Virtual reality cognitive-behavioural therapy versus cognitive-behavioural therapy for paranoid delusions: a study protocol for a single-blind multi-Centre randomised controlled superiority trial.

BACKGROUND: Seventy per cent of patients with psychotic disorders has paranoid delusions. Paranoid delusions are associated with significant distress, hospital admission and social isolation. Cognitive-behavioural therapy for psychosis (CBTp) is the primary psychological treatment, but the median effect size is only small to medium. Virtual reality (VR) has a great potential to improve the effectiveness of CBTp. In a previous study, we found that VR based CBT (VRcbt) for paranoid delusions is superior to waiting list. As a next step, a direct comparison with CBTp is needed. The present study aims to investigate whether VRcbt is more effective and cost-effective than regular CBTp in treating paranoid delusions and improving daily life social functioning of patients with psychotic disorders. METHODS: A total of 106 patients with DSM-5 diagnosis of psychotic disorder and at least moderate level of paranoid ideations will be recruited for this multicentre randomized controlled trial (RCT). Patients will be randomized to either VRcbt or standard CBTp for paranoid delusions. VRcbt consists of maximum 16 sessions in virtual social situations that trigger paranoid ideations and distress, delivered in an 8-12 week time frame. Standard CBTp also consists of maximum 16 sessions including exposure and behavioural experiments, delivered in an 8-12 week time frame. The two groups will be compared at baseline, post-treatment and six months follow-up. Primary outcome is the level of paranoid ideations in daily life social situations, measured with ecological momentary assessments (EMA) at semi-random moments ten times a day during seven days, before and after treatment. Every session, participants and therapists will rate the level of paranoid ideation and global clinical impression. DISCUSSION: Comparison of VRcbt and CBTp will provide information about the relative (cost-) effectiveness of VRcbt for this population. VRcbt may become a preferred psychological treatment for paranoid delusions and social anxiety in patients with psychotic disorder. TRIAL REGISTRATION: Netherlands Trial Register, NL7758. Registered on 23 May 2019.

Self-esteem treatment in anxiety: A randomized controlled crossover trial of Eye Movement Desensitization and Reprocessing (EMDR) versus Competitive Memory Training (COMET) in patients with anxiety disorders.

BACKGROUND AND PURPOSE: Little is known about treating low self-esteem in anxiety disorders. This study evaluated two treatments targeting different mechanisms: (1) Eye Movement Desensitization and Reprocessing (EMDR), which aims to desensitize negative memory representations that are proposed to maintain low self-esteem; and (2) Competitive Memory Training (COMET), which aims to activate positive representations for enhancing self-esteem. METHODS: A Randomized Controlled Trial (RCT) was used with a crossover design. Group 1 received six sessions EMDR first and then six sessions COMET; group 2 vice versa. Assessments were made at baseline (T0), end of first treatment (T1), and end of second treatment (T2). Main outcome was self-esteem. We included 47 patients and performed Linear Mixed Models. RESULTS: COMET showed more improvements in self-esteem than EMDR: effect-sizes 1.25 versus 0.46 post-treatment. Unexpectedly, when EMDR was given first, subsequent effects of COMET were significantly reduced in comparison to COMET as the first intervention. For EMDR, sequence made no difference. Reductions in anxiety and depression were mediated by better self-esteem. CONCLUSIONS: COMET was associated with significantly greater improvements in self-esteem than EMDR in patients with anxiety disorders. EMDR treatment reduced the effectiveness of subsequent COMET. Improved self-esteem mediated reductions in anxiety and depression symptoms.

Metacognitive training for schizophrenia spectrum patients: a meta-analysis on outcome studies.

BACKGROUND: Metacognitive training (MCT) for schizophrenia spectrum is widely implemented. It is timely to systematically review the literature and to conduct a meta-analysis. METHOD: Eligible studies were selected from several sources (databases and expert suggestions). Criteria included comparative studies with a MCT condition measuring positive symptoms and/or delusions and/or data-gathering bias. Three meta-analyses were conducted on data gathering (three studies; 219 participants), delusions (seven studies; 500 participants) and positive symptoms (nine studies; 436 participants). Hedges' g is reported as the effect size of interest. Statistical power was sufficient to detect small to moderate effects. RESULTS: All analyses yielded small non-significant effect sizes (0.26 for positive symptoms; 0.22 for delusions; 0.31 for data-gathering bias). Corrections for publication bias further reduced the effect sizes to 0.21 for positive symptoms and to 0.03 for delusions. In blinded studies, the corrected effect sizes were 0.22 for positive symptoms and 0.03 for delusions. In studies using proper intention-to-treat statistics the effect sizes were 0.10 for positive symptoms and -0.02 for delusions. The moderate to high heterogeneity in most analyses suggests that processes other than MCT alone have an impact on the results. CONCLUSIONS: The studies so far do not support a positive effect for MCT on positive symptoms, delusions and data gathering. The methodology of most studies was poor and sensitivity analyses to control for methodological flaws reduced the effect sizes considerably. More rigorous research would be helpful in order to create enough statistical power to detect small effect sizes and to reduce heterogeneity. Limitations and strengths are discussed.

Adapted cognitive-behavioural therapy required for targeting negative symptoms in schizophrenia: meta-analysis and meta-regression.

BACKGROUND: There is an increasing interest in cognitive-behavioural therapy (CBT) interventions targeting negative symptoms in schizophrenia. To date, CBT trials primarily focused on positive symptoms and investigated change in negative symptoms only as a secondary outcome. To enhance insight into factors contributing to improvement of negative symptoms, and to identify subgroups of patients that may benefit most from CBT directed at ameliorating negative symptoms, we reviewed all available evidence on these outcomes. METHOD: A systematic search of the literature was conducted in PsychInfo, PubMed and the Cochrane register to identify randomized controlled trials reporting on the impact of CBT interventions on negative symptoms in schizophrenia. Random-effects meta-analyses were performed on end-of-treatment, short-term and long-term changes in negative symptoms. RESULTS: A total of 35 publications covering 30 trials in 2312 patients, published between 1993 and 2013, were included. Our results showed studies' pooled effect on symptom alleviation to be small [Hedges' g = 0.093, 95% confidence interval (CI) -0.028 to 0.214, p = 0.130] and heterogeneous (Q = 73.067, degrees of freedom = 29, p < 0.001, τ 2 = 0.081, I 2 = 60.31) in studies with negative symptoms as a secondary outcome. Similar results were found for studies focused on negative symptom reduction (Hedges' g = 0.157, 95% CI -0.10 to 0.409, p = 0.225). Meta-regression revealed that stronger treatment effects were associated with earlier year of publication, lower study quality and with CBT provided individually (as compared with group-based). CONCLUSIONS: The co-occurring beneficial effect of conventional CBT on negative symptoms found in older studies was not supported by more recent studies. It is now necessary to further disentangle effective treatment ingredients of older studies in order to guide the development of future CBT interventions aimed at negative symptom reduction.

[Imagery in psychosis: EMDR as a new intervention in the treatment of delusions and auditory hallucinations]. / Mentale beelden bij psychose: EMDR als een nieuwe interventie bij het behandelen van stemmen en wanen.

BACKGROUND: Historically, psychotherapy has focused on the treatment of patients' verbal representations (thoughts) and has proved particularly successful in the cognitive behavioural treatment of psychosis. However, there is mounting evidence that visual representations (imagery) play an important role in the onset and maintenance of psychiatric disorders, including psychotic symptoms. There are indications that heightened emotionality and vividness of visual representations are associated with severity of psychotic experiences. This may imply that a reduction in the vividness and emotionality of the psychosis-related imagery can lessen the suffering and stress, caused by the the psychotic symptoms. AIM: To introduce EMDR as a possible type of psychological treatment for patients suffering from psychosis-related imagery. METHOD: Three outpatients who had a psychotic disorder and suffered from auditory hallucinations and delusions were treated with EMDR in an average of six sessions. Treatment was performed by three therapists in different psychiatric institutions. All three were experienced in administrating CBT and EMDR. RESULTS: Treatment with EMDR reduced patients' level of anxiety, depression and the severity of psychotic symptoms. In addition, patients reported less avoidant behaviour and greater cognitive insight. CONCLUSION: The results of the study suggest that EMDR reduces the vividness and emotionality of imagery in psychosis which in turn alleviates the patients' psychotic symptoms. Further research into other possible types of interventions for the treatment of imagery in psychosis is recommended.

Changes in motivation for treatment in precontemplating dually diagnosed patients receiving assertive community treatment.

In a population of dually diagnosed patients receiving assertive community treatment we used the theoretical framework of the transtheoretical model to establish (a) the proportions and characteristics of patients who were not motivated for treatment for psychiatric symptoms and substance use, (b) the proportion of patients who moved towards behavioral change after about 1 year, and examine how this change was related with clinical outcome; and (c) the sequence of change processes. Chi square tests and T tests were used to compare the patient characteristics and outcomes of patients who remained in precontemplation with those who progressed. During follow-up, 47 % of the patients came out of the precontemplation phase for treatment of psychiatric symptoms and 38 % for substance use behavior. Those who remained in precontemplation benefited less from treatment. Of those who did move forward, most appeared to become motivated for psychiatric treatment before becoming motivated to reduce substance use.

The effects of assertive community treatment including integrated dual diagnosis treatment on nuisance acts and crimes in dual-diagnosis patients.

We investigated whether Assertive Community Treatment (ACT) combined with Integrated Dual Diagnosis Treatment (IDDT) is associated with a decrease in nuisance acts and crime convictions in dual-diagnosis repeated offenders. Forty-three patients were monitored from 21 months before until 12 months after the start of ACT-IDDT, using police data and the Health of the Nation Outcome Scales (HoNOS). Results show that while nuisance acts and convictions increased in the 21 months before the start of ACT-IDDT, nuisance acts decreased and convictions stabilized during the next 12 months. The decrease in nuisance acts was associated with a decrease in substance abuse.

Does Treatment Adherence Therapy reduce expense of healthcare use in patients with psychotic disorders? Cost-minimization analysis in a randomized controlled trial.

BACKGROUND: Adherence interventions in psychotic disorders have produced mixed results. Even when an intervention improved adherence, benefits to patients were unclear. Treatment Adherence Therapy (TAT) also improved adherence relative to Treatment As Usual (TAU), but it had no effects on symptoms or quality of life. TAT may or may not reduce healthcare costs. AIM: To determine whether TAT reduces the use of healthcare resources, and thus healthcare costs. METHOD: Randomized controlled trial of TAT versus TAU with 98 patients. Interviews were conducted at baseline (T0), six months later, when TAT had been completed (T1) and at six-month follow-up (T2). We have used admission data and part of the Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness (TiC-P). We compared total costs in the TAT group with those in the control group with the help of multivariate analysis of covariance. RESULTS: TAT did not significantly minimize total costs. In the TAT group, the mean one-year health-treatment cost per patient (including TAT sessions) was € 23 003.64 (SD=19 317.95), whereas in the TAU group it was € 22 489.88 (SD=25 224.57) (F(1)=.652, p=.42). However, there were two significant differences at item-level, both with higher costs for the TAU group: psychiatric nurse contacts and legal proceedings for court-ordered admissions. CONCLUSIONS: Because TAT did not reduce total healthcare costs, it did not contribute to cost-minimization. Its benefits are therefore questionable. No other adherence intervention has included analysis of cost-effectiveness or cost-minimization.

Treatment adherence therapy in people with psychotic disorders: randomised controlled trial.

BACKGROUND: Interventions to improve adherence to treatment in people with psychotic disorders have produced inconclusive results. We developed a new treatment, treatment adherence therapy (TAT), whose intervention modules are tailored to the reasons for an individual's non-adherence. AIMS: To examine the effectiveness of TAT with regard to service engagement and medication adherence in out-patients with psychotic disorders who engage poorly. METHOD: Randomised controlled study of TAT v. treatment as usual (TAU) in 109 out-patients. Most outcome measurements were performed by masked assessors. We used intention-to-treat multivariate analyses (Dutch Trial Registry: NTR1159). RESULTS: Treatment adherence therapy v. TAU significantly benefited service engagement (Cohen's d = 0.48) and medication adherence (Cohen's d = 0.43). Results remained significant at 6-month follow-up for medication adherence. Near-significant effects were also found regarding involuntary readmissions (1.9% v. 11.8%, P = 0.053). Symptoms and quality of life did not improve. CONCLUSIONS: Treatment adherence therapy helps improve engagement and adherence, and may prevent involuntary admission.

Involuntary admission may support treatment outcome and motivation in patients receiving assertive community treatment.

OBJECTIVE: Patients with severe mental illness who are treated in assertive community treatment (ACT) teams are sometimes involuntarily admitted when they are dangerous to themselves or others, and are not motivated for treatment. However, the consequences of involuntary admission in terms of psychosocial outcome and treatment motivation are largely unknown. We hypothesized that involuntary admission would improve psychosocial outcome and not adversely affect their treatment motivation. METHODS: In the context of routine 6-monthly outcome monitoring in the period January 2003-March 2008, we used the Health of the Nation Outcome Scales (HoNOS) and a motivation-for-treatment scale to assess 260 severely mentally ill patients at risk for involuntary admission. Mixed models with repeated measures were used for data analyses. RESULTS: During the observation period, 77 patients (30%) were involuntarily admitted. Relative to patients who were not involuntarily admitted, these patients improved significantly in HoNOS total scores (F = 17,815, df = 1, p < 0.001) and in motivation for treatment (F = 28.139, df = 1, p < 0.001). Patients who were not involuntarily admitted had better HoNOS and motivation scores at baseline, but did not improve. CONCLUSIONS: Involuntary admission in the context of ACT was associated with improvements in psychosocial outcome and motivation for treatment. There are no indications that involuntary admission leads to deterioration in psychosocial outcome or worsening of motivation for treatment.

Stigma moderates the associations of insight with depressed mood, low self-esteem, and low quality of life in patients with schizophrenia spectrum disorders.

BACKGROUND: Good insight into illness in patients with schizophrenia is related not only to medication compliance and high service engagement, but also to depression, low self-esteem, and low quality of life. The detrimental effects of insight pose a problem for treatment. AIM: To investigate whether the negative associations of good insight are moderated by perceived stigma. METHOD: Respondents were 114 patients with schizophrenia spectrum disorders. We used Analyses of Variance (ANOVA) and Structural Equation Modeling (SEM) to test moderation. RESULTS: Good insight was associated with high service engagement and high compliance. Also, good insight was associated with depressed mood, low quality of life, and negative self-esteem. This association was strong when stigma was high and weak when stigma was low. SEM showed that the constrained model performed significantly worse than the unconstrained model, in which detrimental associations of insight were free to vary across stigma groups (chi(2)=19.082; df=3; p<.001). CONCLUSIONS: Our results suggest that the associations of insight with depression, low quality of life, and negative self-esteem are moderated by stigma. Patients with good insight who do not perceive much stigmatization seem to be best off across various outcome parameters. Those with poor insight have problems with service engagement and medication compliance. Patients with good insight accompanied by stigmatizing beliefs have the highest risk of experiencing low quality of life, negative self-esteem, and depressed mood. A clinical implication is that when it is attempted to increase insight, perceived stigma should also be addressed.

Fewer symptoms vs. more side-effects in schizophrenia? Opposing pathways between antipsychotic medication compliance and quality of life.

BACKGROUND: Non-compliance with medication often has long-term detrimental effects in patients with schizophrenia. However, when patients are compliant, it is not certain whether they experience short-term improved quality of life. By simultaneously reducing symptoms and increasing side-effects, compliance with antipsychotics may have opposing effects on a patient's perceived quality of life. AIM: This study aimed to identify any clinical-empirical evidence for two pathways between compliance and quality of life. METHOD: To evaluate various pathways between compliance (Service Engagement Scale plus a one-item rating), psychotic symptoms (Positive and Negative Syndromes Scale), adverse medication effects (Subjective Wellbeing under Neuroleptics scale), and quality of life (EQ-5D), we used Structural Equation Modeling on cross-sectional data of 114 patients with a psychotic disorder. RESULTS: Compliance was not directly related to quality of life (r=0.004). The best-fitting model (chi(2)=1.08; df=1) indicated that high compliance was associated with fewer psychotic symptoms (beta=-0.23) and more adverse medication effects (beta=0.22). Symptoms (beta=-0.17) and adverse medication effects (beta=-0.48) were both related to lower quality of life. DISCUSSION: Our results suggest that compliance with antipsychotics has two opposing pathways towards quality of life, albeit indirect ones. While compliance was associated with less severe psychotic symptoms, and was thus related to higher quality of life, it was also associated with more adverse medication effects, and was thus related to lower quality of life. However, due to our study design, we cannot draw firm conclusions on causality. Two possible clinical implications of the results for compliance and interventions are discussed.