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Journal of Affective Disorders Oct 2016Major depressive disorder (MDD) is associated with staggering personal and economic costs, a major proportion of which stem from impaired psychosocial and occupational... (Clinical Trial)
Clinical Trial
BACKGROUND
Major depressive disorder (MDD) is associated with staggering personal and economic costs, a major proportion of which stem from impaired psychosocial and occupational functioning. Few studies have examined the impact of depression-related cognitive dysfunction on work functioning. We examined the association between neurocognitive and work functioning in employed patients with MDD.
METHODS
Employed adult outpatients (n=36) with MDD of at least moderate severity (≥23 on the Montgomery Asberg Depression Rating Scale, MADRS) and subjective cognitive complaints completed neurocognitive tests (CNS Vital Signs computerized battery) and validated self-reports of their work functioning (LEAPS, HPQ) before and after 8 weeks of open-label treatment with flexibly-dosed desvenlafaxine 50-100mg/day. Relationships between neurocognitive tests and functional measures were examined using bivariate correlational and multiple regression analyses, as appropriate. An ANCOVA model examined whether significant change in neurocognitive performance, defined as improvement of ≥1SD in the Neurocognition Index (NCI) from baseline to post-treatment, was associated with improved outcomes.
RESULTS
Patients showed significant improvements in depressive symptom, neurocognitive, and work functioning measures following treatment with desvenlafaxine (e.g., MADRS response=77% and MADRS remission=49%). There were no significant correlations between changes in NCI or cognitive domain subscales and changes in MADRS, LEAPS, or HPQ scores. However, patients demonstrating significant improvement in NCI scores (n=11, 29%) had significantly greater improvement in clinical and work functioning outcomes compared to those without NCI improvement.
LIMITATIONS
The limitations of this study include small sample size, lack of a placebo control group, and lack of a healthy comparison group. Our sample also had more years of education and higher premorbid intelligence than the general population.
CONCLUSIONS
There were no significant correlations between changes in neurocognitive and work functioning measures in this study. However, meaningful improvement in neurocognitive functioning with desvenlafaxine was associated with greater improvement in both mood and occupational outcomes. This suggests that addressing cognitive dysfunction may improve clinical and occupational outcomes in employed patients with MDD. However, the relationship between neurocognitive and work functioning in MDD is complex and requires further study.
Topics: Adult; Antidepressive Agents; Cognition; Depressive Disorder, Major; Desvenlafaxine Succinate; Drug Administration Schedule; Employment; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Occupational Health; Psychiatric Status Rating Scales; Self Report; Treatment Outcome
PubMed: 27280963
DOI: 10.1016/j.jad.2016.05.074 -
Medicina Clinica Jul 2021
Topics: Antidepressive Agents; Depressive Disorder, Major; Desvenlafaxine Succinate; Double-Blind Method; Humans; Infant, Newborn; Serotonin Syndrome
PubMed: 32951880
DOI: 10.1016/j.medcli.2020.04.059 -
PloS One 2020Desvenlafaxine (DES) and Alprazolam (ALP) are the drugs commonly prescribed together for the treatment of Major Depressive Disorders (MDD). A literature survey revealed,...
Desvenlafaxine (DES) and Alprazolam (ALP) are the drugs commonly prescribed together for the treatment of Major Depressive Disorders (MDD). A literature survey revealed, there is no method for the simultaneous determination of these two drugs. The purpose of this research was to develop and validate a simple, accurate, precise, robust, and isocratic RP-HPLC method for simultaneous determination of DES and ALP in human spiked plasma using UV-detector in short analysis time. The method utilized Hypersil BDS C18 (250 mm×4.6 mm, 5 μm) through an isocratic mode of elution using HPLC grade acetonitrile and 0.02M KH2PO4 buffer (65:35) and 0.1% Tri Fluoro Acetic acid (TFA) with pH 4.00 adjusted with 1M KOH. The flow rate was 1.00 mLmin-1 and elution of the drugs was monitored at 230nm. The elution time of DES and ALP was 4.011 and 5.182 minutes respectively. The method was linear for the concentration range 10-150 μgmL-1 for DES and 5.0-75.0 μgmL-1 for ALP. According to the validation results, the method is sensitive with Limit of Detection (LOD) 4.740 μgmL-1 and Limit of Quantification (LOQ) of 14.365 μgmL-1 for DES and LOD 1.891 μgmL-1 & LOQ 5.730 μgmL-1 for ALP. The reproducibility of results with minute deliberate variations in method parameters has proven that the method is robust. The data from stability studies show a non-significant change in drugs solutions for 2 months. The optimized method was validated as per International Conference for Harmonisation (ICH) Q2(R1) guidelines. This method can be used for the estimation of DES and ALP in plasma and can evaluate pharmacokinetic parameters of both drugs simultaneously.
Topics: Alprazolam; Chromatography, High Pressure Liquid; Desvenlafaxine Succinate; Humans; Limit of Detection; Pharmaceutical Solutions; Plasma; Reproducibility of Results
PubMed: 32941505
DOI: 10.1371/journal.pone.0238954 -
International Clinical... Nov 2018We assessed the effect of body weight and BMI on plasma concentrations of venlafaxine (VEN), O-desmethylvenlafaxine (ODVEN), active moiety (AM=VEN+ODVEN), and...
We assessed the effect of body weight and BMI on plasma concentrations of venlafaxine (VEN), O-desmethylvenlafaxine (ODVEN), active moiety (AM=VEN+ODVEN), and dose-corrected plasma concentrations (C/D). A database containing concentrations of VEN and ODVEN including 737 of 1594 eligible patients was analyzed. Analyses included sex, body weight, and BMI as well as concentrations of VEN, ODVEN, AM, and C/D. A positive correlation was detected between body weight and daily dosage (rs=0.168, P<0.001). A negative correlation was found between body weight and AM (rs=-0.124, P=0.001) and ODVEN (rs=-0.137, P<0.001). Negative correlations were also found between body weight and C/D ratios (C/D VEN: rs=-0.134, P<0.001, C/D ODVEN: rs=-0.239, P<0.001, C/D AM: rs=-0.256, P<0.001). No correlations were detected between BMI and concentrations for VEN, ODVEN, and AM. Comparing low-BMI (<20 kg/m²), medium-BMI (20-29.9 kg/m²), and high-BMI (≥30 kg/m²) groups, higher values of some pharmacokinetic variables in the lower BMI group did not remain significant after controlling for sex. Women had higher VEN, ODVEN, AM, and C/D values for AM, VEN, and ODVEN than men (P<0.001 for all comparisons). Our results highlight the role of different pharmacokinetically relevant parameters and foremost of sex as mediators for the effect of BMI on VEN metabolism.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Mass Index; Body Weight; Desvenlafaxine Succinate; Female; Humans; Male; Middle Aged; Sex Characteristics; Venlafaxine Hydrochloride; Young Adult
PubMed: 30028351
DOI: 10.1097/YIC.0000000000000234 -
Biomedical Chromatography : BMC Feb 2016A simple, sensitive and specific liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the quantification of desvenlafaxine in human...
A simple, sensitive and specific liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the quantification of desvenlafaxine in human plasma using desvenlafaxine d6 as an internal standard (IS). Chromatographic separation was performed using a Thermo-BDS hypersil C8 column (50 × 4.6 mm, 3 µm) with an isocratic mobile phase composed of 5 mM ammonium acetate buffer: methanol (20:80, v/v), at a flow rate of 0.80 mL/min. Desvenlafaxine and desvenlafaxine d6 were detected with proton adducts at m/z 264.2/58.1 and 270.2/ 64.1 in multiple reaction monitoring positive mode, respectively. Liquid-liquid extraction was used to extract the drug and the IS. The method was linear over the concentration range 1.001-400.352 ng/mL with a correlation coefficient of ≥0.9994. This method demonstrated intra and inter-day precision within 0.7-5.5 and 1.9-6.8%, and accuracy within 95.3-107.4 and 93.4-99.5%. Desvenlafaxine was found to be stable throughout the freeze-thaw cycles, bench-top and long-term matrix stability studies. The developed and validated method can be successfully applied for the bioequivalence/pharmacokinetic studies of desvenlafaxine in pharmaceutical dosage forms.
Topics: Chromatography, Liquid; Desvenlafaxine Succinate; Drug Stability; Humans; Linear Models; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 26095112
DOI: 10.1002/bmc.3542 -
The Journal of Clinical Psychiatry May 2015To assess short-term efficacy and safety of desvenlafaxine 50 and 100 mg/d versus placebo for treating major depressive disorder (MDD). Assessment of sexual function was... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To assess short-term efficacy and safety of desvenlafaxine 50 and 100 mg/d versus placebo for treating major depressive disorder (MDD). Assessment of sexual function was a secondary objective.
METHOD
Outpatients (≥ 18 years) who met criteria for MDD from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision and had screening and baseline 17-item Hamilton Depression Rating Scale (HDRS17) total scores ≥ 20 were randomly assigned to placebo or desvenlafaxine 50 or 100 mg/d in an 8-week study conducted from October 2011 to August 2012. The primary efficacy end point was change from baseline in HDRS17 total score at week 8, analyzed using a mixed-effects model for repeated measures. Sexual function was assessed using the Arizona Sexual Experiences Scale (ASEX).
RESULTS
The safety population included 909 patients (intent-to-treat population, n = 886). Significantly greater improvement in adjusted mean HDRS17 total score from baseline to week 8 was observed for desvenlafaxine 50 mg (-11.28; P = .006) and desvenlafaxine 100 mg (-11.67; P < .001) compared with placebo (-9.71), with adjustment for multiplicity. In the ASEX total score analysis (n = 422), the treatment by gender interaction was not significant; thus, genders were combined for subsequent analyses. Comparisons for desvenlafaxine versus placebo for change from baseline in ASEX total and all item scores found P > .05, with no adjustment for multiplicity. Rates of sexual dysfunction based on ASEX were comparable among treatment groups.
CONCLUSIONS
These results support previous findings demonstrating antidepressant efficacy, safety, and tolerability of desvenlafaxine 50 and 100 mg/d versus placebo. Sexual function was comparable between desvenlafaxine and placebo.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT01432457.
Topics: Adult; Cyclohexanols; Depressive Disorder, Major; Desvenlafaxine Succinate; Double-Blind Method; Female; Humans; Male; Middle Aged; Neurotransmitter Uptake Inhibitors; Sexual Dysfunction, Physiological; Treatment Outcome
PubMed: 25375652
DOI: 10.4088/JCP.13m08978 -
Asian Journal of Psychiatry Dec 2015This randomized, open label, prospective, observational study compared clinical efficacy, safety alongwith plasma BDNF levels in outpatients of depression treated with... (Randomized Controlled Trial)
Randomized Controlled Trial
This randomized, open label, prospective, observational study compared clinical efficacy, safety alongwith plasma BDNF levels in outpatients of depression treated with fluoxetine and desvenlafaxine. Patients (aged 18-60 years) with moderate to severe major depressive disorder (MDD) diagnosed by DSM-IV criteria, and Hamilton Rating Scale for Depression (HAM-D) score ≥14, who were prescribed fluoxetine or desvenlafaxine were included (n=30 in each group). Patients were followed up for 12 weeks for evaluation of clinical efficacy, safety along with BDNF levels. In the fluoxetine group, HAM-D scores at the start of treatment was 19±4.09 which significantly (p<0.05) reduced to 9.24±3.98 at 12 weeks. In the desvenlafaxine group, HAM-D scores at the start of treatment was 18±3.75 which significantly (p<0.05) reduced to 10±3.75 at 12 weeks. The BDNF levels in the fluoxetine group were 775.32±30.38pg/ml at the start of treatment which significantly (p<0.05) increased to 850.3±24.92pg/ml at 12 weeks. The BDNF levels in the desvenlafaxine group were 760.5±28.53pg/ml at the start of treatment which significantly (p<0.05) increased to 845.8±32.82pg/ml at 12 weeks. Both the antidepressants were found to be safe and well tolerated. The efficacy and the safety profile of desvenlafaxine is comparable to fluoxetine in patients of MDD. BDNF levels were significantly increased post-treatment with both the antidepressive agents. Whether BDNF may have a prognostic value in predicting treatment response to antidepressant drugs needs to be investigated in a larger patient population.
Topics: Adult; Antidepressive Agents; Brain-Derived Neurotrophic Factor; Depressive Disorder, Major; Desvenlafaxine Succinate; Diagnostic and Statistical Manual of Mental Disorders; Drug Monitoring; Female; Fluoxetine; Humans; Male; Middle Aged; Prognosis; Psychiatric Status Rating Scales; Treatment Outcome
PubMed: 26514447
DOI: 10.1016/j.ajp.2015.10.006 -
International Clinical... Sep 2019The aim of this study was to ensure patients' safety and to enhance treatment efficacy, knowledge about pharmacokinetic interactions even in complex clinical situations...
OBJECTIVE
The aim of this study was to ensure patients' safety and to enhance treatment efficacy, knowledge about pharmacokinetic interactions even in complex clinical situations of polypharmacy is invaluable. This study is to uncover the potential of pharmacokinetic interactions between venlafaxine and trimipramine in a naturalistic sample.
METHODS
Out of a therapeutic drug monitoring database with plasma concentrations of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV), we considered two groups of patients receiving venlafaxine without known cytochrome P450 confounding medications, taking solely venlafaxine: V0 (n = 905), and a group of patients co-medicated with trimipramine, VTRIM (n = 33). For VEN, ODV and active moiety (sum of VEN + ODV) plasma concentrations and dose-adjusted concentrations as well as ODV/VEN ratios were compared between groups using the Mann-Whitney U test with a significance level of 0.05.
RESULTS
Patients co-medicated with trimipramine had higher plasma concentrations of VEN (183.0 vs. 72.0, +154%, P = 0.002) and AM (324.0 vs. 267.5, +21%, P = 0.005) and higher dose adjusted plasma concentrations than patients in the control group (P = 0.001 and P = 0.003). No differences were found for ODV and C/D ODV (P < 0.05 for both comparisons). The metabolite to parent ratio, ODV/VEN, was significantly lower in the VTRIM group (1.15 vs. 2.37, P = 0.012).
CONCLUSION
Findings suggest inhibitory effects of trimipramine on venlafaxine pharmacokinetics most likely via an inhibition of CYP 2D6 or by saturated enzyme capacity. The lack of in vitro data hampers the understanding of the exact mechanisms. Clinicians should be aware of drug-drug interactions when combining these agents. Therapeutic drug monitoring helps to ensure treatment efficacy and patients' safety.
Topics: Adult; Desvenlafaxine Succinate; Female; Humans; Male; Middle Aged; Trimipramine; Venlafaxine Hydrochloride
PubMed: 31094902
DOI: 10.1097/YIC.0000000000000268 -
Journal of Clinical Sleep Medicine :... Feb 2017To determine if patients with childhood onsets (CO) of both major depression and insomnia disorder show blunted depression and insomnia treatment responses to concurrent... (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVES
To determine if patients with childhood onsets (CO) of both major depression and insomnia disorder show blunted depression and insomnia treatment responses to concurrent interventions for both disorders compared to those with adult onsets (AO) of both conditions.
METHODS
This study was a secondary analysis of data obtained from a multisite randomized clinical trial designed to test the efficacy of combining a psychological/behavior insomnia therapy with antidepressant medication to enhance depression treatment outcomes in patients with comorbid major depression and insomnia. This study included 27 adults with CO of depression and insomnia and 77 adults with AO of both conditions. They underwent a 16-week treatment including: (1) a standardized two-step pharmacotherapy for depression algorithm, consisting of escitalopram, sertraline, and desvenlafaxine in a prescribed sequence; and (2) either cognitive behavioral insomnia therapy (CBT-I) or a quasi-desensitization control (CTRL) therapy. Main outcome measures were the 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Insomnia Severity Index (ISI) completed pre-treatment and every 2 weeks thereafter.
RESULTS
The AO and CO groups did not differ significantly in regard to their pre-treatment HRSD-17 and ISI scores. Mixed model analyses that adjusted for the number of insomnia treatment sessions attended showed that the AO group achieved significantly lower, subclinical scores on the HRSD-17 and ISI than did the CO group by the time of study exit. Moreover, a significant group by treatment arm interaction suggested that HRSD-17 scores at study exit remained significantly higher in the CO group receiving the CTRL therapy than was the case for the participants in the CO group receiving CBT-I. Greater proportions of the AO group achieved a priori criteria for remission of insomnia (49.3% vs. 29.2%, p = 0.04) and depression (45.5% vs. 29.6%, p = 0.07) than did those in the CO group.
CONCLUSIONS
Patients with comorbid depression and insomnia who experienced the first onset of both disorders in childhood are less responsive to the treatments offered herein than are those with adult onsets of these comorbid disorders. Further research is needed to identify therapies that enhance the depression and insomnia treatment responses of those with childhood onsets of these two conditions.
Topics: Adult; Age of Onset; Antidepressive Agents; Citalopram; Cognitive Behavioral Therapy; Combined Modality Therapy; Depressive Disorder, Major; Desvenlafaxine Succinate; Humans; Middle Aged; Sertraline; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Treatment Outcome; United States
PubMed: 27784414
DOI: 10.5664/jcsm.6448 -
Archiv Der Pharmazie Apr 2024Lipid nanocapsules (LNCs) are lipid nanocarriers developed for drug delivery enhancement. The antidepressant drug desvenlafaxine (DSV) was entrapped in LNC to improve...
Lipid nanocapsules (LNCs) are lipid nanocarriers developed for drug delivery enhancement. The antidepressant drug desvenlafaxine (DSV) was entrapped in LNC to improve its brain delivery. Different DSV-loaded LNCs formulae using different oils and surfactants were studied to obtain the optimum formula for further studies. In vivo biodistribution studies were done using Swiss albino mice by intravenous injection of DSV-loaded LNCs by radioiodination technique. The optimum DSV-loaded LNC formula was obtained by using Labrafil® M1944CS as the oil and Solutol® HS15 as the surfactant in the ratio of 1:1, with a particle size of 34.28 ± 0.41 nm, a polydispersity index of 0.032 ± 0.05, a zeta potential of -25.77 ± 1.41, and good stability for up to 6 months. The in vivo biodistribution and pharmacokinetics data ensure the bioavailability improvement for DSV brain delivery as C and AUC increased more than double for intravenously DSV-loaded LNCs compared with the DSV solution. In conclusion, the results obtained from this study give an insight into the great potential of using DSV-loaded LNC for the enhancement of brain delivery.
Topics: Mice; Animals; Nanocapsules; Desvenlafaxine Succinate; Lipids; Iodine Radioisotopes; Tissue Distribution; Structure-Activity Relationship; Brain
PubMed: 38161231
DOI: 10.1002/ardp.202300618