The excitement over the FDA approval of brexanolone (to be marketed as Zulresso) is a good place to start this week’s roundup. Brexanolone is a derivative of the neurosteroid allopregnanolone, and, while Zulpresso was approved specifically for the treatment of postpartum depression, there is considerable research to indicate that the modulation of neurosteroid systems may be another mechanism for treating depression and may lead to the development of a new class of antidepressants. While all the hoopla in the press focuses on brexanolone as a treatment for postpartum depression, there are multiple studies to indicate that similar neurosteroids may also benefit a wider spectrum of patients (female and male) with mood disorders.
At the bottom of the list are two studies which focus on screening for depression and anxiety in perinatal women. Fellmeth and colleagues observe that directly asking women about depressive symptoms identifies women with depression but that these women are distinct from the women identified using the EPDS. Fairbrother and colleagues compare a variety of instruments which can be used to screen for anxiety disorders in perinatal women but find that only one of them, the Anxiety Disorder – 13 (AD-13), provides clinically useful results in this setting. What these two articles signify to me is that while there is great interest and willingness to screen women for perinatal mood and anxiety disorders, we still have to iron out some of the details.
Ruta Nonacs, MD PhD
Neuroactive Steroids and Affective Symptoms in Women Across the Weight Spectrum.
Dichtel LE, Lawson EA, Schorr M, Meenaghan E, Paskal ML, Eddy KT, Pinna G, Nelson M, Rasmusson AM, Klibanski A, Miller KK. Neuropsychopharmacology. 2018 May;43(6):1436-1444.
Low mean serum allopregnanolone levels were associated with increased depression and anxiety severity, independent of BMI. Neuroactive steroids such as allopregnanolone may be potential therapeutic targets for depression and anxiety in traditionally treatment-resistant groups.
The role of allopregnanolone in depression and anxiety.
Schüle C, Nothdurfter C, Rupprecht R. Prog Neurobiol. 2014 Feb;113:79-87.
The translocator protein (TSPO) which is important for neurosteroidogenesis has been identified as a potential novel target for antidepressant and anxiolytic medications. TSPO ligands such as XBD 173 increase neurosteroidogenesis and have anxiolytic effects with a favorable side effect profile.
Lower allopregnanolone during pregnancy predicts postpartum depression: An exploratory study.
Osborne LM, Gispen F, Sanyal A, Yenokyan G, Meilman S, Payne JL. Psychoneuroendocrinology. 2017 May;79:116-121. Free Article
In 60 pregnant women with a prior diagnosis of a mood disorder, higher allopregnanolone levels during the second and third trimesters of pregnancy were associated with decreased risk of postpartum depression.
Neuroactive Steroids and Perinatal Depression: a Review of Recent Literature.
McEvoy K, Payne JL, Osborne LM. Curr Psychiatry Rep. 2018 Aug 9;20(9):78.
A Bench-to-Bedside Story: The Development of a Treatment for Postpartum Depression (Gordon JA, NIMH)
Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development.
Frieder A, Fersh M, Hainline R, Deligiannidis KM. CNS Drugs. 2019 Mar;33(3):265-282.
Postpartum Depression: Pathophysiology, Treatment, and Emerging Therapeutics.
Stewart DE, Vigod SN. Annu Rev Med. 2019 Jan 27;70:183-196.
Different trajectories of depressive symptoms during pregnancy.
Boekhorst MGBM, Beerthuizen A, Endendijk JJ, van Broekhoven KEM, van Baar A, BerginkV, Pop VJM. J Affect Disord. 2019 Apr 1;248:139-146.
Three trajectories of depressive symptoms (E(P)DS scores) were identified: low stable (class 1, reference group, 83%), decreasing (class 2, 7%), and increasing (class 3, 10%). Factors associated with trajectories 2 and 3 included previous depressive episodes, life events during pregnancy, and unplanned pregnancy. Class 2 (with decreasing EPDS scores) reported high partner involvement, while class 3 (with increasing EPDS scores) reported poor partner involvement throughout pregnancy.
Jacques N, de Mola CL, Joseph G, Mesenburg MA, da Silveira MF. J Affect Disord. 2019 Jan 15;243:201-208.
Six studies were included in this review (170,371). Children of mothers with prenatal and postnatal depressive symptoms or depression had 1.44 (CI95% 1.10 – 1.89) greater risk of hospitalization, and children of mothers with postnatal depressive symptoms or depression had a 1.93 (CI95% 1.02-3.64) greater risk of death before one year of age than those whose mothers did not have the disorder.
Dennis CL, Brown HK, Brennenstuhl S. Nurs Res. 2018 Nov/Dec;67(6):439-446.
The 19-item PCSC had good internal consistency. Exploratory factor analysis revealed the following dimensions: (a) relationship with the partner, (b) caring for the infant, (c) maternal social interactions, and (d) establishing a new routine. The PCSC total and subscale scores at 4 weeks were positively correlated with depressive symptomatology, anxiety, and perceived stress and negatively correlated with global and partner support at 8 weeks postpartum.
Screening for perinatal anxiety disorders: Room to grow.
Fairbrother N, Corbyn B, Thordarson DS, Ma A, Surm D. J Affect Disord. 2019 Mar 8;250:363-370.
To assess the accuracy of the most commonly used and/or recommended screening tools for perinatal AD (i.e., the Edinburgh Postnatal Depression Scale (EPDS) and its anxiety subscale (EPDS-3A), and the Generalized Anxiety Disorder 7 and 2-item Scales (GAD-7 and GAD-2) alongside a clinically derived alternative; the Anxiety Disorder – 13 (AD-13). Only the AD-13 met the standard of a clinically useful screening measure, with an area under the curve (AUC) above 0.8. This was achieved with and without the inclusion of the related disorders.
Fellmeth G, Opondo C, Henderson J, Redshaw M, Mcneill J, Lynn F, Alderdice F. J Affect Disord. 2019 Mar 4;251:8-14.
6752 women were included. At three months postpartum, 6.1% of women self-identified as having depression, 9.1% scored EPDS ? 13, 2.8% were positive on both. Agreement between the two methods was minimal (Cohen’s kappa < 0.3). Women who self-identified as having depression had higher odds of being aged > 40 years (OR 1.8; 95% CI 1.2-2.8). EPDS ? 13 was associated with < 16 years of education (OR 1.4; 95% CI 1.1-1.8), minority ethnicity (OR 1.4; 95% CI 1.1-1.9), living without a partner (OR 1.7; 95% CI 1.3-2.2), and a less than happy reaction to the pregnancy (OR 1.7; 95% CI 1.4-2.1). A direct question about postnatal depression may offer a valuable addition to screening tools to identify women in need of support.