-uptake inhibitors (SSRIs) remediate negative biases in emotional processing in depressed patients in both behavioural and neural outcome measures. However, it is not clear if these effects occur before, or as a consequence of, changes in clinical state. Method In the present study, we investigated the effects of short-term SSRI treatment in depressed patients on the neural response to fearful faces prior to clinical improvement in mood. Altogether, 42 unmedicated depressed patients received SSRI treatment (10 mg escitalopram daily) or placebo in a randomised, parallel-group design. The neural response to fearful and happy faces was measured on day 7 of treatment using functional magnetic resonance imaging. A group of healthy controls was imaged in the same way.
Role of l-5-hydroxytryptophan (l-5-HTP) in depression is relatively less studied but the literature has shown its robust role in depression. The present randomized double blind study was undertaken to assess the role of l-5-HTP as an antidepressant and to compare its antidepressant efficacy with fluoxetine in first depressive episode patients of Indian population.
Major depressive disorder affects around 16 per cent of the world population at some point in their lives. Despite the availability of numerous monoaminergic-based antidepressants, most patients require several weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive, glutamatergic NMDAR (N-methyl-d-aspartate receptor) antagonist (R,S)-ketamine exerts rapid and sustained antidepressant effects after a single dose in patients with depression, but its use is associated with undesirable side effects. Here we show that the metabolism of (R,S)-ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant-related actions in mice. These antidepressant actions are independent of NMDAR inhibition but involve early and sustained activation of AMPARs (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors). We also establish that (2R,6R)-HNK lacks ketamine-related side effects. Our data implicate a novel mechanism underlying the antidepressant properties of (R,S)-ketamine and have relevance for the development of next-generation, rapid-acting antidepressants.
The chiral signature of the antidepressant venlafaxine was used in this study to gain insight into biological attenuation processes and to differentiate abiotic and biotic transformation processes in water. Laboratory scale experiments revealed that sorption and phototransformation processes were not enantioselective while venlafaxine was enantioselectively biotransformed into O-desmethylvenlafaxine. The enantiomeric fraction (EF) variations of venlafaxine appeared to be proportional to its microbial fractional conversion. Enantioselective biotransformation of venlafaxine was also investigated in a eutrophic French river. Venlafaxine was found to be racemic at the output of the main wastewater treatment plant discharging into the river, independently of the sampling date during the year. An analysis of EF variations might provide evidence of biodegradation along a 30km river stretch.
Fluoxetine is used clinically as a racemic mixture of (+)-(S) and (-)-® enantiomers for the treatment of depression. CYP2D6 catalyzes the metabolism of both fluoxetine enantiomers. We aimed to evaluate whether exposure to gasoline results in CYP2D inhibition. Male Wistar rats exposed to filtered air (n = 36; control group) or to 600 ppm of gasoline (n = 36) in a nose-only inhalation exposure chamber for 6 weeks (6 h/day, 5 days/week) received a single oral 10-mg/kg dose of racemic fluoxetine. Fluoxetine enantiomers in plasma samples were analyzed by a validated analytical method using LC-MS/MS. The separation of fluoxetine enantiomers was performed in a Chirobiotic V column using as the mobile phase a mixture of ethanol:ammonium acetate 15 mM. Higher plasma concentrations of the (+)-(S)-fluoxetine enantiomer were found in the control group (enantiomeric ratio AUC((+)-(S)/(-)-®) = 1.68). In animals exposed to gasoline, we observed an increase in AUC(0-∞) for both enantiomers, with a sharper increase seen for the (-)-®-fluoxetine enantiomer (enantiomeric ratio AUC((+)-(S)/(-)-®) = 1.07), resulting in a loss of enantioselectivity. Exposure to gasoline was found to result in the loss of enantioselectivity of fluoxetine, with the predominant reduction occurring in the clearance of the (-)-®-fluoxetine enantiomer (55% vs. 30%). Chirality, 2013. © 2013 Wiley Periodicals, Inc.
A differential contribution of the right and left amygdalae to affective information processing has been proposed. However, the direction of this lateralization has not been confirmed. In this study, we used a pre- and post-treatment (escitalopram) design to analyze the relative differences between neural activity in the right and left amygdalae during exposure to emotional stimuli in currently depressed patients. To the best of our knowledge, this study is to compare neural activity between the left and right amygdalae in people with depression. Our findings could lead to the development of parameters or biomarkers for depressive symptoms and treatment response.
Vortioxetine (Brintellix(®)) is a serotonin (5-HT) transporter inhibitor that also acts on several 5-HT receptors, such as the 5-HT3 and 5-HT1A receptors. It is approved in the US and the EU for the treatment of adult patients with major depressive disorder (MDD); this article reviews the pharmacological properties of oral vortioxetine and its clinical efficacy and tolerability in these patients. Vortioxetine is generally efficacious in patients with MDD in acute treatment trials (including elderly patients), in a relapse-prevention trial, and in open-label extension trials. It is associated with improved cognitive function in patients with MDD; this does not occur solely via improvement in depressive symptom severity. It is well tolerated, but is associated with significantly increased sexual dysfunction at the highest dosage; however, vortioxetine was shown to improve previous-treatment-emergent sexual dysfunction in patients with well-treated MDD to a greater degree than escitalopram. Vortioxetine extends the available treatment options for patients with MDD, and further investigation into its comparative efficacy versus other antidepressants will allow for more accurate placement among these treatment options.
- The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists
- Published over 6 years ago
Objective: To evaluate the role of dextromethorphan/quinidine (DM/Q; Nuedexta™) in the treatment of pseudobulbar affect (PBA).Data Sources: A literature search of MEDLINE/PubMed (January 1966-June 2013) was conducted using search terms pseudobulbar affect, pathological laughing and/or crying, emotional lability, dextromethorphan, and quinidine.Study Selection and Data Extraction: English language clinical trials and case reports evaluating the safety and efficacy of DM/Q in PBA were included for review. Bibliographies of all relevant articles were reviewed for additional citations.Data Synthesis: PBA, a poorly understood disorder, is characterized by involuntary crying and/or laughing. In the past, antidepressants and antiepileptics have been used off-label with mixed results. Four clinical trials have evaluated the use of DM/Q for the treatment of PBA. Although the therapeutic outcomes with DM/Q have been positive, interpretation of the published evidence is limited by small sample size and short treatment duration.Conclusions: Based on the data available, DM/Q may be a viable, short-term treatment alternative for PBA. Long-term safety and efficacy data are lacking.
The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5-20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5-20mg/day) was 4.5-7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5-20mg/day) were nausea (20.9-31.2%) and vomiting (2.9-6.5%). For vortioxetine (5-20mg/day), the incidence of TEAEs associated with insomnia was 2.0-5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6-1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7-0.8kg. Thus, vortioxetine (5-20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder.