What is/are Desvenlafaxine?
Desvenlafaxine (brand name: Pristiq), also known as O-desmethylvenlafaxine, is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class developed and marketed by Wyeth (now part of Pfizer). Desvenlafaxine is a synthetic form of the major active metabolite of venlafaxine (sold under the brand names Effexor and Efexor). It is being targeted as the first non-hormonal based treatment for menopause.
Desvenlafaxine is a synthetic form of the isolated major active metabolite of venlafaxine, and is categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI). It works by blocking the transporter "reuptake" proteins for key neurotransmitters affecting mood, thereby leaving more active neurotransmitters in the synapse. The neurotransmitters affected are serotonin (5-hydroxytryptamine) and norepinephrine (noradrenaline). It is approximately 10 times more potent at inhibiting serotonin uptake than norepinephrine uptake. When most normal metabolizers take venlafaxine - 70% of the benefit comes from venlafaxine being metabolized into desvenlafaxine so the effects are very similar.
Side-effect profiles were consistent for all three studies evaluated, with nausea being the most profound and prevalent. Although rates varied substantially from study to study, nausea was consistently the most common complaint (30-50% vs placebo 9-11%) and the most common reason for discontinuation. Suicidal ideation was monitored and was determined to be significant in 1-2 patients in each study. The most commonly observed adverse reactions in Pristiq-treated MDD patients in short-term fixed-dose studies (incidence ≥ 5% and at least twice the rate of placebo in the 50 or 100 mg dose groups) were nausea, dizziness, insomnia, hyperhidrosis, constipation, somnolence, decreased appetite, priapism, night terrors, anxiety, and delayed ejaculation. These side-effect patterns are consistent with those of other SNRIs venlafaxine (Effexor) and duloxetine (Cymbalta, Yentreve). Relative rates are not available, as there were no head-to-head studies.
Wyeth Pharmaceuticals also reports the following as potential side effects: headache, sweating, diarrhea, hypertension, abnormal bleeding and/or bruising, glaucoma, increased cholesterol and triglyceride levels, low sodium levels in the blood, and seizures.
Increases in blood pressure along with small increases in heart rate were noted in clinical trials of Pristiq, so patients with pre-existing blood pressure problems or cardiovascular diseases should always make sure that their doctor is aware of prior heart or blood pressure conditions. Blood pressure should be regularly checked in those taking Pristiq.
Although Pristiq did not increase mental or physical impairment in individuals consuming normal amounts of alcohol in a clinical study, it is generally a good idea to avoid alcohol consumption while taking Pristiq.
This drug carries the following FDA Black Box Label:
WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of PRISTIQ® or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. 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. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. PRISTIQ is not approved for use in pediatric patients.
In published phase 3 trials, desvenlafaxine was compared only to placebo. In these trials, primary endpoints were powered to measure a reduction in depression (HAM-D17) scores and not the standard response measure of ≥50% reduction in depression scores.
Response scores were secondary measures which the studies may or may not have been powered to address. These trials showed dose-erratic reductions in HAM-D17 scores, reductions which undermined the results. Response rates varied from 43-60%, lower than most current antidepressants, which have a 60-70% response rate. Remission rates of 23-37% for desvenlafaxine are also lower than those of other antidepressants, which have rates of 30-40%. Of course, generalizations of this nature cannot be made without careful statistical testing, and such testing was beyond the scope of this project.
Treatment duration for the three reviewed trials seemed inadequate, given the staging of Major Depressive Disorder (MDD). MDD acute phase lasts 12 weeks, while all three reviewed studies treated patients for only 8 weeks. Although it may not be practical or required to conduct a study of continuing therapy for an entire year, without the data that would result it is difficult to determine whether or not desvenlafaxine is an appropriate therapy.
There may be some differences in efficacy across ethnic backgrounds. One study, with three different dose strengths, showed efficacy in the 100 mg and 400 mg doses, but no efficacy in the 200 mg dose. This group had a notably higher proportion of blacks and Hispanics than the other two active groups. The only other study which listed ethnic distributions had a notably higher proportion of blacks and Hispanics in the placebo group vs. the active group. Although kinetic studies have indicated there are no known active metabolites for desvenlafaxine, the possibility of ethnic variations in response cannot be ruled out. This statement on ethnic backgrounds is solely based on an interpretation of the medication's package insert.
This article uses material from the Wikipedia article Desvenlafaxine, which is released under the Creative Commons Attribution-Share-Alike License 3.0.