Study Also Reinforces Existing Body of Clinical Evidence in Support of the Efficacy, Safety and Tolerability Profiles of PRISTIQ
Pfizer Inc. (NYSE:PFE) today announced the publication of a clinical study in the Journal of Clinical Psychiatry showingcomparable sexual function in adult patients diagnosed with major depressive disorder (MDD) treated daily with PRISTIQ Extended Release Tablets 50mg and 100mg doses versus placebo. Sexual dysfunction is often an issue for patients treated with antidepressants, and Pfizer conducted the study pursuant to a postmarketing requirement by the U.S. Food and Drug Administration (FDA).
“Sexual dysfunction is a common concern for patients treated with antidepressants. This study showed that sexual function was comparable between desvenlafaxine and placebo,” said Dr. Anita Clayton, interim chair, Department of Psychiatry and Neurobehavioral Sciences at the University of Virginia Health System, and lead investigator of the study. “The low potential for sexual dysfunction with desvenlafaxine is encouraging, and physicians and patients would benefit from further study.”
The primary end point of the study showed a statistically significant improvement among patients treated with PRISTIQ compared to placebo in symptoms of major depressive disorder as measured by the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score over an 8-week period. The HAM-D17 is a validated assessment tool used to rate the severity of a patient’s depressive symptoms. Sexual dysfunction was a secondary end point, and measured using the Arizona Sexual Experiences Scale (ASEX), a validated and reliable patient rated sexual function scale in the United States.
An estimated 33 million to 35 million U.S. adults are likely to experience major depression at some point during their lifetime. The criteria for MDD include having five or more of the symptoms of depression listed below during the same two-week period and representing a change from previous functioning. Depressed mood or diminished interest or pleasure must be among the depression symptoms reported from the following list: depressed mood; diminished interest or pleasure; significant weight loss or change in appetite; insomnia/hypersomnia; psychomotor agitation; fatigue or loss of energy; feelings of worthlessness or excessive/inappropriate guilt; difficulty concentrating; and recurrent thoughts of death.
In this Phase 4, multi-center, randomized, double- blind placebo-controlled study, a total of 924 patients, 18-years or older, with a baseline HAM-D17 score of ≥20, were randomly assigned to PRISTIQ 50mg/day, PRISTIQ 100 mg/day or placebo in a 1:1:1 ratio over an 8-week period. The primary efficacy end point for the study was the change from baseline in HAM-D17 total score at week 8. In the primary efficacy analysis, a statistically greater change from baseline was observed in patients receiving PRISTIQ 50 mg and PRISTIQ 100mg compared with placebo. The most common treatment emergent adverse events observed were consistent with the known safety and tolerability profile of PRISTIQ.
Sexual function was assessed using the ASEX Scale. The ASEX was selected over other validated scales because it is a brief but sensitive tool, less burdensome to patients than a more in-depth scale, and has been utilized in previous trials for desvenlafaxine and other antidepressant drugs. It measures five core elements of sexual function (sexual drive, arousal, penile erection/vaginal lubrication, ability to reach orgasm, and satisfaction from orgasm) rated on a six-point Likert scale. A Likert scale is a psychometric scale commonly utilized in research that employs questionnaires. A total score is calculated as the sum of all 5 individual item scores; negative numbers for change from baseline indicate improvement in sexual function.
Incidence of sexual dysfunction was assessed using the ASEX data. In adult outpatients with MDD with baseline sexual activity and at least one post-baseline assessment, effects on ASEX total and item scores were comparable for the PRISTIQ 50 mg and PRISTIQ 100 mg groups and placebo. Rates of sexual dysfunction were comparable between each PRISTIQ dose and placebo at baseline (placebo, 52%; PRISTIQ 50 mg/d, 56%; PRISTIQ 100 mg/d, 54%) and at week 8 (placebo, 45%; PRISTIQ 50 mg/d, 49%; PRISTIQ 100 mg/d, 47%).
“The treatment and management of MDD in adults can be both complex and challenging for physicians and patients,” noted Dr. Salomon Azoulay, global clinical and medical affairs head, Pfizer Global Established Pharma. “As a science-based company, we continue to study PRISTIQ in order to provide clinicians with information that can help guide their treatment decisions and positive health outcomes for patients with MDD.”
About PRISTIQ® (desvenlafaxine)
PRISTIQ, a selective serotonin and norepinephrine reuptake inhibitor (SNRI), is a prescription medication that was approved by the U.S. Food and Drug Administration (FDA) in 2008 for the treatment of MDD in adults. The recommended dose for PRISTIQ is 50 mg once daily, with or without food. In clinical studies, doses of 50-400 mg/day were shown to be effective, although no additional benefit was demonstrated at doses greater than 50 mg/day and adverse events and discontinuations were more frequent at higher doses.
PRISTIQ Extended-Release Tablets are indicated for the treatment of major depressive disorder in adults.
Important Safety Information for PRISTIQ
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.
• 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.
Selected 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, tryptophan, buspirone, 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.
• 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.
• On discontinuation, adverse events, some of which may be serious, have been reported with PRISTIQ and other SSRIs and SNRIs. Abrupt discontinuation of PRISTIQ has been associated with the appearance of new symptoms. Patients should be monitored for symptoms when discontinuing treatment. A gradual reduction in dose rather than abrupt cessation is recommended whenever possible.
• 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.
• 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%).
Full prescribing information and Medication Guide including BOXED WARNING, are available at www.PRISTIQ.com.
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Jennifer Kokell, 212-733-2596