Indications for: Venlafaxine
Major depressive disorder (MDD).
Major Depressive Disorder (MDD)
Study 1 and 2
The efficacy of Effexor XR was based on 2 placebo-controlled, short-term (8 weeks for study 1; 12 weeks for study 2), flexible-dose studies, with doses starting at 75 mg per day and ranging to 225 mg per day in adult outpatients diagnosed with MDD.
Moderately depressed patients were initiated with venlafaxine 75 mg/day.
Both studies showed that treatment with Effexor XR achieved superiority over placebo on the primary efficacy outcome, defined as change from baseline in the HAM-D-21 total score to the endpoint visit, and on the key secondary efficacy outcome, the Clinical Global Impressions (CGI) Severity of Illness scale.
The efficacy of Effexor XR was based on a 4-week study of inpatients diagnosed with MDD with melancholia, with doses of Effexor in a range of 150 to 375 mg/day (divided 3 times daily).
Treatment with Effexor achieved superiority over placebo based on the HAM-D-21 total score.
In the longer-term 26-week Study 4, adult outpatients with MDD who responded to an 8-week open-label study on Effexor XR (75, 150, or 225 mg once daily) were randomly assigned to continuation of their same Effexor XR dose or placebo.
Response during the open-label phase was defined as CGI Severity of Illness item score of at least 3 and a HAM-D-21 total score of less than or equal to 10 at the day 56 evaluation.
Relapse during the double-blind phase was defined as: (1) a reappearance of MDD as defined by DSM-IV criteria and a CGI Severity of Illness item score of at least 4 (moderately ill), (2) two consecutive CGI Severity of Illness item scores of at least 4, or (3) a final CGI Severity of Illness item score of ≥4 for any patient who withdrew from the study for any reason.
Treatment with Effexor XR achieved statistically significantly lower relapse rates over 26 weeks vs placebo.
In the second longer-term 52-week Study 5, adult outpatients with MDD, recurrent type, who had responded (HAM-D-21 total score ≤12 at the day 56 evaluation) and continued to be improved were randomly assigned to continue the same Effexor dose or to placebo.
Treatment with Effexor XR achieved statistically significantly lower relapse rates over 56 weeks vs placebo.
Take with food. ≥18yrs: Initially 75mg/day in 2–3 divided doses; may increase at 4-day intervals in 75mg/day increments to 150mg/day; max 375mg/day, in 3 divided doses. Hepatic impairment: reduce by at least 50%. Renal impairment (mild or moderate): reduce by 25–50%; (severe or undergoing hemodialysis): reduce dose by at least 50%. Withdraw gradually (over 2 weeks).
<18yrs: not established.
During or within 14 days of MAOIs (see Interactions). Concomitant linezolid or IV methylene blue.
Suicidal thoughts and behaviors.
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults; monitor closely for clinical worsening or unusual changes. Screen for bipolar disorder, mania or hypomania prior to initiation. Monitor for serotonin syndrome; discontinue immediately if occurs. Pre-existing hypertension, cardio- or cerebrovascular disease. Monitor BP before and during treatment; consider dose reduction or discontinuation if elevated BP persists. Heart disease (eg, recent MI, heart failure). Risk for bleeding events. Angle-closure glaucoma. Avoid in those with untreated anatomically narrow angles. History of mania/hypomania. Seizure disorders. Volume-depleted. Hyponatremia (esp. in elderly). Sexual dysfunction. Renal or hepatic dysfunction. Avoid abrupt disruption; monitor. Reevaluate periodically. Write ℞ for smallest practical amount. Elderly. Labor & delivery. Pregnancy; see full labeling for effects on mother and neonates. Nursing mothers.
See Contraindications. Allow at least 14 days after MAOI discontinuance before starting venlafaxine; allow at least 7 days after venlafaxine discontinuance before starting an MAOI. Increased risk of serotonin syndrome with concomitant other serotonergic drugs (eg, other SNRIs, SSRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, methadone, meperidine, tryptophan, buspirone, amphetamines, St. John's Wort) or with drugs that impair serotonin metabolism (eg, MAOIs such as linezolid, IV methylene blue). Avoid alcohol. Potentiated by CYP3A inhibitors; consider reducing dose of venlafaxine. Potentiates CYP2D6 substrates; consider reducing dose of substrate. Concomitant weight loss agents (eg, phentermine), serotonin precursors (tryptophan supplements): not recommended. Caution with other CNS drugs, cimetidine, haloperidol, diuretics, metoprolol, drugs that inhibit CYP2D6, CYP3A4. Increased risk of bleeding with aspirin, NSAIDs, warfarin, or other drugs that affect coagulation; monitor closely. False (+) urine immunoassay screening tests for PCP and amphetamine.
Nausea, somnolence, dry mouth, sweating, abnormal ejaculation, anorexia, constipation, erectile dysfunction, decreased libido, weight changes, dizziness, insomnia, headache, nervousness, asthenia, vasodilation, abnormal dreams or vision, tremor, yawn, ecchymosis; rare: interstitial lung disease, eosinophilic pneumonia.
Renal (87%). Half-life: 5±2 hours (for venlafaxine); and 11±2 hours (for O-desmethylvenlafaxine). Mean ± SD plasma apparent clearance at steady-state: 1.3±0.6 L/h/kg (for venlafaxine); and 0.4±0.2 L/h/kg (for O-desmethylvenlafaxine).
Generic Drug Availability:
XR caps—15, 30, 90; Tabs—Contact supplier