Explore the vast range of titles available.

Patients with major depression were treated with an oral γ-aminobutyric acid type A–receptor modulator for 14 days. At day 15, patients who received the drug had a greater reduction in depressive symptoms than patients who received placebo. Headache was the most common adverse event.

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 the lack of long-term 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 γ-aminobutyric acid (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 placebo-controlled randomized clinical trials of brexanolone in postpartum depression demonstrated a rapid reduction in depressive symptoms, and has 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, placebo-controlled phase III study in severe postpartum depression, with reportedly positive results. Finally, a 3β-methylated synthetic analog of allopregnanolone, ganaxolone, is being tested in both intravenous and oral forms, in randomized, double-blind, placebo-controlled phase II studies in severe postpartum depression.

Neuroactive steroids are a large group of substances having effect in the brain and on brain function. The steroids most studied are allopregnanolone (ALLO), tetrahydrodesoxycorticosterone (THDOC), pregnenolone sulfate (PS) dihydroepiandrosteronesulfate (DHEAS), and estradiol (E2). ALLO and THDOC are called gamma-aminobutyric acid (GABA) steroids as they are positive modulators of the GABAA receptor in a similar way as benzodiazepines, barbiturates, and alcohol. GABA steroids not only have similar behavioral effects as benzodiazepines and barbiturates but, possibly, also similar adverse effects as well. This review aims to elucidate the possible role that neuroactive steroids play in the development of mood disorders in women. One of the most clear-cut examples of the interaction between mood, neuroactive steroids, and the GABA system is premenstrual dysphoric disorder (PMDD), which is a cluster of negative mood symptoms occurring during the luteal phase of the menstrual cycle in 2-6% of reproductive women. Furthermore, certain women also experience adverse mood effects during sequential progestin addition to postmenopausal estrogen treatment, which is why the role of neuroactive steroids in postmenopausal women is also addressed in this review.

This paper reviews the current literature available for the efficacy and safety of allopregnanolone agonists and discusses considerations for their place in therapy. A literature search was conducted utilizing PubMed, clinicaltrials.gov, and the manufacturer's website. One phase II trial and two phase III trials evaluating the efficacy and safety of brexanolone were identified. Brexanolone demonstrated efficacy through significantly reduced Hamilton Depression Rating Scale (HAM-D) scores compared to placebo in the treatment of postpartum depression (PPD). Noted adverse effects were somnolence and dizziness, excessive sedation, and loss of consciousness. One published phase II study and the interim results of two phase III trials and one phase II trial on zuranolone were included in this review. Zuranolone, an oral allopregnanolone agonist, is given as a single, 14-day course. A significant reduction in HAM-D scores was demonstrated in patients with major depressive disorder (MDD) at 15 and 28 days compared to placebo. Interim results for zuranolone in PPD and bipolar disorder (BPD) show promising reductions in HAM-D scores. Adverse effects included sedation, dizziness, and headache. Allopregnanolone agonists seem to have a role in PPD when weighing the quick onset of action and potential risks of untreated PPD. The class of medications is limited by the single course for this indication and may fit as a bridge to maintenance therapy with selective serotonin reuptake inhibitors (SSRIs). Brexanolone, specifically, is hindered by the long infusion time, hospitalization associated with administration, and risk evaluation and mitigation strategy program. Zuranolone may also have a role in MDD or BPD, but more data are needed. Allopregnanolone agonists present a novel mechanism of action in the treatment of depressive disorders. Clinical trials and interim results support significant reductions in depression scores for brexanolone in PPD, and for zuranolone in PPD, MDD, and BPD.

Purpose: To study the corneal topographic response to IOP reduction in vernal keratoconjunctivitis (VKC) with steroid-induced glaucoma. Methods: A total of 42 eyes of 21 patients with VKC and steroid-induced glaucoma (Group I) and 66 eyes of 33 patients with VKC without glaucoma (Group II) underwent an evaluation by Orbscan topography. In eyes with glaucoma, the IOP was controlled medically and the corneal topography was repeated at 3 months to evaluate effect on corneal parameters. Results: The mean baseline IOP was 36.40±13.08 mmHg in Group I, 14.67±4.62 mmHg in Group II ( P <0.0001). The IOP after treatment at 3 months follow-up was 15.00±5.41 mmHg in Group I ( P <0.0001). In Group I, the mean maximum Sim K decreased from 44.86±3.21 D to 43.87±2.62 D ( P =0.031) and mean posterior corneal elevation decreased from 64.9±22.36  μ m to 35.7±28.91  μ m at 3 months after reduction of IOP ( P =0.001). There was a significant positive correlation between the reduction in the IOP and the decrease in the posterior corneal elevation ( r =0.664, P =0.001). Conclusion: Eyes with VKC with and without glaucoma have similar corneal topography. Increased IOP associated with steroid-induced glaucoma and VKC may contribute to an increase in the corneal curvature and posterior corneal elevation. These changes may be reversed by a reduction in the IOP with medical therapy.

The anaesthetic effects of pregnanedione and other related steroids were first described in 1941.1 Hydroxydione was the first drug in this group to be used clinically, but it had serious disadvantages.2 Althesin (Glaxo) is a mixture of two water-insoluble pregnanedione derivatives, alphaxalone and alphadolone, dissolved in Cremophor EL (polyoxyethylated castor oil), for intravenous injection. Alphaxalone is the major constituent; alpha-dolone is less potent and is put in to make alphaxalone more soluble in Cremophor. The solution is viscous, but slightly less so than that of propanidid (Epontol - Bayer), which also contains Cremophor.

A non-lethal procedure for identifying pigs apt to develop malignant hyperthermia is described. Susceptible animals were exposed to a variety of anaesthetic and other agents and it was shown that thiopentone sodium and CT 1341 (Glaxo) afforded a measure of protection against the development of the syndrome. Pretreatment with procaine did not prevent the onset of the condition and the administration of procaine when muscle rigidity was present failed to prevent a fatal outcome. The syndrome was induced in susceptible animals by halothane, chloroform, and a combination of halothane with suxamethonium. The effects of cyclopropane in susceptible pigs could not be predicted, and other tests showed that suxamethonium alone would not induce muscle contracture. Pretreatment with lignocaine failed to prevent induction of the syndrome by halothane. We believe that the porcine syndrome may result from more than one defect and that in one particular type the most effective treatment is immediate cooling coupled with the administration of sodium bicarbonate.

A modified bromsulphthalein test has been used to detect alterations in liver function in puerperal women taking either a synthetic oestrogen, stilboestrol, or a pure progestogen, megestrol acetate. The oestrogen appreciably reduced the ability of the liver to excrete dye into the bile. It also reduced significantly the equivalent liver volume and the plasma clearance of dye. The progestogen did not have this effect. In so far as these results represent liver dysfunction they are due to the oestrogen component of the combined preparation.