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The American Journal of Psychiatry Sep 2023Postpartum depression (PPD) is a common perinatal complication with adverse maternal and infant outcomes. This study investigated the efficacy and safety of zuranolone,... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Postpartum depression (PPD) is a common perinatal complication with adverse maternal and infant outcomes. This study investigated the efficacy and safety of zuranolone, a positive allosteric modulator of synaptic and extrasynaptic GABA receptors and neuroactive steroid, as an oral, once-daily, 14-day treatment course for patients with severe PPD.
METHODS
In this double-blind phase 3 trial, women with severe PPD were randomized in a 1:1 ratio to receive zuranolone 50 mg/day or placebo for 14 days. The primary endpoint was change from baseline in total score on the 17-item Hamilton Depression Rating Scale (HAM-D) at day 15; key secondary endpoints were change from baseline in HAM-D score at days 3, 28, and 45 and change from baseline in Clinical Global Impressions severity (CGI-S) score at day 15. Adverse events were monitored.
RESULTS
Among 196 patients randomized (zuranolone, N=98; placebo, N=98), 170 (86.7%) completed the 45-day study. Treatment with zuranolone compared with placebo resulted in statistically significant improvement in depressive symptoms at day 15 (least squares mean [LSM] change from baseline in HAM-D score, -15.6 vs. -11.6; LSM difference, -4.0, 95% CI=-6.3, -1.7); significant improvement in depressive symptoms was also reported at days 3, 28, and 45. CGI-S score at day 15 significantly improved with zuranolone compared with placebo. The most common adverse events (≥10%) with zuranolone were somnolence, dizziness, and sedation. No loss of consciousness, withdrawal symptoms, or increased suicidal ideation or behavior were observed.
CONCLUSIONS
In this trial, zuranolone demonstrated significant improvements in depressive symptoms and was generally well tolerated, supporting the potential of zuranolone as a novel, rapid-acting oral treatment for PPD.
Topics: Pregnancy; Humans; Female; Depression, Postpartum; Treatment Outcome; Pregnanes; Pyrazoles; Double-Blind Method
PubMed: 37491938
DOI: 10.1176/appi.ajp.20220785 -
JAMA Dec 2023
Topics: Female; Humans; Pregnancy; Depression; Depression, Postpartum; Postpartum Period; Prenatal Care; Mass Screening
PubMed: 38010647
DOI: 10.1001/jama.2023.21311 -
The Psychiatric Clinics of North America Sep 2023Perinatal depression is a common psychiatric condition that has negative effects on pregnancy and infant outcomes. Screening for the condition is relatively easy and... (Review)
Review
Perinatal depression is a common psychiatric condition that has negative effects on pregnancy and infant outcomes. Screening for the condition is relatively easy and should be done routinely in all medical care of the pregnant and postpartum woman and her infant. The risk-benefit analysis favors the use of antidepressant medications during pregnancy and lactation compared with the risk of untreated maternal depression. Other, nonpharmacological treatments will be discussed as well as new treatments, including a new class of medications that act on the inhibitory GABAergic neurotransmitter system.
Topics: Pregnancy; Female; Infant; Humans; Depression; Depression, Postpartum; Depressive Disorder; Antidepressive Agents; Pregnancy Complications
PubMed: 37500243
DOI: 10.1016/j.psc.2023.04.003 -
Drugs Nov 2023Zuranolone (ZURZUVAE) is an oral neuroactive steroid and a positive allosteric modulator of the gamma aminobutyric acid A (GABA) receptor being developed by Sage... (Review)
Review
Zuranolone (ZURZUVAE) is an oral neuroactive steroid and a positive allosteric modulator of the gamma aminobutyric acid A (GABA) receptor being developed by Sage Therapeutics and Biogen for the treatment of mood disorders. In August 2023, zuranolone received its first approval in the USA for the treatment of adults with postpartum depression [pending scheduling by the US Drug Enforcement Administration (DEA)]. This article summarizes the milestones in the development of zuranolone leading to this first approval.
Topics: Adult; Female; Humans; Pregnanes; Pyrazoles; Depression, Postpartum; Pregnanolone
PubMed: 37882942
DOI: 10.1007/s40265-023-01953-x -
Psychiatry Research Oct 2023Positive allosteric modulators of γ-aminobutyric acid-A (GABA) receptors, or GABAkines, play important roles in the treatment of depression, epilepsy, insomnia, and... (Meta-Analysis)
Meta-Analysis
Positive allosteric modulators of γ-aminobutyric acid-A (GABA) receptors, or GABAkines, play important roles in the treatment of depression, epilepsy, insomnia, and other disorders. Recently, some new GABAkines (zuranolone and brexanolone) have been administrated to patients with major depressive disorder (MDD) or postpartum depression (PPD) in randomized controlled trials (RCTs). This study aims to systematically review and examine the efficacy and safety of zuranolone or brexanolone for treatment of depression. A systematic literature retrieval was conducted through August 20, 2023. RCTs evaluating the efficacy and safety of zuranolone or brexanolone for treatment of depression were included. Eight studies (nine reports) were identified in the study. The percentages of patients with PPD achieving Hamilton Depression Rating Scale (HAM-D) response and remission were significantly higher after brexanolone or zuranolone administration compared with placebo at different points. The percentages of patients with MDD achieving HAM-D response and remission were significantly increased during the zuranolone treatment period compared with placebo. In addition, zuranolone caused more adverse events in patients with MDD compared with placebo. Our findings support the effects of brexanolone on improving the core symptoms of depression in patients with PPD, and the potential of zuranolone in treating patients with MDD or PPD.
Topics: Female; Humans; Antidepressive Agents; Depression, Postpartum; Depression; Randomized Controlled Trials as Topic; Depressive Disorder, Major
PubMed: 37683318
DOI: 10.1016/j.psychres.2023.115450 -
Current Psychiatry Reports Dec 2023Postpartum depression (PPD) and breastfeeding are important, interrelated health factors. It is established that women who breastfeed exclusively have lowered likelihood... (Review)
Review
PURPOSE OF REVIEW
Postpartum depression (PPD) and breastfeeding are important, interrelated health factors. It is established that women who breastfeed exclusively have lowered likelihood of developing significant PPD. Yet, many questions remain around what factors are involved. The purpose of this review is to provide updated information about the relationship between PPD and breastfeeding.
RECENT FINDINGS
Both psychological and physiological factors have emerged as important moderators and mechanisms of the relationship between postpartum depression and breastfeeding. Breastfeeding self-efficacy, self-compassion, and engagement with the infant during feeding all modify or mediate the relationship, and a complex dynamic relationship among cortisol, oxytocin, progesterone, and estrogen is involved. Importantly, recent intervention studies suggest psychosocial interventions may impact both breastfeeding and mood. Providers and researchers should recognize the interrelationship between the breastfeeding and PPD and apply this understanding to patient care through integrated education and care for both mood and breastfeeding enhancement.
Topics: Infant; Female; Humans; Breast Feeding; Depression, Postpartum; Affect; Estrogens; Progesterone; Postpartum Period; Mothers
PubMed: 37906349
DOI: 10.1007/s11920-023-01471-3 -
JAMA Network Open Mar 2024Postpartum depression (PPD) is one of the most common mental health conditions during the perinatal and postpartum periods, which can have adverse effects on both mother... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Postpartum depression (PPD) is one of the most common mental health conditions during the perinatal and postpartum periods, which can have adverse effects on both mother and infant.
OBJECTIVE
To investigate the efficacy of perioperative adjunctive esketamine administration after cesarean deliveries in the prevention of PPD.
DESIGN, SETTING, AND PARTICIPANTS
A single-center, double-blind, placebo-controlled, randomized clinical trial was conducted from January 1, 2022, to January 1, 2023, at Fujian Provincial Hospital among 298 women aged 18 to 40 years, with an American Society of Anesthesiologists grade I to III classification and singleton full-term pregnancies who were scheduled for elective cesarean deliveries. Primary analyses were performed on a modified intention-to-treat basis.
INTERVENTIONS
Patients were randomly assigned to the esketamine (n = 148) and control (n = 150) groups. Those in the esketamine group received a single intravenous injection of 0.25 mg/kg of esketamine immediately after fetal delivery, followed by 50 mg of esketamine as an adjuvant in patient-controlled intravenous analgesia for 48 hours after surgery. Saline was given to the control group of patients.
MAIN OUTCOMES AND MEASURES
The primary outcome was assessments of PPD symptoms by using the Edinburgh Postnatal Depression Scale (EPDS) at postpartum day 7. Positive screening for PPD was defined as a score of 10 or more points on the EPDS. In addition, the EPDS was analyzed as a continuous variable to evaluate depressive symptoms. Secondary outcomes included the Numeric Rating Scale (NRS) of postoperative pain, along with safety evaluations including adverse events and clinical assessments at postpartum days 14, 28, and 42.
RESULTS
A total of 298 pregnant women were included, with 150 in the control group (median age, 31.0 years [IQR, 29.0-34.0 years]) and 148 in the esketamine group (median age, 31.0 years [IQR, 28.0-34.0 years]). The prevalence of depression symptoms was significantly lower among patients given esketamine compared with controls (23.0% [34 of 148] vs 35.3% [53 of 150]; odds ratio, 0.55; 95% CI, 0.33-0.91; P = .02) on postpartum day 7. In addition, the esketamine group also showed a significantly lower change in EPDS scores (difference of least-squares means [SE], -1.17 [0.44]; 95% CI, -2.04 to -0.31; effect size, 0.74; P = .008). However, there were no differences between the groups in the incidence of positive screening results for PPD or in changes from the baseline EPDS scores at postpartum days 14, 28, and 42. There were no differences in NRS scores at rest and on movement except on movement at 72 hours postoperatively, when scores were significantly lower in the esketamine group (median, 3.0 [IQR, 2.0-3.0] vs 3.0 [IQR, 3.0-3.5]; median difference, 0 [95% CI, 0-0]; P = .03).
CONCLUSIONS AND RELEVANCE
These results suggest that intravenous administration of esketamine during the perioperative period of elective cesarean delivery can improve depression symptoms during the early postpartum period. However, this antidepression effect may not be universally applicable to patients with low EPDS scores.
TRIAL REGISTRATION
Chinese Clinical Trial Registry Identifier: ChiCTR2100054199.
Topics: Adult; Female; Humans; Pregnancy; Adjuvants, Immunologic; Cesarean Section; Depression, Postpartum; Ketamine; Adolescent; Young Adult
PubMed: 38446480
DOI: 10.1001/jamanetworkopen.2024.0953 -
EBioMedicine Dec 2023
Topics: Female; Humans; Depression; Depression, Postpartum; Postpartum Period
PubMed: 38099513
DOI: 10.1016/j.ebiom.2023.104925 -
Social Psychiatry and Psychiatric... Nov 2023This systematic review of systematic reviews aims to provide the first global picture of the prevalence and correlates of perinatal depression, and to explore the... (Review)
Review
PURPOSE
This systematic review of systematic reviews aims to provide the first global picture of the prevalence and correlates of perinatal depression, and to explore the commonalities and discrepancies of the literature.
METHODS
Seven databases were searched from inception until April 2022. Full-text screening and data extraction were performed independently by two researchers and the AMSTAR tool was used to assess the methodological quality.
RESULTS
128 systematic reviews were included in the analysis. Mean overall prevalence of perinatal depression, antenatal depression and postnatal depression was 26.3%, 28.5% and 27.6%, respectively. Mean prevalence was significantly higher (27.4%; SD = 12.6) in studies using self-reported measures compared with structured interviews (17.0%, SD = 4.5; d = 1.0) and among potentially vulnerable populations (32.5%; SD = 16.7, e.g. HIV-infected African women) compared to the general population (24.5%; SD = 8.1; d = 0.6). Personal history of mental illness, experiencing stressful life events, lack of social support, lifetime history of abuse, marital conflicts, maternity blues, child care stress, chronic physical health conditions, preeclampsia, gestational diabetes mellitus, being exposed to second-hand smoke and sleep disturbance were among the major correlates of perinatal depression.
CONCLUSION
Although the included systematic reviews were all of medium-high quality, improvements in the quality of primary research in this area should be encouraged. The standardisation of perinatal depression assessment, diagnosis and measurement, the implementation of longitudinal designs in studies, inclusions of samples that better represent the population and better control of potentially confounding variables are encouraged.
Topics: Female; Humans; Pregnancy; Child; Depression; Prevalence; Systematic Reviews as Topic; Depression, Postpartum; Pregnancy Complications
PubMed: 36646936
DOI: 10.1007/s00127-022-02386-9 -
The American Journal of Psychiatry Dec 2023
Topics: Female; Humans; Depression, Postpartum; Suicide; Depression; Racial Groups; Racism
PubMed: 38037406
DOI: 10.1176/appi.ajp.20230827