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Journal of Child and Adolescent... Feb 2018To evaluate the short-term efficacy and safety of desvenlafaxine (25-50 mg/d) compared with placebo in children and adolescents with major depressive disorder (MDD). (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVES
To evaluate the short-term efficacy and safety of desvenlafaxine (25-50 mg/d) compared with placebo in children and adolescents with major depressive disorder (MDD).
METHODS
Outpatient children (7-11 years) and adolescents (12-17 years) who met DSM-IV-TR criteria for MDD and had screening and baseline Children's Depression Rating Scale-Revised (CDRS-R) total scores >40 were randomly assigned to 8-week treatment with placebo, desvenlafaxine (25, 35, or 50 mg/d based on baseline weight), or fluoxetine (20 mg/d). The primary efficacy endpoint was change from baseline in CDRS-R total score at week 8, analyzed using a mixed-effects model for repeated measures. Secondary efficacy endpoints included week 8 Clinical Global Impressions-Severity, Clinical Global Impressions-Improvement (CGI-I), and response (CGI-I ≤ 2). Safety assessments included adverse events, physical and vital sign measurements, laboratory evaluations, electrocardiogram, and the Columbia-Suicide Severity Rating Scale.
RESULTS
The safety population included 339 patients (children, n = 130; adolescents, n = 209). The primary endpoint, change from baseline in CDRS-R total score at week 8, did not statistically separate from placebo, for either desvenlafaxine (adjusted mean [standard error] change, -22.6 [1.17]) or fluoxetine (-24.8 [1.17]; placebo, -23.1 [1.18]). Week 8 CGI-I response rates were significantly greater for fluoxetine (78.2%; p = 0.017) than for placebo (62.6%); desvenlafaxine (68.7%) did not differ from placebo. Other secondary outcomes were consistent with those obtained with CDRS-R. Rates of treatment-emergent adverse events were comparable among treatment groups (desvenlafaxine, 60.0%; placebo, 70.5%; and fluoxetine, 64.3%).
CONCLUSION
Desvenlafaxine did not demonstrate efficacy for treating MDD in children and adolescents in this trial. Because neither desvenlafaxine nor the reference medication, fluoxetine, demonstrated a statistically significant difference from placebo on the primary endpoint, this was considered a failed trial and no efficacy conclusions can be drawn. Desvenlafaxine 25-50 mg/d was generally safe and well tolerated in children and adolescents in this study.
Topics: Adolescent; Antidepressive Agents; Child; Depressive Disorder, Major; Desvenlafaxine Succinate; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluoxetine; Humans; Male; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome
PubMed: 29189044
DOI: 10.1089/cap.2017.0100 -
Journal of Child and Adolescent... Feb 2018To evaluate the short-term efficacy and safety of desvenlafaxine versus placebo in the treatment of children and adolescents with major depressive disorder (MDD).
OBJECTIVE
To evaluate the short-term efficacy and safety of desvenlafaxine versus placebo in the treatment of children and adolescents with major depressive disorder (MDD).
METHODS
Outpatient children (7-11 years) and adolescents (12-17 years) who met DSM-IV-TR criteria for MDD and had screening and baseline Children's Depression Rating Scale-Revised (CDRS-R) total scores >40 were randomly assigned to 8 weeks of treatment with placebo, low exposure desvenlafaxine (20, 30, or 35 mg/day based on baseline weight), or higher exposure desvenlafaxine (25, 35, or 50 mg/day based on baseline weight). The primary efficacy endpoint was change from baseline in CDRS-R total score at week 8, analyzed using a mixed-effects model for repeated measures. Secondary efficacy assessments included Clinical Global Impressions-Severity and Clinical Global Impressions-Improvement scales. Safety assessments included adverse events and the Columbia-Suicide Severity Rating Scale.
RESULTS
The safety population included 363 patients (children, n = 109; adolescents, n = 254). No statistical separation from placebo was observed for either desvenlafaxine group for CDRS-R total score or for any secondary efficacy endpoint. At week 8, adjusted mean (standard error) changes from baseline in CDRS-R total score for the desvenlafaxine low exposure, desvenlafaxine high exposure, and placebo groups were -23.7 (1.1), -24.4 (1.1), and -22.9 (1.1), respectively. The incidence of adverse events was similar among groups.
CONCLUSION
Low and high exposure desvenlafaxine groups did not demonstrate efficacy for the treatment of MDD in children and adolescents in this double-blind, placebo-controlled trial. Desvenlafaxine (20-50 mg/day) was generally safe and well tolerated with no new safety signals identified in pediatric patients with MDD in this study.
Topics: Adolescent; Antidepressive Agents; Child; Depressive Disorder, Major; Desvenlafaxine Succinate; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Psychiatric Status Rating Scales; Treatment Outcome
PubMed: 29185786
DOI: 10.1089/cap.2017.0099 -
BMJ Case Reports Nov 2017We report a likely false-positive phencyclidine (PCP) result detected with a urine drug screen (UDS) (Medtox, St Paul, Minnesota, USA) in the setting of therapeutic...
We report a likely false-positive phencyclidine (PCP) result detected with a urine drug screen (UDS) (Medtox, St Paul, Minnesota, USA) in the setting of therapeutic desvenlafaxine (Pristiq) use. Desvenlafaxine (O-desmethylvenlafaxine) is the active metabolite of venlafaxine (Effexor). Prior reports have confirmed venlafaxine use resulting in a false-positive for PCP on a UDS. However, there has been a paucity of reporting of commercially available desvenlafaxine formulations (Pristiq, Khedezla) resulting in false-positives for PCP on a UDS.
Topics: Antidepressive Agents; Desvenlafaxine Succinate; False Positive Reactions; Female; Humans; Middle Aged; Phencyclidine; Substance Abuse Detection
PubMed: 29170178
DOI: 10.1136/bcr-2017-222106 -
CNS Spectrums Jun 2019This post-hoc pooled analysis evaluated categorical change in functional impairment in patients with major depressive disorder (MDD) treated with desvenlafaxine versus... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This post-hoc pooled analysis evaluated categorical change in functional impairment in patients with major depressive disorder (MDD) treated with desvenlafaxine versus placebo and examined whether early improvement in functioning predicted functional outcomes at study endpoint.
METHODS
Data were pooled from eight randomized, double-blind, placebo-controlled studies of desvenlafaxine for the treatment of MDD, including adults who were randomly assigned to receive desvenlafaxine 50 or 100 mg/d or placebo (N=3,384). Shift tables were generated for categorical changes in functional impairment from baseline based on Sheehan Disability Scale (SDS) subscale scores. The categories were none/mild (0-3), moderate (4-6), and marked/extreme (7-10). Treatment comparisons for prespecified shifts of interest and predictive value of week 2 or 4 improvement in SDS subscale scores for functional outcome at week 8 were assessed using logistic regression.
RESULTS
Greater proportions of patients receiving desvenlafaxine 50 and 100 mg achieved improvement from baseline to week 8 for each prespecified shift endpoint versus placebo (all p ≤ 0.02). Early improvement in SDS subscale scores was a statistically significant predictor of functional outcome at week 8, both overall and for each treatment group (all p<0.0001).
CONCLUSIONS
Treatment with desvenlafaxine 50 or 100 mg/d led to significantly greater categorical improvement in functional impairment versus placebo, and improvement in SDS subscale scores significantly predicted functional outcome. Monitoring patient progress early in the course of antidepressant treatment using a functional assessment such as the SDS may help clinicians determine whether or not treatment adjustments are needed.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents; Depression; Desvenlafaxine Succinate; Female; Humans; Male; Middle Aged; Quality of Life; Treatment Outcome
PubMed: 29140227
DOI: 10.1017/S1092852917000633 -
Journal of Clinical Psychopharmacology Oct 2017This post hoc analysis examined the time point at which clinically significant improvement in major depressive disorder (MDD) symptoms occurs with desvenlafaxine versus... (Meta-Analysis)
Meta-Analysis
PURPOSE/BACKGROUND
This post hoc analysis examined the time point at which clinically significant improvement in major depressive disorder (MDD) symptoms occurs with desvenlafaxine versus placebo.
METHODS
Data were pooled from 9 short-term, double-blind, placebo-controlled studies in adults with MDD randomly assigned to desvenlafaxine 50 mg/d, 100 mg/d, or placebo. A mixed-effects model for repeated-measures analysis of change from baseline score was used to determine the time point at which desvenlafaxine treatment groups separated from placebo on the 17-item Hamilton Rating Scale for Depression and psychosocial outcomes. The association between early improvement and week 8 outcomes was examined using logistic regression analyses. Time to remission for patients with early improvement versus without early improvement was assessed using Kaplan-Meier techniques. Comparisons between groups were performed with log-rank tests.
RESULTS
In the intent-to-treat population (N = 4279 patients: desvenlafaxine 50 mg/d, n = 1714; desvenlafaxine 100 mg/d, n = 870; placebo, n = 1695), a statistically significant improvement on the 17-item Hamilton Rating Scale for Depression was observed with desvenlafaxine 50 mg/d at week 1 (P = 0.0129) and with desvenlafaxine 100 mg/d at week 2 (P = 0.0002) versus placebo. Early improvement was a significant predictor of later remission. Treatment assignment, baseline depression scale scores, and race were significantly associated with probability of early improvement. On several measures of depressive symptoms and function, desvenlafaxine 50 mg/d and 100 mg/d separated from placebo as early as week 1 and no later than week 4 in patients with MDD.
IMPLICATIONS/CONCLUSIONS
These findings suggest that clinicians may be able to use depression rating scale scores early in treatment as a guide to inform treatment optimization.
Topics: Adolescent; Adult; Aged; Antidepressive Agents; Depressive Disorder, Major; Desvenlafaxine Succinate; Double-Blind Method; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Young Adult
PubMed: 28817491
DOI: 10.1097/JCP.0000000000000775 -
Saudi Pharmaceutical Journal : SPJ :... Jul 2017Desvenlafaxine succinate (DSV) is a water soluble anti-depressant drug, which is rapidly absorbed after oral administration exaggerating its side effects. The current...
Desvenlafaxine succinate (DSV) is a water soluble anti-depressant drug, which is rapidly absorbed after oral administration exaggerating its side effects. The current work aimed to prepare controllable release DSV matrix to reduce DSV side effects related to its initial burst. Fifteen DSV matrix formulations were prepared using different polymers, polymer/drug ratios and matrix excipients and characterized using Differential Scanning Calorimetry (DSC), infrared (IR) spectroscopy, water uptake and DSV release. The release kinetics were calculated to determine the drug release mechanism. DSV absorption via rat intestinal mucosal cells and the calculation of the apparent permeability coefficient (P) were performed using everted sac technique. Maltodextrin was the best matrix excipient (F7 and F10) showing acceptable decrease in the initial burst compared to the innovator. The addition of negatively charged polymers sodium carboxy methyl cellulose (SCMC) or sodium alginate resulted in an interaction that was proved by DSC and IR findings. This interaction slowed DSV release. F10 showed an excellent absorption of more than 80% of DSV after 4 h and the highest similarity factor with the innovator (84.7). A controllable release pattern of DSV was achieved using Methocel, Maltodextrin and SCMC. The obtained results could be used as a platform to control the release of cationic water soluble drugs that suffer from side effects associated with their initial burst after oral administration.
PubMed: 28725139
DOI: 10.1016/j.jsps.2016.10.005 -
The International Journal of... Aug 2017Major depressive disorder is a debilitating illness, which is most commonly treated with antidepressant drugs. As the majority of patients do not respond on their first... (Clinical Trial)
Clinical Trial
BACKGROUND
Major depressive disorder is a debilitating illness, which is most commonly treated with antidepressant drugs. As the majority of patients do not respond on their first trial, there is great interest in identifying biological factors that indicate the most appropriate treatment for each patient. Studies suggest that microRNA represent excellent biomarkers to predict antidepressant response.
METHODS
We investigated the expression of miR-1202, miR-135a, and miR-16 in peripheral blood from 2 cohorts of depressed patients who received 8 weeks of antidepressant therapy. Expression was quantified at baseline and after treatment, and its relationship to treatment response and depressive symptoms was assessed.
RESULTS
In both cohorts, responders displayed lower baseline miR-1202 levels compared with nonresponders, which increased following treatment.
CONCLUSIONS
Ultimately, our results support the involvement of microRNA in antidepressant response and suggest that quantification of their levels in peripheral samples represents a valid approach to informing treatment decisions.
Topics: Antidepressive Agents; Biomarkers; Citalopram; Clinical Decision-Making; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Desvenlafaxine Succinate; Duloxetine Hydrochloride; Humans; MicroRNAs; Psychiatric Status Rating Scales; ROC Curve; Treatment Outcome
PubMed: 28520926
DOI: 10.1093/ijnp/pyx034 -
Basic & Clinical Pharmacology &... Oct 2017Venlafaxine is a commonly used antidepressant agent. We aimed to provide detailed information on the associations between venlafaxine dose and concentrations of... (Comparative Study)
Comparative Study
Venlafaxine is a commonly used antidepressant agent. We aimed to provide detailed information on the associations between venlafaxine dose and concentrations of venlafaxine, by patient age and sex. From a therapeutic drug monitoring (TDM) database located at Odense University Hospital, Denmark, we identified all adults for whom the treating physician had requested clinical advice on the TDM result for venlafaxine between 2002 and 2012. We identified 1077 TDM samples of venlafaxine from 334 males and 743 females (median age 45 years), and the median daily dose was 225 mg. Median plasma concentration of venlafaxine and o-desmethylvenlafaxine (ODV) was 306 nmol/L and 861 nmol/L, respectively. The median dose-corrected serum level for venlafaxine was 1.49 nmol/L/mg., while the dose-corrected serum level of men and women were 1.21 nmol/L/mg and 1.60 nmol/L/mg, respectively. The dose-corrected sum of venlafaxine and ODV was 8.91 nmol/L/mg (IQR 6.56-12.26) versus 5.52 nmol/L/mg (IQR 4.16-7.52) for patients above 64 years and below the age of 65 years, respectively. Dose-corrected plasma concentrations of venlafaxine and ODV are increased to a clinically significant degree in patients above the age of 64, and initiation of venlafaxine therapy in the elderly should be made cautiously and supported by drug measurements.
Topics: Adult; Age Factors; Aged; Antidepressive Agents, Second-Generation; Biotransformation; Databases, Factual; Denmark; Desvenlafaxine Succinate; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Male; Methylation; Middle Aged; Patient Selection; Risk Assessment; Risk Factors; Sex Factors; Venlafaxine Hydrochloride
PubMed: 28397349
DOI: 10.1111/bcpt.12796 -
Revista de Neurologia Mar 2017Desvenlafaxine is the third antidepressant within the group of serotonin-norepinephrine reuptake inhibitors. The latest clinical practice guidelines consulted agree that... (Review)
Review
INTRODUCTION
Desvenlafaxine is the third antidepressant within the group of serotonin-norepinephrine reuptake inhibitors. The latest clinical practice guidelines consulted agree that tricyclic antidepressants, dual (venlafaxine/duloxetine) and gabapentin/pregabalin antiepileptics, are the first-line drugs in the treatment of neuropathic pain, being tramadol, lidocaine 5% patches and capsaicin 8% patches of second-line drugs, while strong opioids constitute a third line treatment. The interaction between the binomial pain and depression is very frequent, being the psychological complication more frequent in patients with chronic pain.
DEVELOPMENT
Following a literature search, this article summarizes the most relevant pharmacological data of desvenlafaxine and its usefulness in clinical practice, as well as the specific literature of this drug in neuropathic pain and chronic pain.
CONCLUSIONS
Although evidence of desvenlafaxine in neuropathic pain is scarce, it presents some interesting pharmacokinetic properties, as it is not substrate or have activity on P-glycoprotein, and have a metabolism which practically does not depend on cytochrome P450 system, which limits the risk of pharmacokinetic interactions and potential problems associated tolerability when administered with drugs that are CYP2D6 moderate or potent inhibitors or other substrates of this isoenzyme. These characteristics make desvenlafaxine a different antidepressant especially useful in some subgroups of patients with chronic pain (as polypharmacy and patients with liver failure), where comorbid depression is frequent.
Topics: Antidepressive Agents; Biological Availability; Biotransformation; Chronic Pain; Clinical Trials as Topic; Cytochrome P-450 Enzyme System; Depressive Disorder; Desvenlafaxine Succinate; Dose-Response Relationship, Drug; Drug Interactions; Duloxetine Hydrochloride; Humans; Multicenter Studies as Topic; Neuralgia; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 28229443
DOI: No ID Found -
Neuropsychopharmacology : Official... Sep 2017MicroRNAs are short non-coding molecules that play a major role in regulating gene expression. Peripheral levels of miR-1202 have been shown to predict and mediate...
MicroRNAs are short non-coding molecules that play a major role in regulating gene expression. Peripheral levels of miR-1202 have been shown to predict and mediate antidepressant response. However, it is not clear to what extent these peripheral measures reflect central neural changes in vivo. We approached this problem with the combined use of peripheral miR-1202 measures and neuroimaging. At baseline and after 8 weeks of desvenlafaxine (50-100 mg die), 20 patients were scanned with 3T magnetic resonance imaging, first at rest then during the Go/NoGo task, a classical test of response inhibition. Blood samples were collected at both time points. During resting state, lower baseline miR-1202 levels were predictive of increased connectivity from T0 to T8 between the posterior cingulate and the prefrontal, parietal, and occipital cortices. Changes in miR-1202 levels following desvenlafaxine treatment were negatively correlated with changes in activity in right precuneus within the default-mode network, and in connectivity between the posterior cingulate and the temporal and prefrontal cortices, and the precuneus. During the Go/NoGo task, baseline miR-1202 levels and changes in these levels were correlated with activity changes in different regions, including bilateral prefrontal, insular, cingulate, and temporal cortices, and left putamen and claustrum. Finally, secondary analyses in a subset of patients showed a trend for a significant correlation between miR-1202 levels and glutamate levels measured by spectroscopy. Changes in peripheral miR-1202 levels were therefore associated with changes in brain activity and connectivity in a network of brain regions associated with depression and antidepressant response. These effects may be mediated by the glutamatergic system.
Topics: Adult; Antidepressive Agents; Brain; Brain Mapping; Depressive Disorder, Major; Desvenlafaxine Succinate; Female; Humans; Inhibition, Psychological; Magnetic Resonance Imaging; Male; MicroRNAs; Motor Activity; Neural Pathways; Neuropsychological Tests; Rest; Serotonin and Noradrenaline Reuptake Inhibitors; Treatment Outcome
PubMed: 28079059
DOI: 10.1038/npp.2017.9