desvenlafaxine-succinate and Drug-Related-Side-Effects-and-Adverse-Reactions

The risk for major depressive disorder (MDD) increases during the menopausal transition. Nonetheless, no large, placebo-controlled studies have prospectively assessed the efficacy of antidepressants in perimenopausal or postmenopausal women. This randomized, double-blind, placebo-controlled trial evaluated the short-term efficacy and safety of desvenlafaxine (administered as desvenlafaxine succinate) in perimenopausal and postmenopausal women with DSM-IV-defined MDD.. 387 depressed perimenopausal and postmenopausal women aged 40 to 70 years were randomly assigned to placebo or desvenlafaxine (100 or 200 mg/d at the discretion of the investigator) in an 8-week, flexible-dose trial conducted from September 2006 to June 2008. The primary efficacy variable was change from baseline in 17-item Hamilton Depression Rating Scale (HDRS(17)) total score, analyzed using a mixed-effects model for repeated-measures analysis. Safety data were collected throughout the trial.. The reduction in adjusted HDRS17 total scores from baseline to week 8 (mean daily dose after titration, 162 to 176 mg/d) was significantly greater for desvenlafaxine (-12.64) compared with placebo (-8.33; P < .001). Statistical separation from placebo was observed at week 1 and was sustained through week 8. Both the perimenopausal and postmenopausal subgroups achieved significant reductions in HDRS(17) total scores with desvenlafaxine treatment (perimenopausal, P = .003; postmenopausal, P < .001). Response (58.6%) and remission (38.2%) rates were significantly higher for desvenlafaxine compared with placebo (31.6% [P < .001] and 22.4% [P = .008], respectively). In all, 19/256 (7.4%) desvenlafaxine-treated patients and 4/125 (3.2%) placebo-treated patients discontinued due to adverse events. Treatment-emergent adverse events were reported by 94/125 (75.2%) placebo-treated patients and 218/256 (85.2%) desvenlafaxine-treated patients.. Short-term treatment with desvenlafaxine was effective and generally well tolerated in perimenopausal and postmenopausal women with MDD.. clinicaltrials.gov Identifier: NCT00369343.

Topics: Adult; Antidepressive Agents; Cyclohexanols; Depressive Disorder, Major; Desvenlafaxine Succinate; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Menopause; Middle Aged; Postmenopause; Psychiatric Status Rating Scales; Treatment Outcome

To assess the efficacy, safety, and tolerability of 50- and 100-mg/day doses of desvenlafaxine (administered as desvenlafaxine succinate), a serotonin-norepinephrine reuptake inhibitor, for the treatment of major depressive disorder (MDD).. Patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) MDD and 17-item Hamilton Rating Scale for Depression (HAM-D(17)) scores > or =20 were randomly assigned to double-blind placebo or desvenlafaxine treatment (fixed dose of 50 mg/day or 100 mg/day) for 8 weeks. The primary efficacy measure was the HAM-D(17). Changes from baseline in HAM-D(17) scores were analyzed using analysis of covariance. The final on-therapy evaluation was the primary endpoint for efficacy analyses, using last-observation-carried-forward data. MAIN OUTCOMES MEASURES AND RESULTS: The intent-to-treat population included 447 patients. Desvenlafaxine 50 mg was associated with a significantly greater adjusted mean change from baseline on the HAM-D(17) (-11.5) compared with placebo (-9.5, p=0.018); the 100-mg dose group (-11.0) did not achieve statistical significance (p=0.065). The 100-mg dose group experienced significant improvements compared with placebo on several secondary efficacy measures, including the 6-item Hamilton Depression Rating Scale (p=0.038) and the Visual Analog Scale-Pain Intensity total score (p=0.041). Both desvenlafaxine doses were generally well-tolerated. The most common adverse events (incidence > or =10% in either desvenlafaxine group and twice the rate of placebo) were dry mouth, constipation, insomnia, decreased appetite, hyperhidrosis, and dizziness.. These results demonstrate efficacy, safety, and tolerability of desvenlafaxine 50 mg/day for treating MDD. The significant findings on secondary measures support the efficacy of desvenlafaxine 100 mg, as seen in other trials. Conclusions may be limited by the exclusion of MDD patients with comorbid conditions and the short-term desvenlafaxine treatment duration.

Topics: Adolescent; Adult; Antidepressive Agents; Cyclohexanols; Depressive Disorder, Major; Desvenlafaxine Succinate; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Outpatients; Placebos; Treatment Outcome

To address the potential correlation between plasma concentrations of venlafaxine (VEN), its active metabolite O-desmethylvenlafaxine (ODVEN) and the active moiety, AM, (ODVEN + VEN) and adverse drug reactions (ADR) in a large naturalistic sample of in- and outpatients. We compared plasma concentrations of VEN, ODVEN and AM and dose-adjusted (C/D) levels as well the ODVEN/VEN ratios between patients complaining ADRs, following the Udvalg for Kliniske Undersogelser side effect rating scales (UKU) (n = 114) and patients without ADRs (control group, n = 688) out of a naturalistic database. We also investigated potential pharmacokinetic correlates of the four UKU categories by comparing patients complaining ADRs with those who did not. Based on previous literature we applied different ODVEN/VEN ratio values as cut-offs to split our sample into two groups at a time and compare frequencies of ADRs between the groups. No differences for demographic and pharmacokinetic variables including plasma and C/D concentrations as well as ODVEN/VEN ratios were observed between study groups. Neither the comparisons between females and males nor between elderly and non-elderly patients revealed significant differences (p > 0.05 in all cases). No differences were also reported exploring the patients complaining ADRs from the 4 UKU categories separately. After applying various ODVEN/VEN cut-offs, groups did not display differences in frequencies of ADRs (p > 0.05 in all cases). Our findings do not demonstrate a direct link between venlafaxine metabolism measures and ADRs. Therefore, additional dimensions are needed to be considered in future trials aiming to disentangle the involved aspects of ADRs in patients receiving venlafaxine.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents, Second-Generation; Databases, Factual; Desvenlafaxine Succinate; Drug-Related Side Effects and Adverse Reactions; Female; Germany; Humans; Male; Middle Aged; Mood Disorders; Venlafaxine Hydrochloride; Young Adult

Few studies in the literature have examined the efficacy of antidepressant drugs in perimenopausal and postmenopausal women. The objective of the current study was to assess the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) separately in perimenopausal and postmenopausal women with major depressive disorder (MDD).. Data were pooled from two double-blind, placebo-controlled clinical trials enrolling perimenopausal and postmenopausal women (40-70 years old) diagnosed with MDD. Patients were randomly assigned to receive desvenlafaxine 100 to 200 mg/day or placebo (8 weeks) or desvenlafaxine 50 mg/day or placebo (10 weeks). The primary efficacy end point for each trial was change from baseline in Hamilton Rating Scale for Depression (HAM-D17) total score at week 8. Secondary end points included change from baseline in Sheehan Disability Scale (SDS) and Menopause Rating Scale (MRS) scores. Changes from baseline in continuous variables were analyzed using analysis of covariance with treatment, region, and baseline in the model. All treatment comparisons were carried out separately in perimenopausal or postmenopausal women, in individual studies, and in the pooled population, adjusting for menopausal status and study.. A total of 798 patients were included in the full analysis set (perimenopausal, n=252; postmenopausal, n=546). Desvenlafaxine significantly reduced HAM-D17 total scores versus placebo at week 8 in both perimenopausal (-10.3 vs. -6.5; p<0.001) and postmenopausal women (-10.1 vs. -7.6; p<0.001). Significant improvements in SDS and MRS total scores were also observed for desvenlafaxine versus placebo in perimenopausal (p ≤ 0.024) and postmenopausal women (p ≤ 0.009). A significant treatment by menopausal status interaction was observed for SDS only (p=0.036).. Desvenlafaxine demonstrated antidepressant efficacy in both perimenopausal and postmenopausal subgroups of women with MDD.. In September 2011, Pfizer received a Complete Response Letter from the United States Food and Drug Administration on its application for approval to market desvenlafaxine for the treatment of moderate to severe vasomotor symptoms associated with menopause. The Complete Response Letter states that the data included in the application are not sufficient to establish an acceptable risk/benefit profile for the treatment of vasomotor symptoms in the general population of postmenopausal women, and therefore desvenlafaxine is not approved for the treatment of vasomotor symptoms in the United States at this time. This decision does not impact desvenlafaxine's approval for the treatment of MDD in adults.

Topics: Administration, Oral; Adult; Aged; Antidepressive Agents; Cyclohexanols; Depressive Disorder, Major; Desvenlafaxine Succinate; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Menopause; Middle Aged; Postmenopause; Psychiatric Status Rating Scales; Treatment Outcome