A 2-year study of sertraline in the treatment of obsessive-compulsive disorder

The present study investigated the tolerability, safety profile, and anti-obsessional efficacy of sertraline, a selective serotonin reuptake inhibitor, during long-term treatment of patients with obsessive-compulsive disorder (OCD). Fifty-nine OCD patients who had completed a 1 year double-blind, fixed dose study comparing sertraline and placebo subsequently entered a 1-year open extension. Among the 51 patients who had been treated with sertraline during the double-blind phase, the mean total duration of sertraline treatment was 690 days. Only treatment responders who completed the 52-week double-blind treatment phase were permitted to enter the open extension. The higher rate (p < 0.02) of sertraline patients (51 out of 241) than of placebo patients (eight out of 84), who responded to treatment and entered the open-label phase is therefore consistent with the greater mean improvement observed in the sertraline group during double-blind treatment. Placebo responders differed from sertraline responders in that they were less impaired at baseline of the double-blind study [Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) of 18.5 versus 23.4] and they exhibited less improvement during double-blind treatment (-6.1 versus -11.4). In the open-label phase all patients received sertraline at a starting dose of 50 mg once a day, titrated in 50 mg increments to a maximum dose of 200 mg according to clinical response. At end-point the mean Y-BOCS score for all patients decreased by a further 3.6 points. Patients previously treated with placebo showed greater improvement after being switched to sertraline than those who received continued sertraline treatment. Patients who completed the study and received 2 full years of sertraline treatment (n = 38) exhibited a mean improvement of 15.6 points using the Y-BOCS. Sertraline was well tolerated during both the double-blind phase and the open extension, and the incidence of adverse experiences was generally reduced during the second year of treatment. Three patients discontinued open treatment because of adverse experiences. Long-term sertraline treatment did not appear to be associated with the emergence, increased incidence, or increased severity of adverse experiences or clinically significant abnormalities in laboratory tests, vital signs, or the electrocardiogram. The study supports the long-term safety and tolerability of sertraline over a 2-year treatment course and the sustained efficacy of sertraline in patients with OCD.     

Neurosurgical treatment of obsessive-compulsive disorder

BACKGROUND: Case reports suggest that neurosurgical operations can improve symptoms in patients with severe treatment-refractory obsessive-compulsive disorder (OCD). However, it is unclear which procedure is best and which may produce the most side-effects. METHOD: I review the literature on the efficacy and complications of four frequently used neurosurgical procedures (cingulotomy, capsulotomy, limbic leucotomy and subcaudate tractotomy) that are used to treat refractory OCD. RESULTS: Since the vast majority of patients who underwent surgery were severely and chronically disabled, it is likely that these procedures were of assistance in alleviating some of their symptoms. It is currently impossible to determine which surgical procedure is the best for a particular patient. CONCLUSIONS: Despite a lack of controlled data and inconsistencies in the literature, it appears that when non-surgical treatments have failed to improve OCD symptoms significantly in severely ill patients, at least partial relief can be obtained by some people with OCD by neurosurgery. Results of cumulative studies strongly support the need for continued research in this area.     

Long-term treatment of psychotic (delusional) depression with fluvoxamine: an open pilot study

The aim of this open pilot study was to evaluate the efficacy of fluvoxamine in the continuation as well as in the maintenance therapy of delusional depression. Thirty patients with recurrent, unipolar depression (DSM-IV criteria) were selected who had at least one depressive episode during the 18 months preceding the delusional depressive index episode and were treated with fluvoxamine 300 mg/day. Twenty-five of them had a sustained response to this short-term treatment and agreed to enter into the 30-month follow up study. All participants completed the follow up period. No relapse was observed during the 6 months of continuation therapy. During the further 24 months of maintenance therapy, 80% of the patients remained well, whereas 20% (five out of 25) had a single recurrence. Based on these observations, fluvoxamine might be a promising drug for long-term therapy of delusional depression. Further controlled studies are required to confirm this finding.     

Body dysmorphic disorder as an obsessive-compulsive spectrum disorder

Considerable evidence supports consideration of body dysmorphic disorder (BDD) and obsessive-compulsive disorder as related disorders. BDD may share common phenomenological and neurobiological features with OGD and other disorders characterized by repetitive thoughts and behaviors and mediated by serotonin dysfunction. Within this substrate, specific psychological and sociological factors may shape the specific BDD syndrome. Further research incorporating dimensional models of these disorders, may delineate specific similarities and differences.     

Concerns regarding study of obsessive-compulsive disorder in dogs

Thromboembolism is rarely considered in discussions of the complications of blunt chest trauma. The few cases of thromboembolism that have been reported in this setting have occurred in association with significant myocardial damage. A previously fit 23 year old woman was admitted to the intensive care unit following a road traffic accident. A day later, left atrial thrombus was demonstrated by transoesophageal echocardiography in the absence of any other evidence of important myocardial injury. Anticoagulation with heparin was cautiously introduced in spite of her extensive injuries, and there were no consequent bleeding complications. At hospital discharge on day 18 she was entirely well. Full anticoagulation with warfarin was continued for a further eight weeks at which time follow up transoesophageal echocardiography showed complete resolution of the thrombus.     

A 1 year double-blind placebo-controlled fixed dose study of sertraline in the treatment of obsessive-compulsive disorder

The objective of this study was to evaluate the safety and efficacy, over a 1 year treatment period, of three dose levels of sertraline and placebo in the treatment of non-depressed adult out-patients with obsessive-compulsive disorder (OCD). Following 1 week of single-blind placebo washout, patients (n = 325) from 11 sites following identical protocols were randomly assigned to 12 weeks of double-blind treatment with one of three fixed doses of sertraline (50, 100 or 200 mg) or placebo. At the end of 12 weeks, treatment responders (including placebo patients) were offered an additional 40 weeks of double-blind treatment at their assigned doses. Efficacy measures were the Yale-Brown Obsessive Compulsive Scale, the NIMH Global Obsessive Compulsive Scale, Clinical Global Impressions of Severity of Illness and Global Improvement and the Maudsley Obsessive Compulsive Inventory. Patients in the pooled sertraline group showed greater improvement than placebo-treated patients on all efficacy measures, based on the endpoint analyses. Moreover, pairwise comparisons at endpoint revealed a significant effect on all three investigator-rated scales in patients receiving 50 or 200 mg of sertraline; in the 100 mg group, there was a significant effect on the NIMH Global Obsessive Compulsive Scale only. Patients completing 3 months of sertraline treatment exhibited excellent toleration and sustained improvement during an additional 40 weeks of therapy. Results support the safety, efficacy and tolerability of daily doses of 50-200 mg of sertraline in the long-term treatment of patients with OCD.     

Beliefs in obsessive-compulsive disorder

Several types of beliefs have been hypothesized to be associated with obsessive-compulsive disorder (OCD), including responsibility for harm, need to control thoughts, overestimates of threat, intolerance of uncertainty, and beliefs about the consequences of anxiety and capacity to cope. The present study compared 62 subjects with OCD, 45 with other anxiety disorders (AD) and 34 controls, using 3 measures of OCD-related beliefs. OCD subjects scored higher than AD and control samples on 2 general belief measures. A closer analysis of specific belief domains indicated that OCD subjects scored higher than AD and control subjects on all 6 specific belief domains (responsibility, control, estimation of threat, tolerance of uncertainty, beliefs about the consequences of anxiety, and the capacity to cope). Four of the 6 domains showed reasonable convergent and discriminant validity with measures of OCD symptoms compared to other psychopathology; anxiety and coping beliefs were the exceptions. In regression analyses, cognitive measures contributed significant explanatory power beyond mood state and worry with uncertainty predicting severity of OCD symptoms above all other belief domains. Further research on OCD-relevant belief domains in etiology, maintenance and treatment is warranted.     

Relapse prevention program for treatment of obsessive-compulsive disorder.

18 participants with obsessive-compulsive disorder received 3 wks of intensive treatment by exposure and response prevention, which were followed by either a relapse prevention (RP) program or associative therapy (AT; an attention-control program). Independent evaluators conducted assessments of obsessive-compulsive symptoms, anxiety, and depression, before and after intensive behavior therapy, after the week of intensive RP or AT and at a 6-mo follow-up. Results indicated that the RP program was effective in preventing relapse: Both treatment groups improved immediately after the intensive treatment, but the RP group remained improved at follow-up, whereas the AT group showed some return of symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stability of diagnosis of obsessive-compulsive disorder in the Epidemiologic Catchment Area study

OBJECTIVE: This study examined the 1-year temporal stability of a National Institute of Mental Health Diagnostic Interview Schedule (DIS) lifetime diagnosis of obsessive-compulsive disorder in the Epidemiologic Catchment Area (ECA) study. METHOD: In that study, 20,862 individuals, aged 18 years and over, at five sites were evaluated by lay interviewers using the DIS (wave 1). All of those who were available 12 months later were reinterviewed (wave 2). In the present study, the temporal stability of wave 1 obsessive-compulsive disorder diagnoses at wave 2 was examined, as well as relationships with comorbid diagnoses. The consistency of reports of "new-onset" illness was also examined. Factors contributing to these measures were evaluated. RESULTS: The temporal stability of the diagnosis of obsessive-compulsive disorder was very low. Subjects with a stable diagnosis of obsessive-compulsive disorder had a higher rate of both obsessions and compulsions, an earlier age at onset, and more comorbid anxiety, affective, and alcohol abuse/dependence disorders at initial assessment. The originally reported 1-year incidence estimates for obsessive-compulsive disorder primarily reflect data from subjects at wave 2 who reported the onset of symptoms as preceding the wave 1 interview. Older and less-educated subjects had significantly higher error rates in reporting onset. CONCLUSIONS: The DIS diagnosis of obsessive-compulsive disorder has poor validity, leaving the true incidence and prevalence of the disorder unknown. Older and less-educated subjects require special attention in the design of instruments for use with community samples.     

Improvement predictors in obsessive-compulsive disorder. An event-related potential study

The maturation of HIV-1 virions is accomplished through the proteolytic cleavage of Gag and GagPol precursor polyproteins by the viral-encoded protease (PR). Since virions are assembled from unprocessed polyproteins, the intracellular activation of PR must be limited. An experimental system was established that allows the investigation of the intracellular regulation of PR activity. By expressing Gag in trans with the GagPol precursor, downregulation of the intracellular PR activity associated with GagPol was demonstrated. Inhibition of PR activity was dependent upon the context of PR expression. Sequences capable of mediating this inhibition were localized to capsid. A mechanism through which Gag regulates PR activity is proposed whereby the disproportionate synthesis of Gag inhibits the activation of PR in the cytoplasm. Further elucidation of the mechanism of intracellular inhibition of PR activity may facilitate the development of novel PR inhibitors capable of inhibiting viral replication in vivo.     

Cognitive-behavioral therapy with and without medication in the treatment of obsessive-compulsive disorder.

Cognitive-behavioral therapy (CBT) and pharmacotherapy with serotonin reuptake inhibitors (SRIs) are established monotherapies for obsessive-compulsive disorder (OCD), yet research on their combined efficacy is lacking. Practicing psychologists who treat OCD are thus unable to say definitively whether exposure and ritual prevention would be more successful with concomitant SRI pharmacotherapy. The authors explored this issue in a clinical sample of 56 outpatients who received fee-for-service CBT; 31 (55%) received CBT alone, and 25 (45%) received CBT plus SRI. Both groups made clinically significant and comparable posttreatment gains, suggesting that CBT is effective with or without concomitant pharmacotherapy. Clinical implications are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cytokine production in obsessive-compulsive disorder

Cytokine production was previously demonstrated to be reduced in untreated major affective patients. In addition, recovery from depression following clomipramine (CMI) treatment was accompanied by the restoration of interleukin-1 beta (IL-1 beta) and interleukin-3-like activity (IL-3-LA) to normal range. In the present study we assessed the in vitro production of IL-1 beta IL-2, and IL-3-LA by peripheral blood mononuclear cells (PBMC) in 11 nondepressed patients with obsessive compulsive disorder (OCD) before and after 8 weeks of CMI treatment. Results were compared with those of 11 healthy subjects. CMI treatment induced a significant improvement in OCD symptoms. No alteration was observed in cytokine production in OCD patients before treatment as compared to control subjects. Moreover, 8 weeks of drug treatment had no effect on cytokine production. In conclusion, OCD per se, as well as CMI treatment, have no effect on interleukin production as measured in this study.     

Disgust implicated in obsessive-compulsive disorder

Psychiatric classificatory systems consider obsessions and compulsions as forms of anxiety disorder. However, the neurology of diseases associated with obsessive-compulsive symptoms suggests the involvement of fronto-striatal regions likely to be involved in the mediation of the emotion of disgust, suggesting that dysfunctions of disgust should be considered alongside anxiety in the pathogenesis of obsessive-compulsive behaviours. We therefore tested recognition of facial expressions of basic emotions (including disgust) by groups of participants with obsessive-compulsive disorder (OCD) and with Gilles de la Tourette's syndrome (GTS) with an without co-present obsessive-compulsive behaviours (GTS with OCB; GTS without OCB). A group of people suffering from panic disorder and generalized anxiety were also included in the study. Both groups with obsessive-compulsive symptoms (OCD; GTS with OCB) showed impaired recognition of facial expressions of disgust. Such problems were not evident in participants with panic disorder and generalized anxiety, or for participants with GTS without obsessions or compulsions, indicating that the deficit is closely related to the presence of obsessive-compulsive symptoms. Participants with OCD were able to assign words to emotion categories without difficulty, showing that their problem with disgust is linked to a failure to recognize this emotion in others and not a comprehension or response criterion effect. Impaired recognition of disgust is consistent with the neurology of OCD and with the idea that abnormal experience of disgust may be involved in the genesis of obsessions and compulsions.     

Computational model of obsessive-compulsive disorder: examination of etiologic hypothesis and treatment strategies

Research has shown that obsessive compulsive disorder (OCD) is related to structural and functional abnormalities in the brain, and several authors have organized these findings into theories of OCD neuropsychiatric dysfunction. In this paper, these theories were used to develop a neural network model of OCD. OCD symptoms were hypothesized to result from a hyperactive orbitofrontal-striato-thalamic-orbitofrontal neural loop. The network was constructed and trained with a backpropagation algorithm, and it was then used to assess etiologic theories of OCD (e.g., basal ganglia dysfunction, inadequate dopaminergic inhibitory influence on basal ganglia and excessive input from the limbic system). The network was also observed in analogues of the treatment of OCD with serotonergic medications and behavior therapy. Results show that a) the network behaved both normally and abnormally, depending on what combinations of perceptual, motivational, and neurochemical inputs were presented to it; b) several etiologic mechanisms produced changes in the networks' behaviors similar to patients' subjective experiences of OCD symptoms; and c) different treatment strategies, both those modeled as pharmacologic and behavioral therapies, produced reductions in simulated OCD symptoms.     

Symptoms of attention-deficit hyperactivity disorder in an Italian school sample: findings of a pilot study

OBJECTIVE: The objective of this study was to complete a teacher questionnaire on a sample of children (N = 232) in nine fourth grade classes in schools in two regions of central Italy to assess the frequency of occurrence of symptoms of attention-deficit hyperactivity disorder (ADHD) and the rates of probable cases in the sample. METHOD: Each ADHD symptom was rated by the teacher as either absent (0), sometimes present (1) or frequently present (2). RESULTS: Of the children 3.9% had eight or more DSM-III-R Criterion A symptoms of ADHD scored at a "frequent" level (score of 2) and were considered to be "likely cases" of ADHD; an additional 6.9% did not meet this threshold but had a total score of 16 or more on the scale and were considered to be "possible cases." CONCLUSIONS: The findings suggest the need for more systematic epidemiological investigations to evaluate the true prevalence of the syndrome and its risk factors in the Italian population.     

Behavior therapy and tricyclic medication in the treatment of obsessive-compulsive disorder: A quantitative review.

A meta-analysis was used to integrate the research literature on the treatment of obsessive-compulsive disorder. Antidepressants, such as clomipramine, and behavior therapy have produced appreciable changes in obsessive-compulsive and depressive symptoms. Patients with obsessions who did not suffer from compulsions have responded less to treatment. No follow-up data have been available for clomipramine, but the benefits of behavior therapy have been shown to be stable at follow-up. Ratings of improvement by assessors have been higher than ratings made by patients. The effects of tricyclic medication and exposure therapies have not significantly differed, but both have proven significantly superior to nonspecific treatment programs. There is a need for a large, randomized comparison of clomipramine and exposure that includes adequate follow-up of subjects after treatment has concluded. (PsycINFO Database Record (c) 2010 APA, all rights reserved)