In a pooled analysis of two 8-week trials,
PRISTIQ demonstrated significant improvement in the Sheehan Disability Scale* total score vs placebo at week 8 (P<0.0001) comprising 3 domains3-5:
In a pooled analysis of two 8-week studies,
Study description
Pooled data from two double-blind, randomized, placebo-controlled, fixed-dose, 8-week studies of 50 mg qd (n=314) and 100 mg qd (n=305) of PRISTIQ vs placebo (n=311) in adults aged 18 and older with MDD. The primary end point was change in HAM-D17 total score vs placebo from baseline at week 8. Final on‑therapy value was defined as the last on-therapy evaluation, regardless of the number of days on therapy, with last-observation-carried-forward (LOCF) statistical analysis.1 Only 50 mg vs placebo data shown.
The Hamilton Rating Scale for Depression is a 17-item, validated, observer-rated scale that assesses depressive symptoms. It is one of the most widely used instruments for the clinical assessment of depressive states. The rater evaluates the severity of symptoms on the basis of information gained during an interview. Symptoms are rated on either a 5-point or 3-point scale, the latter being used when quantifying the variable is difficult or impossible.6
In the 6-month, double-blind phase of a maintenance trial,
Relapse in the double-blind phase was defined as any one or more of the following2:
In a pooled analysis of two 8-week studies,
Significant improvement in SDS total score vs placebo at week 8 (P<0.0001)3,5
Proven efficacy with a low discontinuation rate* due to adverse events and a reduced risk of relapse in PRISTIQ responders1,2
*In a pooled analysis of 8-week studies, discontinuation rates were 4.1% with PRISTIQ 50 mg vs 3.8% with placebo.
PRISTIQ has a low potential for CYP2D6-mediated drug-drug interactions1,2
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older.
In patients of all ages who are started on antidepressant therapy, monitor closely for worsening and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber.
PRISTIQ is not approved for use in pediatric patients.
Contraindications
PRISTIQ is contraindicated in patients with a known hypersensitivity to PRISTIQ or venlafaxine. Angioedema has been reported in patients treated with PRISTIQ.
Serotonin syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with PRISTIQ or within 7 days of stopping treatment with PRISTIQ. Do not use PRISTIQ within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start PRISTIQ in a patient who is being treated with an MAOI such as linezolid or intravenous methylene blue.
Warnings and Precautions
All patients treated with antidepressants should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of treatment and when changing the dose. Consider changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or includes symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, or suicidality that are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with antidepressants should be alerted about the need to monitor patients.
The development of a potentially life-threatening serotonin syndrome has been reported with SSRIs and SNRIs, including with PRISTIQ, both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone,tryptophan, buspirone, amphetamines, and St. John's Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). If such events occur, immediately discontinue PRISTIQ and any concomitant serotonergic agents, and initiate supportive treatment. If concomitant use of PRISTIQ with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increase.
Patients receiving PRISTIQ should have regular monitoring of blood pressure, since increases in blood pressure were observed in clinical studies. Pre-existing hypertension should be controlled before starting PRISTIQ. Caution should be exercised in treating patients with pre-existing hypertension, cardiovascular or cerebrovascular conditions that might be compromised by increases in blood pressure. Cases of elevated blood pressure requiring immediate treatment have been reported. For patients who experience a sustained increase in blood pressure, either dose reduction or discontinuation should be considered.
SSRIs and SNRIs, including PRISTIQ, may increase the risk of bleeding events. Concomitant use of aspirin, NSAIDs, warfarin, and other anticoagulants may add to this risk.
The pupillary dilation that occurs following use of many antidepressant drugs, including PRISTIQ, may trigger an angle closure attack in a patient with anatomically narrow angles (Angle Closure Glaucoma) who does not have a patent iridectomy. Avoid use of antidepressants, including PRISTIQ, in patients with untreated anatomically narrow angles.
PRISTIQ is not approved for use in bipolar depression. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine the risk of bipolar disorder.
PRISTIQ should be used cautiously in patients with a history or family history of mania or hypomania or with a history of seizure disorder.
Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances, tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. Patients should be monitored for symptoms when discontinuing treatment. A gradual reduction in dose rather than abrupt cessation is recommended.
SSRIs and SNRIs, including PRISTIQ, may cause symptoms of sexual dysfunction. Patients should be monitored for changes.
Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including PRISTIQ. Discontinuation of PRISTIQ should be considered in patients with symptomatic hyponatremia.
Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine (the parent drug of PRISTIQ) therapy have been rarely reported.
Third trimester use may result in neonatal discontinuation syndrome.
Adverse Reactions
The most commonly observed adverse reactions in patients taking PRISTIQ vs placebo for MDD in short-term fixed-dose premarketing studies (incidence ≥5% and at least twice the rate of placebo in the 50-mg dose group) were nausea (22% vs 10%), dizziness (13% vs 5%), hyperhidrosis (10% vs 4%), constipation (9% vs 4%), and decreased appetite (5% vs 2%).