Pharmacology Update
Desvenlafaxine Succinate Extended-Release Tablets (Pristiq™)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.
Wyeth Pharmaceuticals has received approval to market desvenlafaxine for the treatment of depression. The drug is the major active metabolite of venlafaxine (Effexor ). Wyeth has formulated the drug in a once-daily extended-release tablet. It will be marketed under the trade name Pristiq.
Indications
Desvenlafaxine is indicated for the treatment of major depressive disorder (MDD).1
Dosage
The initial dose is 50 mg once daily. Additional clinical benefit may not be gained with doses higher than 50 mg. For patients with severe renal impairment the recommended dose is 50 mg every other day. It may be taken without regard to meals. The tablets should be taken whole, not chewed, crushed, or divided. The tablet should be taken at the same time daily.1
Desvenlafaxine is available as 50 mg and 100 mg tablets.
Potential Advantages
Desvenlafaxine may provide a more consistent delivery of the major active component of venlafaxine with potentially less intrasubject and interpatient variability.2 It also has a low potential for drug-drug interaction. Desvenlafaxine is metabolized from venlafaxine via CYP3A4.
Potential Disadvantages
Desvenlafaxine may increase blood pressure. It should not be started in patients with uncontrolled hypertension. Monitoring of blood pressure is recommended during treatment.1 Nausea is the most common adverse event, ranges from 22% to 41%, and occurred during the first week of therapy.3 It became less frequent by week 2. However, it was the leading cause for discontinuation of therapy.
Comments
Desvenlafaxine (O-desmethylvenlafaxine) is the major active metabolite of venlafaxine. It's similar to venlafaxine in its ability to inhibit the reuptake of serotonin and norepinephrine. Its efficacy in major depressive disorder was shown in four 8-week randomized, double-blind, placebo-controlled, fixed-dose studies.1,3,4,5 These ranged from 50 mg to 400 mg daily. The primary endpoint was improvement in the 17-item Hamilton Rating Scale for Depression (HAM-D). In three studies, improvement in the Clinical Global Impression Scale (CGI-S) was used as a secondary endpoint also. In two published studies the results were mixed. One study some no difference between desvenlafaxine and placebo and the second showed significant difference for the 100 mg and 400 mg but not the 200 mg dose.3,4 While desvenlafaxine has been studied with doses up to 400 mg daily, doses larger than 50 mg may not gain additional clinical benefit but is associated increase frequency of adverse events at higher doses.1
There is currently no evidence to suggest any significant difference in efficacy or adverse events compared to venlafaxine. Most common adverse events include nausea, dizziness, insomnia, hyperhidrosis, constipation, somnolence, decreased appetite, anxiety, and abnormal ejaculation/orgasm. It shares the same warning and precautions as venlafaxine in particular (eg, elevated blood pressure, mydriasis) and those of SSRIs, SNRIs (eg, suicide risk, serotonin syndrome, concomitant use with MAOIs). The cost of desvenlafaxine was not available at the time of this review.
Clinical Implications
Desvenlafaxine does not appear to offer any significant clinical advantage over venlafaxine which is available in generic form.
References
1. Pristiq Product Information. Wyeth Pharmaceuticals, Inc. February 2008.
2. Parks V, et al. Poster presentation, American Society for Clinical Pharmacology and Therapeutics; March 2-5; Orlando, FL.
3. DeMartinis NA, et al. J Clin Psychiatry. 2007;68(5):677-688.
4. Liebowitz MR, et al. J Clin Psychiatry. 2007;68:1663-1672.
5. Septien-Velez L, et al. Int Clin Psychopharmacol. 2007;22:338-347
Wyeth Pharmaceuticals has received approval to market desvenlafaxine for the treatment of depression. The drug is the major active metabolite of venlafaxine (Effexor ). Wyeth has formulated the drug in a once-daily extended-release tablet. It will be marketed under the trade name Pristiq.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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