New Drug Evaluation Monograph Template

Desvenlafaxine (Pristiq by Wyeth)

Executive Summary

KEY QUESTIONS FOR THE COMMITTEE

  1. What is/are the primary/approved indication(s) for Desvenlafaxine?
  2. What are the potential secondary/unapproved indications for Desvenlafaxine?
  3. How does Desvenlafaxine efficacy compare to the current standard of therapy?
  4. How does Desvenlafaxine efficacy compare to comparable therapies?
  5. How does Desvenlafaxine safety compare to the current standard of therapy?
  6. How does Desvenlafaxine safety compare to comparable therapies?
  7. What circumstances would Desvenlafaxine be a recommended therapy?
  8. When would Desvenlafaxine not be an appropriate therapy?
  9. When would Desvenlafaxine be contraindicated?
  10. What are the unanswered clinical questions surrounding Desvenlafaxine?

INDICATIONS (include FDA labeled indications and potential off-label uses)

  • DSM-IV Major Depressive Disorder (MDD)

BRIEF BACKGROUND REGARDING CURRENT STANDARD OF THERAPY

APA Guidelines

Pharmacology Textbook:

  • Mental status exam (AMSIT)
  • Hamilton Depression Scale
  • Depression Inventory

Response is definedas a >=50% reduction in Depression scores

Considerations:

  • Hx of tx
  • Family history of Response
  • Exclusions to treatment

Stages of Major Depressive Episode Treatment

  • Acute (12wks)
  • Continuation (4-9 months)
  • Maintenance

CLINICAL PHARMACOLOGY:

Desvenlafaxine is a SNRI and an active metabolite of Venlafaxine (Effexor).

PHARMACOKINETICS

Route of Admin:Oral

Time to Peak:7.5 hours

Bioavailability:80%

Half Life:11 hours

Metabolism/Elimination:Renal 45%, UDP-G 19%, CYP3A4 <5%

Effects of Food:Cmax increases 16%, AUC unchanged

Protein BindingLow

Volume Distribution3.4L/kg

CLINICAL EFFICACY (text summary of the evidence of efficacy from clinical trials)

Side Effects

Journal of Clinical Psychiatry68(5)

Nausea, insomnia, somnolence, dry mouth, dizziness, sweating, nervousness, anorexia, constipation, asthenia, abnormal ejaculation/orgasm.

Clinical Efficacy Evidence Table

Ref./Study Design / Drug Regimens / Patient Population / N / Time / End Points / Results (CI, p-values) / ARR /

NNT/

NNH

/

Comments Regarding Study Appraisal

1.Liebowitz MR, Yeung PP, Entsuah R.
A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in adult outpatients with major depressive disorder.
J Clin Psychiatry. 2007;68(11):1663-72. / 1. [TEXT]
2. [TEXT]
3. [TEXT]
4. [TEXT] /
2. Septien-Velez L, Pitrosky B, Padmanabhan SK, Germain JM, Tourian KA.
A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in the treatment of major depressive disorder.
Int Clin Psychopharmacol. 2007;22(6):338-47. / 1. [TEXT]
2. [TEXT]
3. [TEXT]
4. [TEXT] /
3. DeMartinis NA, Yeung PP, Entsuah R, Manley AL.
A double-blind, placebo-controlled study of the efficacy and safety of desvenlafaxine succinate in the treatment of major depressive disorder.
J Clin Psychiatry. 2007;68(5):677-88. / 1. [100mg/day] n = 114
2. [200mg/day] n = 116
3. [400mg/day] n = 113
4. [Placebo] n = 118 / DSM-IV MDD / n=461 / 8 weeks /
  • HAMD-17 (1°)
  • CGI-I
  • MADRS
  • CGIS
  • Visual Analog Scale-Pain Intensity
  • Response>=50% decrease (HAM-D17)
  • Remission =<7% (HAM-D17)
/ Scores
  • HAM-D17 Significant Reductions for 100mg (12.75, p=0.0038) and 400mg (12.50, p=0.0023) vs Placebo (15.31)
  • HAM-D17 Non-Significant reductions for 200mg (13.31, p = 0.0764)
  • CGI-I, MADRS significant in all groups
  • CGI-S significant in 100mg and 400mg, but not in 200mg
Response Rate
  • Significant in 100mg (51%, p = 0.017) and 400mg (48%, p =0.046) vs placebo (35%)
  • Non-Significant for 200mg (45%, p = 0.142)
Remission
  • Significant in 400mg (32% , p=0.035) vs placebo (19%)
  • Non-Significant in 100mg (30%, p=0.093) and 200mg (28%, p=0.126)

4. / 1. [TEXT]
2. [TEXT]
3. [TEXT]
4. [TEXT] /
*Study design abbreviations: DB = double-blind, RCT = randomized trial, PC = placebo-controlled, PG = parallel -group, XO = crossover.
RRR = relative risk reduction, ARR = absolute risk reduction, NNT = number needed to treat, NNH = number needed to harm, CI = confidence interval

ADVERSE EFFECTS(use a table to list incidence vs. placebo or comparator)

General Summary:

Mild, Common:

Serious:

Monitoring:

ALLERGIES AND INTERACTIONS

Drug-Drug:

Food-Drug:

Allergy/Cross Reactive Substances:

PRECAUTIONS/CONTRAINDICATIONS

DOSAGE AND ADMINISTRATION

COST INFORMATION (Use a table to compare to other alternative therapeutic agents. Include both cost for a course of treatment, if applicable, or for one month’s supply. Present the medication cost to benefit one person. For example, the NNT for a statin used for 5 years is about 25 for prevention of death. At $70/month x 12 months x 5 years x 25 patients, this means the cost to prevent one death is about $105,000. Use AWP for Brand products and MAC for generics)

CONCLUSIONS AND RECOMMENDATIONS

DRUG USE CRITERIA

REFERENCES

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