The mesolimbic dopaminergic system is a neuroanatomical key structure for reward and motivation upon which previous studies indicated that antidepressant drugs exert a stimulatory influence, via still unknown neurobiological mechanisms. Here we examined the effects of chronic administration of antidepressants of several classes (amitriptyline, desipramine, imipramine, fluoxetine and tranylcypromine) and repeated electroconvulsive shock treatments (ECT) on dopamine D 3 receptor expression in the shell of the nucleus accumbens, a major projection area of the mesolimbic dopaminergic system. Short-term drug treatments had variable effects on D

Fluvoxamine (FLUVOX) is an inhibitor of the cytochrome P450 isoenzyme 1 A2 and thereby inhibits clozapine (CLOZ) metabolism. We performed an open clinical study to gather experience in necessary dosages, plasma levels, side effects and clinical efficiency of the coadministration of the two drugs. Eighteen psychotic patients were studied. 50 mg FLUVOX were given throughout the study period, while the CLOZ dosage was increased individually (week 5: 96.9+/-37.2 mg). After 5 weeks the plasma concentrations were as follows: CLOZ 252+/-174 ng/ml, N-desmethylclozapine (DM-CLOZ) 143+/-74 ng/ml and clozapine N-oxide (CLOZ N-OX) 30+/-14 ng/ml. There were no differences in side effects, especially sedation, after 5 weeks compared to the pretreatment condition. Moreover, we found a significant improvement in measures of cognitive speed which might be regarded as a measure of vigilance. The BPRS scores dropped continuously until week 5 (pretreatment: 53.3+/-13.4; week 5: 33.2+/-12.9) and 5 patients were considered treatment responders (BPRS reduction > 50%). Ten patients continued the combination treatment after the study period and 9 of these patients were in clinical remission when discharged. Given strict therapeutic drug monitoring, coadministration of FLUVOX and CLOZ seems to be a safe and efficient treatment strategy with a low occurrence of the side effects associated with CLOZ treatment. This might be due to additive effects of the two drugs and/or metabolic interaction.

Color-coded image of dopamine D3 receptor in situ hybridization in rat brain, in which black is the highest and yellow the lowest signals. The area above the black islands is the shell of nucleus accumbens, the main projection area of the dopamine mesolimbic system, where D3 receptor expression is increased by all chronic antidepressant treatments. For more information on this topic see the article by CH Lammers in the next issue of Molecular Psychiatry.

There is only a paucity of studies concerning the pharmacological treatment of personality disorders per se. On the other hand the clinical use of medication in these conditions is quite high, although there is no effective psychopharmacological treatment of distinct personality disorders. The psychopharmacological treatment of patients suffering from a personality disorder focuses on distinct symptoms and its comorbidity. Some symptoms could also be associated with other disorders like depression or psychosis, which often makes an exact differentiation of these disorders and a personality disorder difficult. Since symptoms of personality disorders are ego-syntonic, chronic and very often dependent on psychosocial factors, it is unlikely that a solely psychopharmacological treatment will be successful in most patients with a personality disorder. However, severe syndromes like depressive, impulsive, aggressive, dissociative, anxious or psychotic features may render a pharmacotherapy necessary. For the treatment of depressive syndromes or impulsivity a medical therapy with serotonin reuptake inhibitors, for the treatment of psychotic syndromes a medication with atypical antipsychotics is recommended. Impulsive or aggressive behaviour could be treated with mood stabilizers as well. Furthermore, there are indications for the use of alpha2-agonists, micro-opiate-antagonists and omega-3 fatty acid. The general use of benzodiazepines should be avoided as well as polypragmasy. Advantages versus potential damage of a high dose pharmacotherapy should be carefully weighed against each other. This article gives an overview over the today's most common psychopharmacological treatment possibilities in patients with a personality disorder.