Signs of an inflammatory process, in particular increased pro-inflammatory cytokines and increased levels of prostaglandine E 2 (PGE 2 ), have repeatedly been described in major depression (MD). As cyclooxygenase-2 (COX-2) inhibitors inhibit the PGE 2 production and the production of pro-inflammatory cytokines, we performed a therapeutic trial with the COX-2 inhibitor celecoxib. In a prospective, double-blind, add-on study, 40 patients suffering from an acute depressive episode were randomly assigned to either reboxetine and celecoxib or to reboxetine plus placebo. After a wash-out period, 20 patients received 4-10 mg reboxetine plus placebo and 20 received reboxetine plus 400 mg celecoxib for 6 weeks. The treatment effect was calculated by analysis of variance. There were no significant differences between groups in age, sex, duration or severity of disease or psychopathology, or reboxetine dose or plasma levels. Over 6 weeks, both groups of patients showed significant improvement in scores of the Hamilton Depression Scale. However, the celecoxib group showed significantly greater improvement compared to the reboxetine-alone group. Additional treatment with celecoxib has significant positive effects on the therapeutic action of reboxetine with regard to depressive symptomatology. Moreover, the fact that treatment with an anti-inflammatory drug showed beneficial effects on MD indicates that inflammation is related to the pathomechanism of the disorder, although the exact mechanisms remain to become elucidated.

With the widespread use of atypical or second-generation antipsychotics, switching treatment has become current practice and more complicated, as the pharmacological profiles of these agents differ substantially despite their similarity in being 'atypical'. All share the ability to block dopamine D₂ receptors, and most of them also block serotonin 5-HT2A receptors. Apart from these common features, some atypical antipsychotics are also able to block or stimulate other dopamine or serotonin receptors, as well as histaminergic, muscarinergic or adrenergic receptors. As a result of the varying receptor affinities, in switching or discontinuing compounds several possible pitfalls have to be considered, including the occurrence of withdrawal and rebound syndromes. This article reviews the pharmacological background of functional blockade or stimulation of receptors of interest in regard to atypical antipsychotics and the implicated potential withdrawal and rebound phenomena. A MEDLINE search was carried out to identify information on withdrawal or rebound syndromes occurring after discontinuation of atypical antipsychotics. Using the resulting literature, we first discuss the theoretical background to the functional consequences of atypical antipsychotic-induced blockade or stimulation of neurotransmitter receptors and, secondly, we highlight the clinical consequences of this. We then review the available clinical literature on switching between atypical antipsychotics, with respect to the occurrence of withdrawal or rebound symptoms. Finally, we offer practical recommendations based on the reviewed findings. The systematic evaluation of withdrawal or rebound phenomena using randomized controlled trials is still understudied. Knowledge of pharmacological receptor-binding profiles may help clinicians in choosing adequate switching or discontinuation strategies for each agent. Results from large switching trials indicate that switching atypical antipsychotics can be performed in a safe manner. Treatment-emergent adverse events during or after switching are not always considered to be, at least in part, associated with the pre-switch antipsychotic. Further studies are needed to substantiate the evidence gained so far on different switching strategies. The use of concomitant medication, e.g., benzodiazepines or anticholinergic drugs, may help to minimize symptoms arising from the discontinuation or switching of antipsychotic treatment.

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Deficits in executive functions, e.g. voluntary selection, are considered central to the attention-deficit/hyperactivity disorder (ADHD). The aim of this simultaneous EEG/fMRI study was to examine associated neural correlates in ADHD patients. Patients with ADHD and healthy subjects performed an adapted go/nogo task including a voluntary selection condition allowing participants to freely decide, whether to press the response button. Electrophysiologically, response inhibition and voluntary selection led to fronto-central responses. The fMRI data revealed increased medial/lateral frontal and parietal activity during the voluntary selection task. Frontal brain responses were reduced in ADHD patients compared to controls during free responses, whereas parietal brain functions seemed to be unaffected. These results may indicate that selection processes are related to dysfunctions, predominantly in frontal brain regions in ADHD patients.

The results may indicate that schizophrenia is a static disorder with trait and state dependent cognitive components especially in the memory domains. The influence of negative and depressive symptoms should be considered in daily clinical routine.