Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development

Abstract

Postpartum depression is one of the most common complications of childbirth. Untreated postpartum depression can have substantial adverse effects on the well-being of the mother and child, negatively impacting child cognitive, behavioral, and emotional development with lasting consequences. There are a number of therapeutic interventions for postpartum depression including pharmacotherapy, psychotherapy, neuromodulation and hormonal therapy among others, most of which have been adapted from the treatment of major depressive disorder outside of the peripartum period. Current evidence of antidepressant treatment for postpartum depression is limited by the small number of randomized clinical trials, underpowered samples and lack of longterm follow-up. The peripartum period is characterized by rapid and significant physiological change in plasma levels of endocrine hormones, peptides and neuroactive steroids. Evidence supporting the role of neuroactive steroids and GABA in the pathophysiology of postpartum depression led to the investigation of synthetic neuroactive steroids and their analogs as potential treatment for postpartum depression. Brexanolone, a soluble, proprietary, intravenous preparation of synthetic allopregnanolone has been developed. A recent series of open-label and placebocontrolled randomized clinical trials of brexanolone in postpartum depression demonstrated rapid reduction of depressive symptoms, and have led to the submission for regulatory approval to the US Food and Drug Administration (decision due in March 2019). SAGE-217, an allopregnanolone analog, with oral bioavailability, was recently tested in a randomized, double-blind, placebocontrolled phase 3 study in severe postpartum depression, with reportedly positive results. Finally,

Parasympathetic nervous activity is associated with oxytocin in multiparous, but not primiparous, women during the perinatal period

“…Furthermore, studies, which examine whether OXT or ANA is associated with maternal feeling quantified by self‐reported scales, duration of labour, maternal stress during labour/delivery, timing of lactation onset, milk volume, or lactation performance including frequency and duration of breast‐feeding or not, are needed to support our findings. In view of the above‐mentioned discussion, it seems likely that perinatal women exposed to synthetic OXT, as well as antidepressants, have a reduced risk of PPA/PPD disorders. However, women with peripartum/intrapartum exposure to synthetic OXT were more likely to experience depressive or anxiety symptoms during the postpartum period .…”

Announcing the Novel Class of GABA–A Receptor Selective Positive Allosteric Modulator Antidepressants

“…The majority of currently available clinical antidepressant drugs increases serotonergic, noradrenergic and/or dopaminergic neurotransmission in the central nervous system (CNS) [1][2][3]. These currently available antidepressants exhibit their unique pharmacoactivities by 14 different distinct pharmacological mechanisms of actions [1][2][3][4][5][6][7][8][9]. Presently, 11 of the 14 different classes of antidepressants accomplish their pharmacological actions by blocking one or more of the reuptake transporter pumps and/or blocking some certain specific subtype of receptors for any of the three monoaminergic (i.e., serotonergic/noradrenergic/dopaminergic) neurotransmission systems [1][2][3].…”

“…Presently, 11 of the 14 different classes of antidepressants accomplish their pharmacological actions by blocking one or more of the reuptake transporter pumps and/or blocking some certain specific subtype of receptors for any of the three monoaminergic (i.e., serotonergic/noradrenergic/dopaminergic) neurotransmission systems [1][2][3]. The 12th class inhibits the enzyme monoamine oxidase [1][2][3], the 13th class works by blocking the N-methyl-Daspartate (NMDA) glutamatergic ionoceptor [1][2][3][4][5], while the 14th class works by acting as a GABA-A receptor selective positive allosteric modulator antidepressant (GASPAMA) [5][6][7][8][9].…”

Randomized controlled trial of the Circle of Security-Intensive intervention for mothers with postpartum depression: maternal unresolved attachment moderates changes in sensitivity

“…In clinical practice, the treatment of PPD usually includes pharmacotherapy, psychotherapy, counseling, and/or care management, with varying beneficial effects on symptom remission and caregiving behaviors (Brummelte & Galea, 2016;Frieder, Fersh, Hainline, & Deligiannidis, 2019). Treatment is usually aimed at addressing the mother's symptoms, but additional specific interventions for minimizing disturbances of the mother-infant interaction and attachment might be necessary to target the potential effects of PPD on the mother-infant relationship and the infant (Forman et al, 2007;Howard & Challacombe, 2018;Letourneau et al, 2015).…”