L. Ravizza

Paroxetine efficacy in the treatment of generalized anxiety disorder.

Recently, there has been a renewed interest in alternatives to the benzodiazepines for the treatment of generalized anxiety disorder (GAD). The aim of the present study was to compare the efficacy of paroxetine vs. imipramine and 2′‐chlordesmethyldiazepam in 81 patients with a DSM‐IV diagnosis of GAD. Approximately two‐thirds of the patients who completed the study improved greatly or moderately on all three active drugs. During the first 2 weeks of treatment, 2′‐chlordesmethyldiazepam treatment resulted in the greatest improvement in anxiety ratings. Both paroxetine and imipramine treatment resulted in more improvement than 2′‐chlordesmethyldiazepam by the fourth week of treatment. Paroxetine and imipramine affect predominantly psychic symptoms, whereas 2′‐chlordesmethyldiazepam affects predominantly somatic symptoms. Our results suggest that paroxetine is effective for the treatment of GAD.

Recent life events and obsessive-compulsive disorder (OCD): the role of pregnancy/delivery.

Conflicting results have been reported on the possible role of life events in triggering OCD onset. Moreover, pregnancy and/or delivery, among life events, appear to influence the OCD course and, in some cases, appear related to its onset. Our purpose was to assess the occurrence of potentially traumatizing events among patients with OCD. The study also provides an initial exploration of the association between OCD and pregnancy or delivery. The number and type of stressful life events which occurred in the 12 months before the onset of OCD were determined for both OCD patients (N = 68, 33 women and 35 men) and a group of comparison subjects (N = 68, 33 women and 35 men) by using a semistructured interview in accordance with Paykels list. The results did not show a significant excess of life events in patients compared with healthy subjects. No differences were detected between OCD patients according to gender. When examining the type of events, OCD female individuals were found to be more likely than normal female subjects to report exposure to postpartum events, and high rates of obstetric complications were observed in these patients. Subjects with postpartum OCD had significantly higher rates of aggressive obsessions to harm the newborn. OCD male subjects did not show an association between a specific event and onset of the disorder. The findings confirm that the postpartum period represents a risk factor for OCD in some individuals, and suggest that obstetric complications may be relevant to the development of the disorder.

Gender-related clinical differences in obsessive-compulsive disorder

The purpose of the present study was to investigate the gender-related differences of clinical features in a sample of obsessive-compulsive (OCD) patients. One hundred and sixty outpatients with a principal diagnosis of obsessive-compulsive disorder (DSM-IV, Y-BOCS = 16) were admitted. Patients were evaluated with a semi-structured interview covering the following areas: socio-demographic data, Axis I diagnoses (DSM-IV), OCD clinical features (age at onset of OC symptoms and disorder, type of onset, life events and type of course). For statistical analysis the sample was subdivided in two groups according to gender. We found an earlier age at onset of OC symptoms and disorder in males; an insidious onset and a chronic course of illness were also observed in that group of patients. Females more frequently showed an acute onset of OCD and an episodic course of illness; they also reported more frequently a stressful event in the year preceding OCD onset. A history of anxiety disorders with onset preceding OCD and hypomanic episodes occurring after OCD onset was significantly more common among males, while females showed more frequently a history of eating disorders. We found three gender-related features of OCD: males show an earlier age at onset with a lower impact of precipitant events in triggering the disorder; OCD seems to occur in a relative high proportion of males who already have phobias and/or tic disorders; and a surfeit of chronic course of the illness in males in comparison with females.

Peripheral-type benzodiazepine receptors in anxiety disorders.

Peripheral benzodiazepine receptors (pBDZr) were analyzed in lymphocyte membranes from patients with anxiety disorders (generalized anxiety disorder (GAD), n= 15; panic disorder (PD), n= 10; obsessive‐compulsive disorder (OCD), n= 18), other mental disorders (n= 40) and 50 healthy controls, by the specific binding of 3H‐PK11195. The number of binding sites (Bmax) was significantly decreased in groups with both GAD and OCD as compared with age‐matched controls, by 45% and 25% respectively, whereas the binding affinity (Kd) was the same in all disorder and control groups. Conversely, no changes in binding capacity was observed in the other disorder groups and particularly in the one with PD. The abnormality in pBDZr observed in patients with GAD was restored to a normal value after long‐term treatment with 2′‐chloro‐N‐desmethyldiazepam, which also coincided with their recovery from anxiety. Our data suggest that the clinical heterogeneity in anxiety disorders might be related to different biological mechanisms and that lymphocyte pBDZr might be useful in demonstrating these differences.

An Exploratory Study on Obsessive-Compulsive Disorder with and without a Familial Component: Are There Any Phenomenological Differences?

Familial studies on obsessive-compulsive disorders (OCD) have suggested that OCD is a heterogeneous condition, with some cases being familial and others being isolated cases in their families. Nevertheless, no studies evaluated whether there are clinical differences between OCD cases with and without a familial component. The current report presents data on the prevalence of OCD in first-degree relatives of OCD probands and compares phenomenological characteristics of familial and non-familial OCD types. The family study and the family history methods were used to estimate the prevalence of OCD in first-degree relatives of 74 OCD probands. A statistical comparison between OCD probands with and without familial loading was performed using Pearson’s χ2 test, Fisher’s exact test, or Student’s t test when appropriate. The rate of OCD was 3.5% in directly interviewed first-degree relatives. Eleven percent of the probands had at least one family member with OCD. There were no differences between the two types of OCD (familial vs. non-familial) except for life events prior to the onset of OCD, which were more common and more severe in non-familial OCD subtypes. In conclusion, our results (1) confirm that there is a familial component in the expression of some forms of OCD and (2) indicate that familial OCD patients are not characterized by peculiar clinical features, but appear to have a lower threshold for precipitating events.

Decrease of the D4 dopamine receptor messenger RNA expression in lymphocytes from patients with major depression

OBJECTIVES The evaluation of the possible role of dopamine in psychiatric disorders has been limited by the relative inadequacy of tools. A tempting approach to examine alterations of dopaminergic system in major depression is to examine the expression of dopamine receptors in peripheral blood mononuclear cells (PBMC). METHODS D4 dopamine receptor (D4DR) messenger RNA (mRNA) expression in PBMC from 12 patients with major depressive disorder was examined before and after an 8-week treatment with paroxetine at 20-50 mg/day. Ten healthy subjects were analyzed in parallel. The relative content of D4DR mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). using beta-actin as internal standard. RESULTS D4DR mRNA levels were significantly decreased in untreated depressed patients as compared to controls. D4DR mRNA expression returned to control levels after paroxetine treatment, when patients achieved a significant improvement of depressive symptoms. CONCLUSIONS Results of our study suggest the role of PBMC D4DR mRNA expression as a peripheral marker of the central dopaminergic function in major depression.

Suicide and depression.

Suicide is difficult to predict, has the potential for catastrophic outcome, and is preventable. Although some persons admit freely to feelings of sadness and wishes for their lives to be over, others offer little, if any, overt forecasting of impending self-harm. Many of these same people seek help under other auspices. Approximately two thirds of those who commit suicide had visited a physician during the preceding month. Recognizing the signs and symptoms with which suicide-prone patients present to emergency departments is central to preventing unnecessary death, injury, and disability caused by failed attempts. The common presentations of patients at risk for suicide and some of the psychiatric conditions that carry a risk for suicide are reviewed.

Peripheral-type benzodiazepine receptors and diazepam binding inhibitor-like immunoreactivity distribution in human peripheral blood mononuclear cells

Peripheral-type benzodiazepine receptors (pBZr) in human lymphocytes have been detected only in mixtures of peripheral blood mononuclear cells (PBMC). The present investigation was designed to describe precisely the location of pBZr in the various sets and subsets of PBMC, purified using monoclonal antibodies to specific PBMC surface markers. Site densities and affinities of pBZr were measured in the intact cells by conventional binding, using 3H-PK 11195 as a ligand. Moreover, we used a specific radioimmunoassay to identify in these cells the presence of the polypeptide diazepam binding inhibitor (DBI), a putative endogenous ligand for various benzodiazepine receptors including the peripheral type. Two major findings are derived from these studies: first, the coexistence of pBZr and DBI, or closely related immunoreactive material, in all major lymphocyte sets and subsets, as well as in monocytes. And second, the significant correlation (r = 0.87, p < 0.001) observed between the density of pBZr in a given cell type and its abundance of DBI like-immunoreactivity (DBI-LI). For both pBZr and DBI-LI content the cell distribution was monocytes > B cells and large granular lymphocytes > T cells (CD3+ set or CD4+ and CD8+ subsets) (ANOVA: pBZr: F = 114.11, p < 0.001; DBI-LI: F = 20.79, p < 0.001). The results are discussed in terms of the possibility that DBI and pBZr might share a relevant interaction in immunocompetent elements, thereby contributing to a new route of connection between the immune and the nervous systems.

A comparison of paroxetine and amisulpride in the treatment of dysthymic disorder.

BACKGROUND The purpose of this study was to provide preliminary data on the effects of paroxetine and amisulpride on depressive dimensions, analyzed by factor analysis, in dysthymic patients. METHODS One hundred and eighteen patients with DSM IV criteria for DD without concurrent major depression were enrolled in this 8-week, open study, and 100 completed it. Symptom dimensions were identified by principal components analysis with the SAS Factor procedure. RESULTS Results of the symptom rating scales indicated that both drugs were equally effective. Response rate was 65% both in the paroxetine and the amisulpride group and the proportions of patients achieving a final HRSD score < or =7 were 46.7 and 55%, respectively. MADRS factor analysis identified two factors at baseline: the first corresponding to the global severity of depression and the second to somatic symptoms. After 8 weeks of treatment only one factor could be substantiated. At week 4 both paroxetine and amisulpride produced significant improvements on factor 1 while at week 8 mean changes of factor 1 were greater in the amisulpride-treated patients. LIMITATIONS The main limitation was the open-label design. CONCLUSIONS Both paroxetine and amisulpride appear to be effective in the short-term management of DD, improving its most characteristic symptoms.

Obsessive‐compulsive syndromes in older adolescents

Objective