S-10-01

Neuroleptic augmentation in OCD: Clinic and neuroimaging of risperidone

S. Pallanti. Istituto di Neuroscienze, Florence, Italy

A double-blind, placebo-controlled trial was performed to determine the efficacy and tolerability of 8 wk of risperidone augmentation of serotonin reuptake inhibitor (SRI) in treatment-resistant obsessivecompulsive disorder (OCD) (failure of at least two SRI trials). Sixteen patients were randomly assigned to augmentation with 8 wk of either risperidone (n=10) (0.5-3.0 mg/d) or placebo (n=6) following at least 12 wk of SRI treatment. Positron emission tomography (PET) with 18F-deoxyglucose and magnetic resonance imaging was obtained at baseline and following eight weeks of either risperidone or placebo. Four patients on risperidone (40%) and none (0%) on placebo were responders with both a CGI-I score of 1 or 2 and a Y-BOCS decrease >=25%. Risperidone was generally well tolerated: there were One subject on risperidone and 2 on placebo dropped out the treatment.. Better Y-BOCS insight score at baseline significantly correlated with a greater CGI-I score at endpoint on risperidone augmentation. Risperidone treatment was associated with significant increases in relative metabolic rate in the swiatum, cingulate gyms, the prefrontal cortex, especially in the orbital region and the thalamus. Patients with low relative metabolic rates in the striatum and high relative metabolic rates in the anterior cingulate gyrus were more likely to show a clinical response. Risperidone may be an effective and well-tolerated augmentation strategy in treatment-resistant OCD. PET results are consistent with a fronto-striatial circuit change related to both dopaminergic and serotonergic systems and with the presence of psychopharmacological subtypes within OCD.

S-10-02

Defining a role for antipsychotics in the treatment of obsessive compulsive disorder

N. Fineberg. Italy

Objectives First generation antipsychotics eg. haloperidol, given in low doses in combination with SRI, showed efficacy in studies of SRI-resistant OCD, with evidence that individuals with comorbid tics and schizotypal disorders responded better. Second-generation antipsychotics are better tolerated. One study demonstrated efficacy for risperidone with no difference between those with and without tics or schizotypy. A smaller study showed advantages for risperidone but not significance on the primary efficacy measure. Olanzapine addition showed no benefit compared to extending the duration of fluoxetine monotherapy in one study; a second smaller study of olanzapine produced a positive result. One 8 week study reported a significant advantage for quetiapine addition from four weeks onwards (Denys et al J. Clin Psychiatry (2004) 65(8): 1040-8) Method 21 cases SRI-resistant OCD randomised to 16 weeks treatment with quetiapine (<=400mg/day) or placebo in addition to ongoing SSRI. Significant comorbidities, including tic-spectrum disorders, disallowed. Results Quetiapine was well tolerated with only one premature dropout in each treatment-group. Primary analysis: individuals in the quetiapine - treated group showed a rically greater mean improvement in baseline YBOCS scores (14%) at study endpoint than those given placebo (6%), but this did not reach statistical significance. 3/11 quetiapine-treated cases met criteria for clinical response, compared to 1/10 given placebo. Conclusion Differences in study design and actions at 5-HT 2A / non 2A receptors or dopamine activation may explain differences in results of different studies. Larger studies are needed to explore the efficacy of second generation antipsychotics in resistant OCD.

S-10-03

The OCD disorder and its relationship with the schizotypal features: A clinical study with temperament and character inventory and schizotypal personality questionnaire

A. Rossi. Universita' dell'Aquila, L'Aquila, Italy

Objective: The aim of this study was to examine differences in temperament and character among subjects with obsessivecompulsive disorder (OCD) and controls.

Methods: We selected 42 subjects with obsessive-compulsive disorder (OCD) and a group of 83 controls. These subjects were evaluated with Temperament and Character Inventory (TCI) reduced version and Schizotypal Personality Questionnaire (SPQ). Results: The patients showed substantial differences when compared to the controls as to the measures of the temperament and the character. In particular a pattern emerges of differences characterized from increase of Harm Avoidance (HAS) and Self- Transcendence (ST) and reduction of Self-Directedness (SD), Reward Dependence (RD) and Cooperativeness (C) and higher SPQ scores.

Conclusion: The data confirm previous observations on the relationships between schizotypal features of personality and OCD.

S-10-04

Antipsychotics in OCD

F. Bogetto, G. Maina. ASO S.Giovanni Battista Neuroscience, Turin, Italy

Drug treatment of OCD entails serotonin reuptake inhibitors as firstline interventions. However, many patients with OCD do not benefit from standard treatments with SRIs; this proportion of patients may be approximately estimated between 40 and 50 percent. One of the most studied approaches in treating patients resistant to treatment is dopaminergic augmentation. Antipsychotic monotherapy is not useful in patients with OCD. Sometimes it might actually precipitate or worsen OCD symptoms. Dopaminergic augmentation consists in adding an antipsychotic to the ongoing SRI. Good results have been obtained when the augmentation was made with a low-dose typical neuroleptic. Given the side-effect profile of typical neuroleptics, researchers have, in the last years, tried atypical ones as augmentation drugs. This speech will review all available studies concerning the use of antipsychotics in OCD, pointing toward benefits and potential side effects of this augmentation strategy. All of the studies that evaluated the addition of an antipsychotic in resistant OCD lasted 6-12 weeks. A question that remains unresolved to date is then how long should a clinician maintain the antipsychotic augmentation in patients who responded to this strategy. A possible way of looking at the problem is to examine whether the discontinuation of the antipsychotic in patients who responded to this strategy is associated with a worsening of obsessive-compulsive symptoms. We will present data on relapse rates in patients who responded to the addition of the antipsychotic and then discontinued it without discontinuing the SSRI.

S-10-05

Immunological alterations in obsessive-compulsive disorder before and after pharmacological treatment

D. Marazziti, F. Mungai, L. Vivarelli, M. Catena, S. Baroni. Universita di Pisa, Pisa, Italy

The role of immune system in obsessive-compulsive disorder (OCD) is mainly supported by the presence of a high percentage of B-cells reacting with a marker for rheumatic fever, the monoclonal antibody D8/17, in some patients. Further supports derive from the observation of decreased production of tumour necrosis factor (TNF) alpha and NK activity. In a previous study on adult OCD, we observed a significant increase of CD8+ and decrease of CD4+ lymphocytes, as compared with a similar group of healthy control subject. In the present study we report the results of an evaluation of the same parameters from six to twelve months after pharmacological treatments. Materials and methods Twenty outpatients (10 male, 10 female, mean age 32+2 years) with a diagnosis of OCD according to DSM-IVR criteria, were selected for the study. They were neither depressed, as assessed by the total score at the Hamilton Rating Scale for Depression, nor suffered from current comorbid conditions. The severity of OCD symptoms was assessed by means of the Yale Brown Obsessive Compulsive Scale (Y-BOCS). The immune subsets were measured by flow cytometry. Evaluations of the OCD symptomatology and immune cells were performed at the baseline, after six or twelve months (T 1) of treatment with S RIs (clomipramine, fluvoxamine, sertraline and citalopram). The balance between T-helper and T-suppressor lymphocytes was evaluated by means of the ratio CD44-/CD8+. Results At baseline, OCD patients had increased CD8+ (Tsuppressor), decreased CD4+ (T-helper) cells in both percentage and absolute number, and the ratio CD4+/CD8+ was 1.4+4. The YBOCS total score at the baseline was 25+4.3. The results of the evaluations at T1 showed a progressive reduction of the Y-BOCS total score and a normalization of the immune cells counts. Discussion and conclusions This study suggests that significant change in immune cells are present in OCD patients and that they could revert after successful treatment with SRIs.