Post Partum Depression

Question 1

Brexanolone

Answer 1

is a neurosteroid: allopregnanolone

modulates GABA receptor

Question 2

Brexanolone: onset effect

Answer 2

rapid (1-2 days)

Question 3

Brexanolone limitation

Answer 3

not studied long-term so don’t know how it will be used in the community

Question 4

what would first line of treatment for PPD be

Answer 4

SSRI
PPD usually co morbid with anxiety and treatment of MDD can be applied to PPD

Question 5

Characterisation of PPD

Answer 5

• feelings of sadness
  -anxiety
  -exaugstion
  -interferance with ability to care for child and self

Question 6

DSM-5 on PPD

Answer 6

• must occur during and for unto 4 weeks after pregnancy
• WHO and CDC argue onset with in 6 weeks of PP unlike the DSM

Question 7

PPD Heterogenous what symptoms accompany it

Answer 7

-persistant sadness
-guilt -irritability
-weight and appetite change
-impaired concentration
-suicidal thoughts or infanticide

Question 8

PPD risk factors
(Leader et. al, 2019)

Answer 8

-history of depression
-fear of childbirth
-tobacco use
-single
-maternal anxiety
-gestational diabetes melitus
- age of more that 40 yrs

Question 9

Benzos vs. Allopregnanolone

Answer 9

Use of benzodiazepines for sleep and anxiety

however they’re limited in their use as can develop dependance or tolerance so only use short term

Bezos target the gamma subunit of GABA a R not the delta subunit that allopregnanolone does therefore they are not the same!

Allopregnalone has low affinity but high potency due to its lipophilic nature it gets trapped in the phospholipid bilayer

Question 10

MoA at receptor Brexanolone

Answer 10

LOOK AT WHIT BOARD

Question 11

name the studies you need to know about brexanolone

Answer 11

3 phase 2: 2 unpublished
1 published (Kanes et al.,2017)

1 phase 3 : Hummingbird (Meltzer-Brody et al.,2018)

Question 12

Hummingbird (meltzer-brody et al.,2018)

Answer 12

n= 43 patients
60ug/kg/hr
or
90ug/kg/hr
given for 60hrs
infusions

showed drug effect was not concentration dependent
e.g., BRX60 = effect size =-5.5
BRX90 = -3.7
both were signf. reduction compared to placebo

is this clinical signf. ?
in each clinical trail the subsequent HRS difference reduced each time. the more it is carried out the less statistical signf is achieved. may be winners curse or due to the larger sample sizes in each trial

Question 13

Brexanolone clinical evidence

Answer 13

ALL patients = moderate to sever ppd
-6months or less
- stopped breast feeding to protect infant from the drug infusion (bc there are GABAa R in the infant brain that we do not want to activate)

Question 14

Common SE (meltzer-brody et al.,2018)

Answer 14

-headache
-solomance
- infusion site pain
-nausea

FDA warns use due to excess sedation
and risk od sudden loss of consciousness

the trial used risk evaluation and mitigation strategy (REMS)

Question 15

BREXANOLONE CRITUQUE

Answer 15

It is unclear what effect size is for PPD cause they used MDE scale which doesn’t accurately represent PPD

placebo and brex weren’t stat signf. at 30 days post infusion (not longterm?)

Edinburgh postnatal depression scale may have been better suitable scale of measure

Longterm effects and SEs are unknown
long infusion time of 60hrs must consider this impact on mother infant bond

there is also lack of head to head trials using current depression therapies eg. SSRIs