The polymethoxylated flavone,Tangeretin improves cognitive memory in rats experiencing a single episode of prolonged post-traumatic stress

Post-traumatic stress disorder (PTSD) is a stress-related psychiatric/mental condition. Tangeretin (TAN), a major polymethoxylated flavone of citrus plants, exhibits anti-inflammatory and neuroprotective activities. However, whether TAN leads to cognitive improvement in PTSD patients remains unclear. In the present study, we explored whether TAN improved cognitive impairment induced in rats by single prolonged stress (SPS episode mimicking PTSD induction) and determined whether TAN reversed reductions in dopamine (DA) and serotonin (5-HT) levels. Rats were intraperitoneally injected with TAN for 14 consecutive days after the SPS, which had induced cognitive deficits evident in the object recognition task and the Morris water maze test; the impairments were improved by TAN (100?mg/kg). TAN rescued the neurochemical abnormalities and the SPS-induced decreases in DA and 5-HT levels in the hippocampus and amygdala. These effects may be attributable in part to induction of hippocampal genes encoding tyrosine hydroxylase and tryptophan hydroxylase-1. Our results support the idea that rats with PTSD exhibit changes in DAergic and serotonergic transmission and in memory impairment. Thus, TAN mediated reversal of memory-related behavioral dysfunction associated with traumatic stress may be a useful therapeutic intervention in PTSD patients.     

Internet-based cognitive behavior therapy vs. cognitive behavioral group therapy for social anxiety disorder: a randomized controlled non-inferiority trial

Background and Aims

Cognitive behavioral group therapy (CBGT) is an effective, well-established, but not widely available treatment for social anxiety disorder (SAD). Internet-based cognitive behavior therapy (ICBT) has the potential to increase availability and facilitate dissemination of therapeutic services for SAD. However, ICBT for SAD has not been directly compared with in-person treatments such as CBGT and few studies investigating ICBT have been conducted in clinical settings. Our aim was to investigate if ICBT is at least as effective as CBGT for SAD when treatments are delivered in a psychiatric setting.

Methods

We conducted a randomized controlled non-inferiority trial with allocation to ICBT (n = 64) or CBGT (n = 62) with blinded assessment immediately following treatment and six months post-treatment. Participants were 126 individuals with SAD who received CBGT or ICBT for a duration of 15 weeks. The Liebowitz Social Anxiety Scale (LSAS) was the main outcome measure. The following non-inferiority margin was set: following treatment, the lower bound of the 95 % confidence interval (CI) of the mean difference between groups should be less than 10 LSAS-points.

Results

Both groups made large improvements. At follow-up, 41 (64%) participants in the ICBT group were classified as responders (95% CI, 52%–76%). In the CBGT group, 28 participants (45%) responded to the treatment (95% CI, 33%–58%). At post-treatment and follow-up respectively, the 95 % CI of the LSAS mean difference was 0.68–17.66 (Cohen’s d between group = 0.41) and −2.51–15.69 (Cohen’s d between group = 0.36) favoring ICBT, which was well within the non-inferiority margin. Mixed effects models analyses showed no significant interaction effect for LSAS, indicating similar improvement across treatments (F = 1.58; df = 2, 219; p = .21).

Conclusions

ICBT delivered in a psychiatric setting can be as effective as CBGT in the treatment of SAD and could be used to increase availability to CBT.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00564967","term_id":"NCT00564967"}}NCT00564967     

Oleuropein reduces anxiety-like responses by activating of serotonergic and neuropeptide Y (NPY)-ergic systems in a rat model of post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experiences. This psychopathological response to traumatic stressors induces anxiety in rats. Oleuropein (OLE), a major compound in olive leaves, reportedly possesses several pharmacological properties, including anti-cancer, anti-diabetic, and anti-atherosclerotic and neuropsychiatric activities. However, the anxiolytic-like effects of OLE and its mechanism of action in PTSD are unclear. The present study used several behavioral tests to examine the effects of OLE on symptoms of anxiety in rats after a single prolonged stress (SPS) exposure by inhibiting the hypothalamic-pituitary-adrenal axis. Male Sprague Dawley rats received OLE (10, 50 and 70?mg/kg, i.p., once daily) for 14 days after SPS exposure. Daily OLE (70?mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index and grooming behavior in the EPM test, and increased the time spent and number of central zone crossings in the open field test. OLE also blocked the SPS-induced decrease in hippocampal serotonin and neuropeptide Y expression in hippocampus. These findings suggest that OLE has anxiolytic-like effects on behavioral and biochemical symptoms similar to those observed in patients with PTSD.     

Effectiveness of enhanced cognitive behavior therapy for bulimia nervosa in Japan: a randomized controlled trial protocol

Although fatigue is a common and distressing symptom in cancer survivors, the mechanism of fatigue is not fully understood. Therefore, this study aims to investigate the relation between the fatigue and mindfulness of breast cancer survivors using anxiety, depression, pain, loneliness, and sleep disturbance as mediators. Path analysis was performed to examine direct and indirect associations between mindfulness and fatigue. Participants were breast cancer survivors who visited a breast surgery department at a university hospital in Japan for hormonal therapy or regular check-ups after treatment. The questionnaire measured cancer-related-fatigue, mindfulness, anxiety, depression, pain, loneliness, and sleep disturbance. Demographic and clinical characteristics were collected from medical records. Two-hundred and seventy-nine breast cancer survivors were registered, of which 259 answered the questionnaire. Ten respondents with incomplete questionnaire data were excluded, resulting in 249 participants for the analyses. Our final model fit the data well (goodness of fit index = .993; adjusted goodness of fit index = .966; comparative fit index = .999; root mean square error of approximation = .016). Mindfulness, anxiety, depression, pain, loneliness, and sleep disturbance were related to fatigue, and mindfulness had the most influence on fatigue (β = − .52). Mindfulness affected fatigue not only directly but also indirectly through anxiety, depression, pain, loneliness, and sleep disturbance. The study model helps to explain the process by which mindfulness affects fatigue. Our results suggest that mindfulness has both direct and indirect effects on the fatigue of breast cancer survivors and that mindfulness can be used to more effectively reduce their fatigue. It also suggests that health care professionals should be aware of factors such as anxiety, depression, pain, loneliness, and sleep disturbance in their care for fatigue of breast cancer survivors. This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN number. 000027720) on June 12, 2017.     

A randomized trial of cognitive rehabilitation in cancer survivors

Aims

The second most frequently reported post-treatment symptom in cancer survivors are concerns about impaired cognition. Despite numerous studies demonstrating significant impairments in a portion of survivors, information on effective treatments remains an emerging area of research. This study examined the effectiveness of a group-based cognitive rehabilitation intervention in cancer survivors.

Main methods

This study was a randomized, controlled study of a 7-week cognitive rehabilitation intervention delivered in group format. Participants were evaluated with subjective symptom questionnaires and objective neurocognitive tests prior to and following treatment.

Key findings

Twenty-eight participants (mean age 58 years) with a median of 3 years (± 6 years) post-primary/adjuvant treatment and various cancer sites (breast, bladder, prostate, colon, uterine) completed the study. Compared to baseline, the treatment group demonstrated improvements in symptoms of perceived cognitive impairments (p < .01), cognitive abilities (p < .01) and overall quality of life with regard to cognitive symptoms (p < .01) as measured by the FACT-Cog. The treatment group also improved on objective measures of attention (p < .05) and a trend toward improvement on verbal memory. Significant improvement was not observed on all cognitive tests.

Significance

A group based cognitive rehabilitation intervention in cancer survivors was effective for improving attention abilities and overall quality of life related to cognition. Results suggest that group based cognitive rehabilitation may be an effective intervention for treating cognitive dysfunction in cancer patients and should be further studied in a larger trial with an active control condition.     

The promise of cognitive behavior therapy for treatment of severe mental disorders: a review of recent developments

Cognitive behavior therapy (CBT), as exemplified by the model of psychotherapy developed and refined over the past 40 years by A.T. Beck and colleagues, is one of the treatments of first choice for ambulatory depressive and anxiety disorders. Over the past several decades, there have been vigorous efforts to adapt CBT for treatment of more severe mental disorders, including schizophrenia and the more chronic and/or treatment refractory mood disorders. These efforts have primarily studied CBT as an adjunctive therapy, i.e., in combination with pharmacotherapy. Given the several limitations of state‐of‐the‐art pharmacotherapies for these severe mental disorders, demonstration of clinically meaningful additive effects for CBT would have important implications for improving public health. This paper reviews the key developments in this important area of therapeutics, providing a summary of the current state of the art and suggesting directions for future research.     

A controlled trial of internet-based cognitive-behavioural therapy for panic disorder with face-to-face support from a general practitioner or email support from a psychologist

Background Panic disorder (PD) is one of the most common anxiety disorders seen in general practice, but provision of evidence-based cognitive-behavioural treatment (CBT) is rare. Many Australian GPs are now trained to deliver focused psychological strategies, but in practice this is time consuming and costly.Objective To evaluate the efficacy of an internet-based CBT intervention (Panic Online) for the treatment of PD supported by general practitioner (GP)-delivered therapeutic assistance.Design Panic Online supported by GP-delivered face-to-face therapy was compared to Panic Online supported by psychologist-delivered email therapy.Methods Sixty-five people with a primary diagnosis of PD (78% of whom also had agoraphobia) completed 12 weeks of therapy using Panic Online and therapeutic assistance with his/her GP (n = 34) or a clinical psychologist (n = 31). The mean duration of PD for participants allocated to these groups was 59 months and 58 months, respectively. Participants completed a clinical diagnostic interview delivered by a psychologist via telephone and questionnaires to assess panic-related symptoms, before and after treatment.Results The total attrition rate was 20%, with no group differences in attrition frequency. Both treatments led to significant improvements in panic attack frequency, depression, anxiety, stress, anxiety sensitivity and quality of life. There were no statistically significant differences in the two treatments on any of these measures, or in the frequency of participants with clinically significant PD at post assessment.Conclusions When provided with accessible online treatment protocols, GPs trained to deliver focused psychological strategies can achieve patient outcomes comparable to efficacious treatments delivered by clinical psychologists. The findings of this research provide a model for how GPs may be assisted to provide evidence-based mental healthcare successfully.     

TOXGB: Teamwork Optimization Based XGBoost model for early identification of post-traumatic stress disorder

Post-traumatic stress (PTSD) is considered a clinical issue that influences numerous people from diverse trades all over the world. Numerous research scholars recorded diverse complexities to estimate the severity of the PTSD symptoms in the patients. But diagnosing PTSD and obtaining accurate diagnosing techniques becomes a more complicated task. Therefore, this paper develops a speech based post-traumatic stress disorder monitoring method and the significant objective of the proposed method is to determine if the patients are affected by PTSD. The proposed approach utilizes three different steps: pre-processing or pre-emphasis, feature extraction as well as classification to evaluate the patients affected by PTSD or not. The input speech signal is initially provided to the pre-processing phase where the speech gets segmented into frames. The speech frame is then extracted and classified using XGBoost based Teamwork optimization (XGB-TWO) algorithm. In addition to this, we utilized two different types of datasets namely TIMIT and FEMH to evaluate and classify the PSTD from the speech signals. Furthermore, based on the evaluation of the proposed model to diagnose PTSD patients, various evaluation metrics namely accuracy, specificity, sensitivity, and recall are evaluated. Finally, the experimental investigation and comparative analysis are carried out and the evaluation results demonstrated that the accuracy rate achieved for the proposed technique is 98.25%.     

Cells, biomarkers, and post-traumatic stress disorder: evidence for peripheral involvement in a central disease

Post-traumatic stress disorder (PTSD) is a complicated CNS syndrome. Looking beyond the CNS, recent studies suggest that peripheral blood mononuclear cells could cause and/or exacerbate PTSD. This review summarizes the literature, describes associations between circulating peripheral blood cells and PTSD, proposes a novel mechanism, and analyzes several biomarkers that appear to associate with PTSD symptoms. Several experimental animal models have shown that peripheral blood mononuclear cell activity can cause hippocampal volume loss and PTSD-like symptoms. Data from these models suggest that a traumatic event and/or traumatic events can trigger peripheral cells to migrate, mediate inflammation, and decrease neurogenesis, potentially leading to CNS volume loss. Biomarkers that associate with PTSD symptoms have the potential to differentiate PTSD from traumatic brain injury, but more work needs to be done. Research examining the mechanism of how traumatic events are linked to peripheral blood mononuclear cell functions and biomarkers may offer improved diagnoses and treatments for PTSD patients.     

Flavonoids and cognitive function: a review of human randomized controlled trial studies and recommendations for future studies

Evidence in support of the neuroprotective effects of flavonoids has increased significantly in recent years, although to date much of this evidence has emerged from animal rather than human studies. Nonetheless, with a view to making recommendations for future good practice, we review 15 existing human dietary intervention studies that have examined the effects of particular types of flavonoid on cognitive performance. The studies employed a total of 55 different cognitive tests covering a broad range of cognitive domains. Most studies incorporated at least one measure of executive function/working memory, with nine reporting significant improvements in performance as a function of flavonoid supplementation compared to a control group. However, some domains were overlooked completely (e.g. implicit memory, prospective memory), and for the most part there was little consistency in terms of the particular cognitive tests used making across study comparisons difficult. Furthermore, there was some confusion concerning what aspects of cognitive function particular tests were actually measuring. Overall, while initial results are encouraging, future studies need to pay careful attention when selecting cognitive measures, especially in terms of ensuring that tasks are actually sensitive enough to detect treatment effects.     

A novel nonsurgical therapy for peri-implantitis using focused pulsed electromagnetic field: A pilot randomized double-blind controlled clinical trial

Pulsed electromagnetic field (PEMF) therapy modulates the immune response and is successfully used in orthopedics to treat osteoarthritis and improve bone regeneration. This may suggest that this treatment may consequently reduce peri-implant soft tissue inflammation and marginal bone loss. To compare clinical, radiographic, and immunological results following nonsurgical treatment for peri-implantitis with or without PEMF therapy. Patients with peri-implantitis were included: pocket probing depth (PPD) between 6 and 8 mm with bleeding on probing (BOP); crestal bone loss between 3 and 5 mm. A novel healing abutment that contained active (test) or inactive (control) PEMF was connected. PEMF was administered via the abutment at exposure ratio of 1/500–1/5000, intensity: 0.05–0.5 mT, frequency: 10–50 kHz for 30 days. Nonsurgical mechanical implant surface debridement was performed. Patients were examined at baseline, 1 and 3 months. Clinical assessment included: plaque index, BOP, PPD, recession, and bone crest level which was radiography measured. Samples of peri-implant crevicular fluid were taken to analyze interleukin-1β (IL-1β). Twenty-three patients (34 implants; 19 control, 15 test) were included. At the follow-up, mean crestal bone loss was lower in the test group at 1 and 3 months (2.48 mm vs. 3.73 mm, p < 0.05 and 2.39 vs. 3.37, p < 0.01). IL-1β levels were also lower in the test group at 2 weeks (72.86 pg/mL vs. 111.7, p < 0.05). Within all the limitation of this preliminary study, the test group improved clinical parameters after a short-term period compared to the control group.     

Furazolidone‐containing triple and quadruple eradication therapy for initial treatment for Helicobacter pylori infection: A multicenter randomized controlled trial in China

Background

The efficacy of Helicobacter pylori (H. pylori) eradication has steadily declined, primarily because of antibiotic resistance. This study aimed to evaluate the efficacy and safety of furazolidone eradication therapies as initial treatments for H. pylori infection.

Methods

A national, multicenter, open‐label, randomized controlled trial was performed at 16 sites across 13 provinces in China to evaluate the efficacy and safety of furazolidone‐containing therapies for H. pylori infection. Treatment naïve patients were randomly assigned to: esomeprazole 20 mg, bismuth 220 mg, amoxicillin 1000 mg, and furazolidone 100 mg twice daily for 10 and 7 days (FAB 10 and FAB 7; the same therapy without bismuth (FA 10 and FA 7). The primary and secondary outcomes were the eradication rate and regimen safety, respectively. Treatment success was assessed by the ¹³C urea breath test at least 4 weeks after treatment completion.

Results

Overall, according to intention‐to‐treat (ITT) analysis, the eradication rates for FAB 10 and FAB 7 were 86.6% (95% confidence interval [CI], 79.9%‐93.2%) and 83.6% (95% CI, 76.3%‐90.9%) and for FA 10 and FA 7 were 82.4% (95% CI, 74.9%‐89.8%) and 77.6% (95% CI, 69.4%‐85.8%), respectively. According to per‐protocol analysis, the overall eradication rates for FAB 10 and FAB 7 were 94.7% (95% CI, 90.3%‐99.1%) and 90.8% (95% CI, 85.1%‐96.5%) and for FA 10 and FA 7 were 90.6% (95% CI, 84.9%‐96.3%) and 85.1% (95% CI, 78.2%‐92.1%), respectively. The overall prevalence of side effects was 8.1%.

Conclusions

Furazolidone‐containing therapies, particularly the tested 10‐day quadruple therapy, exhibited satisfactory efficacy and safety. This 10‐day quadruple therapy represents a promising initial treatment strategy for Chinese patients.     

Effectiveness of cognitive behaviour therapy for the treatment of catastrophisation in patients with fibromyalgia: a randomised controlled trial

Introduction  

No randomised, controlled trials have been conducted to date on the efficacy of psychological and pharmacological treatments of pain catastrophising (PC) in patients with fibromyalgia. Our aim in this study was to assess the effectiveness of cognitive-behaviour therapy (CBT) and the recommended pharmacological treatment (RPT) compared with treatment as usual (TAU) at the primary care level for the treatment of PC in fibromyalgia patients.     

Supervised exercise with or without laser-guided feedback for people with non-specific chronic low back pain. A randomized controlled clinical trial

BackgroundAmong the most effective therapeutic interventions in non-specific chronic low back pain (NSCLBP), clinical practice guidelines highlight exercise therapy and patient education; However, regarding the combined intervention of exercise and Pain Neuroscience Education (PNE), there is no consensus on the most effective form of exercise.ObjetiveTo find out what changes occurred after the application of two exercise modalities [Supervised Exercise (SE) and Laser-Guided Exercise (LGE)] and PNE on pain, pain pressure thresholds, disability, catastrophizing, kinesiophobia and lumbar proprioception in subjects with NSCLBP.MethodsSingle-blind randomized clinical controlled trial. 60 subjects with NSCLBP. Both groups performed a a total of 16 therapeutic exercise sessions and 8 Pain Neuroscience Education sessions. With the Laser-Guided Exercise Therapy group performing laser-guided exercises.ResultsA significant decrease was observed for pain intensity for both groups between baseline and post-intervention and the 3 month follow-up (p < 0.001). There was a significant between-group difference between baseline and post-intervention scores in terms of pain intensity and kinesiophobia in favour of the LGE group.ConclusionSupervised exercise with or without laser feedback, when combined with PNE, reduces pain intensity, disability, pain catastrophizing, kinesiophobia and improves proprioception and PPTs in patients with NSCLBP. At a 3-month follow-up, the combination of LGE plus PNE is most effective for reducing pain intensity.     

Childhood adversity during the post-apartheid transition and COVID-19 stress independently predict adult PTSD risk in urban South Africa: A biocultural analysis of the stress sensitization hypothesis

Objectives

The COVID-19 pandemic in South Africa introduced new societal adversities and mental health threats in a country where one in three individuals are expected to develop a psychiatric condition sometime in their life. Scientists have suggested that psychosocial stress and trauma during childhood may increase one's vulnerability to the mental health consequences of future stressors—a process known as stress sensitization. This prospective analysis assessed whether childhood adversity experienced among South African children across the first 18 years of life, coinciding with the post-apartheid transition, exacerbates the mental health impacts of psychosocial stress experienced during the 2019 coronavirus (COVID-19) pandemic (ca. 2020–2021).

Materials and Methods

Data came from 88 adults who participated in a follow-up study of a longitudinal birth cohort study in Soweto, South Africa. Childhood adversity and COVID-19 psychosocial stress were assessed as primary predictors of adult PTSD risk, and an interaction term between childhood adversity and COVID-19 stress was calculated to evaluate the potential effect of stress sensitization.

Results

Fifty-six percent of adults exhibited moderate-to-severe PTSD symptoms. Greater childhood adversity and higher COVID-19 psychosocial stress independently predicted worse post-traumatic stress disorder symptoms in adults. Adults who reported greater childhood adversity exhibited non-significantly worse PTSD symptoms from COVID-19 psychosocial stress.

Discussion

These results highlight the deleterious mental health effects of both childhood trauma and COVID-19 psychosocial stress in our sample and emphasize the need for greater and more accessible mental health support as the pandemic progresses in South Africa.     

Treatment effectiveness of a mindfulness-based inpatient group psychotherapy in adolescent substance use disorder - study protocol for a randomized controlled trial

Background

Current treatments for adolescents with substance use disorder (SUD) have had only limited success. In recent years, research has underlined the role of self-regulatory processes and impulsivity in the development and maintenance of SUD in adolescents. Mindfulness has gained much attention due to its capacity to influence self-regulatory processes, particularly in adult populations. Initial studies have shown the potential of mindfulness-based approaches in younger SUD patients. The aim of the present clinical trial is to evaluate the added treatment effect of a mindfulness-based group psychotherapy (“Mind it!”) for adolescents with SUD in comparison to the current standard treatment. Moreover, we seek to explore the feasibility of the intervention and possible mediators of treatment effects.

Methods/design

There will be N?=?340 participants aged between 13 and 19?years who are receiving child or adolescent psychiatric or psychotherapeutic inpatient or day treatment targeting their SUD and who have reported substance use 30?days before detoxification and do not show acute psychotic or suicidal symptoms at baseline. The study is a prospective randomized controlled multi-center trial in which patients are assessed: (1) after completing a prior detoxification phase (t₀), (2) at 4 weeks (t₁), (3) at 8 weeks (t₂), and (4) at 6 months after t₂ (t₃). Participants in the intervention group will receive mindfulness-based group psychotherapy in addition to their existing treatment regime. The primary outcome is substance use in the past 30?days at follow-up based on the Timeline Followback self-report. Secondary outcomes include craving, severity of dependence, and abstinence motivation. Mindfulness, impulsivity, and emotion regulation will be analyzed as possible mediators of treatment effects.

Discussion

This trial is expected to provide evidence of the added effect of a novel, safe, and feasible treatment option for adolescents with SUD.

Trial registration

German Register of Clinical Studies, DRKS00014041. Registered on 17 April 2018.

     

A double blind randomized controlled trial to evaluate the efficacy of green tea in gingivitis

Gingivitis is the most common form of oral disease especially among patients undergoing fixed orthodontic treatment. Green tea, which is extensively used in Asian countries, can help to improve the overall gingival health, which can be assessed by using the gingival indices. Evaluation of the effectiveness of green tea on the gingival health of patients undergoing Orthodontic treatment is of interest. 40 otherwise healthy patients undergoing fixed orthodontic treatment were randomly divided in two groups namely (1) study group and (2) control group. Gingival indices were scored for all the patients. Study group was given mouth rinse with green tea extract and control group was given placebo with no green tea extract. Gingival indices were measured for all the patients after 21 days. Mann Whitney U test and Wilcoxon test was used for statistical analysis. The gingival indices scoring in which the values before and after the use of mouthwash were compared. The p value was found to be statistically significant (p<0.05) in study group. But in control group statistical significant could not be reached.     

Feasibility of guided cognitive behaviour therapy (CBT) self-help for childhood anxiety disorders in primary care

Anxiety disorders in childhood are common, disabling and run a chronic course. Cognitive behaviour therapy (CBT) is effective but expensive and trained therapists are scarce. Guided self-help treatments may be a means of widening access to treatment. This study aimed to examine the feasibility of guided CBT self-help in primary care for childhood anxiety disorders, specifically in terms of therapist adherence, patient and therapist satisfaction and clinical gain.Participants were children aged between five and 12 years referred to two primary child and adolescent mental health services (PCAMHSs) in Oxfordshire, UK, who met diagnostic criteria for a primary anxiety disorder. Of the 52 eligible children, 41 anxious children were assessed for anxiety severity and interference before and after receiving CBT self-help delivered via a parent (total therapy time = five hours) by primary mental health workers (PMHWs). Therapy sessions were rated for treatment adherence and parents and PMHWs completed satisfaction questionnaires after treatment completion. Over 80% of therapy sessions were rated at a high level of treatment adherence. Parents and PMHWs reported high satisfaction with the treatment. Sixty-one percent of the children assessed no longer met the criteria for their primary anxiety disorder diagnosis following treatment, and 76% were rated as 'much'/'very much' improved on the Clinical Global Impression-Improvement (CGI-I) scale. There were significant reductions on parent and child report measures of anxiety symptoms, interference and depression. Preliminary exploration indicated that parental anxiety was associated with child treatment outcome. The findings suggest that guided CBT self-help represents a promising treatment for childhood anxiety in primary care.     

Study protocol for a randomized controlled trial comparing mindfulness-based cognitive therapy with maintenance anti-depressant treatment in the prevention of depressive relapse/recurrence: the PREVENT trial

Background

The total effect of a medication is the sum of its drug effect, placebo effect (meaning response), and their possible interaction. Current interpretation of clinical trials' results assumes no interaction. Demonstrating such an interaction has been difficult due to lack of an appropriate study design.

Methods

180 adults were randomized to caffeine (300 mg) or placebo groups. Each group received the assigned intervention described by the investigators as caffeine or placebo, in a randomized crossover design. 4-hour-area-under-the-curve of energy, sleepiness, nausea (on 100 mm visual analog scales), and systolic blood pressure levels as well as caffeine pharmacokinetics (in 22 volunteers nested in the caffeine group) were determined. Caffeine drug, placebo, placebo-plus-interaction, and total effects were estimated by comparing outcomes after, receiving caffeine described as placebo to receiving placebo described as placebo, receiving placebo described as caffeine or placebo, receiving caffeine described as caffeine or placebo, and receiving caffeine described as caffeine to receiving placebo described as placebo, respectively.

Results

The placebo effect on area-under-the-curve of energy (mean difference) and sleepiness (geometric mean ratio) was larger than placebo-plus-interaction effect (16.6 [95% CI, 4.1 to 29.0] vs. 8.4 [-4.2 to 21.0] mm*hr and 0.58 [0.39 to 0.86] vs. 0.69 [0.49 to 0.97], respectively), similar in size to drug effect (20.8 [3.8 to 37.8] mm*hr and 0.49 [0.30 to 0.91], respectively), and its combination with the later was larger than total caffeine effect (29.5 [11.9 to 47.1] mm*hr and 0.37 [0.22 to 0.64]). Placebo-plus-interaction effect increased caffeine terminal half-life by 0.40 [0.12 to 0.68] hr (P = 0.007).

Conclusions

Drug and placebo effects of a medication may be less than additive, which influences the interpretation of clinical trials. The placebo effect may increase active drug terminal half-life, a novel mechanism of placebo action.

Trial Registration

ClinicalTrials.gov identification number - NCT00426010.