An evaluation of treatment response and remission definitions in adult obsessive-compulsive disorder: A systematic review and individual-patient data meta-analysis.

INTRODUCTION: Expert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. METHODS: We conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. RESULTS: Individual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. CONCLUSION: While the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.

Body Dysmorphic Disorder and Self-esteem in Adolescents and Young Adults with Acne Vulgaris.

Body dysmorphic disorder is a mental health disorder characterized by a preoccupation with a perceived flaw, which is commonly seen among dermatology patients. The objective of this study was to determine the frequency of body dysmorphic disorder and assess self-esteem among a clinical sample of adolescents and young adults being managed for acne vulgaris. A total of 105 patients, age range 13-24 years, receiving acne treatment at 1 of 2 dermatology outpatient clinic were included. A self-report questionnaire was used, which included a body dysmorphic disorder screening tool (based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria) and the Rosenberg Self-Esteem Scale (RSES). Acne was graded with the Cook's acne grading scale. Out of 105 adolescents and young adults visiting a dermatologist due to acne, 13 (12.4%) screened positive for body dysmorphic disorder (95% confidence interval (95% CI) 6.8-20.2%). Patients with body dysmorphic disorder were more likely to have female gender (p = 0.020) and had lower self-esteem (RSES 15.8 vs 20.5, respectively, p = 0.013) compared with patients without body dysmorphic disorder. No differences were found in the frequency of body dysmorphic disorder with DSM-IV or DSM-5 criteria. This is the first study to report on the frequency of body dysmorphic disorder and self-esteem in adolescents and young adults with acne. Ultimately, more awareness of body dysmorphic disorder among adolescents and young adults presenting with dermatological disorders could lead to more rapid recognition and referral to psychiatric units.

Effectiveness of an innovative treatment protocol for misophonia in children and adolescents: Design of a randomized controlled trial.

Background: Misophonia is a recently identified disorder in which individuals experience intense, uncontrollable and disproportional irritation, anger or disgust when confronted with specific sounds or stimuli associated with these sounds. Prevalence rates in children and adolescents are currently still to be investigated. The reported average age of onset is around 13 years, in clinical practice children from 8 years old are referred.Misophonia is associated with avoidance and anticipation anxiety, possibly leading to serious educational and social consequences for children and families. Worldwide, no evidence-based treatment exists specifically for children and adolescents with misophonia.This article presents the design of a randomized controlled trial testing the effectiveness of cognitive behavioral therapy (CBT) combined with psychomotor therapy (PMT) for misophonia in children and adolescents (aged 8-18). Methods: In total, 82 patients will be randomly assigned to a treatment condition or waiting list condition of 3 months (WCG). Treatment consists of 7 weekly group therapy sessions (1.5 h CBT plus 1.5 h PMT) and a follow-up after 3 weeks. Pre and post treatment assessments will be conducted during a baseline assessment, after 3 and 6 months. The primary outcome will be assessed by the Amsterdam Misophonia Scale - Youth (AMISOS-Y) and secondary outcomes (e.g. quality of life) and putative predictors (e.g. parenting burden) will be studied. Conclusion: This trial is the first study worldwide testing the effectiveness of a combined CBT plus PMT protocol for misophonia in children and adolescents. If proven effective, this protocol provides an innovation to improve care for youth with misophonia.

[Post-scabies itch: an overview of causes and treatment strategies]. / Postscabiësjeuk.

The main manifestation of scabies infection is intense itching. This itch is experienced by nearly every individual affected by the infestation and may persist even after successful treatment of scabies. In certain cases, this post-scabies itch can persist for several weeks to months. In rare cases, it can even progress into a delusional parasitosis related to scabies. This article highlights three cases and explores the underlying causes of itch as well as treatment strategies.

Drug-induced Delusional Infestation.

It is considered that certain drugs might induce delusional infestation, yet, to date, no studies have been performed to identify the pharmacodynamics associated with these treatments. The aim of this review is to summarize current available knowledge of drug-induced delusional infestation. A literature search was performed for primary studies on suspected drugs reported to induce delusional infestation. Included articles were evaluated systematically using the Naranjo criteria. In addition, drug mechanisms of action were compared. The final selection included 31 studies, in which a total of 26 classes of drugs were identified. Anti-Parkinson drugs were most frequently associated with delusional infestation, followed by antidepressants, antiepileptics, antibiotics, prescription stimulants, and a few other drug groups. The current available literature suggests that the onset of delusional infestation is initiated by drug-induced alterations in neurotransmitter levels, predominantly dopamine, in the central nervous system.

Cognitive behavioral therapy for misophonia: A randomized clinical trial.

BACKGROUND: Patients with misophonia suffer from anger or disgust confronted with specific sounds such as smacking or breathing. Avoidance of cue-related situations results in social isolation and significant functional impairment. This is the first randomized, controlled cognitive behavioral therapy (CBT) trial for misophonia, evaluating the short- and long-term efficacy. METHODS: The evaluator-blinded, randomized clinical trial was conducted from May 2017 until December 2018 at an academic outpatient clinic. Misophonia patients were randomly assigned to 3 months of weekly group-CBT or a waiting list and tested at baseline, 3 months (following CBT or waiting list), 6 months (after cross-over), and 15/18 months (1-year follow-up). CBT consisted of task concentration and arousal reduction, positive affect labeling, and stimulus manipulation. Co-primary outcomes were symptom severity assessed by the Amsterdam Misophonia Scale-Revised (AMISOS-R) and improvement on the Clinical Global Impression-Improvement (CGI-I). Secondary outcomes were self-assessed ratings of general psychopathology (Symptom Checklist-90-Revised [SCL-90-R]) and quality of life (five-dimensional EuroQol [EQ5-D], Sheehan Disability Scale [SDS], WHO Quality of Life-BREF [WHOQoL-BREF]). RESULTS: In all, 54 out of 71 patients were included (mean age, 33.06 [SD, 14.13] years; 38 women [70.4%]) and 46 (85%) completed the study. In the randomized phase, CBT resulted in statistically significant less misophonia symptoms in the short-term (-9.7 AMISOS-R; 95% CI, -12.0 to -7.4; p < .001, d = 1.97). The CBT group had an observed clinical improvement (CGI-I < 3) in 37% compared to 0% in the waiting list group (p < .001). The effect of CBT was maintained at 1-year follow-up on primary and secondary outcomes. CONCLUSIONS: This first randomized control trial shows both short-term and long-term efficacy of CBT for misophonia.

NMDA Receptor Antagonist Ketamine Distorts Object Recognition by Reducing Feedback to Early Visual Cortex.

It is a well-established fact that top-down processes influence neural representations in lower-level visual areas. Electrophysiological recordings in monkeys as well as theoretical models suggest that these top-down processes depend on NMDA receptor functioning. However, this underlying neural mechanism has not been tested in humans. We used fMRI multivoxel pattern analysis to compare the neural representations of ambiguous Mooney images before and after they were recognized with their unambiguous grayscale version. Additionally, we administered ketamine, an NMDA receptor antagonist, to interfere with this process. Our results demonstrate that after recognition, the pattern of brain activation elicited by a Mooney image is more similar to that of its easily recognizable grayscale version than to the pattern evoked by the identical Mooney image before recognition. Moreover, recognition of Mooney images decreased mean response; however, neural representations of separate images became more dissimilar. So from the neural perspective, unrecognizable Mooney images all "look the same", whereas recognized Mooneys look different. We observed these effects in posterior fusiform part of lateral occipital cortex and in early visual cortex. Ketamine distorted these effects of recognition, but in early visual cortex only. This suggests that top-down processes from higher- to lower-level visual areas might operate via an NMDA pathway.

[Delusional infestation, a therapeutic challenge]. / Parasieten- of infestatiewaan: een therapeutische uitdaging.

Delusional infestation, formally known as delusional parasitosis, poses a therapeutic challenge. This article provides tools to engage these patients with psychiatric treatment. We present two men aged 49 and 48 who saw the dermatologist with skin symptoms due to primary and secondary delusional infestation, respectively. Despite their anosognosia, both patients were successfully treated with antipsychotics thanks to the collaboration between dermatology and psychiatry. To increase the acceptability of treatment with antipsychotics, emphasis should be placed on their antipruritic properties and the effect on degree of preoccupation with the infection rather than their antipsychotic properties. Follow-up is important, as patients mostly do not attribute their recovery to antipsychotics and the risk of recurrence is high after cessation of antipsychotic medication.

Obsessive-compulsive disorder and female reproductive cycle events: results from the OCD and reproduction collaborative study.

BACKGROUND: Women with obsessive-compulsive disorder (OCD) often report that symptoms first appear or exacerbate during reproductive cycle events; however, little is known about these relationships. The goals of this study were to examine, in a US and a European female OCD sample, onset and exacerbation of OCD in reproductive cycle events, and to investigate the likelihood of repeat exacerbation in subsequent pregnancies and postpartum periods. METHODS: Five hundred forty-two women (United States, n = 352; Dutch, n = 190) who met DSM-IV criteria for OCD, completed self-report questionnaires designed to assess OCD onset and symptom exacerbation associated with reproductive events. RESULTS: OCD onset occurred within 12 months after menarche in 13.0%, during pregnancy in 5.1%, at postpartum in 4.7%, and at menopause in 3.7%. Worsening of pre-existing OCD was reported by 37.6% of women at premenstruum, 33.0% during pregnancy, 46.6% postpartum, and 32.7% at menopause. Exacerbation in first pregnancy was significantly associated with exacerbation in second pregnancy (OR = 10.82, 95% CI 4.48-26.16), as was exacerbation in first postpartum with exacerbation in second postpartum (OR = 6.86, 95% CI 3.27-14.36). Results were replicated in both samples. CONCLUSIONS: Reproductive cycle events are periods of increased risk for onset and exacerbation of OCD in women. The present study is the first to provide significant evidence that exacerbation in or after first pregnancy is a substantial risk factor for exacerbation in or after a subsequent pregnancy. Further research is needed to identify factors related to exacerbation, so that physicians may provide appropriate recommendations to women regarding clinical issues involving OCD and reproductive cycle events.

NMDA receptor antagonist ketamine impairs feature integration in visual perception.

Recurrent interactions between neurons in the visual cortex are crucial for the integration of image elements into coherent objects, such as in figure-ground segregation of textured images. Blocking N-methyl-D-aspartate (NMDA) receptors in monkeys can abolish neural signals related to figure-ground segregation and feature integration. However, it is unknown whether this also affects perceptual integration itself. Therefore, we tested whether ketamine, a non-competitive NMDA receptor antagonist, reduces feature integration in humans. We administered a subanesthetic dose of ketamine to healthy subjects who performed a texture discrimination task in a placebo-controlled double blind within-subject design. We found that ketamine significantly impaired performance on the texture discrimination task compared to the placebo condition, while performance on a control fixation task was much less impaired. This effect is not merely due to task difficulty or a difference in sedation levels. We are the first to show a behavioral effect on feature integration by manipulating the NMDA receptor in humans.

Catechol-O-methyltranferase gene expression is associated with response to citalopram in obsessive-compulsive disorder.

OBJECTIVE: To determine whether polymorphisms of the dopamine D(2) receptor (DRD2) and catechol-O-methyl-transferase (COMT) receptor genes affect the efficacy of quetiapine addition to citalopram in patients with OCD. METHODS: Sixty-four drug-free or drug-naïve patients meeting DSM-IV criteria for OCD were randomized to 10 weeks double-blind treatment with citalopram (60 mg/day) with quetiapine (300 -450 mg/day) or with placebo. The change from baseline to endpoint on the total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the response to treatment were the primary outcome measures. Response was defined as a 25% decrease in Y-BOCS score. Responders and nonresponders were stratified according to DRD2 TaqI A and COMT Val(158)Met genotypes. RESULTS: No significant differences in genotype distribution or allele frequencies of the COMT or DRD2 receptor were found between responders and nonresponders to citalopram with quetiapine. However, nearly half of responders to citalopram with placebo carried the Met/Met (48%) genotype of the COMT polymorphism compared to none of the nonresponders (χ(2) = 10.06, df = 2, P = 0.007). CONCLUSIONS: The Met allele load of the COMT receptor gene was associated with response to 10 weeks of treatment with citalopram in drug-free or drug-naïve OCD patients.

Review of atypical antipsychotics in anxiety.

Atypical antipsychotics are increasingly used for treatment of anxiety disorders, either in mono- or combination therapy. This is the first review reporting on the use of atypical antipsychotics in monotherapy or augmentation in patients with primary anxiety disorders or anxiety (disorders) comorbid to schizophrenia, bipolar disorder (BPD) and major depressive disorder (MDD). We included 49 open-label trials, 32 randomized, placebo-controlled trials (RCTpls) and five randomized controlled trials without placebo arm with almost 6000 patients (open-label: 1710, randomized: 4145). An increasing number of RCTpls show promising results in 27-71% of patients with primary or comorbid anxiety disorders who were treated with monotherapy atypical antipsychotics or augmentation therapy. However, methodological flaws of included studies may limit conclusions of this review and larger placebo-controlled trials are warranted comparing standard treatment with monotherapy and augmentation therapy of atypical antipsychotics and placebo. In addition, higher dropout rates and side effects from treatment with atypical antipsychotics may limit the use of atypical antipsychotics in patients with anxiety disorders.

Quetiapine augments the effect of citalopram in non-refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled study of 76 patients.

OBJECTIVE: To assess the efficacy of quetiapine addition to citalopram in treatment-naive or medication-free obsessive-compulsive disorder (OCD) patients. METHOD: Seventy-six patients who met DSM-IV criteria for OCD and who were drug-free or drug-naive at entry were randomly assigned in a 10-week, double-blind trial with citalopram (60 mg/day) plus quetiapine (300-450 mg/day) or placebo; treatment-refractory OCD patients were excluded. Of the 76 eligible patients, 66 patients completed the trial-31 in the quetiapine and 35 in the placebo group. The change from baseline to endpoint on the total Yale-Brown Obsessive Compulsive Scale (YBOCS) and the response to treatment in the quetiapine addition compared with the placebo addition group were the primary outcome measures. Response was defined as a 35% or greater reduction on the YBOCS and a Clinical Global Impressions-Improvement (CGI-I) score at endpoint of 1 or 2. The study was conducted from November 2003 to June 2005 at the University Medical Centre Utrecht, The Netherlands. RESULTS: As measured by the mean reduction in YBOCS scores following an intent-to-treat, last-observation-carried-forward analysis, quetiapine addition (11.9) was significantly superior to placebo (7.8; p = .009). Quetiapine addition was also significantly superior to placebo on the CGI-I scale, with a mean +/- SD CGI-I score of 2.1 +/- 1.3 versus 1.4 +/- 1.2, respectively (p = .023). Quetiapine addition (N = 22, 69%) was also associated with a significantly greater number of patients responding to treatment compared with placebo addition (N = 15, 41%; p = .019). More patients receiving quetiapine (N = 8) than placebo (N = 2; NS) discontinued treatment due to adverse events. CONCLUSIONS: The combination of quetiapine and citalopram was more effective than citalopram alone in reducing OCD symptoms in treatment-naive or medication-free OCD patients. TRIAL REGISTRATION: www.trialregister.nl Identifier NTR116.

Female hormones affect symptom severity in obsessive-compulsive disorder.

There is circumstantial evidence that reproductive events can influence symptom severity of obsessive-compulsive disorder (OCD). We sent self-report questionnaires to 350 female outpatients with OCD to examine the relationship between the menstrual cycle, pregnancy, menopause, hormonal contraceptives, selective serotonin reuptake inhibitors and symptom severity of OCD. Yale-Brown Obsessive-Compulsive Scale scores were used at three serial time points during the menstrual cycle to assess symptom severity. One hundred and one out of 350 questionnaires (29%) were returned and completed. Forty-nine patients reported an exacerbation of OCD symptoms during the premenstrual period, nine during the menopause and 17 patients during pregnancy, whereas 11 patients mentioned improvement of OCD symptoms during pregnancy. Premenstrual dysphoric disorder could only partly explain a premenstrual exacerbation of OCD symptoms. Exacerbation of OCD could be related to reproductive events in a considerable number of patients, especially the premenstrum. Because reproductive cycle events influence the symptom severity of OCD, the menstrual cycle should be taken into account when assessing the severity of OCD symptoms during pharmacological studies.

Sexual pleasure in women with obsessive-compulsive disorder?

BACKGROUND: Although patients with OCD have reported sexual dissatisfaction frequently, controlled studies are sparse. This study compared subjective appreciation of sexuality and sexual functioning between OCD patients and healthy subjects and controlled for the influence of medication or OCD subtypes on sexual functioning and satisfaction. METHODS: Self-report questionnaires were sent to 350 female outpatients with OCD and 101 questionnaires were completed. RESULTS: OCD patients reported significantly more sexual disgust (t = 4.48, p < 0.001), less sexual desire (t = 5.52, p < 0.001), sexual arousal (t = 4.28, p < 0.001), and satisfying orgasms (t = 4.94, p < 0.001), than controls. Neither medication nor OCD phenotypes did affect outcome. LIMITATIONS: A self-report questionnaire and relatively low response-rate (29%) could have biased the results and the sample was limited to women so results might not be generalisable to men. CONCLUSIONS: Female patients with OCD report low sexual pleasure, high sexual disgust and diminished sexual functioning, which are not only attributed to medication or contamination obsessions. In the future, clinicians should explicitly ask for sexual function in the assessment of patients with OCD.

Bupropion for patients with obsessive-compulsive disorder: an open-label, fixed-dose study.

OBJECTIVE: In the present study, we examined the efficacy of bupropion for patients with obsessive-compulsive disorder (OCD). METHOD: Twelve patients with OCD according to DSM-IV criteria were included in an open trial with bupropion, maximum dosage 300 mg per day, during 8 weeks. The primary efficacy parameter was the Yale-Brown Obsessive Compulsive Scale (YBOCS). A responder was defined by a reduction in score on the YBOCS of > or = 25%. Data were collected from February 2003 to July 2003. RESULTS: An intent-to-treat analysis using the last observation carried forward demonstrated that bupropion had no mean effect on OCD symptoms (mean YBOCS decrease was 1.1 +/- 9.6). Four patients improved, with a mean decrease on the YBOCS of 31%, and 2 of them met responder rate criteria. Eight patients experienced an exacerbation of OCD symptoms, with a mean increase on the YBOCS of 21%. CONCLUSION: Bupropion is not an effective treatment for OCD, but the bimodal distribution of the effect supports the notion that dopamine might be involved in the pathophysiology of OCD.