Abstracts for Obsessive-Compulsive Disorder

Pharmacotherapies in the Management of Obsessive-Compulsive Disorder

Blier P, Habib R, Flament MF

Canadian Journal of Psychiatry 6 2006; 51(7): 417– 30

Available online at http://ww1.cpa-apc.org:8080/Publications/Archives/CJP/2006/june/cjp-june-06-blier-IR.pdf

Few medications are effective in treating obsessive-compulsive disorder (OCD). As monotherapy, only potent serotonin (5-HT) reuptake inhibitors (SRIs) consistently exert an intrinsic therapeutic action in OCD. Their use in OCD, however, differs from their use in depression. This paper first reviews the evidence supporting the key role of 5-HT as a pivotal neurotransmitter in the anti-OCD response. Then, we describe the practicalities of SRI use, followed by the steps that can be taken when these medications do not produce an adequate clinical response. We provide specifics for the treatment of children and adolescents with OCD. We include a brief description of the brain circuitry involved in OCD and the mechanisms of action of the pharmacologic agents reported to be effective in this disorder, as well as those that are useful in depression but not in OCD. We present this information to promote better understanding of the research endeavours needed to develop new pharmacotherapeutic approaches.

Brain Stimulation Techniques in the Treatment of Obsessive-Compulsive Disorder: Current and Future Directions

Dell'Osso B, Altamura AC, Allen A, Hollander E

CNS Spectrums 12 2005; 10(12): 966– 79, 983

Recent studies on the epidemiology of obsessive-compulsive disorder (OCD) estimate 50 million patients suffer from OCD worldwide, thus making it a global problem. The treatment of OCD has changed substantially over the last 2 decades following the introduction of selective serotonin reuptake inhibitors, which provide symptom improvement in approximately 60% of patients. However, some patients remain resistant to the standard pharmacologic and behavioral treatments. Although some treatment-resistant patients respond to pharmacologic augmentations, others do not, and there is evidence that some of the most severe cases benefit from treatment with neurosurgical interventions. Besides pharmacologic, behavioral, and neurosurgical approaches, different brain stimulation methods-transcranial magnetic stimulation, deep brain stimulation, and electroconvulsive therapy-have been investigated in treatment-resistant patients with OCD. However, available data about the use of these techniques in OCD treatment are quite limited in terms of sample size and study design, given the difficulty in conducting standard blinded trials for these procedures. In addition, none of the mentioned treatments have received Food and Drug Administration approval for the treatment of OCD. Nevertheless, promising findings regarding efficacy, tolerability, and non-invasiveness and/or reversibility of these techniques have increased interest in investigating their use in treatment-resistant OCD.

Cognitive Therapy and Exposure in Vivo Alone and in Combination with Fluvoxamine in Obsessive-Compulsive Disorder: A 5-Year Follow-Up

van Oppen P, van Balkom AJ, de Haan E, van Dyck R

Journal of Clinical Psychiatry 11 2005; 66(11): 1415– 22

Background: Information regarding the long-term effectiveness of the combination of pharmacotherapy and cognitive-behavioral therapy (CBT) in the treatment of obsessive-compulsive disorder (OCD) is limited. Our study is the first to examine the long-term effectiveness of cognitive therapy (CT) and to compare long-term effectiveness of CT alone, exposure in vivo with response prevention (ERP) alone, and CBT (either CT or ERP) in combination with fluvoxamine in the treatment of OCD. Method: Of 122 outpatients with primary DSM-III-R-defined OCD originally enrolled in 2 randomized controlled trials, 102 patients (45 male/57 female; mean +/− SD age = 36.2 +/− 10.7 years; range, 19–64 years) were available to be assessed for the presence and severity of OCD and comorbid psychopathology at follow-up. Follow-up data were collected from November 1996 to June 1999. Results: After 5 years, 54% of the participants no longer met the DSM-III-R criteria for OCD. Long-term outcome did not differ between the 3 treatment groups. At follow-up, treatment dropouts appeared to have more severe OCD complaints compared with treatment completers. Compared with patients receiving CT alone, significantly (p <.005) more patients receiving CBT with fluvoxamine used antidepressants 5 years later. Conclusions: This study demonstrates that at 5-year follow-up (1) prevalence of OCD had declined in all 3 treatment conditions, (2) the clinical benefits of all 3 treatment conditions were maintained, (3) OCD complaints were more severe for treatment dropouts than for treatment completers, and (4) about half of the patients initially treated with fluvoxamine continued antidepressant use.

Behavior Therapy Augments Response of Patients with Obsessive-Compulsive Disorder Responding to Drug Treatment

Tenneij NH, van Megen HJ, Denys DA, Westenberg HG

Journal of Clinical Psychiatry 9 2005; 66(9): 1169– 75

Objective: In many patients with obsessive-compulsive disorder (OCD), residual symptoms persist despite a clinically meaningful response. The objective of this study was to examine whether addition of behavior therapy would augment treatment outcome in these patients. Method: Ninety-six patients with DSM-IV OCD who had responded to 3 months of drug treatment were randomly assigned to either receive addition of behavior therapy or continue on drug treatment alone for 6 months. Patients who continued on drug treatment alone eventually received addition of behavior therapy for 6 months. Data were gathered from October 1998 to June 2002. Results: OCD patients who received addition of behavior therapy showed a greater improvement in obsessive-compulsive symptoms (Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score change = −3.9 in the completers sample) than those who continued on drug treatment alone (Y-BOCS score change = +3.9 for completers). Significantly more patients who received addition of behavior therapy were in remission compared with those who continued on drug treatment alone (p < .0001 for completers). Patients who received behavior therapy after 6 months of drug treatment alone showed a nonsignificant decline in obsessive-compulsive symptoms (Y-BOCS score change = −2.7 for completers); however, the remission rate found in this group was comparable to the remission rate found in the group of patients receiving addition of behavior therapy directly after responding to drug treatment. Conclusion: The results indicate that addition of behavior therapy is beneficial for patients who have responded to drug treatment. The data also suggest that the effect is greater when behavior therapy is added immediately after attainment of the drug response.

Obsessive-Compulsive Disorder Phenotypes: Implications for Genetic Studies

Miguel EC, Leckman JF, Rauch S, do Rosario-Campos MC, Hounie AG, Mercadante MT, Chacon P, Pauls DL

Molecular Psychiatry 3 2005; 10(3): 258– 75

Obsessive-compulsive disorder (OCD) clinical presentation is remarkably diverse, and can vary both within and across patients over time. This variability in the phenotypic expression has led to the hypothesis that OCD is a heterogeneous disorder and that this heterogeneity obscures the findings of clinical, natural history and treatment response studies and complicates the search for vulnerability genes. A complete understanding of what comprises OCD and the underlying etiological mechanisms will require a dramatic change in how the disorder is conceptualized. In this review, several different approaches that may represent the first steps in this reconceptualization are discussed. These approaches include (1) narrowing the phenotype to identify categorically defined more homogeneous and mutually exclusive subtypes of OCD, (2) considering OC symptom dimensions as quantitative components of the more complex OCD phenotype and (3) broadening the phenotype to include other etiologically related conditions. A combined dimensional approach within distinctive subgroups is proposed as probably the most effective in helping to identify the heritable components of OCD. By identifying heritable components of OCD, it should be possible to find genes for these separate components. The review continues with the illustration of the possible role of some epigenetic risk and protective factors in the OCD presentation and the relevance of examining associated traits and/or endophenotypes to enhance our ability to understand the genetic basis of OCD. To conclude, we discuss the variability in treatment outcome and the significance of the development of specific pharmacological and/or behavioral based therapies tailored to each of these phenotypes.

A Multidimensional Model of Obsessive-Compulsive Disorder

Mataix-Cols D, Rosario-Campos MC, Leckman JF

American Journal of Psychiatry 2 2005; 162(2): 228– 38

Objective: Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition. This heterogeneity can reduce the power and obscure the findings from natural history studies to genome scans, neuroimaging, and clinical trials. The authors review the evidence supporting a multidimensional model of OCD. Method: Computerized and manual literature searches were performed to identify factor-analytic studies of obsessive-compulsive symptoms before data from disciplines that bear on the potential usefulness of these dimensions were considered. Selection criteria included the novelty and importance of studies and their relevance to outcomes of interest to well-informed mental health professionals. Results: Twelve factor-analytic studies involving more than 2,000 patients were identified that consistently extracted at least four symptom dimensions: symmetry/ordering, hoarding, contamination/cleaning, and obsessions/checking. These dimensions were associated with distinct patterns of comorbidity, genetic transmission, neural substrates, and treatment response. The evidence supporting the hoarding dimension is particularly robust. Conclusions: The complex clinical presentation of OCD can be summarized with a few consistent, temporally stable symptom dimensions. These can be understood as a spectrum of potentially overlapping syndromes that may 1) coexist in any patient, 2) be continuous with normal obsessive-compulsive phenomena, and 3) extend beyond the traditional nosological boundaries of OCD. Although the dimensional structure of obsessive-compulsive symptoms is imperfect, this quantitative approach to phenotypic traits has the potential to advance our understanding of OCD and may aid in the identification of more robust endophenotypes. The need for a dimensional rating scale and suggestions for future research aimed at reducing the burden of this disorder are discussed.

Cognitive-Behavior Therapy, Sertraline, and Their Combination for Children and Adolescents with Obsessive-Compulsive Disorder: the Pediatric OCD Treatment Study (POTS) Randomized Controlled Trial

Pediatric OCD Treatment Study (POTS) Team

The Journal of the American Medical Association 10; 27 2004; 292(16): 1969– 76

Context: The empirical literature on treatment of obsessive-compulsive disorder (OCD) in children and adolescents supports the efficacy of short-term OCD-specific cognitive-behavior therapy (CBT) or medical management with selective serotonin reuptake inhibitors. However, little is known about their relative and combined efficacy. Objective: To evaluate the efficacy of CBT alone and medical management with the selective serotonin reuptake inhibitor sertraline alone, or CBT and sertraline combined, as initial treatment for children and adolescents with OCD. Design, Setting, and Participants: The Pediatric OCD Treatment Study, a balanced, masked randomized controlled trial conducted in 3 academic centers in the United States and enrolling a volunteer outpatient sample of 112 patients aged 7 through 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD and a Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score of 16 or higher. Patients were recruited between September 1997 and December 2002. Interventions: Participants were randomly assigned to receive CBT alone, sertraline alone, combined CBT and sertraline, or pill placebo for 12 weeks. Main Outcome Measures: Change in CY-BOCS score over 12 weeks as rated by an independent evaluator masked to treatment status; rate of clinical remission defined as a CY-BOCS score less than or equal to 10. Results: Ninety-seven of 112 patients (87%) completed the full 12 weeks of treatment. Intent-to-treat random regression analyses indicated a statistically significant advantage for CBT alone (P = .003), sertraline alone (P = .007), and combined treatment (P = .001) compared with placebo. Combined treatment also proved superior to CBT alone (P = .008) and to sertraline alone (P = .006), which did not differ from each other. Site differences emerged for CBT and sertraline but not for combined treatment, suggesting that combined treatment is less susceptible to setting-specific variations. The rate of clinical remission for combined treatment was 53.6% (95% confidence interval [CI], 36%–70%); for CBT alone, 39.3% (95% CI, 24%–58%); for sertraline alone, 21.4% (95% CI, 10%–40%); and for placebo, 3.6% (95% CI, 0%–19%). The remission rate for combined treatment did not differ from that for CBT alone (P = .42) but did differ from sertraline alone (P = .03) and from placebo (P < .001). CBT alone did not differ from sertraline alone (P = .24) but did differ from placebo (P = .002), whereas sertraline alone did not (P = .10). The 3 active treatments proved acceptable and well tolerated, with no evidence of treatment-emergent harm to self or to others. Conclusion: Children and adolescents with OCD should begin treatment with the combination of CBT plus a selective serotonin reuptake inhibitor or CBT alone.

PANDAS: Current Status and Directions for Research

Snider LA, Swedo SE

Molecular Psychiatry 10 2004; 9(10): 900– 7

The recognition of the five criteria for PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) by Swedo et al established a homogenous subgroup of children with childhood onset obsessive-compulsive disorder (OCD) and/or tic disorders. The five clinical characteristics that define the PANDAS subgroup are the presence of OCD and/or tic disorder, prepubertal age of onset, abrupt onset and relapsing-remitting symptom course, association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity), and a temporal association between symptom exacerbations and a Group-A beta-hemolytic streptococcal (GAS) infection. These five criteria have been used for the purpose of systematic research on the phenomenology and unique therapies for the PANDAS subgroup as well as studies of the pathophysiology of post-streptococcal OCD and tic disorders. The etiology of OCD and tics in the PANDAS subgroup is unknown, but is theorized to occur as a result of post-streptococcal autoimmunity in a manner similar to that of Sydenham's chorea. The working hypothesis for the pathophysiology begins with a GAS infection in a susceptible host that incites the production of antibodies to GAS that crossreact with the cellular components of the basal ganglia, particularly in the caudate nucleus and putamen. The obsessions, compulsions, tics, and other neuropsychiatric symptoms seen in these children are postulated to arise from an interaction of these antibodies with neurons of the basal ganglia.