Drug design, development and therapy
January 1, 2024
Chao-Bang Ma, Cheng-Yang Zhang, Cai-Li Gou et al.
27 citations
A randomized controlled trial tested whether low-dose esketamine reduces postoperative delirium in elderly patients after total hip or knee replacement. Two hundred sixty participants received either esketamine (a loading dose of 0.20 mg/kg, infusion of 0.125 mg/kg/h, and 0.5 mg/kg for postoperative pain) or a placebo of normal saline. Delirium occurred in 8.5% of the esketamine group and 10.8% of the placebo group, a difference that was not statistically significant. The timing, duration, and subtype of delirium also did not differ between groups. Esketamine provided more stable blood pressure after anesthesia induction and lowered pain with movement during the first two days after surgery, but increased dizziness. Repeated low-dose esketamine did not reduce delirium in the first three days after surgery.
Drug design, development and therapy
January 1, 2024
Sarah A Norring, Michael G Spigarelli
22 citations
Psilocybin, a tryptamine psychedelic, has been promoted as a potential mental health therapeutic. An observational study of ClinicalTrials.gov data found 134 psilocybin trials over the past 20 years, typically unblinded studies with 10-20 participants at a single site. Only three advanced trials (1 Phase 2/3 and 2 Phase 3) have been submitted, all within the last two years. The authors argue that the large number of small, exploratory trials covering many indications may be slowing FDA approval and wasting capital. They conclude that little real progress has been made toward approval and the field lacks clear direction.
Drug design, development and therapy
January 1, 2024
Bo-Ran Deng, Yang Zhang, Zi-Feng Xie et al.
18 citations
In elderly patients undergoing painless colonoscopies, a combination of remimazolam and esketamine causes fewer drops in blood pressure and other hemodynamic complications than propofol plus esketamine. In a randomized trial with 754 patients, hypotension occurred in 9.78% of those given remimazolam-esketamine versus 23.57% in the propofol-esketamine group. The remimazolam group also had lower rates of sinus tachycardia, sinus bradycardia, and less need for blood-pressure-supporting drugs. Both sedative regimens achieved 100% sedation success, but the remimazolam combination led to a longer time to fall asleep yet faster recovery, along with less respiratory depression and injection pain. The findings indicate remimazolam with esketamine provides superior hemodynamic stability and safety for this population.
Drug design, development and therapy
January 1, 2024
Mengcao Weng, Dongdong Wang, Jia Zhong et al.
17 citations
For hysteroscopy, the 95% effective dose (ED95) of esketamine combined with propofol was 0.254 mg/kg, while alfentanil's ED95 was 9.121 μg/kg. In a randomized trial, the anesthesia success rate with these ED95 doses was 93.0% for esketamine and 95.2% for alfentanil, with no significant difference. Induction time was shorter with esketamine (60 seconds) than alfentanil (67 seconds). Esketamine caused significantly lower rates of respiratory depression, hypoxia, and hypotension, and had less effect on breathing and blood pressure. Postoperative pain did not differ between groups. Esketamine is an effective and safer alternative to alfentanil for hysteroscopic anesthesia.
Drug design, development and therapy
January 1, 2024
Yanling Liao, Siyu Xie, Yifen Zhuo et al.
14 citations
In children aged 2-5 years undergoing tonsillectomy and/or adenoidectomy with sevoflurane anesthesia, intranasal premedication combining dexmedetomidine and esketamine reduces emergence delirium more effectively than esketamine alone (9.4% vs 38.1%) and reduces postoperative negative behavioral changes at day 7 more effectively than dexmedetomidine alone (28.1% vs 48.4%). The combination also provides better sedation, easier separation from parents, better mask acceptance, shorter emergence time, and higher parental satisfaction than either drug alone, without significant adverse effects. No significant difference in emergence delirium was found between the combination and dexmedetomidine alone.
Drug design, development and therapy
January 1, 2025
Xingyu Geng, Yutian Pu, Ziwei Hu et al.
7 citations
Postoperative sleep disturbance (POSD) is common after breast cancer surgery. In a randomized trial of 100 patients, intraoperative infusion of esketamine combined with dexmedetomidine did not significantly reduce the incidence of POSD compared to control or either drug alone over the first three days. However, on postoperative day 3, each drug alone reduced POSD risk when the other was absent. Dexmedetomidine decreased rapid eye movement (REM) sleep on day 1, while esketamine reduced nighttime awakening time on days 1 and 3. The combination showed no added benefit for POSD, but each drug had distinct effects on sleep architecture.
Drug design, development and therapy
January 1, 2024
Yanping Shen, Lijun Yin, Binnan Hu et al.
7 citations
A higher dose of esketamine reduces propofol injection pain, but patients who are anxious before surgery need a larger dose than those who are not. In a trial of 150 women undergoing painless abortion, those with preoperative anxiety (STAI-S score ≥40) required an effective dose for 50% of patients (ED50) of 0.133 mg/kg, compared to 0.114 mg/kg for non-anxious women—a statistically significant difference. No differences in side effects or blood pressure stability were seen between groups. Tailoring esketamine dose to a patient's anxiety level may improve pain management during anesthesia.
Drug design, development and therapy
January 1, 2025
Xiao Huang, Xueyang Li, Yuan Sun et al.
5 citations
In patients undergoing bronchoscopy, combining esketamine with propofol reduced the risk of dangerously low oxygen levels during the procedure compared with the standard combination of sufentanil and propofol. In a randomized trial, 27.2% of patients given esketamine experienced hypoxemia versus 66.7% given sufentanil. The esketamine group also had shorter episodes of low oxygen, higher minimum oxygen saturation, and faster recovery from anesthesia, though they required more propofol. Adverse reactions did not differ between groups. The authors suggest esketamine plus propofol may be a better option for preventing hypoxemia during bronchoscopy, but note that optimal dosing needs further study.
Drug design, development and therapy
January 1, 2025
Yuting Li, Hongxiang Li, Feng Zhang et al.
3 citations
In patients with septic shock on mechanical ventilation, adding esketamine to propofol sedation, compared with adding remifentanil, may reduce the dose of norepinephrine needed to maintain blood pressure. The two sedation regimens produced similar pain scores, and there were no significant differences in heart rate, mean arterial pressure, or 28-day survival. Esketamine appears to be a safe option that helps stabilize hemodynamics in this critically ill population.
Drug design, development and therapy
January 1, 2025
Xiaoshan Li, Shengchao Li, Chanyan Xu et al.
3 citations
A low dose of esketamine (0.2 mg/kg bolus, 5 μg/kg/min infusion for 30 minutes) raised the Bispectral Index (BIS) from 49.9±4.5 to 59.6±6.0 during propofol-remifentanil general anesthesia. A closed-loop target-controlled infusion (TCI) system that adjusted its drug delivery based on this new BIS baseline performed as well as a system using the original baseline of 50, with both falling within the range of high-performance systems. The adjusted system reduced propofol consumption (5.58±1.12 vs 6.69±1.36 mg·kg⁻¹·h⁻¹) without increasing adverse events such as intraoperative awareness, postoperative pain, nausea, vomiting, or shivering. Operating the closed-loop TCI system with an adjusted BIS baseline is feasible when low-dose esketamine is used.
Drug design, development and therapy
January 1, 2024
Liangliang Gao, Xinyu Lu, Aiping Tan et al.
3 citations
Pretreating patients with a small dose of esketamine (0.15 mg/kg) two minutes before administering the anesthetic etomidate significantly reduces the occurrence and severity of muscle jerks (myoclonus) that etomidate often causes. In a trial with 100 adults undergoing general surgery, myoclonus occurred in 20% of those given esketamine versus 62% of those given a placebo. The pretreatment also lessened moderate and severe myoclonus, though it did not affect mild cases. Blood pressure and heart rate remained stable, and side effects such as dizziness, slow heart rate, low blood pressure, and hallucinations were similar between groups.
Drug design, development and therapy
January 1, 2026
Yanhong Li, Kuangyu Zhao, Peipei Cao et al.
A single intravenous dose of esketamine (0.25 mg/kg) given at the start of surgery reduces postoperative anxiety in adolescents aged 13–18 years, with lower anxiety scores on days 1, 3, 7, and 14 after surgery. Depression scores were lower only on day 14. The drug did not significantly change inflammatory markers (CRP and IL-6) or cause more adverse events than placebo. Esketamine was a protective factor against postoperative anxiety (odds ratio 0.38). The findings suggest a safe, short-term benefit for anxiety, with limited effect on depression, in this age group.
Drug design, development and therapy
January 1, 2026
Fan Bu, Lan Qin, Zhengchi Lou et al.
Depressive disorders remain a leading cause of disability, and many patients do not achieve lasting remission with current treatments, especially those with treatment-resistant depression (TRD) or bipolar depression. This narrative review examines next-generation pharmacotherapy from a drug-centered and mechanism-informed perspective. It covers NMDA receptor modulators, dextromethorphan-bupropion, multimodal antidepressants, neuroactive steroids like brexanolone and zuranolone, psychedelic-assisted therapy, kappa-opioid receptor antagonists, and bipolar-specific mood stabilizers. The review also discusses optimizing existing drugs through repurposing, augmentation, combination therapy, and precision approaches like pharmacogenomics. Progress depends on both developing new compounds and improving treatment selection, sequencing, and monitoring across unipolar depression, bipolar depression, and TRD.
Drug design, development and therapy
January 1, 2026
Jie Yang, Qiqi Yan, Ting Zhang et al.
Among women without prenatal depression who delivered by caesarean section, a single bolus injection of 0.25 mg/kg esketamine reduced the rate of postpartum depression (PPD) at six weeks to 9.15%, compared with 19.33% in the saline placebo group. Continuous infusion of the same dose produced a PPD rate of 11.54%, which did not differ statistically from the bolus group. Pain scores were similar across all three groups. The bolus route caused fewer intraoperative adverse events—45.75% versus 65.38% with infusion—especially less dizziness and nausea or vomiting. For preventing PPD, bolus and continuous infusion appear equally effective, but bolus administration may be preferable because it is better tolerated.
Drug design, development and therapy
January 1, 2025
Yingchao Guan, Haochen Wang, Xiaojing Cong et al.
Esketamine anesthesia during first-trimester surgical abortion maintains more stable blood pressure and heart rate compared with sufentanil, and keeps end-tidal carbon dioxide at preoperative levels while sufentanil increases it. The risk of apnea was 68% lower and hypoxemia 87% lower with esketamine. However, esketamine increased the incidence of intraoperative body movement (50% vs 27%), postoperative dizziness (45% vs 30%), and nausea (7% vs 0%). No differences were found in anesthesia recovery time, sedation scores, pain, or vomiting. Esketamine provides better hemodynamic and respiratory stability but raises the risk of dizziness and nausea.
Drug design, development and therapy
January 1, 2025
Jiajia Li, Gaili Jia, Ruixian Wang et al.
Intranasal esketamine at 0.5 mg/kg significantly reduces emergence agitation after pediatric adenotonsillectomy. In a trial of 204 children aged 3–6 years, the incidence of emergence agitation (PAED ≥ 10) was 10.45% in the low-dose esketamine group versus 29.85% in the saline group. The higher 1 mg/kg dose did not further reduce agitation (12.12%) and prolonged extubation time. Children receiving 0.5 mg/kg also had lower pain scores and required less rescue propofol and fentanyl. The findings suggest 0.5 mg/kg intranasal esketamine is effective for preventing emergence agitation, while 1 mg/kg adds no benefit and may delay recovery.