Proton magnetic resonance spectroscopy reveals an abnormality in the anterior cingulate of a subgroup of obsessive-compulsive disorder patients

Numerous neuroimaging studies have suggested that obsessive-compulsive disorder (OCD) patients had a neurobiological abnormality in the frontal-subcortical circuits. On the other hand, there are distinct differences in the responses to pharmacological treatment among OCD patients. In the present study, we measured the concentration of N-acetyl aspartate (NAA), a putative marker of neuronal viability, with proton magnetic resonance spectroscopy (MRS) in OCD patients with different pharmacological responses. Participants comprised 20 patients and 26 healthy control subjects. OCD patients were divided into three groups according to the pharmacological response; responders to a selective serotonin reuptake inhibitor (SSRI) (group A: n=7), responders to SSRI with an atypical antipsychotic (group B: n=8) and non-responders to either SSRI or SSRI with an atypical antipsychotic (group C: n=5). Short echo proton MRS was used to measure NAA concentrations in the anterior cingulate, the left basal ganglia and the left prefrontal lobe of subjects. A significantly lower NAA concentration was observed only in group B compared with control subjects in the anterior cingulate. Our results suggest that a subgroup of OCD patients who respond to an SSRI with an atypical antipsychotic have distinct biological abnormalities in the anterior cingulate.     

Proton magnetic resonance spectroscopy reveals an abnormality in the anterior cingulate of a subgroup of obsessive–compulsive disorder patients

Numerous neuroimaging studies have suggested that obsessive–compulsive disorder (OCD) patients had a neurobiological abnormality in the frontal-subcortical circuits. On the other hand, there are distinct differences in the responses to pharmacological treatment among OCD patients. In the present study, we measured the concentration of N-acetyl aspartate (NAA), a putative marker of neuronal viability, with proton magnetic resonance spectroscopy (MRS) in OCD patients with different pharmacological responses. Participants comprised 20 patients and 26 healthy control subjects. OCD patients were divided into three groups according to the pharmacological response; responders to a selective serotonin reuptake inhibitor (SSRI) (group A: n = 7), responders to SSRI with an atypical antipsychotic (group B: n = 8) and non-responders to either SSRI or SSRI with an atypical antipsychotic (group C: n = 5). Short echo proton MRS was used to measure NAA concentrations in the anterior cingulate, the left basal ganglia and the left prefrontal lobe of subjects. A significantly lower NAA concentration was observed only in group B compared with control subjects in the anterior cingulate. Our results suggest that a subgroup of OCD patients who respond to an SSRI with an atypical antipsychotic have distinct biological abnormalities in the anterior cingulate.     

The role of avoidance in the phenomenology of obsessive-compulsive disorder

BackgroundPathologic levels of ritualistic avoidance (also known as active avoidance) are common in the clinical presentation of obsessive-compulsive disorder (OCD). Despite its clinical relevance, there has been little examination of active avoidance as a ritualistic compulsion in adults with OCD.ObjectiveThe objective of this study is to determine if adults with OCD who engage in ritualistic avoidance have greater obsessive-compulsive, anxiety, and depressive symptom severity and different comorbidity patterns than adults who do not engage in ritualistic avoidance.MethodAdults with OCD (n = 133) completed an evaluation that included clinician ratings of obsessive-compulsive severity; overall illness severity; and self-reported ratings of anxiety, depression, and obsessive-compulsive severity.ResultsRitualized avoidance was endorsed by greater than 25% of the sample. Avoidant subjects and, more specifically, contaminant avoidant and reading-writing avoidant subjects presented with elevated levels of obsessive-compulsive symptom severity and greater overall clinical severity than comparison patients who did not engage in each respective avoidance ritual.ConclusionsPatients who engage in ritualized avoidance exhibited greater obsessive-compulsive symptom severity than patients who did not. These findings suggest that ritualized avoidance functions as a compulsion for adults with OCD and that avoidance should receive careful consideration in assessment and treatment.     

Olanzapine augmentation of fluvoxamine-refractory obsessive-compulsive disorder (OCD): a 12-week open trial

A few studies have tried antipsychotic augmentation in obsessive-compulsive disorder (OCD) patients who are non-responders to selective serotonin reuptake inhibitors. The aim of this study was to investigate the efficacy and tolerability of olanzapine addition to fluvoxamine-refractory OCD patients and to assess if a comorbid chronic tic disorder or a concomitant schizotypal personality disorder was associated with response. Twenty-three OCD non-responders to a 6-month, open-label trial with fluvoxamine (300 mg/day) entered a 3-month open-label trial of augmentation with olanzapine (5 mg/day). OC symptom change was measured with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression (CGI) scale. Differences between responders and non-responders were assessed with regard to age, sex, duration of illness, baseline Y-BOCS score, and comorbidity with chronic tic disorders or schizotypal personality disorder. A significant decrease of mean Y-BOCS score between pre- and post-treatment (26. 8+/-3.0 vs. 18.9+/-5.9) was found at endpoint. Ten patients (43.5%) were rated as responders. The most common side effects were mild to moderate weight gain and sedation. In our sample, three patients (13. 04%) had a chronic motor tic disorder, and four (17.39%) had a codiagnosis of schizotypal personality disorder. Concomitant schizotypal personality disorder was the only factor significantly associated with response. It appears that augmentation of olanzapine in fluvoxamine-refractory OCD may be effective in a large number of patients, including those with comorbid schizotypal personality disorder.     

Brain reactivity to specific symptom provocation indicates prospective therapeutic outcome in OCD

A pertinent question in biological psychiatry is what differentiates responders and non-responders to pharmacological treatment. One possibility is that individual differences in the symptomatic spectrum as well as in the underlying biology of the disorder lead to the known 40% failure in pharmacological treatment. Our study aimed to maximize individual brain markers of obsessive-compulsive disorder (OCD) by applying single photon emission computed tomography (SPECT) during a provoked symptomatic state prior to and following treatment. Four brain SPECT scans were obtained from 26 OCD patients prior to and at 6 months of sertraline treatment. At each time point, two SPECT scans were performed in a counterbalanced order of two specific states; one a symptom-provoking condition and the other a relaxed condition. At 6 months of treatment, patients were divided into responders and non-responders according to a predetermined clinical criterion. Prospective responders showed significantly lower brain perfusion in the dorsal-caudal anterior cingulum and higher brain perfusion in the right caudate, when compared to non-responders, only during symptom provocation. When pre- and post-treatment scans during symptom provocation were compared, only responders showed significant change in brain response: increased perfusion in the left anterior temporal cortex and prefrontal cortex at 6 months' treatment. These findings suggest that obtaining functional brain imaging during specific symptom provocation emphasizes individual differences in brain reactivity. Thus can indicate prospective responders to symptom-related treatment in OCD and mark the relevant brain regions for effective response to treatment.     

Topiramate augmentation in treatment-resistant obsessive-compulsive disorder: a retrospective, open-label case series

Serotonin reuptake inhibitors (SRIs) are considered first-line treatments for obsessive-compulsive disorder (OCD). Many patients achieve some response but remain symptomatic despite an adequate SRI trial. Recent neuroimaging data found abnormally high glutamatergic concentrations in children with OCD. Following selective serotonin reuptake inhibitor (SSRI) treatment, a decrease in OCD symptom severity was associated with a decrease in caudate glutamatergic concentrations. We initiated an investigation of adjunctive topiramate (an anticonvulsant agent with glutamatergic properties) in the treatment of patients with OCD who were partially or nonresponsive to SRI treatment. Sixteen consecutive outpatients with OCD (mean age = 41.1 years; range = 21-58 years), who were partial or nonresponders to SRI monotherapy or SRI combination therapy (antipsychotic, other antidepressant, or benzodiazepines), and had topiramate added over a minimum of 14 weeks, were reviewed. Baseline and endpoint Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I) were evaluated retrospectively. Eleven of 16 patients were responders (68.8%) with a CGI-I score of much improved or very much improved. The mean dose of topiramate was 253.1 +/- 93.9 mg/day. The mean time to response was 9.2 +/- 4.5 weeks. CGI-S scores decreased significantly from initiation of topiramate until 26 weeks, from 6.1 +/- 0.9 to 4.5 +/- 1.3 (P < .001). This case series suggests some preliminary evidence that the addition of topiramate may be useful in treatment-resistant OCD.     

The use of aripiprazole in obsessive-compulsive disorder: preliminary observations in 8 patients

OBJECTIVE: To assess the effectiveness of aripiprazole, an atypical antipsychotic with dopamine- and serotonin-stabilizing properties, as monotherapy in treating obsessive-compulsive disorder (OCD). METHOD: Adult subjects meeting DSM-IV criteria for OCD who were not currently receiving pharmacotherapy for the disorder were entered into an 8-week open-label trial of treatment with aripiprazole (10-30 mg/day). Efficacy assessments included the Yale-Brown Obsessive Compulsive Scale (YBOCS) and the Clinical Global Impressions-Improvement scale. Safety assessments included evaluation of vital signs, weight, and treatment-emergent side effects. Data were collected from June 2003 to August 2004. RESULTS: Eight subjects were enrolled, 7 of whom took at least 1 dose of study medication. Using the last observation carried forward, the mean total YBOCS score decreased from 23.9 at baseline to 17.6 at the final visit (p = .06). More pronounced improvement was observed in compulsive symptoms (p < .05) compared with obsessive symptoms (p = .09). Three subjects (43%) responded to treatment, showing a 30% or greater reduction in YBOCS total score. Two subjects discontinued treatment within 1 week due to side effects (akathisia, nausea). While no changes were noted in vital signs, a mean weight gain of 1.8 kg was observed. CONCLUSION: Although from a small, open-label study, these results suggest that aripiprazole holds promise for treating OCD. Larger, controlled studies of aripiprazole as monotherapy and as augmentation in partial responders to selective serotonin reuptake inhibitors are needed.     

Antipsychotic treatment in obsessive-compulsive disorder: a literature review

OBJECTIVE: To review the role of antipsychotic medications in the treatment of obsessive-compulsive disorder (OCD); to explore current hypothesized conceptualizations of their mechanism of action; to highlight evolving interest in the validation of meaningful OCD subtypes within a heterogeneous spectrum of OCD, based on treatment response and other psychobiological variables. METHOD: A computerized literature search (MEDLINE: 1966 to December 2003, EMBASE: 1982 to December 2003) was used to locate relevant literature, using the terms obsessive-compulsive, antipsychotic and subtypes, with no restrictions imposed on searches. RESULTS: Earlier studies of augmentation of serotonergic antidepressants (SRIs) with typical antipsychotics including haloperidol and pimozide in OCD demonstrated favourable responses, also highlighting patient subgroups with robust treatment response. Studies examining augmentation with atypical agents are emerging. SRI-resistant OCD patients are likely to benefit from augmentation with atypical antipsychotics in around 50% of cases. CONCLUSIONS: While there is little role for antipsychotic monotherapy in OCD, there is growing evidence in support of adjunctive antipsychotics in OCD refractory to serotonin-reuptake inhibitors (SRIs). Further controlled trials are warranted. Particular subgroups of OCD patients, notably those with comorbid tic disorder and those with schizotypal personality disorder, have been shown to respond more robustly to augmentation strategies in some trials of both typical and atypical antipsychotics. Dopaminergic mediation with or without a moderating effect on serotonergic systems is likely to be important in the pharmacodynamic mechanisms of action of antipsychotic-SRI combinations in OCD.     

Obsessive-compulsive disorder and schizophrenia. A critical review

Co-occurrence of psychotic and obsessive-compulsive symptoms has been recognized for decades. This paper reviews published reports from five perspectives: schizophrenia with obsessive-compulsive symptoms, obsessive-compulsive disorder (OCD) with psychotic symptoms, schizophrenia-spectrum-personality disorder with obsessive-compulsive symptoms, obsessive-compulsive symptoms induced by atypical antipsychotics and similarities of functional neural circuits theory in OCD and schizophrenia. A MEDLINE search was conducted to identify relevant articles from 1960 until 2004. Only a few systematic data that explore the nature and significance of such occurrence have been published. More recent studies using systematic diagnostic criteria suggest that the rate of occurrence may not be rare at all. In schizophrenia, a similar dorsolateral prefrontal cortex circuit shares anatomic substrates similar to those of the OCD orbitofrontal circuit. Exploring the interface of schizophrenic and obsessive-compulsive symptoms is important for diagnostic clarity and could have important implications for treatment and long-term prognosis. The review emphasizes the different origins and natural course of co-occurrence of schizophrenic and obsessive-compulsive symptoms and their various outcome under atypical antipsychotics and selective serotonin reuptake inhibitors (SSRI). Further double-blind, randomized, placebo-controlled investigations in larger cohorts of schizophrenic and OCD patients are needed in order to identify a schizo-obsessive schizophrenia and a schizotypal subtype of obsessive compulsive disorder and to substantiate the algorithm for treatment.     

Neuropsychological performance in children and adolescents with obsessive-compulsive disorder and influence of clinical variables.

BACKGROUND: Several studies have found impairment in visual memory and visual organization in adults with obsessive-compulsive disorder (OCD), but little is known about the neuropsychological profile of children and adolescents with this disorder. The influence of clinical variables such as age, severity of obsessive-compulsive symptomatology, depressive symptomatology, and pharmacological treatment on cognitive performance in these patients has not been thoroughly studied. METHODS: A neuropsychological battery designed for this study was administered to 35 patients with DSM-IV-TR diagnosis of OCD without psychiatric comorbidity aged between 7 and 18 years and 35 gender- and age-matched healthy subjects. RESULTS: Children and adolescents with OCD performed significantly worse on verbal and visual memory and velocity. When depressive symptomatology was controlled, impairment in visual memory, visual organization, and velocity again was found, but impairment in verbal memory was not. Neuropsychological impairment was not related to age, obsessive-compulsive severity, and pharmacological treatment. CONCLUSIONS: Children and adolescents with OCD without psychiatric comorbidity with acute illness show impairment in visual memory, visual organization, and velocity, similar to adults. The influence of depressive symptomatology is important in cognitive performance. No relation was found between neuropsychology and age, severity of obsessive-compulsive symptomatology, or pharmacological treatment in this study.     

Troubles obsessionnels compulsifs résistants et antipsychotiques : données neurobiologiques et thérapeutiques actuelles

Introduction

Forty to sixty percent of patients with obsessive compulsive disorder (OCD) are resistant to well conducted treatment with selective serotonin reuptake inhibitors (SSRIs) over 8 weeks. The data concerning effectiveness of the addition of antipsychotics in this indication is controversial.

Aims of the study

To synthesize the neurobiological mechanisms at work in order to understand the action of pharmacological treatments in this disease and to propose a systematic review of the literature on effectiveness of different antipsychotic drugs according to their pharmacological profiles, in monotherapy or in combination with SSRIs in OCD.

Method

We conducted a systematic review of the literature using the criteria according to the PRISMA research paradigm “obsessive compulsive disorder AND antipsychotic agents”. Research bases MEDLINE, Cochrane and Web of science have been explored.

Results

Unlike the classical serotonergic hypothesis, OCD may result from striatal dopaminergic hyperactivity, modulated in some patients by an underlying serotonergic hypoactivity. Most studies report effectiveness of first-generation antipsychotics (amisulpride and haloperidol) and some second-generation antipsychotics (risperidone, olanzapine, aripiprazole, quetiapine) in combination with an SSRI in the treatment of resistant OCD. Recrudescence or onset of OCD in patients with schizophrenia have been described in a relay from first generation antipsychotic to olanzapine, risperidone, aripiprazole or clozapine in case reports, but not amisulpride and quetiapine.     

Proton magnetic resonance spectroscopy in obsessive-compulsive disorder: a pilot investigation comparing treatment responders and non-responders

Proton magnetic resonance spectroscopic imaging was performed to compare brain metabolism in patients with obsessive-compulsive OCD. Evaluation was done on responders and non-responders to pharmacotherapy and on healthy controls. The results showed significantly lower NAA/Cr ratios in the right basal ganglia in non-responders than in responders or in controls and higher Cho/Cr ratios in the right thalamus in non-responders than responders. Abnormal neuronal metabolism in the right basal ganglia and right thalamus may be indicating lack of response to treatment to selective serotonin reuptake inhibitor.     

Quantitative electroencephalography in OCD patients treated with paroxetine.

The effectiveness of drugs that have a specific effect on the activity of the serotonergic neurotransmitter systemhas changed the outlook for patients suffering from obsessive-compulsive disorder (OCD). With a response rate of about 70% to such compounds and the great amount of brain imaging studies conducted over the past decades, an understanding of the biochemical nature and origins of OCD is beginning to unfold. Convergent data including ethological and experimental observations, clinico-pathological findings and different imaging methods have implicated the basal ganglia along with the cortical and related thalamic structures to be involved in the pathophysiology of OCD. In a previous study using the quantitative electroencephalographic (QEEG) method known as neurometrics, in which QEEG data from OCD patients were compared statistically with those from an age-appropriate normative population, two subtypes within a clinically homogeneous patient group were classified. Patients with relative excess theta activity, especially in the frontal regions, were nonresponders to treatment with serotonin reuptake inhibitors (SSRI), while those with increased relative power in alpha activity were responders to pharmacological treatment. These findings suggested at least two subgroups in a patient population with similar symptoms but differential responses to treatment. In the present study we used neurometric QEEG to subtype a group of 20 non-depressed OCD patients, fulfilling DSM-R-III criteria, treated with paroxetine, of whom 18 were responders to treatment. Of the treatment responders, 94.4% were predicted by subtype membership to be SSRI responsers. In these subjects there was a strong relative alpha baseline activity; after successful treatment through at least 3 months this activity decreased, looking more normal. The group average topographic maps showed none of the characteristics seen in the nonresponder cluster (no excess relative power in theta). As in the previous investigation, baseline QEEG profile membership points to a predictive value with regard to therapeutic response.     

Quetiapine addition to serotonin reuptake inhibitor treatment in patients with treatment-refractory obsessive-compulsive disorder: an open-label study

OBJECTIVE: Although patients with obsessive-compulsive disorder (OCD) benefit from treatment with serotonin reuptake inhibitors (SRIs), it is estimated that 40% to 60% of the patients remain unimproved. The objective of this study was to examine whether addition of the atypical antipsychotic quetiapine to SRIs is useful for patients with OCD who do not respond to SRI monotherapy. METHOD: Ten patients with OCD (DSM-IV criteria) who had not responded to at least 3 previous treatments with an SRI at maximum dose and duration were assigned to receive quetiapine in addition to an SRI for 8 weeks. Treatment response was assessed using the Yale-Brown Obessive-Compulsive Scale (YBOCS). RESULTS: Seven of 10 patients responded to the quetiapine addition. The mean +/- SD baseline YBOCS score of 31.4 +/- 7.8 dropped to a mean of 20.8 +/- 8.4 at endpoint with a mean reduction of 35.4%. CONCLUSION: This is the first study to show that treatment-refractory OCD patients may benefit from addition of quetiapine to ongoing SRI therapy.     

A benzisothiazole derivative and antipsychotic agent,perospirone, for augmentation of selective serotonin reuptake inhibitors (SSRIs) in refractory obsessive-compulsive disorder (OCD): two patient case series

Even though selective serotonin reuptake inhibitors (SSRIs) are the mainstay of pharamacological treatment for obsessive-compulsive disorder (OCD), as many as 40% of patients do not have an adequate response to these medications. For such SSRI-refractory patients, the augmentation of SSRIs with new-generation antipsychotics that modulate both 5-HT and DA systems has recently been proven effective in controlled augmentation studies. The benzisothiazole derivative perospirone is a new serotonin 5-HT2 and dopamine D2 antagonist available in Japan for the treatment of schizophrenia. As its unique property, perospirone also exhibits 5-HT1A agonistic action. We present two SSRI-refractory OCD patients who showed little improvement with adequate trials of SSRI monotherapy, but exhibited significant improvement in their OCD symptoms after the addition of perospirone to ongoing SSRI treatment. The cases suggest that perospirone augmentation may be an effective and well-tolerated strategy for SSRI-refractory OCD patients. Controlled studies are required to further confirm the efficacy and tolerability of perospirone augmentation for treatment-resistant OCD.     

Decreased thalamic blood flow in obsessive-compulsive disorder patients responding to fluvoxamine

Functional imaging studies have pointed to a role of the orbitofrontal cortex (OFC), striatum and thalamus in the pathophysiology of obsessive-compulsive disorder (OCD). Effective treatment has been found to change brain activity within this circuitry. The aim of the present study was to explore possible differential effects of OCD responders and non-responders to drug treatment on the regional cerebral blood flow (rCBF). Measurements of rCBF were carried out in 15 out of 22 patients with OCD who completed an open-label trial with fluvoxamine. Patients were studied with 99mTc-HMPAO single photon emission computed tomography (SPECT) before and after 12 weeks of treatment. In addition, structural magnetic resonance imaging was obtained on all patients. Regions of interest comprised the OFC, caudate nucleus, putamen and thalamus. Seven patients responded to treatment. Levels of rCBF decreased significantly in the left caudate nucleus and the left and right putamen in both responders and non-responders to treatment. In responders, but not in non-responders, a significant decrease in rCBF was found in the right thalamus. Pre-treatment cerebellar and whole brain HMPAO uptake was significantly higher in responders to treatment compared with non-responders. We suggest that the thalamus plays a central role in the response to drug treatment.     

Serotonin and dopamine antagonism in obsessive-compulsive disorder: effect of atypical antipsychotic drugs

BACKGROUND: Previous reports suggest that some atypical antipsychotics may have obsessogenic as well as antiobsessional effects. Given their higher affinity for serotonin 5HT2 receptors than dopamine D2 receptors, it has been speculated that atypical antipsychotics may induce obsessive-compulsive (OC) symptoms, even at low doses, due to high 5HT2 antagonism, whereas improvement in OC symptoms is thought to occur only at high doses due to high D2 antagonism. METHOD: In this open case series, the dose-response relationship of atypical antipsychotic augmentation in the treatment of obsessive compulsive disorder (OCD), and the dose-severity relationship in atypical anti psychotic-induced OC symptoms were examined. Three patients were identified who had either refractory OCD or OC symptoms following administration of atypical antipsychotics such as olanzapine and risperidone. RESULTS: Case 1: A linear dose-response relationship between increasing doses of olanzapine and improvement in OC symptoms was observed in an OCD patient resistant to 5-HT reuptake inhibitors. 2: OC symptoms induced by low doses of risperidone (1 mg) were reversed by increasing the doses of risperidone (3 mg) in a bipolar disorder patient suggesting an inverse dose-severity relationship. 3: No inverse dose-severity relationship was noted between olanzapine induced OC symptoms and its dosage in an asymptomatic OCD patient. Tretment-emergence OC symptoms responded to increasing the doses of maintanance clomipramine treatment. CONCLUSIONS: Controlled studies are needed to investigate the dose-response or dose-severity relationships between OCD and atypical antipsychotics.     

Serotonin and dopamine transporter imaging in patients with obsessive-compulsive disorder

In obsessive-compulsive disorder (OCD), the success of pharmacological treatment with serotonin re-uptake inhibitors and atypical antipsychotic drugs suggests that both the central serotonergic and dopaminergic systems are involved in the pathophysiology of the disorder. We applied [123I]-2beta-carbomethoxy-3beta-(4-idiophenyl)tropane (beta-CIT) and a brain-dedicated high-resolution single photon emission computed tomography (SPECT) system to quantify dopamine transporter (DAT) and serotonin transporter (SERT) availability. By comparing 15 drug-na?ve patients with OCD and 10 controls, we found a significantly reduced availability (corrected for age) of striatal DAT and of thalamic/hypothalamic, midbrain and brainstem SERT in OCD patients. Severity of OCD symptoms showed a significant negative correlation with thalamic/hypothalamic SERT availability, corrected for age and duration of symptoms. Our data provide evidence for imbalanced monoaminergic neurotransmitter modulation in OCD. Further studies with more selective DAT and SERT radiotracers are needed.     

Caudate volume differences among treatment responders,non-responders and controls in children with obsessive–compulsive disorder

Treatment response in obsessive–compulsive disorder (OCD) is heterogeneous and the neurobiological underpinnings of such variability are unknown. To investigate this issue, we looked for differences in brain structures possibly associated with treatment response in children with OCD. 29 children with OCD (7–17 years) and 28 age-matched controls underwent structural magnetic resonance imaging. Patients then received treatment with fluoxetine or group cognitive-behavioral therapy during 14 weeks, and were classified as treatment responders or non-responders. The caudate nucleus, thalamus and orbitofrontal cortex were selected a priori, according to previous evidence of their association with OCD and its treatment. Gray matter (GM) volume comparisons between responders, non-responders and controls were performed, controlling for total GM volume. 17 patients were classified as responders. Differences among responders, non-responders and controls were found in both caudate nuclei (both p-values = 0.041), but after Bonferroni correction for multiple comparisons, these findings were non-significant. However, after excluding the effect of an outlier, findings were significant for the right caudate (p = 0.004). Pairwise comparisons showed larger caudate GM volume in responders versus non-responders and controls, bilaterally. The right caudate accounted for 20.2% of the variance in Y-BOCS changes after treatment in a linear regression model, with a positive correlation (p = 0.016). We present a possible neural substrate for treatment response in pediatric OCD, which is in line with previous evidence regarding the caudate nucleus. Considering the limitations, further research is needed to replicate this finding and elucidate the heterogeneity of treatment response in children with OCD (National Clinical Trials Registration Number: NCT01148316).

     

A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder

As many as half of obsessive-compulsive disorder (OCD) patients treated with an adequate trial of serotonin reuptake inhibitors (SRIs) fail to fully respond to treatment and continue to exhibit significant symptoms. Many studies have assessed the effectiveness of antipsychotic augmentation in SRI-refractory OCD. In this systematic review, we evaluate the efficacy of antipsychotic augmentation in treatment-refractory OCD. The electronic databases of PubMed, PsychINFO (1967-2005), Embase (1974-2000) and the Cochrane Central Register of Controlled Trials (CENTRAL, as of 2005, Issue 3) were searched for relevant double-blind trials using keywords 'antipsychotic agents' or 'neuroleptics' and 'obsessive-compulsive disorder'. Search results and analysis were limited to double-blind, randomized control trials involving the adult population. The proportion of subjects designated as treatment responders was defined by a greater than 35% reduction in Yale Brown Obsessive-Compulsive Scale (Y-BOCS) rating during the course of augmentation therapy. Nine studies involving 278 participants were included in the analysis. The meta-analysis of these studies demonstrated a significant absolute risk difference (ARD) in favor of antipsychotic augmentation of 0.22 (95% confidence interval (CI): 0.13, 0.31). The subgroup of OCD patients with comorbid tics have a particularly beneficial response to this intervention, ARD=0.43 (95% CI: 0.19, 0.68). There was also evidence suggesting OCD patients should be treated with at least 3 months of maximal-tolerated therapy of an SRI before initiating antipsychotic augmentation owing to the high rate of treatment response to continued SRI monotherapy (25.6%). Antipsychotic augmentation in SRI-refractory OCD is indicated in patients who have been treated for at least 3 months of maximal-tolerated therapy of an SRI. Unfortunately, only one-third of treatment-refractory OCD patients show a meaningful treatment response to antipsychotic augmentation. There is sufficient evidence in the published literature, demonstrating the efficacy of haloperidol and risperidone, and evidence regarding the efficacy of quetiapine and olanzapine is inconclusive. Patients with comorbid tics are likely to have a differential benefit to antipsychotic augmentation.