Eye movement desensitization and reprocessing (EMDR) therapy or supportive counseling prior to exposure therapy in patients with panic disorder: study protocol for a multicenter randomized controlled trial (IMPROVE).

BACKGROUND: Exposure-based therapy is the treatment of choice for anxiety disorders, but many patients do not benefit sufficiently from it. Distressing images of threat related to the future or past may maintain the anxiety symptomatology or impede exposure therapy. An intervention that targets threat-related imagery is eye movement desensitization and reprocessing (EMDR) therapy. The main goal of this multicenter randomized controlled trial is to investigate whether EMDR therapy plus exposure therapy, relative to supportive counseling plus exposure therapy, improves treatment efficacy, tolerability, and adherence in patients with panic disorder. In addition, we will examine potential predictors of optimal treatment allocation, mechanisms of change as well as the long term effects of treatment. Finally, we will assess cost-effectiveness. METHODS: A multicenter randomized controlled trial mixed design will be conducted. Participants will be 50 patients, aged ≥ 18, diagnosed with a panic disorder. They will be randomly assigned to one of two conditions: EMDR therapy (i.e., flashforward strategy) or supportive counseling (each consisting of four weekly sessions of 90 min each) prior to exposure therapy (consisting of eight weekly sessions of 90 min each). Assessments will be made pre-treatment (T1), between-treatments (T2), post-treatment (T3), one month post-treatment (FU1) and six months post-treatment (FU2) by an assessor blind to treatment condition. The primary outcome measure is severity of panic-related symptoms. Secondary outcome measures are: tolerability of exposure therapy (initial avoidance, willingness to start exposure therapy, considered drop-out; no-show and drop-out), related symptomatology (generalized anxiety, depression), and functional impairment. DISCUSSION: The primary goals of this research are to compare the efficacy, tolerability, and adherence of EMDR therapy plus exposure therapy and supportive counseling plus exposure therapy and to identify predictors, moderators, and mediators for treatment success. This multi-center research aims to make a significant contribution to our understanding as to how treatment for patients with anxiety disorders can be optimized, and elucidate who can benefit most from this novel approach. TRIAL REGISTRATION: ISRCTN-ISRCTN29668369: Improving anxiety treatment by modifying emotional memories before real-life exposure. Registered 27 June 2022-retrospectively registered. ISRCTN-ISRCTN29668369.

The effect of multiple family therapy on mental health problems and family functioning: A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to provide an overview of existing controlled trials focusing on the impact of multiple family therapy (MFT) on mental health problems and family functioning, and to examine the efficacy of MFT. Relevant studies were selected following a screening of 3376 studies identified by a systematic search of seven databases. The following data were extracted: participant characteristics, program characteristics, study characteristics, and information of mental health problems and/or family functioning. A total of 31 peer-reviewed, English, controlled studies evaluating the effect of MFT were included in the systematic review. Sixteen studies presenting 16 trials were included in the meta-analysis. All but one of the studies was at risk of bias, with problems concerning confounding, selection of participants and missing data. The findings confirm that MFT is offered in diverse settings, with studies presenting a variety of therapeutic modalities, focal problems, and populations. Individual studies reported some positive findings, including improvements in mental health, vocational outcomes, and social functioning. The findings of the meta-analysis suggest that MFT is associated with improvements in symptoms of schizophrenia. However, this effect was found not to be significant due to the large amount of heterogeneity. In addition, MFT was associated with small improvements in family functioning. We found little evidence to suggest that MFT successfully alleviates mood and conduct problems. To conclude, more methodologically rigorous research is needed to further examine the potential benefits of MFT, as well as the working mechanisms and core components of MFT.

Mental threat rehearsal increases fear generalization.

BACKGROUND AND OBJECTIVES: Fear generalization to harmless stimuli characterizes anxiety-related disorders, but much remains unknown about its determinants. Based on studies showing that mental imagery of threat can increase conditioned fear responding, we tested whether it also facilitates fear generalization, and whether threat inflation moderates this effect. METHODS: In a fear conditioning study, 120 participants first completed an acquisition phase, in which one of two pictures was followed by an aversive sound (human scream). Then, the sound was presented 11 times at an increasing (threat inflation) or constant volume (no threat inflation). Finally, a generalization stimulus was presented, and some participants were asked to imagine the last sound (threat rehearsal) and others were not (no threat rehearsal). RESULTS: Bayesian informative hypotheses tests indicated that imagery-based threat rehearsal increased generalization of threat expectancy, and, combined with threat inflation, it also resulted in stronger generalized distress. LIMITATIONS: due to the absence of a test phase, it is unclear whether our effects would transfer to other GSs and whether they would persist beyond the manipulation phase. CONCLUSIONS: Mental imagery of threat may put individuals at risk for fear generalization. Future studies should examine whether modulating imagery may prevent clinical anxiety.

Positive mood induction does not reduce return of fear: A virtual reality exposure study for public speaking anxiety.

Previous laboratory work has shown that induction of positive mood prior to fear extinction decreases the negative valence of the conditional stimulus (CS) and reduces reinstatement of fear. Before translating these insights to clinical practice, it is important to test this strategy in anxious individuals. Students with a high fear of public speaking (N = 62) were randomized to either a positive mood induction, a negative mood induction, or no induction control group. All participants performed two weekly sessions of virtual reality exposure and a 1-week follow-up test including a spontaneous recovery test and reinstatement test after a social rejection (unconditional stimulus). We used self-reported fear measures and skin conductance responses. We expected that the positive group, compared to the other groups, would evaluate the CS (i.e., speaking in front of an audience) as less negative following exposure and would show less spontaneous recovery and reinstatement of fear following a social rejection. Although mood was successfully manipulated, there were no group differences in CS valence following exposure. In all conditions, VR exposure successfully reduced public speaking fear, and these effects were stable at follow-up. In contrast with expectations, the positive group showed more spontaneous recovery of CS negative valence than the negative group. To conclude, we found no evidence that positive mood induction prior to exposure optimizes exposure effects for anxious individuals.

Treatments for partial remission of major depressive disorder: a systematic review and meta-analysis.

QUESTION: Partial remission of major depressive disorder (MDD) is a debilitating and distressing clinical state related to chronicity, morbidity and relapse. Although one-third of patients remit partially, evidence for treatment efficacy is unclear. We provide an overview of treatment options and their efficacy. STUDY SELECTION AND ANALYSIS: Embase, PsycINFO, Medline and SCOPUS were systematically searched through February 2023. Included were randomised controlled trials (RCTs) examining any treatment in patients with partially remitted MDD aged 13-65 years, reporting data on severity, remission or relapse. FINDINGS: Seven RCTs examining psychotherapy including 1024 patients were eligible. There were not enough RCTs to examine effects of pharmacotherapy. Psychotherapy was associated with lower depressive symptom severity at post-treatment (Hedges' g=0.50; 95% CI 0.23 to 0.76), but not at follow-up up to 1 year (Hedges' g=0.36; 95% CI -0.30 to 1.02) or longer (Hedges' g=0.02; 95% CI -0.09 to 0.12). Psychotherapy was associated with superior remission rates at post-treatment (OR 2.57; 95% CI 1.71 to 3.87) and follow-up 6 months or longer (OR 1.75; 95% CI 1.21 to 2.53), although not with improved relapse rates at post-treatment (OR 0.17; 95% CI 0.01 to 4.83) or follow-up 6 months or longer (OR 0.46; 95% CI 0.21 to 1.03). Overall methodological quality was poor. CONCLUSIONS: Psychotherapy targeting partial remission may be effective in lowering depressive symptom severity and patients may potentially achieve full remission twice as likely. Yet, long-term and prophylactic effects are lacking. Given the risk of chronicity, more high-quality RCTs are needed. PROSPERO REGISTRATION NUMBER: CRD42020188451.

The degree of safety behaviors to a safety stimulus predicts development of threat beliefs.

Safety behaviors are behavioral responses that aim to prevent or minimize an imminent threat when confronting a feared stimulus. Despite its adaptive purpose, preliminary evidence suggests that unnecessary safety behaviors to a safety stimulus induce threat beliefs to it. By allowing participants to engage in safety behaviors dimensionally, this study tested whether the degree of safety behaviors to a safety stimulus predicts the subsequent level of threat expectancies to it. To this end, participants first acquired safety behaviors to a threat-related stimulus (A). Safety behaviors then became available only for one safety stimulus (C), but not to another safety stimulus (B). After engaging in safety behaviors to C, participants exhibited greater threat expectancies to C compared to B, albeit with a small effect size. Importantly, the degree of safety behaviors predicted an increase in threat expectancies. The current findings suggest that safety behaviors to safety stimuli are linked to the development of threat beliefs.

Safety behaviors toward innocuous stimuli can maintain or increase threat beliefs.

Safety behaviors can prevent or minimize a feared outcome. However, in relatively safe situations, they may be less adaptive, presumably because people will misattribute safety to these behaviors. This research aimed to investigate whether safety behaviors in safe situations can lead to increased threat beliefs. In Study 1, we aimed to replicate a fear conditioning study (N = 68 students) in which the experimental, but not the control group, received the opportunity to perform safety behavior to an innocuous stimulus. From before to after the availability of the safety behavior, threat beliefs persisted in the experimental group, while they decreased in the control group. In Study 2, we examined whether threat beliefs had actually increased for some individuals in the experimental group, using a multi-dataset latent class analysis on data from Study 1 and two earlier studies (N = 213). Results showed that about a quarter of individuals who performed safety behavior toward the innocuous stimulus showed increased threat expectancy to this cue, while virtually nobody in the control group exhibited an increase. Taken together, safety behavior in relatively safe situations may have maladaptive effects as it generally maintains and sometimes even increases threat beliefs.

Future-Oriented Positive Mental Imagery Reduces Anxiety for Exposure to Public Speaking.

Exposure therapy is the recommended treatment for anxiety disorders, but many anxious individuals are unwilling to expose themselves to feared situations. Episodic simulation of future situations contributes to adaptive emotion regulation and motivates behavior. This study investigated whether future-oriented positive mental imagery reduces anticipatory anxiety and distress during exposure, and increases exposure willingness and duration. Forty-three individuals with moderate public speaking anxiety were randomized to a standardized positive mental imagery exercise about future public speaking or no-task. All participants were then asked to present in a virtual reality environment. Anticipatory anxiety reduced in the positive mental imagery group, but not in the control group. Additionally, the positive mental imagery group reported lower distress during exposure than the control group, but groups did not differ in exposure willingness. Due to limited variance, effects on exposure duration could not be tested. Future-oriented positive mental imagery is promising to prepare individuals for exposure to previously avoided situations.

A meta-analysis of conditioned fear generalization in anxiety-related disorders.

Generalization of conditioned fear is adaptive in some situations but maladaptive when fear excessively generalizes to innocuous stimuli with incidental resemblance to a genuine threat cue. Recently, empirical interest in fear generalization as a transdiagnostic explanatory mechanism underlying anxiety-related disorders has accelerated. As there are now several studies of fear generalization across multiple types of anxiety-related disorders, the authors conducted a meta-analysis of studies reporting behavioral measures (subjective ratings and psychophysiological indices) of fear generalization in anxiety-related disorder vs. comparison groups. We conducted systematic searches of electronic databases (conducted from January-October 2020) for fear generalization studies involving anxiety-related disorder groups or subclinical analog groups. A total of 300 records were full-text screened and two unpublished datasets were obtained, yielding 16 studies reporting behavioral fear generalization measures. Random-effects meta-analytic models and meta-regressions were applied to the identified data. Fear generalization was significantly heightened in anxiety-related disorder participants (N = 439) relative to comparison participants (N = 428). We did not identify any significant clinical, sample, or methodological moderators. Heightened fear generalization is quantitatively supported as distinguishing anxiety-related disorder groups from comparison groups. Evidence suggests this effect is transdiagnostic, relatively robust to experimental or sample parameters, and that generalization paradigms are a well-supported framework for neurobehavioral investigations of learning and emotion in anxiety-related disorders. We discuss these findings in the context of prior fear conditioning meta-analyses, past neuroimaging investigations of fear generalization in anxiety-related disorders, and future directions and challenges for the field.

Old Fears Die Hard: Return of Public Speaking Fear in a Virtual Reality Procedure.

Exposure-based therapy is an effective treatment for social anxiety, but some patients relapse. We used a novel virtual reality procedure to examine spontaneous recovery (i.e., a return of fear over time) and fear renewal (i.e., the return of fear after a context switch) in individuals with fear of public speaking. On Day 1, 32 participants received exposure training before a virtual audience. On Day 8, participants completed a spontaneous recovery phase, followed by a fear renewal test, in which they gave a presentation in front of a new (context switch) or the same audience (no context switch). After exposure, participants exhibited a lower heart rate, subjective distress, negative valence, and arousal. One week later, participants showed spontaneous recovery of heart rate, and the context switch group showed renewal of subjective distress, negative valence, and arousal. Future studies can use this procedure to test interventions aimed at improving long-term exposure effects in individuals with public speaking fear.

Long-term Outcomes of Cognitive Behavioral Therapy for Anxiety-Related Disorders: A Systematic Review and Meta-analysis.

Importance: Cognitive behavioral therapy is recommended for anxiety-related disorders, but evidence for its long-term outcome is limited. Objective: This systematic review and meta-analysis aimed to assess the long-term outcomes after cognitive behavioral therapy (compared with care as usual, relaxation, psychoeducation, pill placebo, supportive therapy, or waiting list) for anxiety disorders, posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). Data Sources: English-language publications were identified from PubMed, PsycINFO, Embase, Cochrane, OpenGrey (1980 to January 2019), and recent reviews. The search strategy included a combination of terms associated with anxiety disorders (eg, panic or phobi*) and study design (eg, clinical trial or randomized controlled trial). Study Selection: Randomized clinical trials on posttreatment and at least 1-month follow-up effects of cognitive behavioral therapy compared with control conditions among adults with generalized anxiety disorder, panic disorder with or without agoraphobia, social anxiety disorder, specific phobia, PTSD, or OCD. Data Extraction and Synthesis: Researchers independently screened records, extracted statistics, and assessed study quality. Data were pooled using a random-effects model. Main Outcomes and Measures: Hedges g was calculated for anxiety symptoms immediately after treatment and at 1 to 6 months, 6 to 12 months, and 12 months or more after treatment completion. Results: Of 69 randomized clinical trials (4118 outpatients) that were mainly of low quality, cognitive behavioral therapy compared with control conditions was associated with improved outcomes after treatment completion and at 1 to 6 months and at 6 to 12 months of follow-up for a generalized anxiety disorder (Hedges g, 0.07-0.40), panic disorder with or without agoraphobia (Hedges g, 0.22-0.35), social anxiety disorder (Hedges g, 0.34-0.60), specific phobia (Hedges g, 0.49-0.72), PTSD (Hedges g, 0.59-0.72), and OCD (Hedges g, 0.70-0.85). At a follow-up of 12 months or more, these associations were still significant for generalized anxiety disorder (Hedges g, 0.22; number of studies [k] = 10), social anxiety disorder (Hedges g, 0.42; k = 3), and PTSD (Hedges g, 0.84; k = 5), but not for panic disorder with or without agoraphobia (k = 5) and could not be calculated for specific phobia (k = 1) and OCD (k = 0). Relapse rates after 3 to 12 months were 0% to 14% but were reported in only 6 randomized clinical trials (predominantly for panic disorder with or without agoraphobia). Conclusions and Relevance: The findings of this meta-analysis suggest that cognitive behavioral therapy for anxiety-related disorders is associated with improved outcomes compared with control conditions until 12 months after treatment completion. At a follow-up of 12 months or more, effects were small to medium for generalized anxiety disorder and social anxiety disorder, large for PTSD, and not significant or not available for other disorders. High-quality randomized clinical trials with 12 months or more of follow-up and reported relapse rates are needed.

Reducing negative stimulus valence does not attenuate the return of fear: Two counterconditioning experiments.

Exposure-based treatment for anxiety disorders is effective for many patients, but relapse is not uncommon. One predictor of the return of fear is the negative valence of fear-relevant stimuli. The aim of the current experiments was to examine whether counterconditioning with positive film clips reduces this negative stimulus valence as well as the return of fear, compared to standard extinction training and to an extinction training with non-contingent exposure to the positive film clips. Participants were 87 students in Experiment 1 (three-day paradigm), and 90 students in Experiment 2 (one-day paradigm). They first underwent a differential acquisition phase, in which one of three pictures was paired with an electric shock. They were then randomly allocated to one of the three intervention groups. Afterwards, they underwent a test phase in which pictures were presented without shock (to measure spontaneous recovery of fear), which was followed by unsignaled shocks to induce reinstatement of extinguished fear. Outcome variables were self-reported stimulus valence, shock expectancy, skin conductance, and fear-potentiated startle. In both experiments, counterconditioning decreased negative stimulus valence, relative to the other interventions, but it did not reduce spontaneous fear recovery or fear reinstatement. Overall, our findings do not support the notion that counterconditioning reduces return of fear.

Reduced return of threat expectancy after counterconditioning verus extinction.

Exposure-based therapies are effective for anxiety disorders, but relapse remains a problem. One explanation might be that exposure therapy reduces threat expectancy but not related feelings of unpleasantness (negative valence of the conditioned stimulus; CS+), which may promote return of threat expectancy and associated fear. Laboratory research has indeed shown that fear extinction leaves negative valence of the conditioned stimulus (CS+) intact. Here, we tested whether adding positive consequences to the CS+ during extinction, a procedure known as counterconditioning, would change the valence of the CS+ and thereby prevent return of threat expectancy. Participants underwent Acquisition (day 1), Intervention (counterconditioning or extinction; day 2), and Spontaneous recovery and Reinstatement (day 3). As expected, threat expectancy ratings during the Spontaneous recovery and Reinstatement tests were lower after counterconditioning than after extinction, but counterconditioning did not reduce CS + negative valence more than extinction. Alternative mechanisms and clinical implications are discussed.