Helen Blair Simpson

A Randomized, Controlled Trial of Cognitive-Behavioral Therapy for Augmenting Pharmacotherapy in Obsessive-Compulsive Disorder

OBJECTIVE Although serotonin reuptake inhibitors (SRIs) are approved for the treatment of obsessive-compulsive disorder (OCD), most OCD patients who have received an adequate SRI trial continue to have clinically significant OCD symptoms. The purpose of this study was to examine the effects of augmenting SRIs with exposure and ritual prevention, an established cognitive-behavioral therapy (CBT) for OCD. METHOD A randomized, controlled trial was conducted at two academic outpatient clinics to compare the effects of augmenting SRIs with exposure and ritual prevention versus stress management training, another form of CBT. Participants were adult outpatients (N=108) with primary OCD and a Yale-Brown Obsessive Compulsive Scale total score > or = 16 despite a therapeutic SRI dose for at least 12 weeks prior to entry. Participants received 17 sessions of CBT (either exposure and ritual prevention or stress management training) twice a week while continuing SRI pharmacotherapy. RESULTS Exposure and ritual prevention was superior to stress management training in reducing OCD symptoms. At week 8, significantly more patients receiving exposure and ritual prevention than patients receiving stress management training had a decrease in symptom severity of at least 25% (based on Yale-Brown Obsessive Compulsive Scale scores) and achieved minimal symptoms (defined as a Yale-Brown Obsessive Compulsive Scale score < or = 12). CONCLUSIONS Augmentation of SRI pharmacotherapy with exposure and ritual prevention is an effective strategy for reducing OCD symptoms. However, 17 sessions were not sufficient to help most of these patients achieve minimal symptoms.

Randomized sham-controlled trial of repetitive transcranial magnetic stimulation in treatment-resistant obsessive-compulsive disorder

In open trials, 1-Hz repetitive transcranial magnetic stimulation (rTMS) to the supplementary motor area (SMA) improved symptoms and normalized cortical hyper-excitability of patients with obsessive-compulsive disorder (OCD). Here we present the results of a randomized sham-controlled double-blind study. Medication-resistant OCD patients (n=21) were assigned 4 wk either active or sham rTMS to the SMA bilaterally. rTMS parameters consisted of 1200 pulses/d, at 1 Hz and 100% of motor threshold (MT). Eighteen patients completed the study. Response to treatment was defined as a > or = 25% decrease on the Yale-Brown Obsessive Compulsive Scale (YBOCS). Non-responders to sham and responders to active or sham rTMS were offered four additional weeks of open active rTMS. After 4 wk, the response rate in the completer sample was 67% (6/9) with active and 22% (2/9) with sham rTMS. At 4 wk, patients receiving active rTMS showed on average a 25% reduction in the YBOCS compared to a 12% reduction in those receiving sham. In those who received 8-wk active rTMS, OCD symptoms improved from 28.2+/-5.8 to 14.5+/-3.6. In patients randomized to active rTMS, MT measures on the right hemisphere increased significantly over time. At the end of 4-wk rTMS the abnormal hemispheric laterality found in the group randomized to active rTMS normalized. The results of the first randomized sham-controlled trial of SMA stimulation in the treatment of resistant OCD support further investigation into the potential therapeutic applications of rTMS in this disabling condition.

Imipramine in the treatment of social phobia

We report the results of an 8-week open trial of imipramine in 15 patients with social phobia. Nine patients completed the trial; six dropped out early because of adverse effects. The mean reduction in the Liebowitz Social Anxiety Scale was 15% and 18% for the intent-to-treat and completer groups, respectively; the overall response rate (based on the Clinical Global Impression Scale of 1 or 2, very much or much improved) was 20% (3/15) and 22% (2/9), respectively. The results from this open trial do not support the efficacy of imipramine as a treatment for social phobia.

Cognitive-Behavioral Therapy vs Risperidone for Augmenting Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder: A Randomized Clinical Trial

IMPORTANCE Obsessive-compulsive disorder (OCD) is one of the worlds most disabling illnesses according to the World Health Organization. Serotonin reuptake inhibitors (SRIs) are the only medications approved by the Food and Drug Administration to treat OCD, but few patients achieve minimal symptoms from an SRI alone. In such cases, practice guidelines recommend adding antipsychotics or cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP). OBJECTIVE To compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial (conducted January 2007-August 2012) at 2 academic outpatient research clinics that specialize in OCD and anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of at least moderate severity despite a therapeutic SRI dose for at least 12 weeks prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n = 40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial. INTERVENTIONS While continuing their SRI at the same dose, patients were randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17 sessions delivered twice weekly), or pill placebo. Independent assessments were conducted every 4 weeks. MAIN OUTCOME AND MEASURE The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity. RESULTS Patients randomized to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on mixed-effects models (vs risperidone: mean [SE], -9.72 [1.38]; P < .001 vs placebo: mean [SE], -10.10 [1.68]; P < .001). Patients receiving risperidone did not significantly differ from those receiving placebo (mean [SE], -0.38 [1.72]; P = .83). More patients receiving EX/RP responded (Y-BOCS score decrease ≥25%: 80% for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients receiving EX/RP achieved minimal symptoms (Y-BOCS score ≤12: 43% for EX/RP, 13% for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to risperidone and placebo in improving insight, functioning, and quality of life. CONCLUSIONS AND RELEVANCE Adding EX/RP to SRIs was superior to both risperidone and pill placebo. Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered EX/RP before antipsychotics given its superior efficacy and less negative adverse effect profile. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00389493.

Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept

Serotonin reuptake inhibitors (SRIs), the first-line pharmacological treatment for obsessive-compulsive disorder (OCD), have two limitations: incomplete symptom relief and 2–3 months lag time before clinically meaningful improvement. New medications with faster onset are needed. As converging evidence suggests a role for the glutamate system in the pathophysiology of OCD, we tested whether a single dose of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, could achieve rapid anti-obsessional effects. In a randomized, double-blind, placebo-controlled, crossover design, drug-free OCD adults (n=15) with near-constant obsessions received two 40-min intravenous infusions, one of saline and one of ketamine (0.5 mg/kg), spaced at least 1-week apart. The OCD visual analog scale (OCD-VAS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess OCD symptoms. Unexpectedly, ketamine’s effects within the crossover design showed significant (p<0.005) carryover effects (ie, lasting longer than 1 week). As a result, only the first-phase data were used in additional analyses. Specifically, those receiving ketamine (n=8) reported significant improvement in obsessions (measured by OCD-VAS) during the infusion compared with subjects receiving placebo (n=7). One-week post-infusion, 50% of those receiving ketamine (n=8) met criteria for treatment response (⩾35% Y-BOCS reduction) vs 0% of those receiving placebo (n=7). Rapid anti-OCD effects from a single intravenous dose of ketamine can persist for at least 1 week in some OCD patients with constant intrusive thoughts. This is the first randomized, controlled trial to demonstrate that a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an SRI and is consistent with a glutamatergic hypothesis of OCD.

Patient adherence predicts outcome from cognitive behavioral therapy in obsessive-compulsive disorder.

OBJECTIVE To examine the effects of patient adherence on outcome from exposure and response prevention (EX/RP) therapy in adults with obsessive-compulsive disorder (OCD). METHOD Thirty adults with OCD were randomized to EX/RP (n = 15) or EX/RP augmented by motivational interviewing strategies (n = 15). Both treatments included 3 introductory sessions and 15 exposure sessions. Because there were no significant group differences in adherence or outcome, the groups were combined to examine the effects of patient adherence on outcome. Independent evaluators assessed OCD severity using the Yale-Brown Obsessive Compulsive Scale. Therapists assessed patient adherence to between-session EX/RP assignments at each session using the Patient EX/RP Adherence Scale (PEAS). Linear regression models were used to examine the effects of PEAS scores on outcome, adjusting for baseline severity. The relationship between patient adherence and other predictors of outcome was explored using structural equation modeling. RESULTS Higher average PEAS ratings significantly predicted lower posttreatment OCD severity in intent-to-treat and completer samples. PEAS ratings in early sessions (5-9) also significantly predicted posttreatment OCD severity. The effects of other significant predictors of outcome in this sample (baseline OCD severity, hoarding subtype, and working alliance) were fully mediated by patient adherence. CONCLUSIONS Patient adherence to between-session EX/RP assignments significantly predicted treatment outcome, as did early patient adherence and change in early adherence. Patient adherence mediated the effects of other predictors of outcome. Future research should develop interventions that increase adherence and then test whether increasing adherence improves outcome. If effective, these interventions could then be used to personalize care.

Impulse control disorders and “behavioural addictions” in the ICD-11

Psychiatric classifications have traditionally recognized a number of conditions as representing impulse control disorders. These have included pathological gambling, intermittent explosive disorder, kleptomania, pyromania, and trichotillomania.

Challenges Using Motivational Interviewing as an Adjunct to Exposure Therapy for Obsessive-Compulsive Disorder

Exposure and response prevention (EX/RP) is an efficacious treatment for obsessive-compulsive disorder (OCD). However, patients often do not adhere fully to EX/RP procedures. Motivational interviewing (MI) has been shown to improve treatment adherence in other disorders. This pilot study used a randomized controlled design to examine whether MI can be successfully added to EX/RP and whether this intervention (EX/RP+MI) could improve patient adherence to between-session EX/RP procedures relative to EX/RP alone. Thirty adults with OCD were randomized to 18 sessions of EX/RP or EX/RP+MI. Therapists rated patient adherence at each exposure session. Independent evaluators assessed change in OCD and depressive symptoms, and patients completed self-report measures of readiness for change and quality of life. The two treatment conditions differed in degree of congruence with MI but not in conduct of EX/RP procedures. Both groups experienced clinically significant improvement in OCD symptoms, without significant group differences in patient adherence. There are several possible reasons why EX/RP+MI had no effect on patient adherence compared to standard EX/RP, each of which has important implications for the design of future MI studies in OCD. We recommend that MI be further evaluated in OCD by exploring alternative modes of delivery and by focusing on patients less ready for change than the current sample.

Adding motivational interviewing to exposure and ritual prevention for obsessive-compulsive disorder: an open pilot trial.

Exposure and ritual prevention (EX/RP) is an efficacious treatment for obsessive–compulsive disorder (OCD), but high dropout rates and variable treatment adherence limit its effectiveness. Motivational interviewing (MI) has shown promise as an adjunct to symptom‐focused treatments for improving treatment adherence and outcomes. The authors developed a manual integrating MI with EX/RP, consisting of three information‐gathering/motivational enhancement sessions and 15 EX/RP sessions with an optional MI module to be used as needed. Six patients with moderate to severe OCD symptoms (Yale‐Brown Obsessive Compulsive Scale [Y‐BOCS] score⩾16) underwent treatment. Five showed a decrease in their baseline Y‐BOCS scores and an increase in their quality of life, with three achieving an excellent response (i.e. Y‐BOCS⩽12 at Session 18). The authors briefly describe the motivational strategies used in the six cases and suggest that integrating MI with standard EX/RP is a promising method to increase and sustain patient engagement with EX/RP. Challenges in combining these treatments and maintaining the integrity of each as well as limitations of the study are discussed.

The classification of Obsessive-Compulsive and Related Disorders in the ICD-11.

BACKGROUND To present the rationale for the new Obsessive-Compulsive and Related Disorders (OCRD) grouping in the Mental and Behavioural Disorders chapter of the Eleventh Revision of the World Health Organizations International Classification of Diseases and Related Health Problems (ICD-11), including the conceptualization and essential features of disorders in this grouping. METHODS Review of the recommendations of the ICD-11 Working Group on the Classification for OCRD. These sought to maximize clinical utility, global applicability, and scientific validity. RESULTS The rationale for the grouping is based on common clinical features of included disorders including repetitive unwanted thoughts and associated behaviours, and is supported by emerging evidence from imaging, neurochemical, and genetic studies. The proposed grouping includes obsessive-compulsive disorder, body dysmorphic disorder, hypochondriasis, olfactory reference disorder, and hoarding disorder. Body-focused repetitive behaviour disorders, including trichotillomania and excoriation disorder are also included. Tourette disorder, a neurological disorder in ICD-11, and personality disorder with anankastic features, a personality disorder in ICD-11, are recommended for cross-referencing. LIMITATIONS Alternative nosological conceptualizations have been described in the literature and have some merit and empirical basis. Further work is needed to determine whether the proposed ICD-11 OCRD grouping and diagnostic guidelines are mostly likely to achieve the goals of maximizing clinical utility and global applicability. CONCLUSION It is anticipated that creation of an OCRD grouping will contribute to accurate identification and appropriate treatment of affected patients as well as research efforts aimed at improving our understanding of the prevalence, assessment, and management of its constituent disorders.