Residential cognitive therapy versus residential interpersonal therapy for social phobia: a randomized clinical trial

Eighty patients meeting DSM-IV criteria for social phobia were randomly assigned to 10 weeks of residential cognitive therapy (RCT) or residential interpersonal therapy (RIPT). Subjects were assessed at pretreatment, midtreatment, posttreatment, and 1 year after end of treatment. The patients reported chronic, highly comorbid social phobia. Most had tried other treatments without success. Existing individual treatment protocols for cognitive therapy and interpersonal therapy were extensively modified for an integrated group, individual, and residential format. The RCT and RIPT patients improved significantly on the primary outcome measures from pre- to posttreatment. No significant differences were observed between treatments. Patients also completed three weekly secondary outcome measures; on one, social role security, RCT was superior to RIPT. The entire sample reported continued improvement from posttreatment to 1-year follow-up, indicating that improvements were robust. RCT in the present trial was associated with less improvement compared to individual CT in other recent trials.     

Intolerance of uncertainty as a mediator of reductions in worry in a cognitive behavioral treatment program for generalized anxiety disorder

Growing evidence suggests that intolerance of uncertainty (IU) is a cognitive vulnerability that is a central feature across diverse anxiety disorders, including generalized anxiety disorder (GAD). Although cognitive behavioral therapy (CBT) has been shown to reduce IU, it remains to be established whether or not reductions in IU mediate reductions in worry. This study examined the process of change in IU and worry in a sample of 28 individuals with GAD who completed CBT. Changes in IU and worry, assessed bi-weekly during treatment, were analyzed using multilevel mediation models. Results revealed that change in IU mediated change in worry (ab = −0.20; 95% CI [−.35, −.09]), but change in worry did not mediate change in IU (ab = −0.16; 95% CI [−.06, .12]). Findings indicated that reductions in IU accounted for 59% of the reductions in worry observed over the course of treatment, suggesting that changes in IU are not simply concomitants of changes in worry. Findings support the idea that IU is a critical construct underlying GAD.     

Implementing a randomized clinical trial on a pediatric psychiatric inpatient unit at a children's hospital: the case of clonidine for post-traumatic stress

Randomized clinical trials (RCTs) of psychotropic medications are uncommon among child and adolescent populations, and even rarer on pediatric, psychiatric inpatient units. We mention some of these studies, and then discuss the advantages and challenges of conducting a RCT among youngsters on an inpatient psychiatric unit in a pediatric hospital, using as an example our ongoing study of clonidine for intrusive symptoms of post-traumatic stress. Our purpose is to alert potential investigators to the obstacles they may encounter while implementing a RCT, while also pointing the way to potential resources. Advantages of inpatient units for RCTs include easy access to patients, with the potential for careful monitoring of both patients’ clinical status and of medication administration. Challenges include the need for the psychiatric researcher to form liaison with other important areas within the hospital, such as the Institutional Review Board, the Pharmacy, and sometimes a General Clinical Research Center and a Clinical Research Program. The functions of these departments are discussed, and additional support for clinicians in hospital settings without these departments is described. Other issues include training clinical nurses to conduct research while making adequate provisions for their time to do so. Attitudes on a clinical psychiatric inpatient unit toward research also merit consideration. Furthermore, as with any study in a hospital setting, recruitment presents its own set of challenges. Finally, one must be cognizant of how clinical information flows between clinicians and researchers.     

A randomised controlled trial of a worry intervention for individuals with persistent persecutory delusions

Recent research has shown that worry is associated with distressing paranoia. Therefore, the aim was to target worry in a therapeutic intervention for individuals with delusions. It was predicted that a worry intervention would reduce levels of worry and paranoia distress. Twenty-four individuals with persistent persecutory delusions and high levels of worry were randomly assigned to receive a four session cognitive-behavioural worry intervention (W-CBT) or treatment as usual (TAU). The worry intervention was specifically designed not to target the content of delusions. In this open-label evaluation, assessments of worry and paranoia were conducted at baseline, at one month (end of treatment) and at two months. The worry intervention achieved a statistically significant reduction in worry which was maintained at two month follow up. A significant reduction in delusional distress was also reported. There was an indication that the worry intervention may also reduce the frequency of paranoid thoughts but this was not statistically significant. In the first trial specifically for persecutory delusions, a brief worry intervention was shown to have benefits. The results support a causal role for worry in paranoid experience.     

Local injection versus surgery in carpal tunnel syndrome: Neurophysiologic outcomes of a randomized clinical trial

ObjectiveThe aim of our study was to characterize the neurophysiologic outcomes in a randomized clinical trial comparing local corticosteroid injection and decompressive surgery in idiopathic carpal tunnel syndrome.MethodsClinical and neurophysiologic assessments were done at baseline and 12 months after treatment. Four parameters were evaluated in the nerve conduction study (NCS): distal motor latency, motor amplitude, sensory conduction velocity and sensory amplitude. Statistic signification was established by the Student’s t test, independent and paired samples, and Mann–Whitney test. Repeated measures analysis of variance was used by the three domains of symptoms. Correlations between the changes showed in clinical parameters and those evidenced by electromyography were calculated by the Pearson’s test.ResultsBoth groups of therapy were comparable at baseline. In 95 wrists, a second NCS was done 12 months post-treatment. Although clinical outcome improved in a similar way in both groups, we found statistically significant improvement in three (distal motor latency, sensory conduction velocity and sensory amplitude) of four neurophysiologic parameters only in the surgery group, when compared to baseline values.ConclusionsAlthough local corticosteroid injection and decompressive surgery are clinically effective in reducing symptoms of carpal tunnel syndrome, only surgery results in an improvement of the neurophysiologic parameters, at 12-months follow-up.SignificanceOnly decompressive surgery allows resolution of neurophysiologic changes. The symptoms of the syndrome are resolved with corticosteroid injections.     

The contribution of attentional bias to worry: distinguishing the roles of selective engagement and disengagement

This study investigated the effect on worry of biased attentional engagement and disengagement. Variants of a novel attention modification paradigm were developed, designed to induce a group difference either in participants’ tendency to selectively engage with, or disengage from, threatening meanings. An index of threat bias, reflecting relative speeding to process threat word compared to non-threat word content, confirmed that both procedures were effective in inducing differential attentional bias. Importantly, when the induced group difference in attentional bias followed the procedure designed to influence selective engagement with threat meanings, it also gave rise to a corresponding group difference in worry. This was not the case when it was induced by the procedure designed to influence selective disengagement from threat meanings. These findings suggest that facilitated attentional engagement with threat meanings may causally contribute to variability in worry.     

Effects of a home-based intervention program on anxiety and depression 6 months after coronary artery bypass grafting: a randomized controlled trial

OBJECTIVE: The objective of this study was to evaluate the effects of a home-based intervention program (HBIP) on anxiety and depression 6 months after coronary artery bypass grafting (CABG). METHODS: In a prospective randomized controlled trial, 203 elective CABG patients were included. An HBIP structured for respondents in the intervention group was performed 2 and 4 weeks after surgery. Anxiety and depression symptoms were measured by the Hospital Anxiety and Depression Scale (HADS) in both patient groups before surgery, 6 weeks after surgery, and 6 months after surgery. RESULTS: A total of 185 patients completed the study: 93 patients in the intervention group and 92 patients in the control group. On 6-week and 6-month follow-ups, significant improvements in anxiety and depression symptoms were found in both groups. These improvements did not differ significantly between the groups. However, in a predefined subgroup of patients with anxiety and/or depression symptoms at baseline (n=65), improvement was significantly larger in the intervention group (n=29) than in the control group (n=36) after 6 months (P<.05). CONCLUSIONS: Patients experiencing high levels of psychological distress before CABG surgery benefited from a structured informational and psychological HBIP. Implementation of psychological screens of patients scheduled for CABG might serve to identify patients experiencing anxiety and/or depression. These patients could then be targeted to receive individualized HBIP.     

SIESTA - Home sleep study with BresoDx for obstructive sleep apnea: a randomized controlled trial

Study objectivesThe objectives of this study were to evaluate (1) the accuracy of the clinical diagnosis of obstructive sleep apnea (OSA) informed by the home sleep study with a Type 4 portable monitor BresoDx® versus Type 1 polysomnography (PSG); and (2) agreement of the apnea-hypopnea index (AHI) compared between BresoDx and PSG.Material and methodsThis was a randomized, parallel, multicentre, single-blind, pragmatic controlled trial enrolling adults referred to three Ontario sleep clinics for suspected OSA. Participants were randomized to BresoDx followed by PSG (one-night apart) or PSG followed by BresoDx sleep testing sequence arms. The primary outcomes included the accuracy of clinical diagnosis and OSA severity measured by AHI between tests.ResultsIn sum, 233 participants completed both sleep studies and 206 completed physician consultation visits. The agreement between clinical diagnosis informed by PSG versus BresoDx was fair (Cohen's kappa coefficient = 0.28). The sensitivity of BresoDx-informed clinical diagnosis against PSG was between 0.86 and 0.89, and the specificity between 0.38 and 0.44. For AHI cut-off of ≥5 events/hour the sensitivity, specificity and positive and negative predictive values were 0.85, 0.48, 0.81 and 0.54.ConclusionsHome sleep apnea testing with BresoDx can be used in a referral population with a high pretest probability of OSA similar to other Type IV devices. This study complements the existing body of evidence suggesting that home testing with portable devices plays a valuable role for diagnosing of OSA in a variety of settings.SIESTA trial registrationwww.clinicaltrials.gov (Identifier: NCT02003729).     

Evaluation of brief interventions for managing depression and anxiety symptoms during early discharge period after stroke: a pilot randomized controlled trial

Abstract

Background:

Prevalence estimates for depression and anxiety in individuals post-stroke are approximately 33 and 29%, yet there are few effective preventive interventions. Interventions which commence pre-discharge and continue during the early post-discharge period may support individuals during the critical transition to home adjustment period. This study aimed to evaluate the efficacy of a self-management intervention and a coping skills intervention, compared to usual care, on anxiety and depression post-stroke.

Methods:

A pilot, three-arm randomized trial involving 33 stroke patients (coping skills: n?=?11, self-management: n?=?12, usual care: n?=?10) recruited from an Australian stroke unit. Both interventions were eight 1-hour weekly sessions, with the first two pre-discharge and the remainder at home; targeted both anxiety and depression; and tailored content to individuals. Primary outcome was severity of depressive and anxiety symptoms (measured using Montgomery andÅsberg Depression Rating Scale and Hospital Anxiety and Depression Scale). Secondary measures were: self-efficacy, stroke knowledge, basic and extended activities of daily living, and quality of life. Outcome measures were administered at baseline, one week post-intervention, and at a three month follow-up by a blinded assessor.

Results:

Thirty (91%) participants completed the trial. Immediately post-intervention there was a small improvement in stroke knowledge and a small increase in depression symptoms (on one of the two measures of depression symptoms) in the coping skills group compared to usual care. These differences did not remain significant at the 3-month follow-up, nor were there any other significant differences.

Conclusion:

Neither a coping skills nor self-management intervention reduced anxiety nor depression symptoms early post-stroke more than usual care. Lack of statistical power may have contributed to the non-significant findings in this pilot study.     

A randomized clinical trial to evaluate home-based assessment of people over 75 years old

IntroductionThere is an unmet need for effective methods for conducting dementia prevention trials.MethodsHome-based assessment study compared feasibility and efficiency, ability to capture change over time using in-home instruments, and ability to predict cognitive conversion using predefined triggers in a randomized clinical trial in (1) mail-in questionnaire/live telephone interviews, (2) automated telephone/interactive voice recognition, and (3) internet-based computer Kiosk technologies. Primary endpoint was defined as cognitive conversion.ResultsAnalysis followed a modified intent-to-treat principle. Dropout rates were low and similar across technologies but participants in Kiosk were more likely to dropout earlier. Staff resources needed were higher in Kiosk. In-home instruments distinguished conversion and stable groups. Cognitively stable group showed improvement in cognitive measures. Triggering was associated with higher likelihood of conversion but statistically significant only in mail-in questionnaire/live telephone interviews.DiscussionRelatively low efficiency of internet-based assessment compared with testing by live-assessors has implications for internet-based recruitment and assessment efforts currently proposed for diverse populations.     

The effects of music listening and art production on negative mood: A randomized, controlled trial

A large literature now exists to examine the effects of music listening on negative mood. However, few studies both isolate music as the active ingredient in mood improvement and compare music to a placebo condition designed to reduce demand effects. In the present study, 60 adult participants recruited from the local community were randomly assigned to one of four conditions: music listening + art production (drawing), music listening + art sorting, no music + art production, or no music + art sorting. By giving participants in all four groups an “arts” task, we intended to equate expectations of improvement and thereby better rule out demand effects as a source of group differences. Self-report measures of negative mood were collected before and after the 10 min intervention period. Participants in the two music listening conditions showed greater mood enhancement compared to the two non-music conditions. However, there were no significant effects of the art conditions (production vs. sorting). These results document that music listening has specific efficacy in enhancing mood even when expectations of improvement are equated across groups.     

盐酸美金刚治疗阿尔茨海默病的多中心随机对照研究

目的 与盐酸多奈哌齐对照评价盐酸荚金刚片治疗阿尔茨海默病(AD)的有效性和安全性.方法 241例AD患者(MMSE评分3-24分)随机分为2组,采用双盲双模拟的方法,埘照组给予盐酸多奈哌齐10 mg/d,试验组给予盐酸美金刚20 mg/d,疗程24周,分别在基线、第4、12和24周进行随访.主要疗效指标为印象变化(CIBIC-Plus)、AD评估量表-认知部分(ADAS-cog)和日常生活能力(ADL)量表,次要疗效指标为神经精神症状问卷(NPI)和MMSE.结果 207例患者完成试验,盐酸美金刚组和盐酸多奈哌齐组治疗24周后各量表评分均较基线有显著改善.盐酸美金刚组与盐酸多奈哌齐组相比较,各量表的评分变化分别为:CIBIC-Plus评分:3.4±0.8、3.5±0.8;ADAS-cog评分:-4.7±5.8、-4.6±6.5;ADL评分:-2.4±6.7、-2.2±5.3;NPI评分:-5.8±9.0、-3.1±8.5;MMSE评分:1.7±3.1、1.8±2.8;差异均无统计学意义.不良事件发生率盐酸多奈哌齐组41.88%,盐酸美金刚组30.58%.结论 盐酸美金刚作为治疗AD的新药,町以改善AD患者的总体功能、认知障碍、日常生活能力和精神行为症状,疗效与盐酸多奈哌齐相当,且具有良好的安全性和耐受性.     

Factor mixture modeling of the Penn State Worry Questionnaire: Evidence for distinct classes of worry

Worry, the anticipation of future threat, is a common feature of anxiety and mood psychopathology. Considerable research has examined the latent structure of worry to determine whether this construct reflects a dimensional or taxonic structure. Recent taxometric investigations have provided support for a unidimensional structure of worry; however, the results of these studies are limited in that taxometric approaches are unable to assess for the presence of more than two classes of a given construct. Given the complex nature of worry, it is possible that worry may actually reflect a latent structure comprised of multiple classes that cannot be assessed through taxometric approaches. Thus, it is important to utilize newer statistical techniques, such as factor-mixture modeling (FMM), which allow for a more nuanced assessment of the latent structure of a given psychological construct. The aim of the current study was to examine the latent structure of worry using FMM. It was predicted that worry would reflect a three-class structure comprised of (1) a class of low, normative levels of worry, (2) a class of moderate, subclinical worry, and (3) a class of high, pervasive worry. The latent class structure of worry was assessed using FMM in a sample of 1337 participants recruited from the community through a research clinic. Results revealed a three-class structure of the PSWQ comprising low, moderate-high, and high classes of worry. We also provided convergent and discriminant validity of the worry classes by demonstrating that the high worry class was most associated with GAD and that the low worry class was the least associated with GAD. The clinical utility of the worry classes, including the creation of empirically based cut-scores, and the implications for future research are discussed.     

Mindfulness-based cognitive therapy for people with diabetes and emotional problems: Long-term follow-up findings from the DiaMind randomized controlled trial

Objective

The DiaMind trial showed beneficial immediate effects of mindfulness-based cognitive therapy (MBCT) on emotional distress, but not on diabetes distress and HbA_1c. The aim of the present report was to examine if the effects would be sustained after six month follow-up.

Methods

In the DiaMind trial, 139 outpatients with diabetes (type-I or type-II) and a lowered level of emotional well-being were randomized into MBCT (n = 70) or a waiting list with treatment as usual (TAU: n = 69). Primary outcomes were perceived stress, anxiety and depressive symptoms, and diabetes distress. Secondary outcomes were, among others, health status, and glycemic control (HbA_1c).

Results

Compared to TAU, MBCT showed sustained reductions at follow-up in perceived stress (p < .001, d = .76), anxiety (p < .001, assessed by HADS d = .83; assessed by POMS d = .92), and HADS depressive symptoms (p = .004, d = .51), but not POMS depressive symptoms when using Bonferroni correction for multiple testing (p = .016, d = .48). No significant between-group effect was found on diabetes distress and HbA_1c.

Conclusion

This study showed sustained benefits of MBCT six months after the intervention on emotional distress in people with diabetes and a lowered level of emotional well-being.

Trial registration

Dutch Trial Register NTR2145, http://www.trialregister.nl.     

Efficacy and tolerability of lamotrigine in Juvenile Myoclonic Epilepsy in adults: A prospective,unblinded randomized controlled trial

PurposeControlled randomized studies recommending the clinical use of lamotrigine in adult populations with the diagnosis of Juvenile Myoclonic Epilepsy are still lacking. To compare the efficacy and tolerability of lamotrigine versus valproate in adult patients with JME.MethodsThis was a prospective, randomized, controlled, pragmatic, long-term and open-label treatment trial. Patients were randomized to use valproate or lamotrigine. The primary end points of the study were: (1) time from randomization to treatment failure (withdrawal); (2) time from randomization to seizures remission. Secondary ending points were: (1) frequency of clinically important adverse events and (2) change in the QOLIE-31 after randomization. The definition of seizure remission was based on disappearance of all seizure types and EEG discharges.ResultsWe found that the time to withdraw treatment after randomization was not significantly different in lamotrigine and valproate groups. Long-term seizures freedom was equal in the both groups of the trial; only 8 (19.1%) patients randomized to lamotrigine and 6 (19.4%) randomized to valproate were not seizure free after 4 months of treatment. Between 17.03% (lamotrigine) and 35.3% (valproate) of patients reported adverse reactions at some point in the intention-to treat study (p = 0.07). All subscales of the QOLIE-31 questionnaire, except that related to side effects of medication, improved more than 5 points with respect to baseline period in both groupsConclusionLamotrigine is effective in adult patients with Juvenile Myoclonic Epilepsy and better tolerated than valproate, although the incidence of idiosyncratic reactions could be a cause of concern.     

Disorder-specific versus transdiagnostic and clinician-guided versus self-guided treatment for major depressive disorder and comorbid anxiety disorders: A randomized controlled trial

Disorder-specific cognitive behavior therapy (DS-CBT) is effective at treating major depressive disorder (MDD) while transdiagnostic CBT (TD-CBT) addresses both principal and comorbid disorders by targeting underlying and common symptoms. The relative benefits of these two models of therapy have not been determined. Participants with MDD (n = 290) were randomly allocated to receive an internet delivered TD-CBT or DS-CBT intervention delivered in either clinician-guided (CG-CBT) or self-guided (SG-CBT) formats. Large reductions in symptoms of MDD (Cohen’s d ≥ 1.44; avg. reduction ≥ 45%) and moderate-to-large reductions in symptoms of comorbid generalised anxiety disorder (Cohen’s d ≥ 1.08; avg. reduction ≥ 43%), social anxiety disorder (Cohen’s d ≥ 0.65; avg. reduction ≥ 29%) and panic disorder (Cohen’s d ≥ 0.45; avg. reduction ≥ 31%) were found. No marked or consistent differences were observed across the four conditions, highlighting the efficacy of different forms of CBT at treating MDD and comorbid disorders.     

Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results from a randomized controlled trial

Purpose:   To evaluate the efficacy and safety of lacosamide (200 and 400 mg/day) when added to one to three concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures.
Methods:   This multicenter, double-blind, placebo-controlled trial randomized patients (age 16–70 years) with partial-onset seizures with or without secondary generalization to placebo, lacosamide 200, or lacosamide 400 mg/day. The trial consisted of an 8-week baseline, a 4-week titration, and a 12-week maintenance period.
Results:   Four hundred eighty-five patients were randomized and received trial medication. Among these, 87% were taking two or more concomitant AEDs. Median percent reduction in seizure frequency per 28 days from baseline to maintenance period (intent-to-treat, ITT) was 20.5% for placebo, 35.3% for lacosamide 200 mg/day (p   =   0.02), and 36.4% for 400 mg/day (p   =   0.03). In the per protocol population, the reductions were 35.3% for lacosamide 200 mg/day (p   =   0.04) and 44.9% for 400 mg/day (p   =   0.01) compared to placebo (25.4%). The 50% responder rate for lacosamide 400 mg/day (40.5%) was significant (p   =   0.01) over placebo (25.8%), but was not for 200 mg/day (35.0%). In the per protocol population, the 50% responder rate for lacosamide 400 mg/day (46.3%) was significant (p   <   0.01) compared with the placebo responder rate (27.5%). Dose-related adverse events (AEs) included dizziness, nausea, and vomiting. Clinically relevant changes in the mean plasma concentrations of commonly used AEDs were not observed.
Discussion:   Results of this trial demonstrated the efficacy and tolerability of adjunctive lacosamide 200 and 400 mg/day and support that lacosamide may be an advantageous option for the treatment of partial-onset seizures in patients with epilepsy.     

Pilot efficacy and tolerability: a randomized, placebo-controlled trial of levetiracetam for essential tremor.

The purpose of this pilot single-site study was to assess efficacy and safety of levetiracetam for essential tremor, using a placebo-controlled, double-blind, randomized crossover design with an interim analysis planned after completion of the first 10 to 15 subjects. The study was designed to detect a mean 30% reduction in composite tremor score, comparable to that of primidone or propranolol, which can be demonstrated with 30 or fewer subjects. Each treatment arm included baseline tremor assessments, a 4-week medication titration, 2 weeks of stable dose, and treatment tremor assessments. Levetiracetam was titrated to 3,000 mg/day or to a lower maximal tolerated dose. The median age was 72 years, with 28 years median tremor duration. There was no statistically significant difference in response between placebo and levetiracetam on any tremor rating scale or accelerometry measure. The 95% confidence interval for the true mean difference between placebo and levetiracetam treatments was +18.5 to -22.5%, which excludes the minimum 30% drop required to consider levetiracetam clinically effective to a degree comparable to primidone or propranolol. Whether levetiracetam has lesser-degree antitremor efficacy was not addressed in this pilot study.     

Design considerations for a multicenter randomized controlled trial of early surgery for mesial temporal lobe epilepsy

Purpose: To describe the trial design for the multicenter Early Randomized Surgical Epilepsy Trial (ERSET). Patients with pharmacoresistant epilepsy are generally referred for surgical treatment an average of two decades after onset of seizures, often too late to avoid irreversible disability. ERSET was designed to assess the safety and efficacy of early surgical intervention compared to continued pharmacotherapy. Methods: ERSET is a randomized controlled, parallel group clinical trial with blinded outcome adjudication. Participants are patients with mesial temporal lobe epilepsy (MTLE) older than the age of 12 who have had pharmacoresistant seizures for not >2 years and are determined by detailed evaluation to be surgical candidates prior to randomization. The primary outcome measure is seizure freedom in the second year of a 2‐year follow‐up period. Health‐related quality of life (HRQOL), neurocognitive function, ancillary outcomes, and adverse events were also measured. Results: Significant methodologic problems addressed by the study design included the following: recruitment of participants early in the course of epilepsy; establishment of operational definitions for “pharmacoresistant” and “early”; and standardization of diagnostic testing, medical treatment, and surgical interventions across multiple centers. Discussion: Rigorous trial designs to assess surgical interventions in epilepsy are necessary to provide evidence to guide treatment. This article is the first of a series; trial results will be reported in subsequent publications.     

Variability of stroke patients meeting endovascular stroke trial criteria in a non-clinical trial setting

Background

Five randomized trials proving the efficacy and safety of mechanical embolectomy for ischemic stroke within 8 hours used differing radiological methods to select patients. We aimed to evaluate the proportion of patients in clinical practice that would meet radiological criteria for inclusion in these trials.