Acupuncture for chemotherapy-associated insomnia in breast cancer patients: an assessor-participant blinded, randomized, sham-controlled trial.

BACKGROUND: Insomnia is a highly prevalent symptom occurred during and post-chemotherapy. Acupuncture may have beneficial effects in the management of chemotherapy-associated insomnia. This study was conducted to determine the efficacy and safety of acupuncture in improving chemotherapy-associated insomnia in breast cancer patients. METHODS: This assessor-participant blinded, randomized, sham-controlled trial was conducted from November 2019 to January 2022 (follow-up completed July 2022). Participants were referred by oncologists from two Hong Kong hospitals. Assessments and interventions were conducted at the outpatient clinic of School of Chinese Medicine, the University of Hong Kong. The 138 breast cancer patients with chemotherapy-associated insomnia were randomly assigned to receive either 15 sessions of active acupuncture regimen by combining needling into body acupoints and acupressure on auricular acupoints or sham acupuncture control (69 each) for 18 weeks, followed by 24 weeks of follow-up. The primary outcome was measured using Insomnia Severity Index (ISI). Secondary outcomes included the Pittsburgh Sleep Quality Index, Actiwatch and sleep diary for sleep parameters, depression and anxiety, fatigue and pain, and quality of life. RESULTS: There were 87.7% (121/138) participants who completed the primary endpoint (week-6). The active acupuncture regimen was not superior to the sham control in reducing ISI score from baseline to 6 weeks (mean difference: - 0.4, 95% CI - 1.8-1.1; P = 0.609), but produced short-term treatment and long-term follow-up better outcomes in improving sleep onset latency, total sleep time, sleep efficiency, anxiety, depression, and quality of life. Participants of the active acupuncture group had a pronouncedly higher cessation rate of sleeping medications than the sham control (56.5% vs. 14.3%, P = 0.011). All treatment-related adverse events were mild. No participants discontinued treatments due to adverse events. CONCLUSION: The active acupuncture regimen could be considered as an effective option for the management of chemotherapy-associated insomnia. It also could serve as a tapering approach to reduce and even replace the use of sleeping medications in breast cancer patients. Trial registration Clinicaltrials.gov : NCT04144309. Registered 30 October 2019.

Berberine ameliorates depression-like behaviors in mice via inhibiting NLRP3 inflammasome-mediated neuroinflammation and preventing neuroplasticity disruption.

OBJECTIVES: Neuroinflammation has been suggested that affects the processing of depression. There is renewed interest in berberine owing to its anti-inflammatory effects. Herein, we investigated whether berberine attenuate depressive-like behaviors via inhibiting NLRP3 inflammasome activation in mice model of depression. METHODS: Adult male C57BL/6N mice were administrated corticosterone (CORT, 20 mg/kg/day) for 35 days. Two doses (100 mg/kg/day and 200 mg/kg/day) of berberine were orally administrated from day 7 until day 35. Behavioral tests were performed to measure the depression-like behaviors alterations. Differentially expressed gene analysis was performed for RNA-sequencing data in the prefrontal cortex. NLRP3 inflammasome was measured by quantitative reverse transcription polymerase chain reaction, western blotting, and immunofluorescence labeling. The neuroplasticity and synaptic function were measured by immunofluorescence labeling, Golgi-Cox staining, transmission electron microscope, and whole-cell patch-clamp recordings. RESULTS: The results of behavioral tests demonstrated that berberine attenuated the depression-like behaviors induced by CORT. RNA-sequencing identified that NLRP3 was markedly upregulated after long-term CORT exposure. Berberine reversed the concentrations of peripheral and brain cytokines, NLRP3 inflammasome elicited by CORT in the prefrontal cortex and hippocampus were decreased by berberine. In addition, the lower frequency of neuronal excitation as well as the dendritic spine reduction were reversed by berberine treatment. Together, berberine increases hippocampal adult neurogenesis and synaptic plasticity induced by CORT. CONCLUSION: The anti-depressants effects of berberine were accompanied by reduced the neuroinflammatory response via inhibiting the activation of NLRP3 inflammasome and rescued the neuronal deterioration via suppression of impairments in synaptic plasticity and neurogenesis.

Minocycline, a classic antibiotic, exerts psychotropic effects by normalizing microglial neuroinflammation-evoked tryptophan-kynurenine pathway dysregulation in chronically stressed male mice.

The dysregulation of tryptophan-kynurenine pathway (TKP) is extensively involved in the pathophysiology of Alzheimer's disease, depression, and neurodegenerative disorders. Minocycline, a classic antibiotic, may exert psychotropic effects associated with the modulation of TKP. In this study, we examined the effects of minocycline in improving behaviour and modulating TKP components in chronically stressed male mice. Following repeated treatment with 22.5 mg/kg and 45 mg/kg minocycline for 27 days, the stressed mice particularly with higher dose displayed significant improvement on cognitive impairment, depression- and anxiety-like behaviour. Minocycline suppressed stress-induced overexpression of pro-inflammatory cytokines and restored anti-inflammatory cytokines. Chronic stress dramatically suppressed blood and prefrontal cortical levels of the primary substrate tryptophan (TRP), the neuroprotective metabolite kynurenic acid (KYNA), and KYNA/KYN ratio, but increased the intermediate kynurenine (KYN), 3-hydroxykynurenine (3-HK), KYN/TRP ratio, and the neurotoxic metabolite quinolinic acid (QUIN). Minocycline partially or completely reversed changes in these components. Minocycline also inhibited stress-induced overexpression of QUIN-related enzymes, indoleamine 2, 3-dioxygenase 1(iDO-1), kynureninase (KYNU), kynurenine 3-monooxygenase (KMO), 3-hydroxyanthranilate 3,4-dioxygenase (3-HAO), but rescued the decreased expression of kynurenine aminotransferase (KAT) in brain regions. Behavioral improvements were correlated with multiple TKP metabolites and enzymes. These results suggest that the psychotropic effects of minocycline are mainly associated with the restoration of biodistribution of the primary substrate in the brain and normalization of neuroinflammation-evoked TKP dysregulation.

Transcutaneous electrical cranial-auricular acupoint stimulation versus escitalopram for mild-to-moderate depression: An assessor-blinded, randomized, non-inferiority trial.

AIM: Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. An assessor-blinded, randomized, non-inferiority trial was designed to compare the efficacy of TECAS and escitalopram in mild-to-moderate major depressive disorder. METHODS: 468 participants received two TECAS sessions per day at home (n = 233) or approximately 10-13 mg/day escitalopram (n = 235) for 8 weeks plus 4-week follow-up. The primary outcome was clinical response, defined as a baseline-to-endpoint ≥50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Secondary outcomes included remission rate, changes in the severity of depression, anxiety, sleep and life quality. RESULTS: The response rate was 66.4% on TECAS and 63.2% on escitalopram with a 3.2% difference (95% confidence interval [CI], -5.9% to 12.9%) in intention-to-treat analysis, and 68.5% versus 66.2% with a 2.3% difference (95% CI, -6.9% to 11.4%) in per-protocol analysis. The lower limit of 95% CI of the differences fell within the prespecified non-inferiority margin of -10% (P ≤ 0.004 for non-inferiority). Most secondary outcomes did not differ between the two groups. TECAS-treated participants who experienced psychological trauma displayed a markedly greater response than those without traumatic experience (81.3% vs 62.1%, P = 0.013). TECAS caused much fewer adverse events than escitalopram. CONCLUSIONS: TECAS was comparable to escitalopram in improving depression and related symptoms, with high acceptability, better safety profile, and particular efficacy in reducing trauma-associated depression. It could serve an effective portable therapy for mild-to-moderate depression.

Adiponectin regulates electroacupuncture-produced analgesic effects in association with a crosstalk between the peripheral circulation and the spinal cord.

Neurotransmitter-mediated acupuncture analgesia has been widely studied in nervous systems. It remains largely unclear if peripheral substances are involved the acupuncture analgesia. Adiponectin (APN), a circulating adipokine, shows analgesic effects. The study aimed to examine whether APN regulates analgesic effects of electroacupuncture (EA) in the complete Freund's adjuvant (CFA)-induced mouse model. APN wild type (WT) and knockout (KO) mouse were employed in the study. We found that EA attenuates the CFA-induced pain as demonstrated by the Hargreaves thermal test and the von Frey filament test. The deletion of APN significantly reduced the acupuncture analgesia in the CFA-treated APN KO mice while the intrathecal administration of APN mimicked the analgesic effects of EA. We further revealed that EA produced analgesic effects mainly via APN/AdipoR2-mediated AMPK pathway by the siRNA inhibitions of APN receptors (adipoR1/2) in the spinal cord. The immunofluorescence staining analysis showed that EA increased the APN accumulation in spinal cord through the blood circulation. In conclusion, the study indicates a novel mechanism that acupuncture produces analgesic effects at least partially via APN/AdipoR2-AMPK pathway in the spinal cord.

Adjunctive berberine reduces antipsychotic-associated weight gain and metabolic syndrome in patients with schizophrenia: a randomized controlled trial.

AIM: The aim of this study was to evaluate the efficacy and safety of berberine as an adjuvant in treating antipsychotic-associated weight gain and metabolic syndrome. METHODS: One hundred thirteen participants with schizophrenia spectrum disorders who had developed metabolic syndrome were recruited. They were randomly assigned to berberine (600 mg/d, n = 58) or placebo (n = 55) groups for 12 weeks. The primary outcome was the change from baseline to week 12 in net weight. Secondary outcomes included body mass index, waist circumference, serum glucose and lipid profiles, and the severity of psychotic symptoms. RESULTS: Compared with the placebo group, the berberine group showed a significantly greater reduction in weight gain at 9 weeks (mean difference [MD], -0.75; 95% CI, -1.42 to -0.07 [P = 0.031, d = 0.41]) and 12 weeks (MD, -1.08; 95% CI, -1.76 to -0.40 [P = 0.002, d = 0.59]). Patients who received berberine also showed statistically significant improvements in end point in body mass index (MD, -0.41; 95% CI, -0.65 to -0.17 [P = 0.001, d = 0.64]), total cholesterol (MD, -0.58; 95% CI, -0.74 to -0.41 [P < 0.001, d = 1.31]), low-density lipoprotein (MD, -0.52; 95% CI, -0.68 to -0.35 [P < 0.001, d = 1.19]), and glycated hemoglobin (MD, -0.09; 95% CI, -0.18 to 0 [P = 0.05, d = 0.37]). Berberine was well tolerated without serious adverse events and aggravation of psychotic symptoms compared with placebo. CONCLUSION: The findings suggest that berberine is effective in attenuating antipsychotic-associated weight gain and metabolic syndrome.

Plant-based Medicines (Phytoceuticals) in the Treatment of Psychiatric Disorders: A Meta-review of Meta-analyses of Randomized Controlled Trials: Les médicaments à base de plantes (phytoceutiques) dans le traitement des troubles psychiatriques: une méta-revue des méta-analyses d'essais randomisés contrôlés.

OBJECTIVES: Plant-based medicines have had a long-standing history of use in psychiatric disorders. Highly quantified and standardized extracts or isolates may be termed "phytoceuticals," in a similar way that medicinal nutrients are termed as "nutraceuticals." Over the past 2 decades, several meta-analyses have examined the data for a range of plant-based medicines in the treatment of psychiatric disorders. The aim of this international project is to provide a "meta-review" of this top-tier evidence. METHODS: We identified, synthesized, and appraised all available up to date meta-analyses... of randomized controlled trials (RCTs) reporting on the efficacy and effectiveness of individual phytoceuticals across all major psychiatric disorders. RESULTS: Our systematic search identified 9 relevant meta-analyses of RCTs, with primary analyses including outcome data from 5,927 individuals. Supportive meta-analytic evidence was found for St John's wort for major depressive disorder (MDD); curcumin and saffron for MDD or depression symptoms, and ginkgo for total and negative symptoms in schizophrenia. Kava was not effective in treating diagnosed anxiety disorders. We also provide details on 22 traditional Chinese herbal medicine formulas' meta-analyses (primarily for depression studies), all of which revealed highly significant and large effect sizes. Their methodology, reporting, and potential publication bias were, however, of marked concern. The same caveat was noted for the curcumin, ginkgo, and saffron meta-analyses, which may also have significant publication bias. CONCLUSIONS: More rigorous international studies are required to validate the efficacy of these phytoceuticals before treatment recommendations can be made. In conclusion, the breadth of data tentatively supports several phytoceuticals which may be effective for mental disorders alongside pharmaceutical, psychological therapies, and standard lifestyle recommendations.

Electroacupuncture trigeminal nerve stimulation plus body acupuncture for chemotherapy-induced cognitive impairment in breast cancer patients: An assessor-participant blinded, randomized controlled trial.

Chemotherapy causes various side effects, including cognitive impairment, known as 'chemobrain'. In this study, we determined whether a novel acupuncture mode called electroacupuncture trigeminal nerve stimulation plus body acupuncture (EA/TNS + BA) could produce better outcomes than minimum acupuncture stimulation (MAS) as controls in treating chemobrain and other symptoms in breast cancer patients. In this assessor- and participant-blinded, randomized controlled trial, 93 breast cancer patients under or post chemotherapy were randomly assigned to EA/TNS + BA (n = 46) and MAS (n = 47) for 2 sessions per week over 8 weeks. The Montreal Cognitive Assessment (MoCA) served as the primary outcome. Digit span test was the secondary outcomes for attentional function and working memory. The quality of life and multiple functional assessments were also evaluated. EA/TNS + BA treated group had much better performance than MAS-treated group on reverse digit span test at Week 2 and Week 8, with medium effect sizes of 0.53 and 0.48, respectively, although no significant differences were observed in MoCA score and prevalence of chemobrain between the two groups. EA/TNS + BA also markedly reduced incidences of diarrhoea, poor appetite, headache, anxiety, and irritation, and improved social/family and emotional wellbeing compared to MAS. These results suggest that EA/TNS + BA may have particular benefits in reducing chemotherapy-induced working memory impairment and the incidence of certain digestive, neurological, and distress-related symptoms. It could serve as an effective intervention for breast cancer patients under and post chemotherapy (trial registration: https://www.clinicaltrials.gov: NCT02457039).

Electroacupuncture on Trigeminal Nerve-Innervated Acupoints Ameliorates Poststroke Cognitive Impairment in Rats with Middle Cerebral Artery Occlusion: Involvement of Neuroprotection and Synaptic Plasticity.

Poststroke cognitive impairment (PSCI) is a severe sequela of stroke. There are no effective therapeutic options for it. In this study, we evaluated whether electroacupuncture (EA) on the trigeminal nerve-innervated acupoints could alleviate PSCI and identified the mechanisms in an animal model. The male Sprague-Dawley rat middle cerebral artery occlusion (MCAO) model was used in our study. EA was conducted on the two scalp acupoints, EX-HN3 (Yintang) and GV20 (Baihui), innervated by the trigeminal nerve, for 14 sessions, daily. Morris water maze and novel object recognition were used to evaluate the animal's cognitive performance. Neuroprotection and synaptic plasticity biomarkers were analyzed in brain tissues. Ischemia-reperfusion (I/R) injury significantly impaired spatial and cognition memory, while EA obviously reversed cognitive deterioration to the control level in the two cognitive paradigms. Moreover, EA reversed the I/R injury-induced decrease of brain-derived neurotrophic factor, tyrosine kinase B, N-methyl-D-aspartic acid receptor 1, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, γ-aminobutyric acid type A receptors, Ca2+/calmodulin-dependent protein kinase II, neuronal nuclei, and postsynaptic density protein 95 expression in the prefrontal cortex and hippocampus. These results suggest that EA on the trigeminal nerve-innervated acupoints is an effective therapy for PSCI, in association with mediating neuroprotection and synaptic plasticity in related brain regions in the MCAO rat model.

Assessor- and participant-blinded, randomized controlled trial of dense cranial electroacupuncture stimulation plus body acupuncture for neuropsychiatric sequelae of stroke.

AIM: Acupuncture has benefits in the rehabilitation of neuropsychiatric sequelae of stroke. This study was aimed to evaluate the effectiveness of dense cranial electroacupuncture stimulation plus body acupuncture (DCEAS+BA) in treating poststroke depression (PSD), functional disability, and cognitive deterioration. METHODS: In this assessor- and participant-blinded, randomized controlled trial, 91 stroke patients who initially had PSD were randomly assigned to either DCEAS+BA (n = 45) or minimum acupuncture stimulation as controls (n = 46) for three sessions per week over 8 consecutive weeks. The primary outcome was baseline-to-end-point change in score of the 17-item Hamilton Depression Rating Scale. Secondary outcomes included the Montgomery-Åsberg Depression Rating Scale for depressive symptoms, the Barthel Index for functional disability, and the Montreal Cognitive Assessment for cognitive function. RESULTS: DCEAS+BA-treated patients showed strikingly greater end-point reduction than MAS-treated patients in scores of the three symptom domains. The clinical response rate, defined as an at least 50% baseline-to-end-point reduction in 17-item Hamilton Depression Rating Scale score, was markedly higher in the DCEAS+BA-treated group than that of controls (40.0% vs 17.4%, P = 0.031). Incidence of adverse events was not different in the two groups. Subgroup analysis revealed that DCEAS+BA with electrical stimulation on forehead acupoints was more apparent in reducing Barthel-Index-measured disability than that without electrical stimulation. CONCLUSION: DCEAS+BA, particularly with electrical stimulation on forehead acupoints, reduces PSD, functional disability, and cognitive deterioration of stroke patients. It can serve as an effective rehabilitation therapy for neuropsychiatric sequelae of stroke.

Effectiveness of acupuncture for vascular cognitive impairment no dementia: a randomized controlled trial.

OBJECTIVE:: To evaluate the effectiveness of acupuncture in patients with vascular cognitive impairment no dementia (VCIND) in comparison with citicoline, an agent for cognitive disturbances associated with chronic cerebral disorders. DESIGN:: A randomized controlled multicenter trial. SETTING:: In three hospitals in Beijing, China. SUBJECTS:: A total of 216 patients with VCIND were recruited. INTERVENTIONS:: Patients with VCIND (mean age of 65.4 years) were randomized to receive acupuncture (two sessions per week) or oral citicoline (100 mg three times daily) over three months. MAIN MEASURES:: The primary outcome was the change from baseline to three months in cognitive symptom, measured by Alzheimer's disease Assessment Scale, cognitive subscale (ADAS-cog). Secondary outcomes included changes from baseline to six months in ADAS-cog, executive function measured by the Clock Drawing Test (CDT), and functional disability measured by the Ability of Daily Living (ADL) scale at three and six months. RESULTS:: At three months, the acupuncture group had a greater decrease in mean ADAS-cog score (-2.33 ± 0.31) than the citicoline group (-1.38 ± 0.34) with a mean difference of -0.95 (95% CI, -1.84 to -0.07, P = 0.035). The mean change from baseline to six months in ADAS-cog also significantly favored acupuncture treatments (acupuncture change -2.61 vs citicoline -1.25, difference: -1.36 points; 95% CI, -2.20 to -0.51; P = 0.002). There was no difference between the two groups on CDT and ADL scores at either time point. CONCLUSION:: Compared with citicoline, acupuncture has comparable and even superior efficacy with improved cognitive and daily living performance as a complementary and alternative medicine treatment for VCIND.

Transcutaneous electrical acupoint stimulation for post-traumatic stress disorder: Assessor-blinded, randomized controlled study.

AIM: Transcutaneous electrical acupoint stimulation (TEAS) has the potential to alleviate post-traumatic stress disorder (PTSD). The purpose of this study was to determine whether adding TEAS to sertraline or cognitive behavioral therapy (CBT) could improve the anti-PTSD efficacy. METHODS: In this randomized controlled trial, 240 PTSD patients (60 in each group) were assigned to receive simulated TEAS combined with sertraline (group A) or with CBT (group B), active TEAS combined with CBT (group C), or active TEAS combined with CBT plus sertraline (group D) for 12 weeks. The outcomes were measured using the Clinician-Administered PTSD Scale, PTSD Check List-Civilian Version, and 17-item Hamilton Rating Scale for Depression. RESULTS: While PTSD symptoms reduced over time in all patients, groups C and D had markedly greater improvement in both PTSD and depressive measures than groups A and B in all post-baseline measurement points, with moderate to very large effect sizes of 0.484-2.244. Groups C and D also had a significantly higher rate than groups A and B on clinical response (85.0% and 95.0% vs 63.3% and 60.0%, P < 0.001) and on remission (15.0% and 25.0% vs 3.3% and 1.7%, P < 0.001). The incidence of adverse events was similar between groups A and D and between groups B and C. CONCLUSIONS: Additional TEAS augments the anti-PTSD and antidepressant efficacy of antidepressants or CBT, without increasing the incidence of adverse effects. TEAS could serve as an effective intervention for PTSD and comorbid depression. This trial was registered with www.chictr.org (no.: ChiCTR1800017255).

Application of UPLC-MS/MS to simultaneously detect four bioactive compounds in the tumour-shrinking decoction (FM1523) for uterine fibroids treatment.

INTRODUCTION: The Chinese medicine formulation, tumour-shrinking decoction (TSD, FM1523), which consists of 15 natural medicines, is used for uterine fibroids (UFs) therapy and possesses excellent clinical therapeutic effect. OBJECTIVE: To develop a sensitive and validated analytical method for the simultaneous quantification of four crucial bioactive compounds including isorhamnetin-3-O-neohesperidoside, curcumin, peimine and tetrahydropalmatine in the principal formulation of this decoction. METHODS: An ultra-performance liquid chromatography coupled tandem mass spectrometry (UPLC-MS/MS) with an electrospray ionisation (ESI) source in multiple reaction monitoring (MRM) mode was conducted to investigate these bioactive compounds in the TSD. The chromatographic separation was performed on a C18 column when the flow rate was adjusted at 0.2 mL/min with gradient elution of acetonitrile-water with 0.1% formic acid. Accelerated solvent extraction (ASE) method with higher extraction efficiency was employed for TSD sample pre-treatment. RESULTS: The linearity, limit of detection (LOD) and limit of quantification (LOQ) were determined for this analytical method. The mean recoveries of the compounds were determined between 100.23% and 104.02% with satisfactory relative standard deviation (RSD) in the ranges of 2.65% to 3.81%. The precision was evaluated by intra-day and inter-day tests, which revealed RSD within the ranges of 1.21% to 2.14% and 1.24% to 2.32%, respectively. CONCLUSION: The bioactive compounds of TSD samples were successfully quantified via UPLC-MS/MS with MRM mode. This study could help to evaluate the pharmacokinetic study of TSD during clinical applications and present a facile strategy for quantifying bioactive compounds in traditional Chinese Medicine decoction.

Traditional Chinese Medicine Explanatory Models of Depressive Disorders: A Qualitative Study.

Traditional Chinese medicine (TCM) is an alternative medical system utilised by many Chinese. However, the knowledge of TCM concepts of depression is limited amongst clinicians with training in Western biomedicine. The purpose of this study was to obtain a better understanding of the conceptualisation of depression from a group of TCM practitioners. Semi-structured interviews in Chinese were carried out with 10 TCM practitioners in Hong Kong. A case description of major depression disorder (MDD) was used as a basis. Interview texts were transcribed, translated and analysed using qualitative content analysis. Most informants identified the case as a depression pattern, a term that lacked clear definition and standardised criteria. The mechanism of disease for MDD symptoms were regarded to be liver-qi dysregulation and an imbalance of yin and yang. The TCM practitioners implemented individualised diagnosis, treatment, and a holistic concept without clear distinction between the mind and the body. This contrasted with the biomedical tradition of separating psychologisation and somatisation. The meanings given to the concept of depression did not correspond with current DSM or ICD definitions, and the TCM normativity can result in variations in explanatory models.

Resveratrol, a natural polyphenol, prevents chemotherapy-induced cognitive impairment: Involvement of cytokine modulation and neuroprotection.

Chemotherapy-induced cognitive impairment, also known as "chemobrain," is a common side effect. The purpose of this study was to examine whether resveratrol, a natural polyphenol that has nootropic effects, could prevent chemobrain and its underlying mechanisms. Mice received three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination, a common chemotherapy regimen, at two-day intervals within one week. Resveratrol (50 and 100 mg/kg per day) was orally administered for three weeks, beginning one week before the DAC treatment. Water maze test and manganese-enhanced magnetic resonance imaging were used to evaluate animals' cognitive performance and brain neuronal activity, respectively. Blood and brain tissues were collected for measurement of cytokines, cytokine regulators, and biomarkers for neuroplasticity. DAC treatment produced a striking cognitive impairment. Cotreatment with 100 mg/kg resveratrol ameliorated DAC-induced cognitive impairment and decreases in prefrontal and hippocampal neuronal activity. Mice co-treated with both doses of resveratrol displayed significantly lower levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but markedly higher levels of the anti-inflammatory cytokines IL-4 and IL-10 in several sera and brain tissues than those co-treated with vehicle. Resveratrol modulated the cytokine-regulating pathway peroxisome proliferator activated receptor (PPAR)-γ/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and protected against DAC-induced decreases in the expression of the neuroplasticity biomarkers, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), amino acid neurotransmitter receptors, and calmodulin-dependent protein kinase II (CaMKII). These results demonstrate the efficacy of resveratrol in preventing chemobrain and its association with cytokine modulation and neuroprotection.

Self-administered acupressure for insomnia disorder: a pilot randomized controlled trial.

Self-administered acupressure has potential as a low-cost alternative treatment for insomnia. To evaluate the short-term effects of self-administered acupressure for alleviating insomnia, a pilot randomized controlled trial was conducted. Thirty-one subjects (mean age: 53.2 years; 77.4% female) with insomnia disorder were recruited from a community. The participants were randomized to receive two lessons on either self-administered acupressure or sleep hygiene education. The subjects in the self-administered acupressure group (n = 15) were taught to practise self-administered acupressure daily for 4 weeks. The subjects in the comparison group (n = 16) were advised to follow sleep hygiene education. The primary outcome was the Insomnia Severity Index (ISI). Other measures included a sleep diary, Hospital Anxiety and Depression Scale and Short-form Six-Dimension. The subjects in the self-administered acupressure group had a significantly lower ISI score than the subjects in the sleep hygiene education group at week 8 (effect size = 0.56, P = 0.03). However, this observed group difference did not reach a statistically significant level after Bonferroni correction. With regard to the secondary outcomes, moderate between-group effect sizes were observed in sleep onset latency and wake after sleep onset based on the sleep diary, although the differences were not significant. The adherence to self-administered acupressure practice was satisfactory, with 92.3% of the subjects who completed the lessons still practising acupressure at week 8. In conclusion, self-administered acupressure taught in a short training course may be a feasible approach to improve insomnia. Further fully powered confirmatory trials are warranted.

Electroacupuncture for tapering off long-term benzodiazepine use: study protocol of randomized controlled trial.

BACKGROUND: Conventional approaches for benzodiazepine tapering have their limitations. Anecdotal studies have shown that acupuncture is a potential treatment for facilitating successful benzodiazepine tapering. As of today, there was no randomized controlled trial examining its efficacy and safety. The purpose of the study is to evaluate the efficacy of using electroacupuncture as an adjunct treatment to gradual tapering of benzodiazepine doses in complete benzodiazepine cessation in long-term benzodiazepine users. METHODS/DESIGN: The study protocol of a randomized, assessor- and subject-blinded, controlled trial is presented. One hundred and forty-four patients with histories of using benzodiazepines in ≥50% of days for more than 3 months will be randomly assigned in a 1:1 ratio to receive either electroacupuncture or placebo electroacupuncture combined with gradual benzodiazepine tapering schedule. Both experimental and placebo treatments will be delivered twice per week for 4 weeks. Major assessments will be conducted at baseline, week 6 and week 16 post-randomization. Primary outcome is the cessation rate of benzodiazepine use. Secondary outcomes include the percentage change in the doses of benzodiazepine usage and the severity of withdrawal symptoms experienced based on the Benzodiazepine Withdrawal Symptom Questionnaire, insomnia as measured by the Insomnia Severity Index, and anxiety and depressive symptoms as evaluated by the Hospital Anxiety and Depression Scale. Adverse events will also be measured at each study visit. DISCUSSION: Results of this study will provide high quality evidence of the efficacy and safety of electroacupuncture as an adjunct treatment for benzodiazepine tapering in long-term users. TRIAL REGISTRATION: ClinicalTrials.gov NCT02475538 .

Peony-Glycyrrhiza Decoction for Antipsychotic-Related Hyperprolactinemia in Women With Schizophrenia: A Randomized Controlled Trial.

OBJECTIVES: An herbal preparation called peony-glycyrrhiza decoction (PGD) may have the potential in reducing antipsychotic-related hyperprolactinemia (hyperPRL). This double-blind, randomized placebo-controlled study aimed to reevaluate the efficacy of PGD against antipsychotic-related hyperPRL. METHODS: Ninety-nine schizophrenic women who were under antipsychotic therapy and had symptomatic hyperPRL were randomly assigned to additional treatment with placebo (n = 50) or PGD (n = 49, 45 g/d) for 16 weeks. The severity of hyperPRL, psychosis, and abnormal involuntary movements was assessed at baseline and weeks 8 and 16 using standard instruments including the Prolactin Related Adverse Event Questionnaire. Blood levels of prolactin (PRL) and related pituitary and sex hormones were measured at the same time points. RESULTS: Peony-glycyrrhiza decoction treatment produced a significantly greater reduction of the Prolactin Related Adverse Event Questionnaire score at weeks 8 and 16 and a greater improvement on abnormal involuntary movements at end point compared with placebo, without altering the severity of psychosis. The group treated with PGD showed significantly higher proportion of having overall improvement on hyperPRL symptoms (χ = 4.010, P = 0.045) and menstrual resumption (χ = 4.549, P = 0.033) at week 8 than placebo. Serum PRL levels were similar in the 2 groups. CONCLUSIONS: Peony-glycyrrhiza decoction is effective in reducing antipsychotic-related hyperPRL and abnormal involuntary movement symptoms, but no reduction in blood PRL concentrations was observed. The underlying mechanisms of PGD's effects need further investigation (trial registration of NCT01852331 at www.clinicaltrials.gov).

18ß-Glycyrrhetinic Acid, a Novel Naturally Derived Agent, Suppresses Prolactin Hyperactivity and Reduces Antipsychotic-Induced Hyperprolactinemia in In Vitro and In Vivo Models.

The purpose of this study was to examine the effects of 18ß-glycyrrhetinic acid (GA), a novel naturally derived agent, in suppressing prolactin (PRL) hyperactivity and reducing antipsychotic-induced hyperprolactinemia (hyperPRL) and the underlying mechanisms in in vitro and in vivo models. GA treatment for 24 h inhibited PRL synthesis and secretion in MMQ cells and cultured pituitary cells in a dose-dependent fashion; but this effect was not reproduced in GH3 cells that lack the expression of functional dopamine D2 receptors. GA suppressed elevated PRL level and growth hormone, and normalized several sex hormones in a rat model of hyperPRL, produced by repeated injection of the dopamine blocker metoclopramide. GA also modulated the expression 5-HT1A and 5-HT2A receptors in both in vivo and in vitro models. These results indicate that GA is effective in suppressing PRL hyperactivity caused by the blockade of dopamine D2 receptors. This suppressive effect of GA may be related to its modulation of the serotonergic system. This study provides additional evidence in support of GA as an adjunct for the treatment of hyperPRL.

A proprietary herbal medicine (5-Ling Granule) for Tourette syndrome: a randomized controlled trial.

BACKGROUND: Tourette syndrome (TS) is a common tic disorder in children and adolescents. There is preliminary evidence that herbal medicine may possess the potential to treat tics. The purpose of this study was to formally evaluate the efficacy and safety of 5-Ling Granule (5-LGr), a proprietary polyherbal product, for the treatment of patients with TS in comparison with tiapride and placebo. METHODS: In this multisite, double-blind, double-dummy, randomized, placebo-controlled trial, 603 patients with TS aged 5-18 years were randomly assigned to treatment with placebo (n = 117), tiapride (n = 123, 200-400 mg/day) or 5-LGr (n = 363, 15-22.5 g/day) for 8 weeks. The primary outcome was measured using the Yale Global Tic Severity Scale (YGTSS) and its subscales, total tic Score (TTS) and tic-related impairment. Incidence of adverse events was compared among the three groups. RESULTS: While tics of all patients were reduced over time, 5-LGr and tiapride treatment produced significantly greater improvement on the YGTSS overall scale and subscale for TTS and impairment at endpoint than the placebo. Seventy-four percentage of patients in the 5-LGr arm and 68.3% in the tiapride arm had clinical response and these rates of response were significantly higher than those on placebo (44.0%, p < .001). The incidence of overall adverse events was significantly fewer for patients on placebo and 5-LGr compared to tiapride (11.2% and 13.8% vs. 26.0%, p = .002); in particular physical tiredness, dizziness and sleep disturbance. CONCLUSIONS: The clinical efficacy of 5-LGr is comparable to tiapride in reducing tics. Its safety profile is better than tiapride. 5-LGr can be considered a safe and effective therapy for TS (Trial registration: www.clinicaltrials.gov: NCT01501695).