DIAGNOSIS AND TREATMENT OF POSTPARTUM DEPRESSION Learning - - PowerPoint PPT Presentation

DIAGNOSIS AND TREATMENT OF POSTPARTUM DEPRESSION

Learning Objectives

• Improve the recognition of postpartum

depression

• Optimize treatment for patients with

postpartum depression

Epidemiology of Postpartum Depression (PPD)

Gelaye B et al. Lancet Psychiatry 2016;3(10):973-82; Shorey S et al. J Psychiatr Res 2018;104:235-48; Stewart DE, Vigod SN. Annu Rev Med 2019;70:183-96.

• Worldwide incidence and prevalence of PPD is

approximately 12% and 17%, respectively

• Prevalence is 6.9–12.9% in high-income countries

and >20% in low-income countries

• Highest prevalence in Middle Eastern countries

(26%)

• Lowest prevalence in European countries (8%)

Suicide in the Postpartum

• Suicide deaths and attempts are lower during

postpartum than in the general population of women

• Suicide is the second leading cause of mortality in

postpartum women

• Postpartum suicide is characterized by violent and lethal

means

Lindahl V et al. Arch Womens Ment Health 2005;8(2):77-87.

PPD in Adolescence

• Higher prevalence of PPD among adolescents

(~25%) than adults (~17%)

• Suicidal behavior in postpartum adolescents is

higher than the general population of adolescent girls and women

• Adolescent mothers face more psychosocial

challenges (e.g., lower social support and socioeconomic status) that increase risk for PPD

Dinwiddie KJ et al. J Psychosom Obstet Gynaecol 2018;39(3):168-75; Lindahl V et al. Arch Womens Ment Health 2005;8(2):77-87.

“Major Depressive Disorder, With Peripartum Onset” DSM-5 Diagnostic Criteria

• Diagnostic criteria are the same

as major depression

• Peripartum specifier stipulates

symptom onset within 4 weeks

• f delivery
• In clinical practice and research,

symptom onset within 12 months of delivery may be considered PPD

Five or more symptoms present ≥2 weeks; change from previous functioning; causing clinically significant distress

• Depressed mood
• Anhedonia
• Sleep and appetite disturbance
• Impaired concentration
• Psychomotor disturbance
• Fatigue
• Feelings of guilt or worthlessness
• Suicidal thoughts

Major Depression Diagnostic Criteria

Stewart DE, Vigod SN. Annu Rev Med 2019;70:183-96.

Additional Symptoms Common to PPD

Obsessional worries or preoccupations with baby Feeling

• verwhelmed

Irritability Thoughts of harming child Mood lability Anxiety

Stewart DE, Vigod SN. Annu Rev Med 2019;70:183-96.

PPD Detection

Score indicating PPD in a screening tool

Clinical interview to confirm diagnosis

If positive answer to either question:

Administer Edinburgh Postnatal Depression Scale (EPDS) or

• ther screening questionnaire

Ask all postpartum women about feelings in past month:

Feeling down, depressed, or hopeless? Bothered by little interest or pleasure in doing things?

Stewart DE, Vigod SN. Annu Rev Med 2019;70:183-96; ACOG Committee Opinion No. 736. Obstet Gynecol 2018;131(5):e140-50.

The American College

• f Obstetrics and

Gynecology (ACOG) recommends all mothers be screened for PPD within 3 weeks of giving birth

Edinburgh Postnatal Depression Scale (EPDS)

• Easy to administer, 10-item questionnaire about

feelings in the past 7 days

• Items scored 0–3 depending on severity of

symptoms

• Total score is sum of all 10 items (max score 30)
• A score ≥10 or a positive response to item 10 (i.e.,

self-harm ideation) indicate possible depression and require clinical evaluation

Cox JL et al. Br J Psychiatry 1987;150:782-6; Wisner KL et al. JAMA Psychiatry 2013;70(5):490-8.

Differential Diagnosis

Depressive symptoms secondary to untreated medical conditions (e.g., thyroid dysfunction, anemia) or alcohol or other substance abuse must also be ruled out Condition Distinguishing Features From PPD Postpartum blues

• Less severe and persistent symptoms
• Onset of symptoms always during postpartum
• Typically no severe obsessional preoccupations or suicidality

Adjustment disorders

• Fewer and less severe symptoms
• Improvement after mitigating stressors

Posttraumatic stress disorder (PTSD)

• Remote or recent traumatic events associated with nightmares,

flashbacks, or other symptoms of PTSD Bipolar disorder

• Manic or hypomanic symptoms

Postpartum psychosis (PPP)

• Delusions, grandiosity, hallucinations, confusion, bizarre behavior,
• r disorganized thoughts, accompanied by depression or mania

Stewart DE, Vigod SN. Annu Rev Med 2019;70:183-96.

Strongest Risk Factors for PPD

Domestic violence, previous abuse Negative life events, low social support Low partner support, marital difficulties Migration status*

Depression or unhappiness in pregnancy Anxiety in pregnancy* History of depression

*Only in high-income countries

Howard LM et al. Lancet 2014;384(9956):1775-88; Wisner KL et al. JAMA Psychiatry 2013;70(5):490-8; English S et al. Sci Rep 2018;8(1):12799.

The strongest risk factor is a history of mood or anxiety disorder, especially if symptomatic during pregnancy

Postpartum Anxiety Is More Common Than You Think

• An estimated 8.5% of postpartum women are diagnosed with
• ne or more anxiety disorders
• Approximately two-thirds of women with PPD have a

comorbid anxiety disorder or symptoms

• Women with postpartum depression and anxiety diagnoses

display poorer quality of life and their illness is slower to remit than women with postpartum depression only

• DSM-5 specifies no diagnosis of postpartum anxiety disorder

and no standardized diagnostic criteria exist

Goodman JH et al. J Affect Disord 2016;203:292-331; Farr SL et al. J Womens Health (Larchmt) 2014;23(2):120-8; Wisner KL et al. JAMA Psychiatry 2013;70(5):490-8; Misri S, Swift E. J Obstet Gynecol Can 2015;37(9):798-803; Jordan V, Minikel M. J Fam Pract 2019;68(3):165-74.

Course of PPD Illness

• 33% of women experience depression during pregnancy (i.e.,

antepartum depression)

• With treatment, most cases resolve within a few months
• 24% are depressed 1 year after giving birth despite receiving

treatment

• 13% are depressed 2 years after giving birth despite receiving

treatment

• 40% will relapse during subsequent pregnancy or unrelated to

pregnancy

Stewart DE, Vigod SN. Annu Rev Med 2019;70:183-96.

PPD Outcomes

↓ Physical health ↓ Psychological health ↓ Quality of life ↑ Relationship problems ↑ Risky behavior

Mother

↓ Quality of sleep ↓ Cognitive development ↓ Language development ↑ Health concerns ↑ Behavioral problems

Infant

↓ Bonding and attachment ↓ Maternal care ↑ Breastfeeding problems

Mother-Infant Interactions

Slomian J et al. Womens Health (Lond) 2019;15:1745506519844044.

Reduction in Rate of Subsequent Live Births Following Postpartum Psychiatric Illness

• Women with postpartum psychiatric illness after their first birth

demonstrate a decline in subsequent live births

• The reduction in subsequent live births is
• 33% for women with any postpartum psychiatric illness;
• 39% for women with postpartum depression; and
• 47% for women with any postpartum psychiatric illness with hospitalization

(indicating greater severity)

• In women with postpartum psychiatric illness whose first child died,

there is no reduction in subsequent births, suggesting that the reduction in subsequent live births in this population is at least, in part, voluntary

Liu X et al. Hum Reprod 2020;35(4):958-67.

Pathophysiological Mechanisms Implicated in PPD

Postpartum Depression

Neurotransmitter Alterations

(GABA, glutamate, serotonin, dopamine)

Neuroendocrine Changes

(allopregnanolone, progesterone, estrogen, oxytocin, prolactin, cortisol, ACTH, CRH)

Neuroinflammation

(IL-6, IL-1ꞵ, IL-8, TNF- α, IFN-γ)

Neurocircuit Dysfunction

(amygdala, prefrontal cortex, cingulate cortex, insula)

Genetics/ Epigenetics

(ESR1, 5-HTT, MOAO, COMT, TPH2, OXT/OXTR, HMNC1, HPA pathways) Payne LJ, Maguire J. Front Neuroendocrinol 2019;52:165-80.

5-HTT:serotonin transporter ACTH:adrenocorticotropic hormone COMT:catechol-O-methyltransferase CRH:corticotropin releasing hormone ESR1:estrogen receptor alpha gene GABA:gamma aminobutyric acid HMNC1:Hemicentin 1 gene HPA:hypothalamic-pituitary-adrenal IFN:interferon IL:interleukin MOAO:monoamine oxidase A OXT:oxytocin OXTR:oxytocin receptor TNF:tumor necrosis factor TPH2:tryptophan hydroxylase 2

Evidence-Based Treatment Recommendations

All PPD

Self-care Sleep protection Exercise Psychosocial support strategies Investigate and manage social stressors, medical and psychiatric comorbidities

Moderate PPD

Psychological treatments, including cognitive behavioral therapy and interpersonal therapy Add selective serotonin reuptake inhibitor (SSRI) if insufficient response Brexanolone

Severe PPD

SSRI alone or with psychological intervention Consider antidepressant switch and augmentation strategies if no response to SSRI alone Brexanolone Consider electroconvulsive therapy with severe suicidality or treatment resistance

Stewart DE, Vigod SN. Annu Rev Med 2019;70:183-96; Zheng W et al. Psychiatry Res 2019;279:83-9.

Psychological Interventions Reduce Depression Symptoms in Women With PPD

Stephens S et al. Ann Fam Med 2016;14(5):463-72.

Data from meta-analysis of 10 studies with randomized controlled design (N=1,324) examining change in depressive symptoms following psychological interventions for PPD in primary care Intervention Change in Depression Symptoms Immediately Post-intervention, SMD (95% CI) Cognitive behavioral therapy

• 0.36 (-0.52 to -0.21) *

Interpersonal therapy

• 0.93 (-1.27 to -0.59) *

Counseling

• 0.29 (-0.53 to -0.05) *

Other psychological interventions

• 0.23 (-0.46 to 0.01) #

Total

• 0.38 (-0.49 to -0.27) *

SMD=standardized mean difference; CI=confidence interval. *p<0.05, #p=0.06 test for

• verall effect.

Psychological interventions also significantly reduced depressive symptoms 6 months post-intervention (SMD = -0.21) and were significantly better than control conditions for reducing symptoms below threshold (odds ratio [OR] = 2.24)

Efficacy of SSRIs for the Treatment of PPD

Meta-analysis of 3 randomized controlled trials with parallel group design (N=146, PPD onset up to 6 months after giving birth) comparing effects of SSRIs (sertraline [2 studies] and paroxetine [1 study]) and placebo. Post-Treatment Response Rate Post-Treatment Remission

Molyneaux E et al. Cochrane Database Syst Rev 2014;9:CD002018

Sertraline

• Sertraline is the SSRI with the most

evidence in the treatment of PPD

• Effects of sertraline treatment may

be more pronounced in women who have an onset of PPD within 4 weeks of childbirth

• There is evidence of sertraline

efficacy in combination with CBT for treating PPD

Frieder A et al. CNS Drugs 2019;33(3):265-82; Hantsoo L et al. Psychopharmacology (Berl) 2014;231(5):939-48; Milgrom J et al. Aust N Z J Psychiatry 2015;49(3):236-45.

Brexanolone

• The only FDA-approved (2019) treatment for postpartum depression
• Neuroactive steroid chemically similar to allopregnanolone, a positive

allosteric modulator of GABAA receptor

• Administered intravenously over 60 hours in a single dose
• Most common adverse events:
• Sedation/somnolence, dry mouth, loss of consciousness, and flushing/hot

flush

• Use with antidepressants may increase sedation
• Ongoing clinical trial to test safety, tolerability, and pharmacokinetics in

adolescents with PPD (NCT03665038)

Meltzer-Brody S, Kanes SJ. Neurobiol Stress 2020;12:100212.

Efficacy of Brexanolone for the Treatment of PPD

65.0 50.7 44.7 24.0

PEAK RESPONSE (36 H) PEAK REMISSION (60 H)

PERCENT

Brexanolone Placebo

Meta-analysis of randomized control trials (3 studies; n=267) comparing brexanolone vs. placebo effects

• n depression response (≥50% reduction of Hamilton Depression Rating Scale [HAMD] total score) and

remission (HAMD total score ≤7) in women with moderate-to-severe PPD.

Zheng W et al. Psychiatry Res 2019;279:83-9.

* *p≤0.02 compared to placebo *

Brexanolone: Barriers to Access

• Very expensive: ~$34,000 per treatment alone and additional indirect costs for

infusion, continuous monitoring, health care providers, and required hospital stay

• Available only through a restricted program under a Risk Evaluation and Mitigation

Strategy (REMS)

• No published data to support its use for mild PPD
• Concerns remain about sustained efficacy
• Interruption in normal mother-child interactions due to patients being isolated from
• r supervised in the presence of their children during infusions
• May be advantageous for patients requiring rapid response due to disease severity

Burval J, Reed K. Nursing 2020;50(5):48-53; Hutcherson TC et al. Am J Health Syst Pharm 2020;77(5):336-45.

Efficacy and Safety of Zuranolone for Severe PPD (ROBIN Study)

Results from a phase 3, randomized, double-blind study of women with severe PPD (N=151) treated with daily oral zuranolone (30 mg) or placebo for 2 weeks

• Decrease in Hamilton Depression Rating Scale (HAMD-17)
• Day 3: zuranolone -12.5 vs placebo -9.8 (p=0.0255)
• Day 14 (primary endpoint): zuranolone -17.8 vs placebo -13.6 (p=0.0029)
• Difference was maintained to the end of the 4-week follow-up period (p=0.0027)
• Response at Day 14: zuranolone 72% vs placebo 48% (p=0.0050)
• Remission at Day 14: zuranolone 45% vs placebo 23% (p=0.0122)
• The most common adverse events (≥ 5%) were somnolence/sedation,

headache, dizziness, upper respiratory infections, and diarrhea

https://investor.sagerx.com/news-releases/news-release-details/sage- therapeutics-announces-sage-217-meets-primary-and-secondary

Other Treatments With Limited Research Evidence of Efficacy in PPD

• Venlafaxine
• Desvenlafaxine
• Bupropion
• Nefazodone
• Nortriptyline
• Transdermal estradiol patches
• Repetitive transcranial magnetic

stimulation

• Transcranial direct-current

stimulation

• Omega-3 fatty acids
• Vitamin D
• Yoga

Frieder A et al. CNS Drugs 2019;33(3):265-82; Reza N et al. Obstet Gynecol Clin North Am 2018;45(3):441-54.

Considerations for Breastfeeding: Antidepressants

Berle JO, Spigset O. Curr Womens Health Rev 2011;7(1):28-34; Chad L et al. Can Fam Physician 2013;59(6):633-34; McDonagh MS et al. Obstet Gynecol 2014;124(3):526-34. Relative Infant Doses of Commonly Used Antidepressants Antidepressant Relative Infant Dose, %a Bupropion 2 Citalopram 3 – 10 Desvenlafaxine 5.5 – 8.1 Duloxetine < 1 Escitalopram 3 – 6 Fluoxetine < 12 Fluvoxamine < 2 Mirtazapine 0.5 – 3 Paroxetine 0.5 – 3 Sertraline 0.5 – 3 Venlafaxine 6 – 9

a Relative infant dose ≤10% is associated with decreased risk to infant.

• Infant exposure through

lactation should be considered when recommending pharmacological treatment

• Most antidepressants are

not contraindicated during breastfeeding

• No direct evidence that

antidepressants are unsafe in pregnancy

Considerations for Breastfeeding: Brexanolone

• Relative infant dose in breast milk

36 hours after brexanolone infusion is 1-2%

• Oral bioavailability is low (<5%)
• No data on effects of milk

production or effects on breastfed infants

Hutcherson TC et al. Am J Health Syst Pharm 2020;77(5):336-45.

Considerations for Breastfeeding: Pump and Dump

• Infant daily dose in breastfeeding

with SSRI use can be reduced by “pump and dump” at 8 to 9 hours after maternal medication

• Drug concentrations tend to be

higher in hindmilk because of its lipophilic nature

Newport DJ et al. J Clin Psychiatry 2002;63(Suppl 7):31-44; Lattimore KA et al. J Perinatol 2005;25(9):595-604; Sie SD et al. Arch Dis Child Fetal Neonatal Ed 2012;97(6):F472-76.

PPD Prevention in Pregnant and Postpartum Women

• Counseling services (i.e., cognitive behavioral therapy and

interpersonal therapy) are recommended for high-risk women

US Preventive Services Task Force et al. JAMA 2019;321(6):580-7.

History of depression Current depressive symptoms Low income Young or single parenthood

High Risk

Summary

• PPD has a prevalence of 17% and is the second leading

cause of death among postpartum women

• Screening for PPD should occur regularly beginning within 3

weeks of giving birth

• Severity of PPD symptoms and patient preferences should

guide treatment selection

• Mild: psychosocial support strategies
• Moderate: CBT/IPT alone or with SSRI; brexanolone
• Severe: SSRI alone or with CBT/IPT; brexanolone; ECT (with

severe suicidality, treatment resistance)

Posttest Question 1

Monica is a first-time, single mother who gave birth to a healthy son 4 weeks prior. She lives alone with her child and has been receiving help from her mother a few times a week since her son was born. During a postpartum visit she reports feeling

• verwhelmed, fatigued and irritable since the birth of her son. She is having trouble

concentrating and reports feeling like a “terrible mother.” She denies suicidal thoughts

• r behavior. Screening with the Edinburgh Postnatal Depression Scale results in a

score of 11. Based on this information, what intervention would be most appropriate for Monica at this time?

• A. Psychosocial support strategies
• B. Cognitive behavioral therapy
• C. Treatment with sertraline
• D. Treatment with brexanolone

Posttest Question 2

A 31-year-old woman is diagnosed with severe postpartum depression 3 weeks after giving birth. The patient is hesitant about starting pharmacological treatment because she would like to continue breastfeeding her child. Which statement is the most accurate regarding pharmacological treatments for postpartum depression?

• A. Serotonin-norepinephrine reuptake inhibitors have the best lactation safety profile
• B. Brexanolone has minimal effects on breast milk production
• C. Most antidepressants are not contraindicated during breastfeeding