Exploratory analyses for age and gender effects on outcome did not suggest any differential responsiveness on the basis of age or sex.In one longer-term study, adult outpatients meeting DSM-IV criteria for major depressive disorder who had responded during an 8 week open trial on venlafaxine hydrochloride extended release capsules (75,150,or 225 mg, qAM) were randomized to continuation of their same venlafaxine hydrochloride extended release capsule dose or to placebo, for up to 26 weeks of observation for relapse. Combined AUCs of venlafaxine and ODV increased on average by approximately 23% in EMS and 53% in PMs (range in PMs - 4 to 134%).Concomitant use of CYP3A4 inhibitors and venlafaxine may increase levels of venlafaxine and ODV. Venlafaxine may cause a serious condition called serotonin syndrome if taken together with certain medicines. Pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative, and cardiovascular effects seen with other psychotropic drugs. Protein-binding-induced drug interactions with venlafaxine are not expected.Steady-state concentrations of both venlafaxine and ODV in plasma were attained within 3 days of multiple-dose therapy. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.

Therefore, caution is advised with such patients.Under steady-state conditions for venlafaxine administered at 150 mg/day, a single 10 mg dose of diazepam did not appear to affect the pharmacokinetics of either venlafaxine or ODV in 18 healthy male subjects.

It is recommended that patients receiving venlafaxine have regular monitoring of blood pressure. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. None of the patients receiving venlafaxine hydrochloride extended-release capsules discontinued for anorexia or weight loss.During Phase 2 and Phase 3 trials, hypomania or mania occurred in 0.5% of patients treated with venlafaxine.

Venlafaxine Cmax increased by 26% in EM subjects and 48% in PM subjects. Symptoms associated with discontinuation of venlafaxine tablets other SNRIs, and SSRIs, have been reported (see ODV was not mutagenic in the in vitro CHO cell chromosomal aberration assay. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. When increasing the dose, increments of up to 75 mg/day should be made at intervals of no less than 4 days. False positive test results may be expected for several days following discontinuation of venlafaxine therapy. Evaluation of the electrocardiograms for 769 patients who received venlafaxine hydrochloride in 4 to 6 week double-blind placebo-controlled trials, however, showed that the incidence of trial-emergent conduction abnormalities did not differ from that with placebo. The overall pharmacological activity of venlafaxine plus ODV is expected to increase only slightly, and no dosage adjustment should be necessary for most normal adults. Data from the 2 fixed-dose outpatient studies were suggestive of a dose-response relationship in the range of 75 to 225 mg/day. Lithium.