Efficacy and acceptability of cognitive-behavioral therapy and serotonin reuptake inhibitors for pediatric obsessive-compulsive disorder: a network meta-analysis.

BACKGROUND: Cognitive-behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs) are recommended treatments for pediatric obsessive-compulsive disorder (OCD), but their relative efficacy and acceptability have not been comprehensively examined. Further, it remains unclear whether the efficacy of in-person CBT is conserved when delivered in other formats, such as over telephone/webcam or as Internet-delivered CBT (ICBT). METHODS: PubMed, PsycINFO, trial registries, and previous systematic reviews were searched for randomized controlled trials (RCTs) comparing CBT (in-person, webcam/telephone-delivered, or ICBT) or SRIs with control conditions or each other. Network meta-analyses were conducted to examine efficacy (post-treatment Children's Yale-Brown Obsessive Compulsive Scale) and acceptability (treatment discontinuation). Confidence in effect estimates was evaluated with CINeMA (Confidence in Network Meta-Analysis). RESULTS: Thirty eligible RCTs and 35 contrasts comprising 2,057 youth with OCD were identified. In-person CBT was significantly more efficacious than ICBT, waitlist, relaxation training, and pill placebo (MD range: 3.95-11.10; CINeMA estimate of confidence: moderate) but did not differ significantly from CBT delivered via webcam/telephone (MD: 0.85 [-2.51, 4.21]; moderate), SRIs (MD: 3.07 [-0.07, 6.20]; low), or the combination of in-person CBT and SRIs (MD: -1.20 [-5.29, 2.91]; low). SRIs were significantly more efficacious than pill placebo (MD: 4.59 [2.70, 6.48]; low) and waitlist (MD: 8.03 [4.24, 11.82]; moderate). No significant differences for acceptability emerged, but confidence in estimates was low. CONCLUSIONS: In-person CBT and SRIs produce clear benefits compared to waitlist and pill placebo and should be integral parts of the clinical management of pediatric OCD, with in-person CBT overall having a stronger evidence base. The combination of in-person CBT and SRIs may be most efficacious, but few studies hinder firm conclusions. The efficacy of CBT appears conserved when delivered via webcam/telephone, while more trials evaluating ICBT are needed.

Obsessive-Compulsive Disorder in Children and Adolescents.

Obsessive-compulsive disorder (OCD) in children and adolescents is a neurobehavioral condition that can lead to functional impairment in multiple domains and decreased quality of life. We review the clinical presentation, diagnostic considerations, and common comorbidities of pediatric OCD. An overview of the biological and psychological models of OCD is provided along with a discussion of developmental considerations in youth. We also describe evidence-based treatments for OCD in childhood and adolescence, including cognitive behavioral therapy (CBT) with exposure and response prevention (ERP) and pharmacotherapy. Finally, research evaluating the delivery of CBT in different formats and modalities is discussed, and we conclude with suggestions for future research directions.

A Low-Intensity Transcranial Focused Ultrasound Parameter Exploration Study of the Ventral Capsule/Ventral Striatum.

OBJECTIVES: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is effective for treatment-resistant obsessive-compulsive disorder (OCD); however, DBS is associated with neurosurgical risks. Transcranial focused ultrasound (tFUS) is a newer form of noninvasive (ie, nonsurgical) stimulation that can modulate deeper regions, such as the VC/VS. tFUS parameters have just begun to be studied and have often not been compared in the same participants. We explored the effects of three VC/VS tFUS protocols and an entorhinal cortex (ErC) tFUS session on the VC/VS and cortico-striato-thalamo-cortical circuit (CSTC) in healthy individuals for later application to patients with OCD. MATERIALS AND METHODS: Twelve individuals participated in a total of 48 sessions of tFUS in this exploratory multisite, within-subject parameter study. We collected resting-state, reward task, and arterial spin-labeled (ASL) magnetic resonance imaging scans before and after ErC tFUS and three VC/VS tFUS sessions with different pulse repetition frequencies (PRFs), pulse widths (PWs), and duty cycles (DCs). RESULTS: VC/VS protocol A (PRF = 10 Hz, PW = 5 ms, 5% DC) was associated with increased putamen activation during a reward task (p = 0.003), and increased VC/VS resting-state functional connectivity (rsFC) with the anterior cingulate cortex (p = 0.022) and orbitofrontal cortex (p = 0.004). VC/VS protocol C (PRF = 125 Hz, PW = 4 ms, 50% DC) was associated with decreased VC/VS rsFC with the putamen (p = 0.017), and increased VC/VS rsFC with the globus pallidus (p = 0.008). VC/VS protocol B (PRF = 125 Hz, PW = 0.4 ms, 5% DC) was not associated with changes in task-related CSTC activation or rsFC. None of the protocols affected CSTC ASL perfusion. CONCLUSIONS: This study began to explore the multidimensional parameter space of an emerging form of noninvasive brain stimulation, tFUS. Our preliminary findings in a small sample suggest that VC/VS tFUS should continue to be investigated for future noninvasive treatment of OCD.

Efficacy of deep brain stimulation for treatment-resistant obsessive-compulsive disorder: systematic review and meta-analysis.

Deep brain stimulation (DBS) is an established and growing intervention for treatment-resistant obsessive-compulsive disorder (TROCD). We assessed current evidence on the efficacy of DBS in alleviating OCD and comorbid depressive symptoms including newly available evidence from recent trials and a deeper risk of bias analysis than previously available. PubMed and EMBASE databases were systematically queried using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We included studies reporting primary data on multiple patients who received DBS therapy with outcomes reported through the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Primary effect measures included Y-BOCS mean difference and per cent reduction as well as responder rate (≥35% Y-BOCS reduction) at last follow-up. Secondary effect measures included standardised depression scale reduction. Risk of bias assessments were performed on randomised controlled (RCTs) and non-randomised trials. Thirty-four studies from 2005 to 2021, 9 RCTs (n=97) and 25 non-RCTs (n=255), were included in systematic review and meta-analysis based on available outcome data. A random-effects model indicated a meta-analytical average 14.3 point or 47% reduction (p<0.01) in Y-BOCS scores without significant difference between RCTs and non-RCTs. At last follow-up, 66% of patients were full responders to DBS therapy. Sensitivity analyses indicated a low likelihood of small study effect bias in reported outcomes. Secondary analysis revealed a 1 standardised effect size (Hedges' g) reduction in depressive scale symptoms. Both RCTs and non-RCTs were determined to have a predominantly low risk of bias. A strong evidence base supports DBS for TROCD in relieving both OCD and comorbid depression symptoms in appropriately selected patients.

Primary Outcomes for Adults Receiving the Unified Protocol after Hurricane Harvey in an Integrated Healthcare Setting.

The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) has demonstrated efficacy for treating anxiety and depression. However, there are limited effectiveness data when conducted in real-world settings with diverse populations, including those with trauma. We evaluated treatment outcomes in a naturalistic, community setting among 279 adults who received UP following Hurricane Harvey. We examined change in overall clinical severity, depression and anxiety symptoms, functional impairment, and baseline outcome predictors (i.e., demographic characteristics, impact from Hurricane Harvey, co-occurrence of depression and anxiety symptoms). Global clinical severity, depression and anxiety symptoms, and functional impairment decreased by end-of-treatment. Participants experienced global symptom improvement to a lesser degree than demonstrated in efficacy trials. Participants who experienced greater storm impact reported larger reductions in anxiety symptoms than those less impacted by Harvey. Further studies evaluating the effectiveness of the UP post-disaster and with diverse samples are needed.

The Relationship Between Adverse Childhood Experiences, Symptom Severity, Negative Thinking, Comorbidity, and Treatment Response in Youth with Obsessive-Compulsive Disorder.

Although youth and adults with obsessive-compulsive disorder (OCD) endorse elevated incidence of exposure to traumatic life events during childhood, the existing literature on adverse childhood experiences (ACEs) and OCD is mixed and studies focusing on pediatric OCD are limited. The present study examines the relationship between ACEs and OCD onset, symptom severity, negative cognitive patterns, comorbidity, and cognitive-behavioral therapy (CBT) response in 142 children and adolescents with OCD. ACEs were ascertained from parent reports. Most parents reported child exposure to ACEs. Out of the parents who reported ACEs, 50% reported ACE exposure prior to OCD diagnosis and 50% reported ACE exposure after OCD diagnosis. No significant associations between ACEs and comorbidity or CBT response were found, suggesting that CBT for pediatric OCD is effective regardless of ACE exposure. Family financial problems were associated with increased obsessive-compulsive symptom severity and negative thinking. Implications for research and practice are discussed.

Anger Outbursts in Youth with ASD and Anxiety: Phenomenology and Relationship with Family Accommodation.

Anger outbursts (AO) are associated with severe symptoms, impairment and poorer treatment outcomes for anxious children, though limited research has examined AO in youth with co-occurring autism and anxiety disorders. This study examined AO in children with autism and anxiety by evaluating clinical characteristics, family accommodation, and changes in AO following anxiety-focused treatment. The sample comprised 167 youth with autism and anxiety enrolled in a multi-site randomized clinical trial comparing standard care CBT for anxiety, CBT adapted for youth with autism, and usual care. Most participants (60%) had AO, which contributed to impairment above and beyond anxiety and autism. AO impacted functional impairment indirectly through a pathway of parental accommodation. AO reduced with anxiety-focused treatment. Findings highlight that AO are common in this population and uniquely contribute to functional impairment, indicating a need for direct targeting in treatment.

Defining functional brain networks underlying obsessive-compulsive disorder (OCD) using treatment-induced neuroimaging changes: a systematic review of the literature.

Approximately 2%-3% of the population suffers from obsessive-compulsive disorder (OCD). Several brain regions have been implicated in the pathophysiology of OCD, but their various contributions remain unclear. We examined changes in structural and functional neuroimaging before and after a variety of therapeutic interventions as an index into identifying the underlying networks involved. We identified 64 studies from 1990 to 2020 comparing pretreatment and post-treatment imaging of patients with OCD, including metabolic and perfusion, neurochemical, structural, functional and connectivity-based modalities. Treatment class included pharmacotherapy, cognitive-behavioural therapy/exposure and response prevention, stereotactic lesions, deep brain stimulation and transcranial magnetic stimulation. Changes in several brain regions are consistent and correspond with treatment response despite the heterogeneity in treatments and neuroimaging modalities. Most notable are decreases in metabolism and perfusion of the caudate, anterior cingulate cortex, thalamus and regions of prefrontal cortex (PFC) including the orbitofrontal cortex (OFC), dorsolateral PFC (DLPFC), ventromedial PFC (VMPFC) and ventrolateral PFC (VLPFC). Modulating activity within regions of the cortico-striato-thalamo-cortical system may be a common therapeutic mechanism across treatments. We identify future needs and current knowledge gaps that can be mitigated by implementing integrative methods. Future studies should incorporate a systematic, analytical approach to testing objective correlates of treatment response to better understand neurophysiological mechanisms of dysfunction.

Obsessive-Compulsive Disorder During the COVID-19 Pandemic: a Systematic Review.

PURPOSE OF REVIEW: This systematic review evaluated the impact of the COVID-19 pandemic on obsessive-compulsive symptoms. RECENT FINDINGS: Most studies showed that obsessive-compulsive symptoms worsened during the early stages of the pandemic, particularly for individuals with contamination-related obsessive-compulsive disorder (OCD), though other symptoms dimensions were found to worsen as well. Many patients and individuals in the general population experienced new obsessive-compulsive-like symptoms centered on COVID-19. Self-reported rates of symptom exacerbation and COVID-19-focused symptoms were consistently lower in studies that recruited patients from specialty clinics (compared to online samples). Most studies were conducted in Spring/Summer, 2020. The COVID-19 pandemic has been an enormous stressor for individuals with OCD, especially for those with contamination symptoms. Regardless, there is strong reason to believe gold standard treatment approaches for OCD have maintained strong efficacy. Disseminating and effectively delivering evidence-based treatments for OCD is an urgent public health priority.

The Relationship of Family Accommodation with Pediatric Anxiety Severity: Meta-analytic Findings and Child, Family and Methodological Moderators.

Given the importance of family accommodation for the course, treatment and prognosis of anxiety in pediatric populations, we conducted a meta-analysis to estimate the magnitude and potential moderators of the relationship between accommodation and anxiety severity. Study selection criteria were: (1) included quantitative measures of accommodation and anxiety severity, (2) sampled participants younger than 19 years, (3) a sample size greater than 10, (4) reported statistical data needed to compute effect sizes, and (4) be in English or Spanish. Search procedures included assessment of electronic databases, systematic reviews and empirical studies, and email inquiries. Effect size was Pearson correlation coefficient, assuming a random-effects model. Positive moderate association was observed for measures administered to parents. This was moderated by the percentage of children with separation anxiety and selective mutism. Global effect sizes were small for measures administered to children and when accommodation was reported by parents and anxiety by children. Implications for assessment and treatment are discussed.

Serious negative consequences associated with exposure and response prevention for obsessive-compulsive disorder: A survey of therapist attitudes and experiences.

OBJECTIVE: Many therapists are reluctant to conduct exposure and response prevention (ERP) for obsessive-compulsive disorder (OCD). Negative beliefs about the safety and tolerability of ERP are common, especially for harm-related OCD symptoms. The study examined the nature and frequency of ERP-related serious negative consequences (SNC) and therapist attitudes and experiences providing ERP for harm-related OCD. METHODS: An anonymous survey was completed by 277 therapists with experience treating OCD using ERP. Questions assessed clinical experiences of harm-related exposures, the nature of SNC, and concerns and clinical considerations regarding ERP. RESULTS: Therapist's willingness to treat harm-related OCD was high. SNCs were reported for 6 clients (per-client risk: adults 0.05%, youth 0.01%) and 13 therapists (per therapist risk 4.73%, therapist per-year risk 0.004%). Qualitative analysis identified themes relating to the conduct of treatment, specific exposure types, professional issues, and negative perceptions of ERP. CONCLUSION: SNC associated with ERP for OCD are rare and primarily represent unintended secondary consequences of OCD or misunderstandings regarding the process and rationale behind ERP. Improving access to ERP will require good communication with clients, families, and other professionals regarding the rationale and safety of ERP.

Predictors of treatment outcome for youth receiving intensive residential treatment for obsessive-compulsive disorder (OCD).

Little is known about the predictors of outcome from intensive residential treatment of OCD. This study aimed to examine age, gender, and baseline OCD severity, as well as measures of comorbid anxiety and depressive, internalizing/externalizing, and inattention symptoms, as predictors of treatment outcome in adolescents receiving intensive residential treatment for OCD. The sample comprised 314 adolescents aged 13-17 years with treatment-resistant OCD and a Children's Yale-Brown Obsessive-Compulsive Scale Self-Report (CY-BOCS-SR) total score ≥16. Bivariate and multiple regression models were used to evaluate the predictors of continuous OCD severity outcome and treatment response. Results of the bivariate regression analyses of predictors demonstrated that length of treatment, pre-treatment OCD severity, and symptoms of anxiety and depression significantly predicted post-treatment OCD severity, while only symptoms of depression and anxiety predicted treatment response. When including all predictors in the same model, only baseline OCD severity remained a significant predictor of post-treatment OCD severity, and none of the assessed variables significantly predicted treatment response. Results indicate that low pre-treatment OCD severity predicts lower OCD severity following treatment, although it did not predict treatment response.

The Impact of Comorbidity on Cognitive-Behavioral Therapy Response in Youth with Anxiety and Autism Spectrum Disorder.

The impact of externalizing comorbidity on treatment outcome was examined in 104 youth ages 7-16 (M = 11.09 years) with autism spectrum disorder and primary anxiety/obsessive compulsive disorder who completed modular cognitive behavioral therapy (CBT) for anxiety/OCD. Three comorbidity profiles were utilized for group comparisons: participants with oppositional defiant or conduct disorder with attention-deficit hyperactivity disorder (ODD; CD; ADHD; group EXT, n = 25); those without ODD/CD and only ADHD (group ADHD, n = 46); and those without externalizing comorbidity (NO-EXT, n = 33). Post-treatment outcomes were measured continuously (Pediatric Anxiety Rating Scale, Clinical Global Impression-Severity) and categorically (treatment response, remission). The ADHD group was four times more likely of being a treatment responder compared to NO-EXT (OR 4.05). Comorbidity group did not impact remission. After controlling for pre-treatment scores, there was a significantly greater reduction of the CGI-S for ADHD versus NO-EXT and EXT versus NO-EXT, but results did not significantly differ for the PARS. Results suggest that a modular CBT approach yields positive impact for treatment outcomes in youth with comorbid externalizing problems, particularly among those with comorbid ADHD.

Psychiatric Diagnoses and Medications for Hurricane Harvey Sheltered Evacuees.

To report on the diagnosis of and pharmacological services provided to 229 evacuees of Hurricane Harvey housed within a large convention center. Retrospective chart review of services rendered. Evacuees were primarily adults who presented with varied diagnoses, most commonly mood, anxiety and/or psychotic disorders. There was significant need for medications and psychosocial support to address preexisting conditions, as well as emerging problems (e.g., insomnia). Individuals presenting for pharmacological services following natural disasters may require medications to continue ongoing care, and/or treatment for insomnia. Therapists can provide direct intervention as well as identify those in need of further evaluation/intervention. Providers should be prepared with a fully stocked pharmacy, accessible but confidential location, and a pre-established method of record keeping.

Parents' Perceptions of Internalizing and Externalizing Features in Childhood OCD.

Although obsessive-compulsive disorder (OCD) has often been characterized as an internalizing disorder, some children with OCD exhibit externalizing behaviors that are specific to their OCD. This study sought to demonstrate that parents perceive both internalizing and externalizing behaviors in childhood OCD by examining the factor structure of the Child Obsessive-Compulsive Externalizing/Internalizing Scale (COCEIS), a parent-report questionnaire intended to measure these constructs. This study also investigated clinical correlates of internalizing and externalizing factors in the COCEIS. A factor analysis of questionnaire responses from 122 parents of youth with OCD revealed both externalizing and internalizing factors in the COCEIS. Externalizing behaviors in childhood OCD were associated with other, co-occurring externalizing behavior problems, while both factors were positively correlated with OCD severity and co-occurring internalizing symptoms. They were positively associated with each other at a trend level, and neither showed a significant relationship with insight. Sixty-two percent of parents endorsed "often" or "always" to at least one externalizing item, though modal responses to items suggested that each individual feature captured by the COCEIS may be relatively uncommon. Mean responses were significantly greater for internalizing items. This study provides evidence for distinct but related externalizing and internalizing behaviors specific to childhood OCD. Treatment for children with OCD presenting with more externalizing behaviors may require a greater emphasis on behavioral parent training and motivational enhancement.

Charting the road forward in psychiatric neurosurgery: proceedings of the 2016 American Society for Stereotactic and Functional Neurosurgery workshop on neuromodulation for psychiatric disorders.

OBJECTIVE: Refractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive-compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials. To discuss next steps, neurosurgeons, neurologists, psychiatrists and representatives from industry convened a workshop sponsored by the American Society for Stereotactic and Functional Neurosurgery in Chicago, Illinois, in June of 2016. DESIGN: Here we summarise the proceedings of the workshop. Participants discussed a number of issues of importance to the community. First, we discussed how to interpret results from the recent pivotal trials of DBS for OCD and depression. We then reviewed what can be learnt from lesions and closed-loop neurostimulation. Subsequently, representatives from the National Institutes of Health, the Food and Drug Administration and industry discussed their views on neuromodulation for psychiatric disorders. In particular, these third parties discussed their criteria for moving forward with new trials. Finally, we discussed the best way of confirming safety and efficacy of these therapies, including registries and clinical trial design. We close by discussing next steps in the journey to new neuromodulatory therapies for these devastating illnesses. CONCLUSION: Interest and motivation remain strong for deep brain stimulation for psychiatric disease. Progress will require coordinated efforts by all stakeholders.

Cognitive Behavioral Therapy for Childhood Anxiety Disorders: a Review of Recent Advances.

PURPOSE OF REVIEW: We review recent research validating cognitive behavioral therapy (CBT) as a first-line intervention for childhood anxiety disorders. We also review recent research aimed at enhancing exposure-based CBT components and adapting CBT to work with specific populations. RECENT FINDINGS: Exposure-based CBT is a well-established intervention. Different research groups have found positive evidence to augment CBT by evaluating inhibitory learning principles, the role of parents in child treatment, an individualized case formulation, computer and online forms of CBT, and virtual and augmented reality systems for exposure practice. Specific programs have been developed to meet specific needs of preschoolers, adolescents, and children with comorbid autism spectrum disorder and anxiety. Successful adaptations to CBT exist and the field should continue to improve the generalizability, feasibility, and expected benefit of CBT to improve its effectiveness.

Impact of the 2016 US presidential election on OCD symptom presentation: A case illustration.

A recent survey of Americans found that the majority experienced stress during and after the 2016 United States presidential election. Psychosocial, environmental stressors can have a unique impact on symptom presentation in mental health disorders. This manuscript details a case illustration of an individual whose symptoms of obsessive-compulsive disorder were directly linked to the election, as well as how these symptoms were addressed via treatment with intensive exposure and response prevention.

Neural correlates of interoception: Effects of interoceptive focus and relationship to dimensional measures of body awareness.

Interoception has been defined as the sensing of the physiological condition of the body, with interoceptive sensibility (IS) characterizing an individual's self-reported awareness of internal sensation. IS is a multidimensional construct including not only the tendency to be aware of sensation but also how sensations are interpreted, regulated, and used to inform behavior, with different dimensions relating to different aspects of health and disease. Here we investigated neural mechanisms of interoception when healthy individuals attended to their heartbeat and skin temperature, and examined the relationship between neural activity during interoception and individual differences in self-reported IS using the Multidimensional Scale of Interoceptive Awareness (MAIA). Consistent with prior work, interoception activated a network involving insula and sensorimotor regions but also including occipital, temporal, and prefrontal cortex. Differences based on interoceptive focus (heartbeat vs skin temperature) were found in insula, sensorimotor regions, occipital cortex, and limbic areas. Factor analysis of MAIA dimensions revealed 3 dissociable components of IS in our dataset, only one of which was related to neural activity during interoception. Reduced scores on the third factor, which reflected reduced ability to control attention to body sensation and increased tendency to distract from and worry about aversive sensations, was associated with greater activation in many of the same regions as those involved in interoception, including insula, sensorimotor, anterior cingulate, and temporal cortex. These data suggest that self-rated interoceptive sensibility is related to altered activation in regions involved in monitoring body state, which has implications for disorders associated with abnormality of interoception. Hum Brain Mapp 38:6068-6082, 2017. © 2017 Wiley Periodicals, Inc.