Silvio Presta

Risperidone augmentation in refractory obsessive-compulsive disorder: an open-label study.

Risperidone, an atypical neuroleptic, has been proposed for augmentation strategies in resistant obsessive-compulsive disorder (OCD). We report the results of an open-label trial on the use of the combination of serotonin reuptake inhibitors (SRIs) with risperidone in 20 refractory OCD outpatients. All patients had been suffering from OCD, according to DSM-IV criteria, for at least 2 years and had various comorbid disorders. All had been treated with a SRI at adequate dosages for at least 6 months, but had failed to respond. Therefore, risperidone was added and the dosage titrated up to the mean dose of 3 mg/day over 8 weeks. After 2 months of this regimen, all patients had shown a reduction in obsessive-compulsive symptoms, as assessed by the decrease in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score, particularly those with a lifetime comorbidity with bipolar disorder; only three patients reported mild sedation and postural hypotension, two mild extrapyramidal side-effects (tremors and akatysia) and two an increased appetite. All these effects were well tolerated and no patient halted the treatment. The addition of risperidone would appear to be a useful strategy for augmenting SRI effectiveness in refractory OCD patients.

EPISODIC COURSE IN OBSESSIVE-COMPULSIVE DISORDER

Abstract The course of obsessive–compulsive disorder (OCD) is variable, ranging from episodic to chronic. We hypothesised that the former course is more likely to be related to bipolar mood disorders. With the use of a specially constructed OCD questionnaire, we studied 135 patients fulfilling DSM-III-R criteria for OCD with an illness duration of at least 10 years and divided by course: 27.4% were episodic and 72.6% chronic. We compared clinical and familial characteristics and comorbidity. Univariate analyses showed that episodic OCD had a significantly lower rate of checking rituals and a significantly higher rate of a positive family history for mood disorder. Multivariate stepwise discriminant analysis revealed a positive and significant relationship between episodic course, family history for mood disorders, lifetime comorbidity for panic and bipolar-II disorders, late age at onset and negative correlation with generalized anxiety disorder. These data suggest that the episodic course of OCD has important clinical correlates which are related to cyclic mood disorders. This correlation has implications for treatment and research strategies on the aetiology within a subpopulation of OCD.

Insight in obsessive-compulsive disorder: a study of an italian sample

Insight is a complex phenomenon that can be interpreted according to a dimensional model. Given the controversial data of insight in obsessive-compulsive disorder (OCD), our study aimed to investigate insight in an Italian sample of patients with OCD by means of the specific item on the Yale-Brown obsessive-compulsive scale (Y-BOCS) and to explore the possible correlations between it and clinical features. One hundred and seventeen out-patients with a DSM-IV diagnosis of OCD and different comorbid psychiatric disorders were included in the study and assessed by means of the Y-BOCS, Hamilton rating scale for depression (HRSD) and the global clinical impression. The results showed that almost 50% of the patients had an excellent level of insight and 15% had a little or no insight. No correlation between levels of insight and clinical features was observed, except for a negative trend with the presence of somatic obsessions. In addition, a trend towards a lower level of insight was observed in those bipolar patients with a positive history of repeated manic or hypomanic episodes. Further studies seem to be necessary in order to establish whether or not OCD patients with poor insight represent a distinct sub-group of patients.

Decreased Platelet 3H-Paroxetine Binding in Obsessive-Compulsive Patients

The similarities between the serotonin (5-HT) transporter in both human platelets and human brain permit us to investigate this structure in patients with different psychiatric disorders. Several reports have shown abnormalities of the 5-HT transporter, by means of the measurement of the 5-HT uptake or of the 3H-imipramine binding, in platelets of patients with obsessive-compulsive disorder (OCD). The availability of the ligand 3H-paroxetine, a selective 5-HT reuptake inhibitor, to label the 5-HT transporter, promoted us to evaluate the binding of 3H-paroxetine in platelets of 18 drug-free patients with OCD. The results, showing that the patients had a lower number of 3H-paroxetine sites, which is inversely correlated with the Yale Brown Obsessive-Compulsive Scale total score, than a similar group of controls, add supporting evidence to the involvement of 5-HT in OCD. In addition, the decreased functionality of the 5-HT transporter seems to be linked to the severity of OC symptoms.

Augmentation strategy with olanzapine in resistant obsessive compulsive disorder: an Italian long-term open-label study

The present study reports the results of an open-label trial on the use of the combination of olanzapine (an atypical antipsychotic) serotonin reuptake inhibitors (SRIs) in 26 resistant outpatients affected by resistant obsessive-compulsive disorder (OCD). All patients had been suffering from OCD, according to DSM IV criteria, for at least 2 years and had different comorbid disorders; they had been treated with an SRI at adequate dosages for at least 6 months, or had tried different augmentation strategies with no or poor response. As a result, olanzapine was added and continued for 1 year. After 12 weeks of this regimen, most of the patients (17) had shown a reduction in OC symptoms, as assessed by a decrease in the Yale-Brown Obsessive Compulsive Scale total score, which continued throughout subsequent months. Only mild side-effects were recorded and no patient halted the treatment. The addition of olanzapine would appear to be a useful short- and long-term strategy for augmenting SRI effectiveness in resistant OCD patients, especially in those presenting comorbidity with bipolar disorders.

Immunological alterations in adult obsessive-compulsive disorder

BACKGROUND Some recent findings suggest the involvement of autoimmune mechanisms in childhood onset of obsessive-compulsive disorder (OCD), on the basis of a parallel drawn with Sydenhams chorea, a manifestation of rheumatic fever. A monoclonal antibody called D8/D17 characterizing a B-lymphocyte antigen, present in almost all patients with rheumatic fever, has been found also in children affected by OCD, Tourette syndrome, and chronic tics to a greater degree than in healthy control subjects. The few observations of disturbances of some immunologic parameters in adult OCD patients, prompted the authors to investigate and compare subsets of peripheral immunological cells for differences in adult patients with OCD and healthy control subjects. METHODS Twenty patients suffering from OCD, with no comorbidity for other psychiatric disorders, were compared with a similar group of healthy control subjects. The immune subsets were measured by flow cytometry. RESULTS The CD8+ lymphocytes were significantly increased and CD4+ lymphocytes significantly decreased in OCD patients, while the other cells did not differ between the two groups. No correlation was found between immunologic and clinical parameters. CONCLUSIONS These data indicate that patients with adult OCD showed increased CD8+, i.e., suppressor T lymphocytes, and decreased CD4+, which identify helper T lymphocytes, as compared with a similar group of healthy control subjects. The findings appear peculiar to patients with OCD and are suggestive of an immunologic imbalance, which might be related to the stress deriving from the frustrating situation determined by the disorder itself.

Citalopram in refractory obsessive - Compulsive disorder: An open study

This study aimed to evaluate the effect of citalopram in patients with refractory obsessive-compulsive disorder (OCD) which had not responded to previous antiobsessional treatments. Eighteen patients were selected for this study: they had been suffering from OCD, according to DSM-IV criteria, for at least 2 years and had various comorbid disorders. All had been treated with serotonin reuptake inhibitors at adequate dosages for at least 6 months, but had failed to respond. Consequently, they were shifted to citalopram, titrated up to the dose of 40 mg, within 2 weeks. After 4 months of this regimen, 14 out of the total of 18 patients had shown a reduction in OC symptoms, as assessed by the decrease in the Yale-Brown Obsessive Compulsive Scale total score; no relevant side-effects were reported, except for a mild nausea in four patients within the first few days of treatment, which quickly disappeared. The use of citalopram would appear to be an useful strategy in refractory OCD cases.

Platelet [3H]paroxetine binding in patients with OCD-related disorders

The recently introduced notion of clinical conditions being related one to another, the spectrum concept, permits the testing of the involvement of serotonergic systems in a broad range of disorders tentatively linked to obsessive-compulsive disorder (OCD) for which no pathophysiological hypotheses yet exist. We therefore compared the binding of [3H]paroxetine ([3H]Par), a ligand that specifically labels the serotonin (5-HT) transporter, in platelets of drug-free outpatients suffering from various OCD-related disorders with binding in platelets of OCD patients and healthy subjects. Diagnoses were made according to DSM-IV criteria. The most frequent diagnosis was that of body dysmorphic disorder, followed by impulse control disorder, kleptomania, Tourettes syndrome and trichotillomania. Platelet membranes and [3H]Par binding were studied according to standardized protocols. The results, showing a similarly decreased density of [3H]Par binding sites in both patient groups as compared with healthy subjects, suggest the presence of a shared abnormality at the level of the presynaptic 5-HT transporter, probably linked to a common dimension yet to be identified.

Effectiveness of long-term augmentation with citalopram to clomipramine in treatment-resistant OCD patients.

INTRODUCTION The high percentage (between 40% and 60%) of resistance to first-line drugs, such as clomipramine or selective serotonin reuptake inhibitors, is a major problem in the pharmacologic management of obsessive-compulsive disorder (OCD). In these cases, different strategies have been employed with controversial outcomes. The meager information available on the association of two serotonergic drugs prompted us to explore the possible effectiveness and tolerability of citalopram+clomipramine in resistant OCD patients. METHODS Twenty outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD, who had failed to respond to at least two trials with a selective serotonin reuptake inhibitor and were currently taking clomipramine at different doses, were administered citalopram at a maximum dose of 60 mg/day. The clinical assessment was carried out at baseline (t0) and at the 4th (t1), 12th (t2), 24th (t3), 36th (t4), and 48th (t5) week by means of the Yale-Brown Obsessive Compulsive Scale, Hamilton Rating Scale for Depression, Clinical Global Impression scale, and the Dosage Record and Treatment Emergent Symptom Scale. The response was defined as a 35% decrease of the Yale-Brown Obsessive-Compulsive Scale total score. RESULTS The results showed that approximately 50% of the patients improved significantly after 1 month of this regimen and after 1 year of treatment. CONCLUSION This study, although carried out in a small sample and in an open fashion, represents one of the few experiences with the association of two serotonergic compounds in resistant OCD and confirms its potential usefulness and good tolerability profile. Controlled research on this association in OCD is recommended.

Increased Inhibitory Activity of Protein Kinase C on the Serotonin Transporter in OCD

Different observations show a reduced functionality of the serotonin (5-HT) transporter in obsessive-compulsive disorder (OCD) that might be due to a disturbance of its regulation at intracellular level. Protein kinase C (PKC) has been reported to provoke a decrease in the number of the 5-HT transporter proteins. Therefore, we investigated whether OCD patients differed from control subjects in the effect of PKC upon the 5-HT transporter, after stimulation of this enzyme with 4β-12-tetradecanoylphorbol 13-acetate (β-TPA). Fifteen patients affected by OCD, according to DSM-IV criteria, were compared with a similar group of healthy subjects. The determination of 5-HT uptake was carried out according to the method of Arora and Meltzer with slight modifications. At baseline, OCD patients showed a significant decrease in the maximal velocity (Vmax) of 5-HT uptake, as compared with control subjects, with no change in the Michaelis-Menten constant (Km). The activation of PKC with β-TPA provoked a significant decrease in Vmax values in both groups, but the effect was significantly more robust in OCD patients who, in turn, also showed also an increase in Km values. These findings could indicate the presence of hyperactivity of PKC in OCD that could be the result of increased activity of the phosphatidylinositol pathway. In addition, this suggests new potential therapeutic targets in OCD.