Trials Of Serotonin Reuptake Inhibitors Research Articles

Predictors of clinical worsening during a discontinuation trial of serotonin reuptake inhibitors for obsessive compulsive disorder

ObjectiveTo explore predictors and moderators of clinical worsening during a double-blind trial in which patients with obsessive-compulsive disorder (OCD) were randomized to either continue or discontinue their Serotonin Reuptake Inhibitor (SRI) medication after achieving wellness from the addition of exposure and response prevention (EX/RP) therapy. MethodThe data came from a double-blind discontinuation trial that included N = 101 participants, 35 of whom were removed from the study due to clinical worsening. We first used LASSO logistic regression to identify which of the 34 potential baseline variables of interest (including demographics, diagnoses, other relevant clinical constructs, and specific genotypes), might moderate or predict this clinical worsening. Then logistic regression was used to examine which of these identified variables were significantly related to later clinical worsening. We verified the validity of our final prediction model using k-fold cross-validation. ResultsThere was one significant predictor of clinical worsening: In both groups, those with more past diagnoses had a greater likelihood of clinical worsening (p = .015). There were several moderators. Rates of clinical worsening were higher in the Discontinuation group compared to the Continuation group for participants who were taking a shorter half-life SRI (p = .044), were female (p = .022), had higher baseline levels of maladaptive metacognitions (p < .001), had fewer sleep problems at baseline (p = .001), and/or had more years of education (p < .001). ConclusionsOur results identified several factors that may predict the development of clinical worsening in OCD patients discontinuing SRI medication following successful EX/RP treatment.

Pilot study of single-dose psilocybin for serotonin reuptake inhibitor-resistant body dysmorphic disorder

ObjectiveBody dysmorphic disorder (BDD) is an often-severe condition in which individuals are preoccupied by misperceptions of their appearance as defective or ugly. Only serotonin reuptake inhibitors and cognitive-behavioral therapy have been demonstrated efficacious in randomized controlled trials. Psilocybin is a psychedelic drug with growing evidence for safety and efficacy in treatment of depression. This study aimed to pilot test the feasibility, tolerability, safety, and efficacy of psilocybin treatment of adults with BDD. Methods: In this open-label trial, 12 adults (8 women, 4 men) with moderate-to-severe non-delusional BDD that had been unresponsive to at least one serotonin reuptake inhibitor trial received a single oral dose of psilocybin 25 mg. There was no control group. Psychological support was provided before, during, and after the dosing session. The primary outcome measure for efficacy was the Yale-Brown Obsessive Compulsive Disorder Scale Modified for BDD (BDD-YBOCS) score during 12 weeks of assessments after dosing. Results: All participants completed dosing and all follow-up assessments. BDD-YBOCS scores decreased significantly over 12 weeks of follow-up (p < .001) with a large effect size (partial eta squared = 0.54), and significant changes from baseline were present at week 1 and persisted through week 12. Secondary efficacy measures of BDD symptoms, conviction of belief, negative affect, and disability also improved significantly, and no serious adverse events occurred. At week 12, seven participants (58%) were rated responders, based on ≥30% decrease in BDD-YBOCS. Conclusion: This study provides promising preliminary support for psilocybin as a treatment of BDD, warranting future controlled studies.

Familial risk of psychosis in obsessive-compulsive disorder: Impact on clinical characteristics, comorbidity and treatment response

BackgroundFamily studies in obsessive-compulsive disorder (OCD) indicate higher rates of psychosis among their first-degree relatives (FDRs). However, the etiological and clinical relationships between the two disorders remain unclear. We compared the clinical characteristics and pharmacological treatment response in patients diagnosed with OCD with a family history of psychosis (OCD-FHP), with a family history of OCD (OCD-FHO) and those with sporadic OCD (OCD-S). MethodsA total of 226 patients who met DSM-IV criteria for OCD (OCD-FHP = 59, OCD-FHO = 112, OCD-S = 55) were included for analysis. All patients were evaluated using the Mini International Neuropsychiatric Interview (MINI 6.0.0), Yale-Brown Obsessive-Compulsive Scale (YBOCS), and the Family Interview for Genetic Studies (FIGS). Treatment response was characterized over naturalistic follow-up. ResultsThe three groups did not differ across any demographic or clinical variables other than treatment response. Patients in the OCD-FHP group were found to have received a greater number of trials with serotonin reuptake inhibitors (SRI) [F (2,223) = 7.99, p < 0.001], were more likely to have failed ≥2 trials of SRIs (χ2 = 8.45, p = 0.014), and less likely to have attained remission (χ2 = 6.57, p = 0.037) ConclusionsWe observed that having a relative with psychosis may predispose to treatment resistance in OCD. Further research on the influence of genetic liability to psychosis on treatment response in OCD may offer novel translational leads.

Adjuvant Priming Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Obsessive-Compulsive Disorder: In Search of a New Paradigm!

Repetitive transcranial magnetic stimulation (rTMS) is used as a therapeutic option for obsessive-compulsive disorder (OCD) in both clinical and research settings. There has been no consensus with regard to target area and other parameters, although 1-Hz rTMS over the supplementary motor area (SMA) is found to be promising. Priming stimulation, which involves high-frequency followed by low-frequency rTMS, has been shown to enhance neural response to low-frequency rTMS. Hence, this study was conducted to investigate the effect of adjunctive priming rTMS over the SMA in treatment-resistant OCD. Thirty patients with OCD who were symptomatic after an adequate selective serotonin reuptake inhibitor trial were randomized into 2 groups: one group receiving active priming stimulation (6-Hz rTMS at 80% resting motor threshold) followed by 1-Hz rTMS (priming rTMS group) and the other receiving sham stimulation followed by 1-Hz rTMS (rTMS-only group). Both groups received 10 sessions of such interventions for 2 weeks. Both the rater and patients were blind to the treatment allocation. Assessments were done using the Yale-Brown Obsessive Compulsive Scale, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Clinical Global Impression-Improvement scale at baseline, 2 weeks, and 4 weeks. Both groups showed a significant improvement in all domains of psychopathology over time. The priming rTMS group was better than the rTMS-only group in reducing the Yale-Brown Obsessive Compulsive Scale compulsion score (P < 0.023) as well as scores of the Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Clinical Global Impression-Improvement scale. None developed any adverse effects requiring medical attention. Priming rTMS over the SMA is safe and has favorable effects in OCD. It seems to have a predominant effect on the reduction of compulsions, presumably rectifying the impaired response inhibition in patients with OCD.

Maximizing remission from cognitive-behavioral therapy in medicated adults with obsessive-compulsive disorder

Practice guidelines for adults with obsessive-compulsive disorder (OCD) recommend augmenting serotonin reuptake inhibitors (SRIs) with exposure and ritual prevention (EX/RP). However, fewer than half of patients remit after a standard 17-session EX/RP course. We studied whether extending the course increased overall remission rates and which patient factors predicted remission. Participants were 137 adults with clinically significant OCD (Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score ≥18) despite an adequate SRI trial (≥12 weeks). Continuing their SRI, patients received 17 sessions of twice-weekly EX/RP (standard course). Patients who did not remit (Y-BOCS ≤12) received up to 8 additional sessions (extended course). Of 137 entrants, 123 completed treatment: 49 (35.8%) remitted with the standard course and another 46 (33.6%) with the extended course. Poorer patient homework adherence, more Obsessive-Compulsive Personality Disorder (OCPD) traits, and the Brain-Derived Neurotrophic Factor (BDNF) Val66MET genotype were associated with lower odds of standard course remission. Only homework adherence differentiated non-remitters from extended course remitters. Extending the EX/RP course from 17 to 25 sessions enabled many (69.3%) OCD patients on SRIs to achieve remission. Although behavioral (patient homework adherence), psychological (OCPD traits), and biological (BDNF genotype) factors influenced odds of EX/RP remission, homework adherence was the most potent patient factor overall.

Self-Stigma and Treatment Effectiveness in Patients with SSRI Non-Responsive Obsessive-Compulsive Disorder.

PurposeObsessive compulsive disorder (OCD) is a debilitating mental disorder that often takes a chronic course. One of the factors influencing the treatment effectiveness in anxiety and depressive disorders is the self-stigma. This study focused on the relationship between the self-stigma, symptomatology, and therapeutic outcomes in patients with OCD.Patients and MethodsNinety-four inpatients with OCD, who did not sufficiently respond to at least one selective serotonin reuptake inhibitor trial, participated in the study. They attended a six-week therapeutic program consisting of exposure and response prevention, transdiagnostic group cognitive behavioral therapy, individual sessions, mental imagery, relaxation, sport, and ergotherapy. The participants completed several scales: the Internalized Stigma of Mental Illness Scale (ISMI), the self-report Yale-Brown Obsessive Compulsive Scale (Y-BOCS-SR), Beck Anxiety Scale (BAI), Beck Depression Scale-II (BDI-II), and Dissociative Experiences Scale (DES). A senior psychiatrist filled in the Clinical Global Impression (CGI-S).ResultsThe average scales’ scores considerably declined in all measurements except for DES. The self-stigma positively correlated with all psychopathology scales. It was also higher in patients with a comorbid personality disorder (PD). The higher self-stigma predicted a lower change in compulsion, anxiety, and depressive symptoms but not the change of obsessions or the overall psychopathology.ConclusionThe self-stigma presents an important factor connected to higher severity of OCD. It is also a minor predictor of a lower change in symptomatology after combined treatment.

Current Pharmacological Treatments for Childhood Onset OCD

Obsessive-compulsive disorder (OCD) is a chronic condition associated with substantial morbidity, comorbidity, and functional impairment in affected youths. Fortunately, efficacy has been established for multiple pharmacotherapies; however, treatment response remains neither universal nor complete; hence, treatment development efforts continue. This review aims to examine evidence for recent trials examining augmentation strategies for partial responders to serotonin reuptake inhibitors (SRIs), the efficacy of adding D-cycloserine (DCS) to cognitive behavioral therapy (CBT), interventions for OCD symptoms associated with infection, and a meta-analytic view of SRI efficacy and dose-response outcomes. Augmentative treatment with SRIs or additional CBT confers additional benefit in CBT partial responders; however, DCS augmentation does not enhance CBT outcomes. Further treatment development is needed to establish effective interventions for infection-related OCD symptoms, and an SRI dose-response curve does not appear to be evident when examining across multiple SRI trials. Implications of these finding for next-stage research efforts and clinical practice are considered.

A Double-Blind Randomized Placebo-Controlled Trial of Citalopram Adjunctive to Stimulant Medication in Youth With Chronic Severe Irritability

Despite the clinical importance of chronic and severe irritability, there is a paucity of controlled trials for its pharmacological treatment. Here, we examine the effects of adding citalopram (CTP) to methylphenidate (MPH) in the treatment of chronic severe irritability in youth using a double-blind randomized placebo-controlled design. After a lead-in phase of open treatment with stimulant, 53 youth meeting criteria for severe mood dysregulation (SMD) were randomly assigned to receive CTP or placebo (PBO) for 8 weeks. A total of 49 participants, 48 of them (98%) meeting disruptive mood dysregulation disorder (DMDD) criteria, were included in the intent-to-treat analysis. The primary outcome measure was the proportion of response based on improvements of irritability at the week 8 of the trial. At the end of the trial, a significantly higher proportion of response was seen in those participants randomly assigned to CTP+MPH compared to PBO+MPH (35% CTP+MPH versus 6% PBO+MPH; odds ratio= 11.70, 95% CI= 2.00-68.16, p= 0.006). However, there were no differences in functional impairment between groups at the end of the trial. No differences were found in any adverse effect between treatment groups, and no trial participant exhibited hypomanic or manic symptoms. Adjunctive CTP might be efficacious in the treatment of chronic severe irritability in youth resistant to stimulant treatment alone. A Controlled Trial of Serotonin Reuptake Inhibitors Added to Stimulant Medication in Youth With Severe Mood Dysregulation; https://clinicaltrials.gov; NCT00794040.

A Systematic Review of Evidence-based Treatment Strategies for Obsessive- compulsive Disorder Resistant to first-line Pharmacotherapy.

Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, a significant proportion of patients do not respond satisfactorily to first-choice treatments. Several options have been investigated for the management of resistant patients. The aim of the present paper is to systematically review the available literature concerning the strategies for the treatment of resistant adult patients with OCD. We first reviewed studies concerning the definition of treatment-resistant OCD; we then analyzed results of studies evaluating several different strategies in resistant patients. We limited our review to double-blind, placebo-controlled studies performed in adult patients with OCD whose resistance to a first adequate (in terms of duration and dosage) SRI trial was documented and where outcome was clearly defined in terms of decrease in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores and/or response/ remission rates (according to the YBOCS). We identified five strategies supported by positive results in placebo-controlled randomized studies: 1) antipsychotic addition to SRIs (16 RCTs, of them 10 positive; 4 head-to-head RCTs); among antipsychotics, available RCTs examined the addition of haloperidol (butyrophenone), pimozide (diphenyl-butylpiperidine), risperidone (SDA: serotonin- dopamine antagonist), paliperidone (SDA), olanzapine (MARTA: multi-acting receptor targeted antipsychotic), quetiapine (MARTA) and aripiprazole (partial dopamine agonist); 2) CBT addition to medication (2 positive RCTs); 3) switch to intravenous clomipramine (SRI) administration (2 positive RCTs); 4) switch to paroxetine (SSRI: selective serotonin reuptake inhibitor) or venlafaxine (SNRI: serotonin-norepinephrine reuptake inhibitor) when the first trial was negative (1 positive RCT); and 5) the addition of medications other than an antipsychotic to SRIs (18 RCTs performed with several different compounds, with only 4 positive studies). Treatment-resistant OCD remains a significant challenge to psychiatrists. To date, the most effective strategy is the addition of antipsychotics (aripiprazole and risperidone) to SRIs; another effective strategy is CBT addition to medications. Other strategies, such as the switch to another first-line treatment or the switch to intravenous administration are promising but need further confirmation in double-blind studies. The addition of medications other than antipsychotics remains to be studied, as several negative studies exist and positive ones need confirmation (only 1 positive study).

Clinical profile and outcome in a large sample of children and adolescents with obsessive–compulsive disorder: A chart review from a tertiary care center in India

Background:Obsessive–compulsive disorder (OCD) is a common psychiatric illness in children and adolescents. Till date, the sample sizes in the Indian studies have been relatively small.Methodology:The present study is a retrospective chart review of a large sample of children and adolescents diagnosed with OCD in a tertiary care centerObjectives:The objectives of this study were to characterize the clinical profile and to evaluate outcome of OCD in children and adolescentsResults:Fear of contamination and washing/cleaning compulsions were the most common presenting symptoms. Most of the patients were male with two-thirds having a comorbid disorder. Major depressive disorder was the most common comorbid disorder. The rates of attention deficit hyperactivity disorder, disruptive behavioral disorders, and tic disorders were low when compared to Western studies. One-third of the patients received adequate trial of serotonin reuptake inhibitors and 36% received cognitive behavior therapy. Fifty-four percent of patients had a poor outcome with hospitalization, longer duration of illness, earlier onset of OC symptoms, and family history of OCD being the predictors of poor outcome.Conclusion:The present study of a large sample of patients with juvenile OCD highlights the low rate of comorbid disruptive behavior disorders as reported in the earlier Indian studies and a favorable short-term outcome in approximately 56% of the patients.

Secondary outcomes from the pediatric obsessive compulsive disorder treatment study II

The Pediatric Obsessive-Compulsive Disorder Treatment Study II (POTS II) investigated the benefit of serotonin reuptake inhibitor (SRI) augmentation with cognitive behavioral therapy (CBT). Primary outcomes focused on OCD symptom change and indicated benefit associated with a full course of CBT. Given that the majority of youth with OCD suffer from significant comorbid symptoms and impaired quality of life, the current study examined POTS II data for effects on secondary outcomes. Participants were 124 youth ages 7–17 years with a primary diagnosis of OCD who were partial responders to an adequate SRI trial. Participants were randomized to medication management, medication management plus instructions in cognitive behavioral therapy (CBT), or medication management plus full CBT. Acute effects on non-OCD anxiety, depression, inattention, hyperactivity, and quality of life were examined across treatment conditions. Improvement across treatment was observed for non-OCD anxiety, inattention, hyperactivity, and quality of life. Changes were generally significantly greater in the group receiving full CBT. Child-rated depression was not found to change. OCD-focused treatment lead to improvement in other areas of psychopathology and functioning. For youth who are partial responders to SRI monotherapy, augmentation with full CBT may yield the greatest benefit on these secondary outcomes. Clinical trials registrationTreatment of Pediatric OCD for SRI Partial Responders, Clinicaltrials.gov Identifier: NCT00074815, http://clinicaltrials.gov/show/NCT00074815.

Intolerance for uncertainty is a prognostic factor of negative response after intensive inpatient CBT for medication-resistant obsessive-compulsive disorder

IntroductionCognitive theories of Obsessive–Compulsive Disorder (OCD) have identified six types of beliefs, which have a role as vulnerability and maintaining factors: Inflated sense of responsibility, Threat overestimation, Importance of thoughts, Control of thoughts, Perfectionism and Intolerance for uncertainty. As previous research showed that strong obsessive beliefs are linked to severe OCD symptoms, it could be hypothesized that they act as prognostic factors of negative response after cognitive behavioural therapy (CBT). However, poor research investigated this aspect.ObjectivesThe aim of the current study was to examine which obsessive beliefs could predict a worse response after intensive CBT in a group of inpatients with medication-resistant OCD.MethodsForty inpatients [mean baseline Y-BOCS = 26.70, SD = 7.01] with medication-resistant OCD underwent 5-week intensive CBT including daily and prolonged exposure and response prevention (2.5 hours in the morning, 2.5 hours in the afternoon). All individuals have had inadequate symptom response after prior serotonin-reuptake inhibitor trials. The Y-BOCS, BAI, OBQ-87, and BDI-II were administered at baseline and post-treatment.ResultsInpatients who endorsed stronger intolerance for uncertainty, measured by higher scores on the OBQ-87 Intolerance for uncertainty scale, showed worse response after CBT, measured by having still higher Y-BOCS scores at post-treatment (β = 0.37, t = 2.48, r2 = 0.14, P &lt; 0.05). No effect of the other beliefs emerged.ConclusionsCurrent data demonstrated the role of intolerance for uncertainty as predictor of negative response after intensive CBT for resistant OCD in inpatient setting. Augmentation strategies should be introduced to improve outcomes of inpatients with intolerance for uncertainty.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Prevalence and impact of obsessive-compulsive symptoms in depression: a STAR*D report.

Obsessive-compulsive symptoms (OCS) may be underrecognized in patients suffering from major depressive disorder. These patients may not receive optimal psychopharmacologic or psychological treatment if their OCS are not attended to. We performed a secondary analysis of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial database, the largest effectiveness study of "real-world" depression ever conducted, to determine the frequency of OCS and their effects on depression outcome. 3,984 adult subjects without a previous selective serotonin reuptake inhibitor trial for their current major depressive episode, per DSM-IV diagnostic criteria, had data for rating scales of interest at entry into Level 1 of the STAR*D trial, a 12-week open trial of citalopram at a dose of 20-60 mg/d to assess rates of depression remission. Our primary interest was the OCD subscale of the Psychiatric Diagnostic Screening Questionnaire. At study entry, 53% of the STAR*D sample (which excluded patients with primary obsessive-compulsive disorder) endorsed ≥ 1 OCS, and 14% endorsed ≥ 4 OCS. Subjects endorsing ≥ 4 OCS had significantly lower corrected odds of depression remission on both the 17-item Hamilton Depression Rating Scale (HDRS-17) (OR = 0.61) and the Quick Inventory of Depressive Symptomatology (odds ratio [OR] = 0.51). Number of OCS endorsed was positively correlated with HDRS-17 score (r = 0.26, P < .0001). Consistent with findings from the Dunedin, New Zealand Community Study, the most common obsessions were doubts of having inadvertently caused harm and violent obsessions. OCS are common in depressed outpatients and are often not attended to. They impact clinical recovery from depression and should be screened for since sufferers are often reluctant to disclose these symptoms. ClinicalTrials.gov identifier: NCT00021528.

A META-ANALYSIS OF COGNITIVE BEHAVIOR THERAPY AND MEDICATION FOR CHILD OBSESSIVE-COMPULSIVE DISORDER: MODERATORS OF TREATMENT EFFICACY, RESPONSE, AND REMISSION.

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. A comprehensive literature search identified 20 RCTs that met inclusion criteria, and produced a sample size of 507 CBT participants and 789 SRI participants. 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. Findings demonstrate the treatment effects for CBT and SRIs across three important outcome metrics, and provide evidence for moderators of CBT across trials.

Electroconvulsive therapy for obsessive-compulsive disorder: a systematic review.

Surgical therapies for treatment-refractory obsessive-compulsive disorder (OCD), such as deep brain stimulation or psychosurgery, remain unattainable for many patients. Despite the long-held view that electroconvulsive therapy (ECT) is an ineffective treatment for OCD, there is no systematic review to support or refute this claim, which is the basis of the current review. A systematic search of MEDLINE, Web of Science, Scopus, and LILACS databases was conducted on December 22, 2013, using the terms obsessive-compulsive disorder and electroconvulsive therapy. Reference lists, specific journals, and clinical trial registries were also scrutinized. No date or language limitation was imposed on the search. After irrelevant and redundant records from the 500 identified titles were excluded, the 50 articles reporting the acute treatment effects of ECT in OCD and related constructs (involving a total of 279 patients) were analyzed for this study. The relevant sociodemographic, clinical, and outcome data of individual cases were extracted. Data from individual cases were used to compare the characteristics of responders versus nonresponders to ECT. Most selected records were case reports/series; there were no randomized controlled trials. A positive response was reported in 60.4% of the 265 cases in which individual responses to ECT were available. ECT responders exhibited a significantly later onset of OCD symptoms (P = .003), were more frequently nondepressed (P = .009), more commonly reported being treated with ECT for severe OCD (P = .01), and received a fewer number of ECT sessions (P = .03). ECT responders were also less frequently previously treated with adequate trials of serotonin reuptake inhibitors (P = .05) and cognitive-behavioral therapy (P = .005). Although 60% of the reported cases reviewed exhibited some form of a positive response to ECT, it cannot be stated that this provides evidence that ECT is indeed effective for OCD.

Treating trichotillomania: A meta-analysis of treatment effects and moderators for behavior therapy and serotonin reuptake inhibitors

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.

Patient-reported outcomes before and after treatment of major depressive disorder

Patient reported outcomes (PROs) of quality of life (QoL), functioning, and depressive symptom severity are important in assessing the burden of illness of major depressive disorder (MDD) and to evaluate the impact of treatment. We sought to provide a detailed analysis of PROs before and after treatment of MDD from the large Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. This analysis examines PROs before and after treatment in the second level of STAR*D. The complete data on QoL, functioning, and depressive symptom severity, were analyzed for each STAR*D level 2 treatment. PROs of QoL, functioning, and depressive symptom severity showed substantial impairments after failing a selective serotonin reuptake inhibitor trial using citalopram (level 1). The seven therapeutic options in level 2 had positive statistically (P values) and clinically (Cohen's standardized differences [Cohen's d]) significant impact on QoL, functioning, depressive symptom severity, and reduction in calculated burden of illness. There were no statistically significant differences between the interventions. However, a substantial proportion of patients still suffered from patient-reported QoL and functioning impairment after treatment, an effect that was more pronounced in nonremitters. PROs are crucial in understanding the impact of MDD and in examining the effects of treatment interventions, both in research and clinical settings.

Treatment of Obsessive-Compulsive and Related Disorders

Pharmacotherapy and cognitive-behavioural therapy (CBT) have been studied in many of the obsessive-compulsive and related disorders (OCRDs). Serotonin reuptake inhibitors (SRIs) and cognitive-behavioural therapies (CBT) are first-line considerations in many, but not all, of these conditions. There are fewer data available on the combination of these treatment modalities in OCRDs. In obsessive-compulsive disorder (OCD), the SRIs and CBT – which include exposure and response prevention (ERP) – are well-established safe and efficacious first-line treatments in adult and paediatric populations. While various pharmacotherapy augmentation strategies have been studied, the most evidence-based approach to date is augmentation with antipsychotic agents. There is also evidence of the value of CBT in the management of treatment-refractory patients. A number of SRIs, such as clomipramine and fluoxetine, have shown efficacy in randomized controlled trials of the pharmacotherapy of body dysmorphic disorder (BDD). There are relatively few data on pharmacotherapy augmentation approaches in BDD. CBT has also been found efficacious in a number of psychotherapy trials of BDD. Less is known about the optimal treatment of the other OCRDs, i.e., hoarding disorder (HD), trichotillomania (hair-pulling disorder, or HPD), and excoriation (skin-picking) disorder (SPD). While patients with HD may have been included in RCTs on OCD, no data from randomized controlled trials of pharmacotherapy specifically for HD have been reported. There is some support for the value of CBT in HD. In HPD, controlled trials of olanzapine, N-acetyl cysteine (NAC), and clomipramine (vs. desipramine) have provided evidence of efficacy. There also is evidence supporting the efficacy of behaviour therapy in reducing hair-pulling. Results from randomized controlled trials of SRIs in SPD have been mixed, with some agents such as fluoxetine and citalopram demonstrating improvement on certain measures of picking behaviour. Behaviour therapy also appears to be useful for SPD.

BEHAVIORAL THERAPY AND SEROTONIN REUPTAKE INHIBITOR PHARMACOTHERAPY IN THE TREATMENT OF OBSESSIVE-COMPULSIVE DISORDER: A SYSTEMATIC REVIEW AND META-ANALYSIS OF HEAD-TO-HEAD RANDOMIZED CONTROLLED TRIALS

Effective treatments for obsessive-compulsive disorder (OCD) include behavioral therapy (exposure and response/ritual prevention and cognitive behavioral therapy) and serotonin-reuptake inhibitors (SRIs); however, the relative efficacy of these treatments is not well established. We sought to review evidence from head-to-head randomized-controlled trials (RCTs) of behavioral therapy and SRIs in the treatment of OCD. A systematic search of multiple databases was conducted from first available date to June 30, 2012, for RCTs in the treatment of OCD among outpatients, comparing behavioral therapy and SRIs, alone or combined. Two independent reviewers evaluated studies for eligibility and risk of bias. The main outcome measure was posttreatment mean Yale-Brown Obsessive-Compulsive Scale (YBOCS) score. We identified 2,186 unique articles. Fifteen articles were included, describing 13 RCTs. Pooled standardized mean difference (SMD; 95% confidence intervals) in YBOCS score significantly favored behavioral therapy over SRIs (0.37; 0.10, 0.64; P = .007), but not in a subset of trials that used selective SRIs (0.22; -0.02, 0.47; P = .070). Within individual trials, effect sizes significantly favored the combination of behavioral therapy plus an SRI over an SRI, but not behavioral therapy, alone. This review provides evidence that, among outpatients with OCD, behavioral therapy is more effective than SRIs, overall, but not selective SRIs. Furthermore, the combination of behavioral therapy plus an SRI is more effective than an SRI alone. These data may be used to inform the development of evidence-based treatment guidelines; however, more studies are also needed to further evaluate the relative efficacy of these interventions.

Double-Blind, Placebo-Controlled, Pilot Trial of Paliperidone Augmentation in Serotonin Reuptake Inhibitor–Resistant Obsessive-Compulsive Disorder

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). 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. 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). 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. ClinicalTrials.gov identifier: NCT00632229.