desvenlafaxine-succinate and Hypertension

To evaluate the effect of the serotonin-norepinephrine re-uptake inhibitor desvenlafaxine on blood pressure and incidence of new onset hypertension in pooled short-term studies and in two longer-term, randomized withdrawal studies.. Data from patients randomly assigned to desvenlafaxine 10 mg to 400 mg/day or placebo in 11 short-term (8-12 weeks), fixed-dose, double-blind, placebo-controlled studies of major depressive disorder (MDD) were pooled for analysis; two desvenlafaxine randomized withdrawal studies (36 and 46 weeks) were analyzed separately.. www.clinicaltrials.gov , NCT00072774, NCT00073762, NCT00277823, NCT00300378, NCT00384033, NCT00798707, NCT00863798, NCT01121484, NCT00824291, NCT01432457, NCT00075257, NCT00887224.. Outcomes included change from baseline in supine systolic blood pressure (SSBP) and supine diastolic blood pressure (SDBP), assessed using a mixed model repeated measures (MMRM) analysis, and incidence of hypertension (defined as three consecutive second SDBP measures ≥90 mm Hg AND increase of ≥10 mm Hg from baseline and/or SSBP ≥140 mm Hg AND increase of ≥10 mm Hg), analyzed using Cochran Mantel Hanzael tests. Potential predictors of change in SSBP and SDBP at LOCF were examined by including predictor variables in a regression model.. In the pooled, short-term studies, mean changes from baseline over time in SSBP and SDBP were statistically significant compared with placebo for the desvenlafaxine doses of 10 mg/day or greater for SSBP (p ≤ 0.0004; MMRM) and 25 mg/day or greater for SDBP (p ≤ 0.0449; MMRM). The proportion of patients with new onset hypertension differed significantly from placebo for the 50, 200, and 400 mg/day doses (1.9%, 2.4%, 4.8%, respectively, vs 0.8%; all p ≤ 0.0244). Predictors of change in BP included baseline SDBP, baseline SSBP, dose, body mass index, gender, age, race, and history of hypertension.. Data were pooled from studies which differed somewhat in study design and patient demographics. None of the studies were originally designed to examine treatment effects on BP. Study entry criteria limit generalization of these results to medically stable patients with a primary diagnosis of MDD.. Short-term desvenlafaxine treatment was associated with small but statistically significant increases in SSBP and SDBP.

Topics: Adult; Antidepressive Agents; Blood Pressure; Cyclohexanols; Depressive Disorder, Major; Desvenlafaxine Succinate; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome

Desvenlafaxine is used to treat major depression. Desvenlafaxine is also the active metabolite of venlafaxine. Venlafaxine overdose can cause serotonin toxicity, seizures and cardiovascular effects, but there is limited information on desvenlafaxine overdose.. We aimed at investigating the clinical effects and complications from desvenlafaxine overdose.. This was a retrospective observational study of desvenlafaxine overdoses over a six-year period. Demographic details, dose and timing of the overdose, together with clinical effects, treatment and complications were extracted from a local hospital network database or the medical records of patients following hospital admission with a desvenlafaxine overdose.. There were 182 cases of desvenlafaxine overdose included in the study. From the 182 cases, 75 were desvenlafaxine (± alcohol) only ingestions and 107 included one or more co-ingested drugs. In single-agent desvenlafaxine ingestions, median age was 25 years (range: 13-68 years) with a median ingested dose of 800 mg (range: 250-3500 mg; interquartile range (IQR): 600-1400 mg), and 54/75 (72%) were female. The Glasgow Coma Score (GCS) was 15 in 68/74 (92%) patients, 13-14 in 5/74 (7%), and was seven in one patient following aspiration. Mild hypertension (systolic blood pressure [BP] > 140-180 mmHg) occurred in 23/71 patients (32%), and tachycardia occurred in 29/74 (39%) patients. There were no abnormal QT intervals and no QRS >120 m s. Serotonin toxicity was diagnosed by the treating physician in 7/75 (9%) patients, but only one of these met the Hunter Serotonin Toxicity Criteria. None of the 75 patients who took desvenlafaxine only (± alcohol) had seizures, were admitted to intensive care or died. In comparison, the 107 patients taking desvenlafaxine in overdose with other medications developed more pronounced toxicity. Generalised seizures occurred in 5/107 (5%), but in three of these cases co-ingestants were possible proconvulsants. Fifteen patients had a GCS ≤9 and none had an abnormal QT or QRS. Severe effects appeared to be associated with coingestants.. Desvenlafaxine overdose causes minor effects with mild hypertension and tachycardia. The risk of seizures or serotonin toxicity is low.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Desvenlafaxine Succinate; Drug Overdose; Female; Glasgow Coma Scale; Humans; Hypertension; Male; Middle Aged; Retrospective Studies; Seizures; Tachycardia; Young Adult

Topics: Antidepressive Agents; Anxiety; Cyclohexanols; Desvenlafaxine Succinate; Female; Humans; Hypertension; Middle Aged