Major Depressive Disorder (MDD)

Major depressive disorder (MDD), a severe mood disorder, is characterized by a persistent sense of sadness, a lack of interest in activities previously enjoyed, and various physical and mental problems. The symptoms are significant enough to impair daily activities, such as work, school, social interactions, or relationships. Although the precise cause of MDD remains unknown, it's postulated to result from a combination of genetic, biological, environmental, and psychological factors.

Vasomotor Symptoms in Postmenopausal Women

Vasomotor symptoms, including hot flashes and night sweats, are among the primary complaints of postmenopausal women and those experiencing menopause due to breast cancer treatment. These symptoms result from fluctuating hormone levels during the menopausal transition and can drastically affect a woman's quality of life, impacting sleep, mood, and overall daily functionality.

Desvenlafaxine Succinate Extended-Release (Pristiq)

Desvenlafaxine succinate extended-release (Pristiq), an SNRI (serotonin-norepinephrine reuptake inhibitor), is indicated for the treatment of adults with major depressive disorder (MDD).

• For major depressive disorder, desvenlafaxine is a valuable treatment option alongside alternatives such as SSRIs, other SNRIs, bupropion, mirtazapine, or tricyclic antidepressants.
• Desvenlafaxine also has recommended use in the management of vasomotor symptoms associated with menopause. It is an important non-hormonal option when other alternatives such as gabapentin, pregabalin, clonidine, or other SSRIs and SNRIs have failed. It offers a way to manage these symptoms effectively, potentially improving the quality of life for postmenopausal women and those experiencing iatrogenic menopause due to breast cancer treatment.

Definitions

"Major depressive disorder"

is a psychiatric condition characterized by a persistent sense of despair, reduced energy, and a diminished interest in pleasurable activities, causing significant interference in daily life. MDD is believed to arise from a blend of genetic, environmental, and psychological factors. Risk factors encompass family history, major life changes, certain medications, chronic health issues, and substance abuse disorder.

"Metabolite"

is the substance produced when the body breaks down a drug. The effects of active metabolites are similar to the original drug.

"Neurotransmitter"

is a molecule that sends signals from neurons to different parts of the body (i.e., muscles).

Medical Necessity Criteria for Authorization

The Plan considers desvenlafaxine succinate ER medically necessary when ALL the following criteria are met for the applicable indication listed below:

For the treatment of major depressive disorder

1. The member is 18 years of age or older; AND
2. The member has a diagnosis of major depressive depression (MDD); AND
3. The member is unable to use, or has adequately tried and failed TWO (2) different formulary alternatives from below, for at least 1 month each:
   • Selective serotonin reuptake inhibitors (SSRIs); and/or
   • Other Serotonin-norepinephrine reuptake inhibitors (SNRIs); and/or
   • Bupropion (IR, SR, or XL); and/or
   • Mirtazapine; and/or
   • Tricyclic antidepressants (such as amitriptyline, amoxapine, and desipramine); AND
4. Chart documentation is provided for review to substantiate the above listed requirements.

For the management of vasomotor symptoms associated with menopause

1. The medication is being requested for the treatment of vasomotor symptoms in a postmenopausal woman OR a woman experiencing iatrogenic menopause due to breast cancer treatment; AND
2. The member has contraindications to hormonal therapy, is not able to tolerate hormonal therapy, or prefers not to use hormonal therapy; AND
3. The member is unable to use, or has tried and failed ALL of the following:
   • Nonhormonal alternatives such as: gabapentin, pregabalin, or clonidine; and/or
   • Selective serotonin reuptake inhibitors (SSRIs) (e.g., escitalopram, paroxetine, sertraline); and/or

• Other serotonin-norepinephrine reuptake inhibitors (SNRIs) (e.g., duloxetine, venlafaxine); AND
• Chart documentation is provided for review to substantiate the above listed requirements.

If the above prior authorization criteria are met, desvenlafaxine ER will be approved for 12 months.

Experimental or Investigational / Not Medically Necessary

Desvenlafaxine succinate ER for any other indication is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven.

Appendix

Vasomotor Symptoms Associated With Menopause

Hormone suppression, brought about by menopause or through treatments such as surgery or chemotherapy, often triggers hot flashes. These symptoms are not life-threatening but can impact the quality of life and daily activities. Long-term estrogen use, which had been a common treatment for menopause-associated vasomotor symptoms, has declined due to its association with increased risk of breast cancer, coronary heart disease, stroke, and venous thromboembolism. This prompts the need for alternative therapies like desvenlafaxine.

1. Desvenlafaxine has been shown to be a viable alternative for managing vasomotor symptoms associated with menopause, particularly in patients unable or unwilling to use hormonal therapy. It is recommended as an effective alternative to hormonal therapy by the Endocrine Society, the North American Menopause Society (NAMS), and the American Cancer Society/American Society of Clinical Oncology (ACS/ASCO).
2. Meta-analyses and controlled trials have shown significant reduction in the frequency and severity of hot flashes among postmenopausal patients using desvenlafaxine compared to placebo.
   • These improvements were observed as early as one week into treatment. However, higher rates of discontinuation due to adverse events were also reported in desvenlafaxine groups.
   • The use of desvenlafaxine is not associated with an increased risk of ischemic cardiovascular events, cerebrovascular events, and hepatic events according to a one- year safety assessment.

References

1. American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder, 3rd edition. 2010 November. Available at: psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed August 10, 2020.
2. Archer DF, Dupont CM, Constantine GD, Pickar JH, Olivier S; Study 319 Investigators. Desvenlafaxine for the treatment of vasomotor symptoms associated with menopause: a double- blind, randomized, placebo-controlled trial of efficacy and safety. Am J Obstet Gynecol. 2009;200(3):238.e1-238.e10.
3. Archer DF, Pinkerton JV, Guico-Pabia CJ, Hwang E, Cheng RF; Study 3353 Investigators. Cardiovascular, cerebrovascular, and hepatic safety of desvenlafaxine for 1 year in women with vasomotor symptoms associated with menopause. Menopause. 2013;20(1):47-56.
4. Archer DF, Seidman L, Constantine GD, Pickar JH, Olivier S. A double-blind, randomly assigned, placebo-controlled study of desvenlafaxine efficacy and safety for the treatment of vasomotor symptoms associated with menopause. Am J Obstet Gynecol. 2009;200(2):172.e1-172.e10.
5. Berhan Y, Berhan A. Is desvenlafaxine effective and safe in the treatment of menopausal vasomotor symptoms? A meta-analysis and meta-regression of randomized double-blind controlled studies. Ethiop J Health Sci. 2014;24(3):209-218.
6. Cobin RH, Goodman NF; AACE Reproductive Endocrinology Scientific Committee. American Association of Clinical Endocrinologists and American College of Endocrinology position statement on menopause—2017 update [published correction appears in Endocr Pract. 2017;23(12):1488]. Endocr Pract. 2017;23(7):869-880.

8. Nonhormonal management of menopause-associated vasomotor symptoms: 2015 position statement of The North American Menopause Society. Menopause. 2015;22(11):1155-1172.
9. Pinkerton JV, Archer DF, Guico-Pabia CJ, Hwang E, Cheng RJ. Maintenance of the efficacy of desvenlafaxine in menopausal vasomotor symptoms: a 1-year randomized controlled trial. Menopause. 2013;20(1):38-46.
10. Pinkerton JV, Constantine G, Hwang E, Cheng RJ; Study 3353 Investigators. Desvenlafaxine compared with placebo for treatment of menopausal vasomotor symptoms: a 12-week, multicenter, parallel-group, randomized, double-blind, placebo-controlled efficacy trial. Menopause. 2013;20(1):28-37.
11. Posternak M. Beginning Antidepressant Treatment: A Recommended Approach. The Carlat Psychiatry Report, July 2017. Volume 15, Issue 7&8.
12. Pristiq (desvenlafaxine) [prescribing information]. Philadelphia, PA: Wyeth Pharmaceuticals LLC; November 2021.
13. Runowicz CD, Leach CR, Henry NL, et al. American Cancer Society/American Society of Clinical Oncology breast cancer survivorship care guideline. J Clin Oncol. 2016;34(6):611-635.
14. Sansone RA, Sansone LA. Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison. Innov Clin Neurosci. 2014;11(3-4):37-42.
15. Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(11):3975-4011.
16. Sun Z, Hao Y, Zhang M. Efficacy and safety of desvenlafaxine treatment for hot flashes associated with menopause: a meta-analysis of randomized controlled trials. Gynecol Obstet Invest. 2013;75(4):255-262.

Clinical Guideline Revision / History Information

Original Date: 11/05/2020
Reviewed/Revised: 10/14/2021, 12/01/2021, 06/23/2022, 06/29/2023