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Objective: Activation Syndrome (AS) is a side-effect of antidepressants consisting of irritability, mania, self-harm, akathisia, and disinhibition. The current study was conducted to analyze how AS may hinder treatment outcome for multimodal treatment for children and adolescents with Obsessive-Compulsive Disorder., Methods: Fifty-six children or adolescents were recruited at two treatment sites in a double-blind randomized-controlled trial where participants received Cognitive-Behavioral Therapy and were randomized to slow titration of sertraline, regular titration of sertraline or placebo., Results: Using a recently developed measure of AS, results suggested that higher average levels of irritability, akathisia, and disinhibition significantly interfered with treatment response and explained 18% of the variance in obsessive-compulsive symptoms during treatment. Interestingly, only session-to-session increases in irritability resulted in a session-to-session increase in obsessive-compulsive symptoms. The observed results were unchanged with the addition of SSRI dosage as a covariate., Conclusions: Results provide empirical support for the proposed hypothesis that AS may hinder multimodal treatment outcome for pediatric OCD. These findings suggest that dosage changes due to AS do not explain why those with higher AS had worse multimodal outcome. Other possible mechanisms explaining this observed disruption are proposed, including how AS may interfere with Cognitive-Behavioral Therapy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Individual randomized controlled trials (RCTs) have demonstrated the efficacy of cognitive behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs) for the treatment of youth with obsessive-compulsive disorder (OCD). Although meta-analyses have confirmed these results, there has been minimal examination of treatment moderators or an examination of treatment response and symptom/diagnostic remission for these two treatment types. The present report examined the treatment efficacy, treatment response, and symptom/diagnostic remission for youth with OCD receiving either CBT or SRIs relative to comparison conditions, and examined treatment moderators., Method: A comprehensive literature search identified 20 RCTs that met inclusion criteria, and produced a sample size of 507 CBT participants and 789 SRI participants., Results: Random effects meta-analyses of CBT trials found large treatment effects for treatment efficacy (g = 1.21), treatment response (relative risk [RR] = 3.93), and symptom/diagnostic remission (RR = 5.40). Greater co-occurring anxiety disorders, therapeutic contact, and lower treatment attrition were associated with greater CBT effects. The number needed to treat (NNT) was three for treatment response and symptom/diagnostic remission. Random effects meta-analyses of SRI trials found a moderate treatment effect for treatment efficacy (g = 0.50), treatment response (RR = 1.80), and symptom/diagnostic remission (RR = 2.06). Greater methodological quality was associated with a lower treatment response for SRI trials. The NNT was five for treatment response and symptom/diagnostic remission., Conclusions: Findings demonstrate the treatment effects for CBT and SRIs across three important outcome metrics, and provide evidence for moderators of CBT across trials., (© 2015 Wiley Periodicals, Inc.)

Selective serotonin reuptake inhibitors (SSRIs) are an efficacious and effective treatment for pediatric obsessive-compulsive disorder (OCD) but have received scrutiny due to a potential side effect constellation called activation syndrome. While recent research introduced a subjective measure of activation syndrome, objective measures have not been tested. This pilot study, using data from a larger randomized-controlled trial, investigated the potential of actigraphy to provide an objective measure of activation symptoms in 44 youths with OCD beginning an SSRI medication regimen. Data were collected over the first four weeks of a multi-site, parallel, double-blind, randomized, placebo controlled psychopharmacological treatment study and statistical modeling was utilized to test how activation syndrome severity predicts daily and nightly activity levels. Results indicated that youths with higher activation symptoms had lower daytime activity levels when treatment averages were analyzed; in contrast youths who experienced onset of activation symptoms one week were more likely to have higher day-time and night-time activity ratings that week. Results support actigraphy as a potential objective measure of activation symptoms. Subsequent studies are needed to confirm these findings and test clinical applications for use by clinicians to monitor activation syndrome during SSRI treatment. National Institutes of Health (5UO1 MH078594-01); NCT00382291., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Few randomized controlled trials (RCTs) exist examining the efficacy of behavior therapy (BT) or serotonin reuptake inhibitors (SRIs) for the treatment of trichotillomania (TTM), with no examination of treatment moderators. The present meta-analysis synthesized the treatment effect sizes (ES) of BT and SRI relative to comparison conditions, and examined moderators of treatment. A comprehensive literature search identified 11 RCTs that met inclusion criteria. Clinical characteristics (e.g., age, comorbidity, therapeutic contact hours), outcome measures, treatment subtypes (e.g., SRI subtype, BT subtype), and ES data were extracted. The standardized mean difference of change in hair pulling severity was the outcome measure. A random effects meta-analysis found a large pooled ES for BT (ES = 1.41, p < 0.001). BT trials with greater therapeutic contact hours exhibited larger ES (p = 0.009). Additionally, BT trials that used mood enhanced therapeutic techniques exhibited greater ES relative to trials including only traditional BT components (p = 0.004). For SRI trials, a random effects meta-analysis identified a moderate pooled ES (ES = 0.41, p = 0.02). Although clomipramine exhibited larger ES relative to selective serotonin reuptake inhibitors, the difference was not statistically significant. Publication bias was not identified for either treatment. BT yields large treatment effects for TTM, with further examination needed to disentangle confounded treatment moderators. SRI trials exhibited a moderate pooled ES, with no treatment moderators identified. Sensitivity analyses highlighted the need for further RCTs of SRIs, especially among youth with TTM., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: This pilot study explored the efficacy and tolerability of paliperidone augmentation of serotonin reuptake inhibitors (SRIs) in adults with treatment-resistant obsessive-compulsive disorder (OCD)., Method: Thirty-four patients aged 24-67 years (mean = 43.7 years, SD = 11.4) who met DSM-IV criteria for OCD and remained symptomatic following 2 or more past adequate SRI trials (including their current medication) were enrolled from May 2008 to March 2012. Participants were treated for 8 weeks in a double-blind study with either paliperidone (up to 9 mg/d) or matching placebo in addition to their SRI. Blinded raters conducted outcome assessments. The primary outcome, obsessive-compulsive symptom severity, was assessed using the Yale-Brown Obsessive Compulsive Scale (YBOCS). Secondary outcomes included the Clinical Global Impressions-Severity of Illness and -Improvement scales., Results: Paliperidone administration resulted in significant baseline-to-posttreatment reductions in obsessive-compulsive symptoms as measured by the YBOCS (P < .01, d = 0.66), although placebo administration also resulted in medium-sized, trend-level significant YBOCS changes (P = .05, d = 0.53). In exploratory analyses examining between-group differences, tests for paliperidone superiority relative to placebo were not significant (P = .14, d = 0.34); however, a numerical trend toward significant between-group differences was found, with a reduction of 7.98 points on the YBOCS for the paliperidone group compared to a reduction of 4.02 points for the placebo group. Paliperidone was generally well tolerated and not associated with significant weight gain (mean [SD] weight: paliperidone, pretreatment 84.70 [27.08] kg, posttreatment 84.84 [18.99] kg; vs placebo, pretreatment 77.50 [25.33] kg, posttreatment 77.43 [19.90] kg; P = .21)., Conclusions: These results suggest that paliperidone augmentation is well tolerated and has potential efficacy in the short-term treatment of some patients with SRI-resistant OCD. Well-powered, randomized, controlled studies are necessary to more definitively address the efficacy of this treatment strategy., Trial Registration: ClinicalTrials.gov identifier: NCT00632229., (© Copyright 2013 Physicians Postgraduate Press, Inc.)

Antidepressants are efficacious for pediatric major depressive disorder, obsessive compulsive disorder (OCD), and non-OCD anxiety disorders. Antidepressants should be used in an evidence-based fashion, with frequent monitoring for side effects, especially when initiating treatment and adjusting dosage. With diligence to appropriate prescribing and monitoring, the benefits of therapy outweigh the potential of treatment related risk.

Currently, there are limited published data evaluating the effects of tics on serotonin reuptake inhibitor (SRI) monotherapy responses in treating obsessive-compulsive disorder (OCD). One retrospective case-controlled analysis of OCD patients treated with SRI monotherapy showed lesser improvement in OCD symptoms in patients with tics than those without. However, more recently there were preliminary reports of OCD subjects treated with SRI monotherapy which did not demonstrate poorer response in subjects with tics or Tourette's Syndrome (TS). The specific aim of this study was to investigate whether the presence of comorbid chronic tics affected "clinically meaningful improvement" [McDougle, C.J., Goodman, W.K., Leckman, J.F., Barr, L.C., Heninger, G.R., Price, L.H., 1993. The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder. Journal of Clinical Psychopharmacology 13, 354-358] of OCD in an 8-week open-label trial of fluoxetine monotherapy. Seventy-four adult subjects (13 patients with comorbid chronic tics and 61 patients without tics) with a primary DSM-IV OCD diagnosis were treated with up to 40mg fluoxetine for 8 weeks and had at least one post-baseline evaluation. The results indicate that there was a significant response by time in both fluoxetine-with-tic subjects and fluoxetine-without-tic subjects. Additionally, there were 3 (23.0%) OCD subjects with tics who had clinically meaningful improvement versus 16 (26.2%) OCD subjects without tics that demonstrated similar levels of improvement. These findings indicate that OCD patients with or without chronic tic disorders did not have a differential response to an 8-week open-label trial of fluoxetine. Limitations include the relatively low number of tic subjects and the open-label nature of the study. Additional data are needed on how comorbid tics may affect SRI treatment response in OCD.

Few data have been reported on the efficacy of cognitive-behavioral therapy (CBT) for youth with obsessive-compulsive disorder (OCD) who have not responded to prior treatment with medication. Given this, we report an open trial of CBT for children who have remained symptomatic following medication trials. Five children with OCD who had an inadequate response to psychotropic medications (e.g., limited response and/or unable to be titrated to a complete dose due to side effects) received treatment in a 3-week intensive CBT program. Assessments were conducted at baseline and after treatment. All participants were classified as treatment responders (much improved or very much improved) and the severity of clinician-rated OCD symptoms and impairment significantly decreased after the intervention. Although a number of limitations of this preliminary report exist, this study provides preliminary support for the utility of an intensive intervention for youth with OCD who have had an inadequate response and/or adverse side effects., ((c) 2006 Wiley-Liss, Inc.)

Despite wide use, relatively little is known about sociodemographic and clinical characteristics that predict early fluoxetine response. What research has been conducted has produced inconsistent findings, which may be due to the statistical procedures used, and no studies to date have examined predictors of early fluoxetine treatment response. Sixty adults with obsessive-compulsive disorder (OCD) completed an open-label fluoxetine trial for 8 weeks (up to 40 mg) after a 1-week, single-blind, placebo run-in before baseline assessment. The baseline and posttreatment assessment battery included the Yale-Brown Obsessive Compulsive Scale, the Hamilton Rating Scale for Depression, and the Yale Global Tic Severity Scale. Patient characteristics included illness duration, age, age of onset, gender, and pharmacological treatment history. Independent t-tests and multiple logistic regression analysis showed that longer illness duration, older age, and greater symptom severity were associated with nonresponse. Our findings highlight the impact of functional psychiatric impairment on determining those who may respond to treatment. Furthermore, findings suggest early predictors of patients with certain characteristics who may ultimately need adjunctive care to facilitate response.

Background: One of the few combination approaches to the treatment of obsessive-compulsive disorder (OCD) with encouraging support is the addition of an antipsychotic to a serotonin reuptake inhibitor., Methods: The study consisted of a 6-week, placebo-controlled addition of olanzapine 5-10 mg (6.1 +/- 2.1 mg, mean +/- SD) to fluoxetine in OCD subjects who were partial or nonresponders to an 8-week, open-label fluoxetine trial (40 mg in 43 subjects, 20 mg in 1 subject)., Results: Both the fluoxetine-plus-olanzapine (n = 22) and fluoxetine-plus-placebo (n = 22) groups improved significantly over 6 weeks [F(3,113) = 11.64, p <.0001] according to Yale-Brown Obsessive Compulsive Scale scores with repeated-measures analysis of variance; however, the treatment x time interaction was not significant for olanzapine versus placebo addition to fluoxetine., Conclusions: These findings indicate no additional advantage of adding olanzapine for 6 weeks in OCD patients who have not had a satisfactory response to fluoxetine for 8 weeks, compared with extending the monotherapy trial.

Anxiety disorders (obsessive-compulsive disorder, social phobia/selective mutism, panic disorder, separation anxiety, generalized anxiety disorder, simple phobia and post-traumatic stress disorder) are the most prevalent psychiatric disorders in children and adolescents. The selective serotonin reuptake inhibitors (SSRIs)--citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline--have demonstrated efficacy in treating anxiety disorders in adults. Although less information is available on the use of these agents in the paediatric population, research into the SSRIs for childhood anxiety disorders is increasing. This article reviews current literature, including case reports as well as open and controlled trials, on the effectiveness and tolerability of the SSRIs in the paediatric population. It also discusses developmental differences in children that should be considered in the utilisation of the SSRIs in paediatric patients.