Internet-Delivered Cognitive Behavioral Therapy for Anxiety Disorders in Open Community Versus Clinical Service Recruitment: Meta-Analysis.

BACKGROUND: Ample studies have shown the effectiveness of internet-delivered cognitive behavioral therapy (iCBT) for anxiety disorders. These studies recruited their participants mainly from the community and, to a lesser extent, from within routine care services. Little is known about whether different recruitment strategies lead to different treatment effects. OBJECTIVE: This meta-analysis compared clinical results obtained in trials with recruitment from the community versus results obtained in trials with clinical service recruitment and explored factors that may mediate differences in treatment outcome. METHODS: We included randomized controlled trials in which the clinical effects of iCBT for anxiety disorders were compared with a control condition (waitlist controls or face-to-face cognitive behavioral therapy). We classified trials as open recruitment trials (recruitment from the community) or clinical service recruitment trials (recruitment through outpatient clinics). Pooled effect sizes based on measures examining anxiety symptoms, depressive symptoms, and quality of life were computed for each type of trial. Subgroup analyses examined whether clinical results from open recruitment trials differed from those obtained in clinical service recruitment trials. Additional analyses explored which demographic, clinical, and treatment-related factors contributed to differences in effect sizes of open recruitment versus clinical service recruitment trials. RESULTS: We included 42 studies with 53 comparisons (43 open recruitment comparisons and 10 clinical recruitment comparisons). Analyses of anxiety measures revealed, first, that iCBT open recruitment studies with waitlist control comparators showed a significantly higher effect size for decrease in anxiety symptoms than did those with clinical recruitment (Q=10.09; P=.001). This association between recruitment method and effect size was no longer significant in a multivariate metaregression with treatment adherence and exclusion of patients with depressive symptoms entered as additional predictors of effect size. Second, effect size for decrease in anxiety symptoms did not differ significantly between clinical recruitment and open recruitment studies with face-to-face cognitive behavioral therapy comparators. The effects of open recruitment trials and clinical recruitment trials did not differ significantly for the secondary outcomes, compared with face-to-face cognitive behavioral therapy and waitlist controls. CONCLUSIONS: iCBT was effective in samples recruited in clinical practice, but effect sizes were smaller than those found in trials with an open recruitment method for studies with waitlist control comparators. Hence, for patients with anxiety disorders in routine care, the impact of iCBT may not be as positive as for study participants recruited from the community. The difference between open recruitment trials and clinical service recruitment trials might be partly explained by patients' greater therapy adherence in open recruitment trials and the stricter exclusion of patients with severe depressive symptoms in these studies. Since most trials in this meta-analysis applied an open recruitment method, more studies with routine care populations are needed to further validate these findings.

Cost-effectiveness of blended vs. face-to-face cognitive behavioural therapy for severe anxiety disorders: study protocol of a randomized controlled trial.

BACKGROUND: Anxiety disorders are among the most prevalent psychiatric conditions, and are associated with poor quality of life and substantial economic burden. Cognitive behavioural therapy is an effective treatment to reduce anxiety symptoms, but is also costly and labour intensive. Cost-effectiveness could possibly be improved by delivering cognitive behavioural therapy in a blended format, where face-to-face sessions are partially replaced by online sessions. The aim of this trial is to determine the cost-effectiveness of blended cognitive behavioural therapy for adults with anxiety disorders, i.e. panic disorder, social phobia or generalized anxiety disorder, in specialized mental health care settings compared to face-to-face cognitive behavioural therapy. In this paper, we present the study protocol. It is hypothesized that blended cognitive behavioural therapy for anxiety disorders is clinically as effective as face-to-face cognitive behavioural therapy, but that intervention costs may be reduced. We thus hypothesize that blended cognitive behavioural therapy is more cost-effective than face-to-face cognitive behavioural therapy. METHODS/DESIGN: In a randomised controlled equivalence trial 156 patients will be included (n = 78 in blended cognitive behavioural therapy, n = 78 in face-to-face cognitive behavioural therapy) based on a power of 0.80, calculated by using a formula to estimate the power of a cost-effectiveness analysis: [Formula: see text]. Measurements will take place at baseline, midway treatment (7 weeks), immediately after treatment (15 weeks) and 12-month follow-up. At baseline a diagnostic interview will be administered. Primary clinical outcomes are changes in anxiety symptom severity as measured with the Beck Anxiety Inventory. An incremental cost-effectiveness ratio will be calculated to obtain the costs per quality-adjusted life years (QALYs) measured by the EQ-5D (5-level version). Health-economic outcomes will be explored from a societal and health care perspective. DISCUSSION: This trial will be one of the first to provide information on the cost-effectiveness of blended cognitive behavioural therapy for anxiety disorders in routine specialized mental health care settings, both from a societal and a health care perspective. TRIAL REGISTRATION: Netherlands Trial Register NTR4912. Registered 13 November 2014.

Movement disorders in nonpsychotic siblings of patients with nonaffective psychosis.

Movement disorders such as dyskinesia and Parkinsonism have frequently been reported in (drug-naïve) patients with nonaffective psychosis. Therefore movement disorders may be related to schizophrenia. Siblings of patients with nonaffective psychosis also appear to have subtle forms of movement disorders. This suggests that motor abnormalities may also be related to the risk of developing the disease. Subtle forms are not always detected with the use of the standard observation-based clinical rating scales, which are less sensitive than mechanical instrument measurement. This study compared the presence and severity of dyskinesia and Parkinsonism in 42 non-psychotic siblings of patients with nonaffective psychosis and in 38 controls as measured by mechanical instruments and clinical rating scales. There were no significant differences in movement disorders between siblings and controls on the basis of clinical assessments. However, mechanical measurements indicated that siblings compared to controls displayed significantly more dyskinesia and Parkinsonism signs. These results suggest that motor signs could be markers of vulnerability for psychosis or schizophrenia. In addition this study shows that mechanical instrument measurement of movement disorders is more sensitive than assessment with clinical rating scales. Therefore, it may be used in screening programs for populations at risk for psychosis.

Does it blend? Exploring therapist fidelity in blended CBT for anxiety disorders.

Blended cognitive-behavioural therapy (bCBT) combines face-to-face CBT (FtFCBT) and Internet-based CBT (iCBT) into one integrated treatment protocol, opening up new ways to deliver therapy, increase cost-effectiveness and resolve scarcity of therapist availability. When traditional therapy is transformed into a new format, there is a need to evaluate whether principles of the new protocol are consistently applied. This study aimed to explore therapist fidelity to bCBT protocols for anxiety disorders in specialised mental health care and to assess whether fidelity is related to patient characteristics. Adult patients (N = 44) received bCBT within a randomised controlled trial. Ratio of FtF to online sessions, session frequency and therapist adherence to instructions were assessed. Overall therapist fidelity with regard to ratio of blending, session frequency and instructions was high. Correlations were found between patients' share of online sessions and both session frequency (r = 0.373, p = .013), as well as patient computer experience (r = 0.314, p = .038). Adherence to instructions in FtF sessions was based on a subset of patients (n = 23) and should therefore be interpreted with caution. The blended approach was generally delivered as intended, indicating that the format is feasible in specialised mental health.

Acceptability, effectiveness and cost-effectiveness of blended cognitive-behavioural therapy (bCBT) versus face-to-face CBT (ftfCBT) for anxiety disorders in specialised mental health care: A 15-week randomised controlled trial with 1-year follow-up.

BACKGROUND: Anxiety disorders are highly prevalent and cause substantial economic burden. Blended cognitive-behavioural therapy (bCBT), which integrates Internet-based CBT and face-to-face CBT (ftfCBT), is an attractive and potentially cost-saving treatment alternative to conventional CBT for patients with anxiety disorders in specialised mental health care. However, little is known about the effectiveness of bCBT in routine care. We examined the acceptability, effectiveness and cost-effectiveness of bCBT versus ftfCBT in outpatient specialised care to patients with panic disorder, social anxiety disorder and generalised anxiety disorder. METHODS AND FINDINGS: Patients with anxiety disorders were randomised to bCBT (n = 52) or ftfCBT (n = 62). Acceptability of bCBT and ftfCBT were evaluated by assessing treatment preference, adherence, satisfaction and therapeutic alliance. Costs and effects were assessed at post-treatment and one-year follow-up. Primary outcome measure was the Beck Anxiety Inventory (BAI). Secondary outcomes were depressive symptoms, general psychopathology, work and social adjustment, quality of life and mastery. Incremental cost-effectiveness ratios (ICERs) were computed from societal and healthcare perspectives by calculating the incremental costs per incremental quality-adjusted life year (QALY). No significant differences between bCBT and ftfCBT were found on acceptability or effectiveness measures at post-treatment (Cohen's d between-group effect size on BAI = 0.15, 95% CI -0.30 to 0.60) or at one-year follow-up (d = -0.38, 95% CI -0.84 to 0.09). The modelled point estimates of societal costs (bCBT €10945, ftfCBT €10937) were higher and modelled point estimates of direct medical costs (bCBT €3748, ftfCBT €3841) were lower in bCBT. The acceptability curves showed that bCBT was expected to be a cost-effective intervention. Results should be carefully interpreted due to the small sample size. CONCLUSIONS: bCBT appears an acceptable, clinically effective and potentially cost-saving alternative option for treating patients with anxiety disorders. Trials with larger samples are needed to further investigate cost-effectiveness. TRIAL REGISTRATION: Netherlands Trial Register: NTR4912.

Haloperidol 2 mg impairs inhibition but not visuospatial attention.

RATIONALE: The dopaminergic system has been implicated in visuospatial attention and inhibition, but the exact role has yet to be elucidated. Scarce literature suggests that attenuation of dopaminergic neurotransmission negatively affects attentional focusing and inhibition. To the best of our knowledge, this is the first study that evaluated the effect of dopaminergic antagonism on stopping performance. METHODS: Dopaminergic neurotransmission was attenuated in 28 healthy male participants by using 2 mg haloperidol. A repeated-measures placebo-controlled crossover design was implemented, and performance indices of attention and inhibition were assessed in the visual spatial cueing task (VSC) and stop signal task (SST). Additionally, the effect of haloperidol on motoric parameters was assessed. It was expected that haloperidol as contrasted to placebo would result in a reduction of the "validity effect," the benefit of valid cueing as opposed to invalid cueing of a target in terms of reaction time. Furthermore, an increase in stop signal reaction time (SSRT) in the SST was expected. RESULTS AND CONCLUSION: Results partially confirmed the hypothesis. Haloperidol negatively affected inhibitory motor control in the SST as indexed by SSRT, but there were no indications that haloperidol affected bias or disengagement in the VSC task as indicated by a lack of an effect on RTs. Pertaining to secondary parameters, motor activity increased significantly under haloperidol. Haloperidol negatively affected reaction time variability and errors in both tasks, as well as omissions in the SST, indicating a decreased sustained attention, an increase in premature responses, and an increase in lapses of attention, respectively.

Instrumental measurements of spontaneous dyskinesia and schizotypy in subjects with auditory verbal hallucinations and healthy controls.

Spontaneous dyskinesia is associated with non-affective psychosis. Few studies investigated dyskinesia in individuals with subclinical psychotic experiences. We examined dyskinesia using instrumental measurements of force variability in 34 individuals with frequent auditory verbal hallucinations but without a clinical psychotic disorder and 31 matched healthy controls. Schizotypy was assessed using the Schizotypal Personality Questionnaire. We found a positive correlation between dyskinesia and schizotypy in the total group. In addition, when using a cut-off point based on the 95th percentile of force variability in the control group, we found a greater proportion of subjects with dyskinesia in the group with auditory verbal hallucinations than in the control subjects. Current findings are in agreement with the concept of psychosis as a continuous phenomenon and with movement disorders being an integral part of psychosis.

Association of two DRD2 gene polymorphisms with acute and tardive antipsychotic-induced movement disorders in young Caucasian patients.

RATIONALE: Pharmacogenetic studies on antipsychotic-induced movement disorders (MD) in schizophrenia so far have focused mainly on tardive dyskinesia. Only a few examined the more acute antipsychotic-induced MD such as parkinsonism and akathisia. Notably, all MD relate to deregulation of the dopamine system. OBJECTIVE: This study aimed to replicate previously reported associations in candidate genes for acute and tardive antipsychotic-induced MD in a young Caucasian sample. METHODS: In 402 patients (median age 26 years), a total of 13 polymorphisms were genotyped in eight dopamine-related candidate genes selected a priori from the literature (regarding dopamine and serotonin receptors, dopamine degradation, and free radicals scavenging enzymes pathways). RESULTS: Patients with MD used on average a higher haloperidol dose equivalent when compared to those without MD. The prevalence of MD was high and did not differ between first- and second-generation antipsychotics. Significant associations were found between (a) the TaqI_D polymorphism and akathisia (OR = 2.3, p = 0.001 for each extra C-allele) and (b) the -141C polymorphism and tardive dyskinesia (OR = 0.20, p = 0.001 for each extra Del allele). The other polymorphisms were not significantly associated with an MD. CONCLUSIONS: Two associations were found between genetic variation TaqI_D and the -141C polymorphisms in the DRD2 gene and antipsychotic-induced MD; one with acute akathisia and one with tardive dyskinesia. These were previously reported to be associated with tardive dyskinesia and acute parkinsonism, respectively. These results suggest that the contribution of these DRD2 gene variants in the vulnerability of antipsychotic-induced MD takes place in a more general or pleiotropic way.

Dyskinesia and parkinsonism in antipsychotic-naive patients with schizophrenia, first-degree relatives and healthy controls: a meta-analysis.

BACKGROUND: Several studies have reported the presence of dyskinesia and parkinsonism in antipsychotic-naive patients with schizophrenia as well as in their first-degree relatives. These movement disorders may therefore form an integral part of the illness and its (genetic) liability. METHOD: A systematic search was conducted in the Medline, EMBASE, and PsychINFO databases to identify studies reporting on dyskinesia and parkinsonism assessed in antipsychotic-naive patients with schizophrenia (n = 213) and controls (n = 242) and separately in nonill first-degree relatives (n = 395) and controls (n = 379). Effect sizes were pooled using random-effect models to calculate odds ratios (ORs) to compare the risk of these movement disorders among patients and healthy relatives each with matched controls. RESULTS: Antipsychotic-naive schizophrenia was found to be strongly associated with dyskinesia (OR: 3.59, 95% confidence interval [CI]: 1.53-8.41) and parkinsonism (OR: 5.32, 95% CI: 1.75-16.23) compared with controls. Dyskinesia and parkinsonism were also significantly more prevalent in healthy first-degree relatives of patients with schizophrenia as compared with healthy controls (OR: 1.38, 95% CI: 1.06-1.81, and OR: 1.37, 95% CI: 1.05-1.79, respectively). CONCLUSION: The results suggest that movement disorders, and by inference abnormalities in the nigrostriatal pathway, are not only associated with schizophrenia itself but may also be related to the (genetic) risk of developing the disease.

Rapid detoxification from opioid dependence under general anaesthesia versus standard methadone tapering: abstinence rates and withdrawal distress experiences.

The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioid-dependents under general anaesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the Novadic addiction centre in St Oedenrode and St Joseph Hospital in Veghel, the Netherlands. Thirty opioid-dependent patients took part. Outcome measures included urine toxicology screening for opiates to determine abstinence and presence of objective and subjective opioid withdrawal distress symptoms. Statistically significant differences in abstinence rate between RD-GA and SMT were present after one (RD-GA 100% vs. SMT 40%, p < 0.01) and 2 months (RD-GA 93% vs. SMT 33%, p < 0.01). After 3 months the difference in abstinence was still substantial, but no longer statistically significant (RD-GA 67% vs. SMT 33%, p = 0.14). Objective and subjective withdrawal symptoms showed largely identical outcomes and were equally low in the two groups for those who remained in the study. There was a considerably higher percentage of abstinence in the RD-GA group after 1, 2 and 3 months of follow-up accompanied by relatively mild withdrawal symptoms of shorter duration. However, if one completes SMT the data suggest a greater chance of staying clean in the long term than those completing RD-GA.