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Background: Electroacupuncture (EA) is a promising therapy for depression. However, a comprehensive review of EA for depression is needed. Methods: We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA 2020) guidelines to evaluate the efficacy and safety of EA for depression. Potentially relevant trials and reviews were searched in MEDLINE, EMBASE, PsycINFO, and CENTRAL from inception to March 2022. EA alone and combined with other therapy were eligible for inclusion. The severity of depression during and after treatment and the number of adverse events were assessed as outcomes. Risk of bias (ROB) evaluation, subgroup analysis, sensitivity analysis, reporting bias assessment, and GRADE system evaluation were also conducted. Results: Thirty-four trials were included. The overall ROB was medium. Low-quality evidence showed that the efficacy of EA was not less than that of antidepressants [EA + selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs)] and manual acupuncture (MA). EA and EA + SSRIs had better efficacy than SSRIs alone in decreasing the severity of depression during the early treatment. Moderate-quality evidence also showed that EA and EA + SSRIs were safer than SSRIs alone. Sensitivity analysis was mostly not feasible. Major publication bias was unlikely. Conclusion: These results indicate that the efficacy of EA is not less than that of antidepressants and MA. Moreover, EA and EA + SSRI treatments show a more rapid onset and greater safety than SSRIs. More high-quality trials are needed for further confirmation. [ABSTRACT FROM AUTHOR]

Gender dysphoria in childhood and adolescence is today more under the domain of queer ideology than within scientific and professional knowledge. This dominance of ideology translates into important practical consequences such as self-determination of gender identity based on sentiment and affirmative therapy of felt identity as the only acceptable option. As a result, psychological aspects are left out of evaluation and pharmaco-surgical transitions are undertaken that do not solve the problem for everyone. In particular, there is the new phenomenon of those who regret having changed their gender and detransitionists who would like to reverse the process The health professions, including psychology, as well as psychiatry and paediatrics, should claim the same scientific and professional standards for gender dysphoria as they apply to other problems, starting with exploration, evaluation, functional analysis, diagnosis, prudence, attentive waiting, instead of simply assuming affirmative therapy. [ABSTRACT FROM AUTHOR]

Antidepressants can be classified into 13 different classes based on their pharmacological mechanisms of action. As of this present moment, 11 out of these 13 classes of antidepressants accomplish their pharmacoactivities by blocking one or more of the reuptake transporter pumps and/or receptors for the three monoaminergic neurotransmitters, namely serotonin, norepinephrine, and dopamine. The 12th class inhibits the enzyme monoamine oxidase, while the 13th class works by blocking the N-methyl-D-aspartate (NMDA)-glutamatergic ionoceptor. Previous experimental results suggest that depression is associated with hyperfunction of NMDA-glutamatergic receptors (NMDARs) in the subcortical regions (i.e., hippocampus, locus coeruleus, and amygdala); whereas at the same time, there is hypofunction of NMDARs in the cortical regions (i.e., prefrontal, perirhinal, and temporal cortices). Moreover, this finding has led to a conclusion that postulates the new “Glutamatergic hypothesis of depression” which is now moving our understanding of the pathophysiology of major depression disorder (MDD), a step further from the several decades' old “Monoaminergic theory of depression.” Collectively, clinical data suggest the involvement of the glutamatergic neurotransmission system in the pathophysiology of MDD or bipolar depression or schizoaffective depression, which includes disruptions in glutamatergic substrate concentrations and NMDAR alterations. Although the role of glutamatergic systems is yet to be fully elucidated, a “proof of concept” clinical study reported that the noncompetitive NMDAR antagonist ketamine produced rapid-onset and prolonged antidepressant effects in patients suffering from MDD or bipolar depression or schizoaffective depression. Still, this has generated tremendous interest in developing new drugs that will target the glutamatergic neurotransmission mechanisms for the treatment of MDD or bipolar depression or schizoaffective depression. These potential drug targets are the NMDAR as antagonist or inverse agonist or partial agonist, metabotropic glutamatergic receptors as positive or negative modulator, excitatory amino acid transporter-2 (EAAT-2) as a reuptake enhancer, and as a terminal presynaptic glutamate release inhibitor.

Antidepressants can be classified into 13 different classes based on their pharmacological mechanisms of action. As of this present moment, 11 out of these 13 classes of antidepressants accomplish their pharmacoactivities by blocking one or more of the reuptake transporter pumps and/or receptors for the three monoaminergic neurotransmitters, namely serotonin, norepinephrine, and dopamine. The 12th class inhibits the enzyme monoamine oxidase, while the 13th class works by blocking the N-methyl-D-aspartate (NMDA)-glutamatergic ionoceptor. Previous experimental results suggest that depression is associated with hyperfunction of NMDA-glutamatergic receptors (NMDARs) in the subcortical regions (i.e., hippocampus, locus coeruleus, and amygdala); whereas at the same time, there is hypofunction of NMDARs in the cortical regions (i.e., prefrontal, perirhinal, and temporal cortices). Moreover, this finding has led to a conclusion that postulates the new "Glutamatergic hypothesis of depression" which is now moving our understanding of the pathophysiology of major depression disorder (MDD), a step further from the several decades' old "Monoaminergic theory of depression." Collectively, clinical data suggest the involvement of the glutamatergic neurotransmission system in the pathophysiology of MDD or bipolar depression or schizoaffective depression, which includes disruptions in glutamatergic substrate concentrations and NMDAR alterations. Although the role of glutamatergic systems is yet to be fully elucidated, a "proof of concept" clinical study reported that the noncompetitive NMDAR antagonist ketamine produced rapid-onset and prolonged antidepressant effects in patients suffering from MDD or bipolar depression or schizoaffective depression. Still, this has generated tremendous interest in developing new drugs that will target the glutamatergic neurotransmission mechanisms for the treatment of MDD or bipolar depression or schizoaffective depression. These potential drug targets are the NMDAR as antagonist or inverse agonist or partial agonist, metabotropic glutamatergic receptors as positive or negative modulator, excitatory amino acid transporter-2 (EAAT-2) as a reuptake enhancer, and as a terminal presynaptic glutamate release inhibitor. [ABSTRACT FROM AUTHOR]

Introduction: Conventional antidepressants, including fluoxetine, have a major disadvantage in delayed onset of efficacy. Yueju, an herbal medicine used to treat mood disorders was recently found to exhibit rapid antidepressant effects. The present study was conducted to evaluate the role of Yueju in rapidly acting on major depressive disorder (MDD). Methods: Participants were MDD patients with scores of 24-item Hamilton Depression Rating Scale (HDRS-24) ≥20 and without history of antidepressant use. They randomly received daily oral doses of Yueju (23 g/day) plus fluoxetine (20 mg/day) (experimental group) or placebo plus fluoxetine (control group) for 7 days. HDRS-24 was used as the primary outcome measurement at baseline, and on days 1, 3, 5, and 7. Concentrations of serum brain-derived neurotrophic factor (BDNF) were assessed at baseline and on days 1 and 7. Results: In all, 18 participants met the criteria for data analysis. Compared to baseline level, only experimental group showed significant decrease of HDRS-24 score from day 3 to day 7 (P<0.05). Experimental group also showed significant improvement compared with control group from day 3 to day 7 (P<0.05). No correlation between treatment outcomes with serum BDNF levels was observed. However, experimental group showed significant correlation for serum BDNF level on day 1 with day 7 (r=0.721, P=0.028), whereas the control group did not. Conclusion: Yueju likely contributes to fast-onset antidepressant effects on MDD. Further investigation is necessary to firmly establish the ancient formula as a safe, efficacious, and rapidly acting alternative medicine for MDD treatment. [ABSTRACT FROM AUTHOR]

This study was to evaluate submicron emulsion as a drug carrier for intranasal delivery of zolmitriptan (ZT). Since the drug distribution in submicron emulsion might influence the nasal absorption, two different formulations separately incorporating the drug in oily phase (ZTSE-1) and aqueous phase (ZTSE-2) were assessed. To find the better formulation for rapid-onset intranasal delivery and improvement in brain targeting of ZT, the in vivo nasal absorption of these two formulations was evaluated. The blood and cerebrospinalfluid (CSF) pharmacokinetics of ZTSE-1, ZTSE-2 and ZT solution (ZTS) were evaluated after intranasal administered to anesthetized Wistar rats. The results demonstrated that ZT from ZTSE-1 and ZTSE-2 had better brain targeting efficiency than the ZTS. In plasma and CSF, the ZTSE-2 reached peak concentration much faster than ZTSE-1 and ZTS. The ZTSE-2 also presented significantly higher initial ZT levels in CSF compared with the ZTSE-1 and ZTS. The results indicated that incorporation of ZT in the aqueous phase of submicron emulsion was effective for rapid intranasal delivery of drug to blood and brain, which would offer patients the benefits of rapid relief from migraine. [ABSTRACT FROM AUTHOR]

Background: Ketamine exerts a robust, rapid, and relatively sustained antidepressant effect in patients with major depression. Understanding the mechanisms underlying the intriguing effects of N-methyl d-aspartate (NMDA) antagonists could lead to novel treatments with a rapid onset of action. Methods: The learned helplessness, forced swim, and passive avoidance tests were used to investigate ketamine’s behavioral effects in mice. Additional biochemical and behavioral experiments were undertaken to determine whether the antidepressant-like properties of ketamine and other NMDA antagonists involve α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor throughput. Results: Subanesthetic doses of ketamine treatment caused acute and sustained antidepressant-like effects. At these doses, ketamine did not impair fear memory retention. MK-801 (dizocilpine) and Ro25-6981, an NR2B selective antagonist, also exerted antidepressant-like effects; these effects, however, were not sustained as long as those of ketamine. Pre-treatment with NBQX, an AMPA receptor antagonist, attenuated both ketamine-induced antidepressant-like behavior and regulation of hippocampal phosphorylated GluR1 AMPA receptors. Conclusions: NMDA antagonists might exert rapid antidepressant-like effects by enhancing AMPA relative to NMDA throughput in critical neuronal circuits. [Copyright &y& Elsevier]

Abstract: Intranasal (IN) administration is a promising approach for rapid-onset delivery of medications and to circumvent their first-pass elimination when taken orally. Metoclopramide (MCP) is a potent antiemetic, effective even for preventing emesis induced by cancer chemotherapy. The feasibility of developing an efficacious intranasal formulation of metoclopramide has been undertaken in this study. The nasal absorption of MCP was studied in anesthetized rats over 60min using the in vivo in situ technique. The influence of several formulation variables, vis., pH and the addition of preservative, viscosity and absorption enhancing agents on the nasal MCP absorption was examined. The data obtained showed that MCP was well absorbed nasally where almost 90% of the drug was absorbed after 60min from the rat nasal cavity. The MCP absorption was pH-dependant such that the apparent first-order rate constant of absorption (K app) was almost tripled when the pH of the solution was increased from 5 to 8. However, deviation from the classical pH-partition theory was observed pointing to the role of aqueous pore pathway in MCP nasal absorption. The K app was significantly increased (P <0.05) by incorporation of 0.01% of the preservative benzalkonium chloride. Conversely, increasing the solution viscosity by the use of hydroxylpropyl methylcellulose adversely affected the rate of absorption. The use of enhancers namely sodium deoxycholate, sodium cholate, chitosan low and high molecular weight, protamine sulphate and poly-l-arginine resulted in significant increase in MCP absorption. The highest promoting effect was observed with the bile salt sodium deoxycholate where about 92% of the drug was absorbed in 25min from the rat nasal cavity and the K app showed more than two-fold increase as compared to control (from 0.0452 to 0.1017min−1). [Copyright &y& Elsevier]

Introduction: Conventional antidepressants, including fluoxetine, have a major disadvantage in delayed onset of efficacy. Yueju, an herbal medicine used to treat mood disorders was recently found to exhibit rapid antidepressant effects. The present study was conducted to evaluate the role of Yueju in rapidly acting on major depressive disorder (MDD)., Methods: Participants were MDD patients with scores of 24-item Hamilton Depression Rating Scale (HDRS-24) ≥20 and without history of antidepressant use. They randomly received daily oral doses of Yueju (23 g/day) plus fluoxetine (20 mg/day) (experimental group) or placebo plus fluoxetine (control group) for 7 days. HDRS-24 was used as the primary outcome measurement at baseline, and on days 1, 3, 5, and 7. Concentrations of serum brain-derived neurotrophic factor (BDNF) were assessed at baseline and on days 1 and 7., Results: In all, 18 participants met the criteria for data analysis. Compared to baseline level, only experimental group showed significant decrease of HDRS-24 score from day 3 to day 7 (P<0.05). Experimental group also showed significant improvement compared with control group from day 3 to day 7 (P<0.05). No correlation between treatment outcomes with serum BDNF levels was observed. However, experimental group showed significant correlation for serum BDNF level on day 1 with day 7 (r=0.721, P=0.028), whereas the control group did not., Conclusion: Yueju likely contributes to fast-onset antidepressant effects on MDD. Further investigation is necessary to firmly establish the ancient formula as a safe, efficacious, and rapidly acting alternative medicine for MDD treatment.