Description
Postpartum depression is a serious and debilitating condition that is characterized by a major depressive episode temporally and pathophysiologically related to pregnancy. It is similar to other forms of depression and characterized by sadness and/or anhedonia and may present with symptoms such as cognitive impairment, feelings of worthlessness or guilt, or suicidal ideation. Brexanolone is chemically similar to endogenous hormone allopregnanolone, which is a positive allosteric modulator of GABAA (γ aminobutyric acid-ligand gated chloride channel) receptors. The level of endogenous allopregnanolone increases during pregnancy, reaches a peak during the third trimester but falls abruptly after delivery. It is hypothesized that a one-time administration of brexanolone infusion ameliorates symptoms of postpartum depression via positive allosteric modulation of both synaptic and extrasynaptic GABAA receptors.

Postpartum Depression
For individuals with postpartum depression who receive brexanolone, the evidence includes 3 randomized, placebo-controlled trials in which 247 patients with HAM-D scores ≥20 were randomized to brexanolone 60 μg/kg/h (n=38), brexanolone 90 μg/kg/h (n=102) and placebo (n=107). The relevant outcomes are change in disease status, functional outcomes, quality of life, and treatment-related mortality and morbidity. The primary efficacy endpoint of change from baseline in the 17-item Hamilton Depression Rating Scale total score at 60 hours resulted in significant and clinically meaningful reductions in the 17-item Hamilton Depression Rating Scale total score compared with placebo.

Brexanolone was associated with a greater frequency of sedation-related side effects than placebo, including sudden loss of consciousness in six patients. Characterization of the safety of brexanolone was inadequate due to notable study limitations. These include exposure to study drug in a limited number of patients in a controlled setting and a relatively short follow-up of 30 days. The observed loss of consciousness during drug infusion is part of the basis for a Risk Evaluation and Mitigation Strategy requirement. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Policy
Individuals may be considered for one time use of brexanolone per pregnancy if they meet all of the following criteria: 

1. Individual is 18 years of age or older and ≤ 6 months postpartum at the time of infusion.
2. Individual meets the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria for a major depressive episode (See Table 1) by a structured clinical interview for DSM-5 disorders.
3. Individual has a onset of depressive episode between 3rd trimester through 4 weeks postpartum.
4. Individual has a diagnosis of moderate to severe postpartum depression based on either of the following:
   1. Hamilton Rating Scale for Depression (HAM-D) score ≥ 20 (see policy guidelines) OR
   2. Edinburgh Postnatal Depression Scale (EPDS) score ≥ 13 (see policy guidelines)
5. Individual does NOT have any FDA labeled contraindications to the requested agent and is intended to be used consistently with the FDA approved label (see policy guidelines).
6. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., psychiatrist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis.
7. Member has not received a prior dose of treatment with Zulresso.  One infusion will be approved per lifetime.

Brexanolone is investigational/unproven therefore is considered NOT MEDICALLY NECESSARY in all other situations.

Policy Guidelines
BREXANOLONE
Brexanolone should be administered as a continuous intravenous infusion over 60 hours (2.5 days) as follows: 

• 0 to 4 hours: Initiate with a dosage of 30 mcg/kg/hour
• 4 to 24 hours: Increase dosage to 60 mcg/kg/hour
• 24 to 52 hours: Increase dosage to 90 mcg/kg/hour (alternatively, consider a dosage of 60 mcg/kg/hour for those who do not tolerate 90 mcg/kg/hour)
• 52 to 56 hours: Decrease dosage to 60 mcg/kg/hour
• 56 to 60 hours: Decrease dosage to 30 mcg/kg/hour

Brexanolone has a black box warning because patients are at risk of excessive sedation or sudden loss of consciousness during administration. Patients must be monitored for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring. Patients must be accompanied during interactions with their child(ren). In addition, a health care provider must be available on-site to continuously monitor the patient, and intervene as necessary, for the duration of the infusion.

Brexanolone is available only through a restricted program called the ZULRESSO REMS. Notable requirements include the following:

• Health care facilities must enroll in the program and ensure that brexanolone is only administered to patients who are enrolled in the ZULRESSO REMS.
• Pharmacies must be certified with the program and must only dispense brexanolone to health care facilities that are certified in the ZULRESSO REMS.
• Patients must be enrolled in the ZULRESSO REMS prior to administration of brexanolone.
• Wholesalers and distributors must be registered with the program and must only distribute to certified health care facilities and pharmacies.

DEPRESSION SCALES
Hamilton Rating Scale for Depression (HAM-D)
HAM-D is a 17-item rating scale to determine the severity level of depression in a patient before, during, and after treatment. The total score ranges from 0 to 52, with the score corresponding to the following classifications:

• 0 – 7: No depression (normal)
• 8 – 16: Mild depression
• 17 – 23: Moderate depression
• ≥ 24: Severe depression

Edinburgh Postnatal Depression Scale (EPDS)
EPDS is a self-report instrument containing 10 items that are ranked from 0 to 3 that reflect the patient’s experience over the past week. The total score ranges from 0 to 30. An EPDS ≥13 is an acceptable cut-point for identifying women at risk for major depression in clinical settings.

Benefit Application
BlueCard/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all devices approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational, and thus these devices may be assessed only on the basis of their medical necessity.

Background
POSTPARTUM DEPRESSION
PPD is a temporal major depressive episode that may occur during pregnancy or within 4 weeks of delivery with an estimated prevalence of approximately 12% of births.¹ As per estimates by Sage Therapeutics, the sponsor of brexanolone, PPD may affect 1 in 9 women who give birth in the U.S. per year, which translates to 400,000 incident cases annually.^2,3 Estimates for patients who may qualify to receive brexanolone in the U.S. are not known.

PPD depression is similar to other forms of depression and characterized by sadness and/or anhedonia and may present with symptoms such as cognitive impairment, feelings of worthlessness or guilt, or suicidal ideation (see Table 1 for the diagnostic criteria for a major depressive episode). However, PPD is distinguishable from postpartum blues (baby blues), where sadness and anxiety are milder, are time-limited (lasting for a few hours to a few days in the first week postpartum) and have few negative sequelae.⁴ PPD can have serious implications, as suicide is the leading cause of maternal death after childbirth in the developed world. PPD has been reported to be one of the strongest predictors of suicidal ideation in new mothers⁵ and carries an increased risk for suicide.^6,7 Recent studies suggest that postpartum suicidal ideation occurs in 19% to 30% of women with PPD.^8,9

Table 1. Diagnostic Criteria for a Major Depressive Episode 

Adapted from FDA Briefing Document¹⁰ and Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed., American Psychiatry Association, 2013.⁷

Current Treatment
The following therapies are currently being used to manage patients with PPD.

Psychotherapy alone is considered first-line treatment for mild to moderate peripartum depression, whereas psychotherapy is often combined with medication in patients with severe symptoms.¹¹ Cognitive behavioral therapy has the most evidence supporting its effectiveness.¹² Evidence is equivocal regarding the use of exercise to treat peripartum depression,¹³ and hypnosis has no demonstrated benefit.¹⁴ In patients with severe peripartum depression that is refractory to medication or who have contraindications to medication use, electroconvulsive therapy is effective.¹¹

No drugs had been specifically approved by the Food and Drug Administration for treatment of PPD prior to the approval of brexanolone.¹⁰ Drugs generally approved for the treatment of major depression are used to treat PPD, but data on their effectiveness is limited. Non-drug treatments such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and psychotherapy are also used. All available depression treatments show a delayed effectiveness response. Antidepressant drugs typically take four to six weeks to demonstrate efficacy. Similarly, a course of electroconvulsive therapy is typically twice per week for 4 or 5 weeks, transcranial magnetic stimulation is given daily for 4 to 6 weeks, and psychotherapy usually involves 8 to 20 weekly sessions.³

Prior to the approval of brexanolone, there was no FDA-approved treatment for PPD.

De Crescenzo et al. (2014) published a systematic review of RCTs comparing selective serotonin reuptake inhibitors to placebo and/or other treatments for PPD that included 6 RCTs with 595 patients.¹⁵ Comparators included cognitive-behavioral intervention, psychosocial community-based intervention, psychodynamic therapy, a second-generation tricyclic antidepressant, and placebo. Limitations in the evidence precluded meta-analytic pooling of data and included small sample size, heterogeneity in interventions, outcomes, duration of follow-up, and a high dropout rate. The response was defined as a reduction of at least 50% from baseline on the HAM-D or Edinburgh Postnatal Depression Scale and calculated on the primary endpoint. Only one of the six included studies reported a statistically significant difference in response rate with selective serotonin reuptake inhibitors vs the comparator.

Molyneaux et al. (2018) published a Cochrane systematic review of antidepressants for preventing postnatal depression.¹⁶ The authors identified 2 RCTs with a total of 81 participants. The first trial compared nortriptyline with placebo and did not find any evidence that nortriptyline was effective in preventing postnatal depression.¹⁷ In this study, 23% (6/26) of women who took nortriptyline and 24% (6/25) of women who took placebo experienced postnatal depression (relative risk 0.96, 95% confidence interval 0.36 to 2.59, very low-quality evidence) in the first 17 weeks postpartum. The second study compared sertraline with placebo.¹⁸ In this study, 7% (1/14) of women who took sertraline developed postnatal depression in the first 17 weeks postpartum compared with 50% (4/8) of women who took a placebo. It is uncertain whether sertraline reduces the risk of postnatal depression (relative risk 0.14, 95% confidence interval 0.02 to 1.07, very low-quality evidence). Authors failed to draw any clear conclusions about the effectiveness of antidepressants for the prevention of postnatal depression because of the limited sample size in both the trials.

REGULATORY STATUS
On March 19, 2019, brexanolone (Zulresso) injection for intravenous use was approved by the U.S. Food and Drug Administration for the treatment of postpartum depression in adult women.

Rationale 
Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life, and ability to function -- including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, two domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent one or more intended clinical uses of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

The clinical development program for brexanolone is summarized in Table 2.

Table 2. Summary of the Clinical Development Program for Brexanolone

HAM-D: Hamilton Depression rating Scale

BREXANOLONE
Clinical Context and Therapy Purpose
The purpose of brexanolone in patients who have PPD is to provide a treatment option that is an improvement on existing therapies. Potential benefits of this therapy may include the following:

• Treatment offers a novel mechanism of action or approach that may allow successful treatment of many patients for whom other available treatments have failed.
• Successful treatment may reduce the potential for significant morbidity and mortality and allow more positive interactions between mother and baby.
• Treatment offers an opportunity to alleviate symptoms faster (known response within 60 hours) than conventional treatments (weeks to months with selective serotonin reuptake inhibitors or non-drug treatments).

The question addressed in this evidence review is: Does treatment with brexanolone improve the net health outcome in individuals with PPD?

The following PICOTS were used to select literature to inform this review.

Patients
The relevant population of interest are individuals with a diagnosis of PPD (See Table 1).

Interventions
The therapy being considered is brexanolone, which is chemically identical to endogenous allopregnanolone, a positive allosteric modulator of γ aminobutyric acid-ligand gated chloride (GABAA) channel receptors.

Allopregnanolone is an endogenous hormone derived from progesterone and formed in the brain and corpus luteum, and during pregnancy, in the placenta. Levels of allopregnanolone increase during pregnancy, reach a peak during the third trimester and then fall abruptly after delivery. Although the mechanism of action is unknown, it is thought to be related to positive allosteric modulator of both synaptic and extrasynaptic GABAA receptors.²¹

Comparators
The relevant comparators are standard medical management (psychotherapy and/or pharmacotherapy).

Outcomes
The general outcomes of interest are change in disease status, functional outcomes, quality of life, treatment-related mortality and treatment-related morbidity. The primary efficacy outcomes measure used in the 3 clinical trials of brexanolone was 17-Item Hamilton Rating Scale for Depression (HAM-D). It is a validated instrument used to rate the severity of depression in patients who are already diagnosed as depressed²² and has been used in a number of registration studies of approved oral antidepressants.³ It  is summarized in Table 2. Sage Therapeutics also collected information on other secondary outcomes using the Clinical Global Impression, the Montgomery-Åsberg Depression Rating Scale and Edinburgh Postnatal Depression Scale. While Clinical Global Impression is a validated measure often utilized in clinical trials to allow clinicians to integrate several sources of information into a single rating of the patient’s condition, it is not a disease-specific measure and was only used to corroborate the results of the primary outcome measure.³ Therefore, such outcome measures are not summarized further in this report.

Table 3. Health Outcome Measures Relevant to Postpartum Depression

Table 4. Summary of Key Randomized Trials of Brexanolone 

DSM: Diagnostic and Statistical Manual of Mental Disorders; HAM-D: Hamilton Depression rating Scale

Table 5. Summary of Key Randomized Trials of Brexanolone 

CI: confidence interval; HAM-D: Hamilton Depression rating Scale; LS: least square; NA: not applicable; NR: not reported; SE: standard error
HAM-D remission is ≤7 HAM-D total score
HAM-D response is ≥50% reduction from baseline in HAM-D total score  

The purpose of the study limitations table (see Table 6) is to display notable limitations identified in each study. This information is synthesized as a summary of the body of evidence following each table and provides the conclusions on the sufficiency of the evidence supporting the position statement. No limitations in study design and conduct were noted. Notable relevance limitations include a relatively short follow-up of 30 days and exposure of drugs in a limited number of patients under controlled setting to adequately characterize the safety of brexanolone. The FDA has proposed the creation of a registry to enroll all patients treated with brexanolone to better characterize the risk of loss of consciousness and management of the risk.

Table 6. Relevance Study Limitations

The evidence limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.

^a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.
^b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. Not the intervention of interest
^c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered
effectively.
^d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not established and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.
^e Follow-up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Section Summary: PPD
The evidence for use of brexanolone for PPD consists of 3 RCTs in which 247 patients were randomized to brexanolone 60 μg/kg/h (n = 38), brexanolone 90 μg/kg/h (n = 102) and placebo (n = 107). The primary efficacy endpoint of change from baseline in the HAM-D total score at 60 hours resulted in significant and clinically meaningful reductions in HAM-D total score at 60 hours compared with placebo. Brexanolone was associated with a greater frequency of sedation-related side effects than placebo, including sudden loss of consciousness in six patients. Therefore, brexanolone has been approved with a Risk Evaluation and Mitigation Strategy program to monitor and manage the risk of loss of consciousness. Notable relevance gaps include a relatively short follow-up of 30 days and exposure of drugs in a limited number of patients under controlled setting to adequately characterize the safety of brexanolone.

SUMMARY OF EVIDENCE
For individuals with postpartum depression who receive brexanolone, the evidence includes 3 randomized, placebo-controlled trials in which 247 patients with HAM-D scores ≥20 were randomized to brexanolone 60 μg/kg/h (n = 38), brexanolone 90 μg/kg/h (n = 102) and placebo (n = 107). The relevant outcomes are change in disease status, functional outcomes, quality of life, and treatment-related mortality and morbidity. The primary efficacy endpoint of change from baseline in the 17-item Hamilton Depression Rating Scale total score at 60 hours resulted in significant and clinically meaningful reductions in the 17-item Hamilton Depression Rating Scale total score compared with placebo.

Brexanolone was associated with a greater frequency of sedation-related side effects than placebo, including sudden loss of consciousness in six patients. Characterization of the safety of brexanolone was inadequate due to notable study limitations. These include exposure to study drug in a limited number of patients in a controlled setting and a relatively short follow-up of 30 days. The observed loss of consciousness during drug infusion is part of the basis for a Risk Evaluation and Mitigation Strategy requirement. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

PRACTICE GUIDELINES AND POSITION STATEMENTS
AMERICAN PSYCHIATRIC ASSOCIATION
No evidence-based guideline specifically related to the treatment of postpartum depression was identified. Relevant excerpts from “Practice Guideline for the Treatment of Patients with Major Depressive Disorder” published in 2010²⁷ are summarized here.

Depression During Pregnancy

• “Depression-focused psychotherapy or other nonmedication therapies may be considered first for some women, and psychotherapy should be considered as part of the treatment plan whenever possible.”
• “Although there is little controlled research, psychotherapies appear efficacious in antenatal and postpartum depression, with IPT being the best studied.”^28,29
• “Antidepressant efficacy has not been determined for pregnant women, and questions remain as to whether medications have equivalent efficacy during pregnancy, compared with the nonpregnant state.”
• “Electroconvulsive therapy is also recommended as a treatment option for major depressive disorder during pregnancy.”

Postpartum Depression
“Antidepressants are often prescribed for postpartum depression, according to the same principles delineated for other types of major depressive disorder, despite a limited number of controlled studies.”

U.S. PREVENTIVE SERVICES TASK FORCE RECOMMENDATIONS
Not applicable 

ONGOING AND UNPUBLISHED CLINICAL TRIALS
Some currently ongoing and unpublished trials that might influence this review are listed in Table 7.

Table 7. Summary of Key Clinical Studies 

CI: NCT: national clinical trial.
^a Denotes industry-sponsored or cosponsored trial.
^b Long-term, safety follow-up study of patients enrolled in NCT02122952.

References

1. Ko JY, Rockhill KM, Tong VT, et al. Trends in Postpartum Depressive Symptoms - 27 States, 2004, 2008, and 2012. MMWR Morb Mortal Wkly Rep. Feb 17 2017;66(6):153-158. PMID 28207685
2. Sage Presentations for the November 2, 2018 Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Psychopharmacol ogicDrugsAdvisoryCommittee/UCM629510.pdf. Accessed February 18, 2019.
3. Sage Briefing Information for the November 2, 2018 Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Psychopharmacol ogicDrugsAdvisoryCommittee/UCM624646.pdf. Accessed February 19, 2019.
4. A-C Bernard-Bonnin, Canadian Paediatric Society, Mental Health and Developmental Disabilities Committee; Maternal depression and child development, Paediatrics & Child Health, Volume 9, Issue 8, 1 October 2004, Pages 575–583, https://doi.org/10.1093/pch/9.8.575.
5. Do T, Hu Z, Otto J, et al. Depression and suicidality during the postpartum period after first time deliveries, active component service women and dependent spouses, U.S. Armed Forces, 2007-2012. MSMR. Sep 2013;20(9):2-7. PMID 24093957
6. Savitz DA, Stein CR, Ye F, et al. The epidemiology of hospitalized postpartum depression in New York State, 1995-2004. Ann Epidemiol. Jun 2011;21(6):399-406. PMID 21549277
7. American Psychiatric Association. DSM 5. Diagnostic and statistical manual of mental disorders. American Psychiatric Press Inc, (5th edition). 2013; Washington, DC: American Psychiatric Association.
8. Mauri M, Oppo A, Borri C, et al. SUICIDALITY in the perinatal period: comparison of two self-report instruments. Results from PND-ReScU. Arch Womens Ment Health. Feb 2012;15(1):39-47. PMID 22215284
9. Wisner KL, Sit DK, McShea MC, et al. Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. JAMA Psychiatry. May 2013;70(5):490-498. PMID 23487258
10. FDA Briefing Information for the November 2, 2018 Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. https://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsA dvisoryCommittee/ucm624642.htm. Accessed February 19, 2019.
11. Yonkers KA, Vigod S, Ross LE. Diagnosis, pathophysiology, and management of mood disorders in pregnant and postpartum women. Obstet Gynecol. Apr 2011;117(4):961-977. PMID 21422871
12. Scope A, Leaviss J, Kaltenthaler E, et al. Is group cognitive behaviour therapy for postnatal depression evidence-based practice? A systematic review. BMC Psychiatry. Nov 28 2013;13:321. PMID 24283266
13. Daley A, Jolly K, MacArthur C. The effectiveness of exercise in the management of post-natal depression: systematic review and meta-analysis. Fam Pract. Apr 2009;26(2):154-162. PMID 19126829
14. Sado M, Ota E, Stickley A, et al. Hypnosis during pregnancy, childbirth, and the postnatal period for preventing postnatal depression. Cochrane Database Syst Rev. Jun 13 2012(6):CD009062. PMID 22696381
15. De Crescenzo F, Perelli F, Armando M, et al. Selective serotonin reuptake inhibitors (SSRIs) for post-partum depression (PPD): a systematic review of randomized clinical trials. J Affect Disord. Jan 2014;152-154:39- 44. PMID 24139299
16. Molyneaux E, Telesia LA, Henshaw C, et al. Antidepressants for preventing postnatal depression. Cochrane Database Syst Rev. Apr 18 2018;4:CD004363. PMID 29669175
17. Wisner KL, Perel JM, Peindl KS, et al. Prevention of recurrent postpartum depression: a randomized clinical trial. J Clin Psychiatry. Feb 2001;62(2):82-86. PMID 11247106
18. Wisner KL, Perel JM, Peindl KS, et al. Prevention of postpartum depression: a pilot randomized clinical trial. Am J Psychiatry. Jul 2004;161(7):1290-1292. PMID 15229064
19. Kanes S, Colquhoun H, Gunduz-Bruce H, et al. Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial. Lancet. Jul 29 2017;390(10093):480-489. PMID 28619476
20. Meltzer-Brody S, Colquhoun H, Riesenberg R, et al. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet. Sep 22 2018;392(10152):1058-1070. PMID 30177236
21. Farrant M, Nusser Z. Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors. Nat Rev Neurosci. Mar 2005;6(3):215-229. PMID 15738957
22. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. Feb 1960;23:56-62. PMID 14399272
23. Zimmerman M, Martinez JH, Young D, et al. Severity classification on the Hamilton Depression Rating Scale. J Affect Disord. Sep 5 2013;150(2):384-388. PMID 23759278
24. Peindl KS, Wisner KL, Hanusa BH. Identifying depression in the first postpartum year: guidelines for office- based screening and referral. J Affect Disord. May 2004;80(1):37-44. PMID 15094256
25. Frank E, Kupfer DJ, Perel JM, et al. Three-year outcomes for maintenance therapies in recurrent depression. Arch Gen Psychiatry. Dec 1990;47(12):1093-1099. PMID 2244793
26. FDA Presentations for the November 2, 2018 Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM629509.pdf. Accessed February 19, 2019.
27. Practice Guideline for the Treatment of Patients With Major Depressive Disorder (Third Edition). https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed February 20, 2019.
28. Spinelli MG, Endicott J. Controlled clinical trial of interpersonal psychotherapy versus parenting education program for depressed pregnant women. Am J Psychiatry. Mar 2003;160(3):555-562. PMID 12611838
29. Stuart S, O'Hara MW, Gorman LL. The prevention and psychotherapeutic treatment of postpartum depression. Arch Womens Ment Health. Aug 2003;6 Suppl 2:S57-69. PMID 14615924
30. Force USPST, Curry SJ, Krist AH, et al. Interventions to Prevent Perinatal Depression: US Preventive Services Task Force Recommendation Statement. JAMA. Feb 12 2019;321(6):580-587. PMID 30747971

Coding

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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