E. Zanalda

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.

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.

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.

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.