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 Binding
Low
Volume Distribution
3.4L/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 Drug
Patient
N
Design
Regimens
Population
Time
End Points
1. Liebowitz MR, 1. [TEXT]
Yeung PP,
2. [TEXT]
Entsuah R.
3. [TEXT]
A randomized,
4. [TEXT]
double-blind,
placebo-controlled
trial of
desvenlafaxine
succinate in adult
outpatients with
major depressive
disorder.
J Clin Psychiatry.
2007;68(11):166372.

2. Septien-Velez 1. [TEXT]
L, Pitrosky B,
2. [TEXT]
Padmanabhan SK, 3. [TEXT]
Germain JM,
4. [TEXT]
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):33847.

Results (CI, p-values)
ARR NNT/ Comments
NNH Regarding Study
Appraisal
Ref./Study
Design
Drug
Regimens
Patient
N
Population
3. DeMartinis NA, 1. [100mg/day] n = DSM-IV MDD n=461
Yeung PP,
114
Entsuah R,
2. [200mg/day] n =
Manley AL.
116
A double-blind, 3. [400mg/day] n =
placebo-controlled 113
study of the
4. [Placebo] n =
efficacy and safety 118
of desvenlafaxine
succinate in the
treatment of major
depressive
disorder.
J Clin Psychiatry.
2007;68(5):67788.
Time
End Points
8 weeks





Results (CI, p-values)
ARR NNT/ Comments
NNH Regarding Study
Appraisal
HAMD-17 (1°) Scores
 HAM-D17 Significant
CGI-I
Reductions for 100mg (12.75,
MADRS
p=0.0038) and 400mg (12.50,
CGIS
p=0.0023) vs Placebo (15.31)
Visual Analog
 HAM-D17 Non-Significant
Scale-Pain
reductions for 200mg (13.31, p =
Intensity
0.0764)
 Response>=50%
decrease (HAM-  CGI-I, MADRS significant in all
groups
D17)

CGI-S significant in 100mg and
 Remission
400mg, but not in 200mg
=<7% (HAMResponse Rate
D17)

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)
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
4.
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
1.
2.